leptin has been researched along with Inflammation* in 1080 studies
234 review(s) available for leptin and Inflammation
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The effects of probiotic and synbiotic supplementation on inflammation, oxidative stress, and circulating adiponectin and leptin concentration in subjects with prediabetes and type 2 diabetes mellitus: a GRADE-assessed systematic review, meta-analysis, an
Probiotics or synbiotics consumption have been suggested to reduce the risk of cardiovascular disease (CVD) through a decline in inflammation and oxidative stress, however, the results from studies are conflicting. This study filled this knowledge gap by evaluating randomized controlled trials (RCTs) investigating probiotics or synbiotics intake on adipokines, inflammation, and oxidative stress in patients with prediabetes and type-2 diabetes mellitus (T2DM).. We systematically did search up to March 2022 in PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library. A random-effect model was applied to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each outcome.. A total of 32 RCTs were included in the meta-analysis. This intervention led to a significant decrease in levels of C-reactive protein (CRP) (WMD - 0.62 mg/l; 95% CI - 0.80, - 0.44; p < 0.001), tumor necrosis factor-α (TNF-α) (WMD - 0.27 pg/ml; 95% CI - 0.44, - 0.10; p = 0.002) and malondialdehyde (MDA) (WMD - 0.51 µmol/l; 95% CI - 0.73, - 0.30; p < 0.001), and also a significant increase in levels of glutathione (GSH) (WMD 69.80 µmol/l; 95% CI 33.65, 105.95; p < 0.001), total antioxidant capacity (TAC) (WMD 73.59 mmol/l; 95% CI 33.24, 113.95; p < 0.001) and nitric oxide (NO) (WMD 7.49 µmol/l; 95% CI 3.12, 11.86; p = 0.001), without significant alterations in interleukin-6 (IL-6) and adipokines levels.. A consumption of probiotics or synbiotics could be a useful intervention to improve cardiometabolic outcomes through a reduced inflammation and oxidative stress in patients with prediabetes and T2DM. Topics: Adipokines; Adiponectin; Diabetes Mellitus, Type 2; Dietary Supplements; Glutathione; Humans; Inflammation; Leptin; Oxidative Stress; Prediabetic State; Probiotics; Randomized Controlled Trials as Topic; Synbiotics | 2023 |
Adipokines as an important link between hidradenitis suppurativa and obesity: a narrative review.
Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating disorder of the pilosebaceous unit. Although its pathophysiology is not fully explained, inflammation seems to play an essential role in the development of HS. A link between obesity - often considered a state of chronic inflammation - and a higher prevalence of HS has been described. Nevertheless, the exact association is not well understood. Adipose tissue is a highly active endocrine organ that produces and secretes a variety of metabolically and immunologically active molecules called adipokines. The imbalances in concentrations of several adipokines in patients with HS have already been described. A shift towards the overproduction of proinflammatory adipokines (including leptin, resistin and visfatin) with the suppression of anti-inflammatory ones (adiponectin) has been noted. We conducted a review of the available data on adipokines in HS, concentrating on the described imbalances in adipokine concentrations, as well as possible implications in HS pathogenesis. Moreover, new, unstudied adipokines with possible implications in the development of HS are proposed. Topics: Adipokines; Adiponectin; Hidradenitis Suppurativa; Humans; Inflammation; Leptin; Obesity | 2023 |
Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies.
Excess body weight is frequently associated with low-grade inflammation. Evidence indicates a relationship between obesity and cancer, as well as with other diseases, such as diabetes and non-alcoholic fatty liver disease, in which inflammation and the actions of various adipokines play a role in the pathological mechanisms involved in these disorders. Leptin is mainly produced by adipose tissue in proportion to fat stores, but it is also synthesized in other organs, where leptin receptors are expressed. This hormone performs numerous actions in the brain, mainly related to the control of energy homeostasis. It is also involved in neurogenesis and neuroprotection, and central leptin resistance is related to some neurological disorders, e.g., Parkinson's and Alzheimer's diseases. In peripheral tissues, leptin is implicated in the regulation of metabolism, as well as of bone density and muscle mass. All these actions can be affected by changes in leptin levels and the mechanisms associated with resistance to this hormone. This review will present recent advances in the molecular mechanisms of leptin action and their underlying roles in pathological situations, which may be of interest for revealing new approaches for the treatment of diseases where the actions of this adipokine might be compromised. Topics: Adipokines; Adipose Tissue; Humans; Inflammation; Leptin; Obesity | 2023 |
Association of obesity and cardiovascular disease and progress in pharmacotherapy: what is next for obesity?
Obesity has recently emerged as one of the most severe health concerns. Obesity is a key autonomous risk factor for heart failure and contributes to cardiovascular disease (CVD) risk factors such as hypertension, type 2 diabetes, and metabolic abnormalities. Obesity is caused by a metabolic imbalance, which occurs when calories burnt are fewer than the number of calories consumed. There are several pathways accountable for the adverse impacts of obesity on the cardiovascular system. Inflammatory cell infiltration develops in the adipose tissue, the pancreas, and other issues similar to the progression of obesity. Inflammation is triggered by immune cells that invade dysfunctional adipose tissue. The atherosclerotic inflammation phase, related to obesity, induces coronary calcification. Obesity is linked to elevated levels of leptin and high blood pressure. Leptin causes systemic vasoconstriction, sodium retention, and increased blood pressure by influencing the synthesis of nitric oxide and activating the sympathetic nervous system. Obesity is a well-known risk factor for CVD and is one of the leading causes of the greater risk of diseases, including dyslipidemia, hypertension, depression, metabolic syndrome, atrial fibrillation, and heart failure in adults and children. When used with dietary improvements, antiobesity drugs improve the probability of experiencing clinically healthy (5%) weight loss. This review aimed to address the consequences of obesity on cardiac structure and function, risk factors, the impact of the obesity paradox, pharmacological treatment strategies for managing and recommended exercise and diet. Topics: Adult; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypertension; Inflammation; Leptin; Obesity | 2023 |
The role of leptin and low testosterone in obesity.
Obesity is a medical condition associated with metabolic disorders and low-grade systemic inflammation. Another characterizing feature of obesity is high circulating levels of leptin (a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance), a phenomenon termed hyperleptinemia. Hyperleptinemia is associated with both low-grade systemic inflammation and metabolic dysfunction in obese human beings. Moreover, obesity is associated with low testosterone in men, which correlates with high body fat. The association between leptin and low testosterone could potentially be explained via the imbalanced leptin levels that results in higher estrogen levels, which further increases the aromatase activity. The increase in aromatase activity in turn reciprocally inhibits the testosterone levels and hypothalamic pituitary gonadal axis. Novel strategies are being used to treat obesity, including leptin and testosterone therapy. However, the efficacy and adverse effects of these strategies need further validation through preclinical and clinical studies. Additionally, further studies are needed to establish the molecular mechanism behind leptin-modulated changes to testosterone in obese men. This review summarizes the available literature on the role of leptin and low testosterone during obesity. Topics: Aromatase; Humans; Inflammation; Leptin; Male; Obesity; Testosterone | 2022 |
Obesity and Adipose Tissue-derived Cytokines in the Pathogenesis of Multiple Sclerosis.
Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, neuronal loss, and permanent neurological impairments. The etiology of MS is not clearly understood, but genetics and environmental factors can affect the susceptibility of individuals. Obesity or a body mass index of (BMI) > 30 kg/m2 is associated with serious health consequences such as lipid profile abnormalities, hypertension, type 2 diabetes mellitus, reduced levels of vitamin D, and a systemic lowgrade inflammatory state. The inflammatory milieu can negatively affect the CNS and promote MS pathogenesis due in part to the increased blood-brain barrier permeability by the actions of adipose tissue-derived cytokines or adipokines. By crossing the blood-brain barrier, the pro-inflammatory adipokines such as leptin, resistin, and visfatin activate the CNS-resident immune cells, and promote the inflammatory responses; subsequently, demyelinating lesions occur in the white matter of the brain and spinal cord. Therefore, better knowledge of the adipokines' role in the induction of obesity-related chronic inflammation and subsequent events leading to the dysfunctional blood-brain barrier is essential. In this review, recent evidence regarding the possible roles of obesity and its related systemic low-grade inflammation, and the roles of adipokines and their genetic variants in the modulation of immune responses and altered blood-brain barrier permeability in MS patients, has been elucidated. Besides, the results of the current studies regarding the potential use of adipokines in predicting MS disease severity and response to treatment have been explored. Topics: Adipokines; Adipose Tissue; Cytokines; Diabetes Mellitus, Type 2; Humans; Inflammation; Leptin; Lipids; Multiple Sclerosis; Neurodegenerative Diseases; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin; Vitamin D | 2022 |
Leptin in Osteoarthritis and Rheumatoid Arthritis: Player or Bystander?
White adipose tissue (WAT) is a specialized tissue whose main function is lipid synthesis and triglyceride storage. It is now considered as an active organ secreting a plethora of hormones and cytokines namely adipokines. Discovered in 1994, leptin has emerged as a key molecule with pleiotropic functions. It is primarily recognized for its role in regulating energy homeostasis and food intake. Currently, further evidence suggests its potent role in reproduction, glucose metabolism, hematopoiesis, and interaction with the immune system. It is implicated in both innate and adaptive immunity, and it is reported to contribute, with other adipokines, in the cross-talking networks involved in the pathogenesis of chronic inflammation and immune-related diseases of the musculo-skeletal system such as osteoarthritis (OA) and rheumatoid arthritis (RA). In this review, we summarize the most recent findings concerning the involvement of leptin in immunity and inflammatory responses in OA and RA. Topics: Adipokines; Arthritis, Rheumatoid; Humans; Immune System Diseases; Inflammation; Leptin; Osteoarthritis | 2022 |
Host immune responses and possible therapeutic targets for viral respiratory tract infections in susceptible populations: a narrative review.
Respiratory viruses are associated with significant global morbidity and mortality, as well as socioeconomic factors. Certain conditions and patient groups are more susceptible to develop severe viral respiratory tract infections (RTIs).. To summarise the data on deregulated immune pathways that have been associated with increased susceptibility to severe viral RTIs in certain populations. We also describe the commonalities of the defective immune pathways across these susceptible populations that may represent possible targets for future therapeutic or preventative approaches.. We conducted free searches in Medline, Scopus, and Google Scholar for studies focusing on potential mechanisms of immune dysfunction that may be associated with severe viral RTIs in susceptible populations with conditions including pregnancy, obesity, diabetes mellitus, hypertension, cardiovascular disease, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and extremes of age. We considered preclinical/animal data, original human studies, and reviews.. Innate and adaptive immune responses become quantitatively and qualitatively compromised in aging, obesity, and diabetes mellitus, with the most pronounced changes affecting T cells. Moreover, immune dysregulation by the so-called inflamm-aging results in chronic low-grade inflammation in such conditions. Increased leptin levels affect the immune system particularly in obesity, while leptin dysregulation plays a role in asthma and COPD pathogenesis. Deficient production of interferon (IFN) type I and III in response to rhinovirus contributes to asthma exacerbations. Similar attenuation of IFN production in response to influenza and rhinovirus has been documented in pregnancy. Dampened type I IFN responses have also been found in diet-induced obese mice and in obese individuals.. Immunosenescence and chronic low-grade inflammation accompanying aging and a variety of chronic conditions, such as diabetes, obesity, asthma, COPD, chronic renal disease, and hypertension, contribute to the poor outcomes observed following viral respiratory infections. Commonly affected pathways may represent potential future therapeutic targets. Topics: Animals; Asthma; Disease Susceptibility; Enterovirus Infections; Humans; Hypertension; Immunity; Inflammation; Interferons; Leptin; Mice; Obesity; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Rhinovirus | 2022 |
Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19.
Obesity, and obesity-associated conditions such as hypertension, chronic kidney disease, type 2 diabetes, and cardiovascular disease, are important risk factors for severe Coronavirus disease-2019 (COVID-19). The common denominator is metaflammation, a portmanteau of metabolism and inflammation, which is characterized by chronically elevated levels of leptin and pro-inflammatory cytokines. These induce the "Suppressor Of Cytokine Signaling 1 and 3" (SOCS1/3), which deactivates the leptin receptor and also other SOCS1/3 sensitive cytokine receptors in immune cells, impairing the type I and III interferon early responses. By also upregulating SOCS1/3, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 adds a significant boost to this. The ensuing consequence is a delayed but over-reactive immune response, characterized by high-grade inflammation (e.g., cytokine storm), endothelial damage, and hypercoagulation, thus leading to severe COVID-19. Superimposing an acute disturbance, such as a SARS-CoV-2 infection, on metaflammation severely tests resilience. In the long run, metaflammation causes the "typical western" conditions associated with metabolic syndrome. Severe COVID-19 and other serious infectious diseases can be added to the list of its short-term consequences. Therefore, preventive measures should include not only vaccination and the well-established actions intended to avoid infection, but also dietary and lifestyle interventions aimed at improving body composition and preventing or reversing metaflammation. Topics: COVID-19; Humans; Inflammation; Interferon Type I; Leptin; Obesity; SARS-CoV-2 | 2022 |
Chronic Inflammation-A Link between Nonalcoholic Fatty Liver Disease (NAFLD) and Dysfunctional Adipose Tissue.
Nonalcoholic fatty liver disease (NAFLD) is a new challenge in modern medicine, due to its high prevalence in the world. The pathogenesis of NAFLD is a complex dysmetabolic process, following the "multiple-hit" hypothesis that involves hepatocytes excessive accumulation of triglycerides, insulin resistance (IR), increased oxidative stress, chronic low-grade inflammatory response and lipotoxicity. In this review, we provide an overview of the interrelation of these processes, the link between systemic and local inflammation and the role of dysfunctional adipose tissue (AT) in the NAFLD development. Multiple extrahepatic triggers of the pathophysiological mechanisms of NAFLD are described: nutritional deficiency or malnutrition, unhealthy food intake, the dysfunction of the liver-gut axis, the involvement of the mesenteric adipose tissue, the role of adipokines such as adiponectin, of food intake hormone, the leptin and leptin resistance (LR) and adipose tissue's hormone, the resistin. In addition, a wide range of intrahepatic players are involved: oxidative stress, fatty acid oxidation, endoplasmic reticulum stress, mitochondrial dysfunction, resident macrophages (Kupffer cells), neutrophils, dendritic cells (DCs), B and T lymphocytes contributing to the potential evolution of NAFLD to nonalcoholic steatohepatitis (NASH). This interdependent approach to complex dysmetabolic imbalance in NAFLD, integrating relevant studies, could contribute to a better clarification of pathogenesis and consequently the development of new personalized treatments, targeting de novo lipogenesis, chronic inflammation and fibrosis. Further studies are needed to focus not only on treatment, but also on prevention strategy in NAFLD. Topics: Adipose Tissue; Humans; Inflammation; Leptin; Non-alcoholic Fatty Liver Disease | 2022 |
Mediation effects of diabetes and inflammation on the relationship of obesity to cognitive impairment in African Americans.
Whether diabetes and adipokine-driven inflammation explain the association of obesity to cognitive impairment is unknown.. Structural equation models estimated the total effects of waist circumference on cognitive outcomes among African American participants cross-sectionally (index exam) and longitudinally. Total effects were deconstructed into direct pathways of waist circumference to cognitive impairment and indirect mediation pathways through leptin, soluble tumor necrosis factor receptor 2 (sTNFR2), and diabetes. Waist circumference, leptin, and sTNFR2 were standardized. Cognitive impairment was defined as MMSE <21 or a z-score < -1.5 standard deviation (SD). Incident cognitive impairment was defined among those without cognitive impairment at the index exam as follow-up MMSE<21, z- score < -1.5, MMSE decline >1 point/year, or z-score decline of >0.1 SD/year.. Among 1008 participants (70% women, mean age 62.9 years, 14.5% with obesity, 26% with diabetes), 132 (13%) had baseline cognitive impairment. Each SD higher waist circumference was associated with higher odds of cognitive impairment, odds ratio (OR) = 1.63; (95% confidence interval: 1.17, 2.24), with mediating pathways explaining 65% of the total effect (58% from diabetes; 7% from inflammation). At follow-up (mean 6.8 years), 106 of 535 (19.8%) had developed cognitive impairment. Each SD higher waist circumference was associated with higher odds of developing cognitive impairment (OR = 1.87; 95%CI: 1.18, 2.74); the direct effect of waist circumference explained 37% of the total effect and mediating pathways explained 63% (61% from diabetes; 2% from inflammation), although individual pathways were not statistically supported in the smaller sample.. Diabetes, and to a lesser degree, adiposity-driven inflammation, appear to explain a substantial proportion of abdominal adiposity relationships with cognitive impairment. The impact of preventing and treating obesity on cognitive outcomes merits study. Topics: Adipokines; Adiposity; Black or African American; Body Mass Index; Cognitive Dysfunction; Diabetes Mellitus; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Obesity; Receptors, Tumor Necrosis Factor, Type II; Risk Factors; Waist Circumference | 2022 |
Emerging role of leptin in joint inflammation and destruction.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by tumor-like hyperplasia and inflammation of the synovium, which causes synovial cell invasion into the bone and cartilage. In RA pathogenesis, various molecules in effector cells (i.e., immune cells and mesenchymal cells) are dysregulated by genetic and environmental factors. Consistent with the early stages of RA, these pathogenic cells cooperate and activate each other directly by cell-to-cell contact or indirectly Topics: Arthritis, Rheumatoid; Cartilage; Humans; Inflammation; Leptin; Synovial Membrane | 2022 |
Molecular and Cellular Bases of Lipodystrophy Syndromes.
Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic or acquired causes, but leads to similar metabolic complications with insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, dysfunctions of the gonadotropic axis and endocrine defects of adipose tissue with leptin and adiponectin deficiency. Diagnosis, based on clinical and metabolic investigations, and on genetic analyses, is of major importance to adapt medical care and genetic counseling. Molecular and cellular bases of these syndromes involve, among others, altered adipocyte differentiation, structure and/or regulation of the adipocyte lipid droplet, and/or premature cellular senescence. Lipodystrophy syndromes frequently present as systemic diseases with multi-tissue involvement. After an update on the main molecular bases and clinical forms of lipodystrophy, we will focus on topics that have recently emerged in the field. We will discuss the links between lipodystrophy and premature ageing and/or immuno-inflammatory aggressions of adipose tissue, as well as the relationships between lipomatosis and lipodystrophy. Finally, the indications of substitutive therapy with metreleptin, an analog of leptin, which is approved in Europe and USA, will be discussed. Topics: Adipocytes; Adipose Tissue; Aging, Premature; Humans; Inflammation; Insulin Resistance; Leptin; Lipodystrophy; Lipomatosis; Syndrome | 2021 |
Psychological distress among health care professionals of the three COVID-19 most affected Regions in Cameroon: Prevalence and associated factors.
The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted. 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Hearing Loss; Heart Failure; Hedgehog Proteins; HEK293 Cells; HeLa Cells; Hemodynamics; Hemorrhage; Hepatocytes; Hippo Signaling Pathway; Histone Deacetylases; Homeostasis; Hospital Mortality; Hospitalization; Humans; Hydantoins; Hydrazines; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydroxylamines; Hypoglycemic Agents; Immunity, Innate; Immunoglobulin G; Immunohistochemistry; Immunologic Factors; Immunomodulation; Immunophenotyping; Immunotherapy; Incidence; Indazoles; Indonesia; Infant; Infant, Newborn; Infarction, Middle Cerebral Artery; Inflammation; Injections, Intramuscular; Insecticides; Insulin-Like Growth Factor I; Insurance, Health; Intention to Treat Analysis; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Intrauterine Devices; Intrauterine Devices, Copper; Iron; Ischemia; Jordan; Keratinocytes; Kidney; Kidney Diseases; Kir5.1 Channel; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Laparoscopy; Lasers; Lasers, Semiconductor; Lenalidomide; Leptin; Lethal Dose 50; Levonorgestrel; Limit of Detection; Lipid Metabolism; Lipid Metabolism Disorders; Lipogenesis; Lipopolysaccharides; Liquid Biopsy; Liver; Liver Abscess, Pyogenic; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Longevity; Lung Neoplasms; Luteolin; Lymph Nodes; Lymphocyte Activation; Macaca fascicularis; Macrophages; Mad2 Proteins; Magnetic Resonance Imaging; Male; Mammary Glands, Human; Manganese; Manganese Compounds; MAP Kinase Signaling System; Materials Testing; Maternal Health Services; MCF-7 Cells; Medicaid; Medicine, Chinese Traditional; Melanoma; Membrane Proteins; Mental Health; Mercury; Metal Nanoparticles; Metals, Heavy; Metformin; Methionine Adenosyltransferase; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Mice, Nude; Microalgae; Microbial Sensitivity Tests; Microglia; MicroRNAs; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Middle Aged; Mitochondria; Mitochondrial Proteins; Mitral Valve; Mitral Valve Insufficiency; Models, Anatomic; Molecular Structure; Molybdenum; Monocarboxylic Acid Transporters; Moths; MPTP Poisoning; Multigene Family; Multiparametric Magnetic Resonance Imaging; Multiple Myeloma; Muscle, Skeletal; Mutagens; Mutation; Myeloid Cells; Nanocomposites; Nanofibers; Nanomedicine; Nanoparticles; Nanowires; Neoadjuvant Therapy; Neomycin; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Stem Cells; Neostriatum; Neovascularization, Pathologic; Netherlands; Neuromuscular Agents; Neurons; NF-E2-Related Factor 2; NF-kappa B; Nickel; Nitrogen Oxides; Non-alcoholic Fatty Liver Disease; Nucleosides; Nucleotidyltransferases; Nutritional Status; Obesity, Morbid; Ofloxacin; Oils, Volatile; Oligopeptides; Oncogene Protein v-akt; Optical Imaging; Organic Cation Transport Proteins; Organophosphonates; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Osteoblasts; Osteogenesis; Oxidation-Reduction; Oxidative Stress; Oxides; Oxygen Isotopes; Pancreas; Pancreaticoduodenectomy; Pandemics; Particle Size; Particulate Matter; Patient Acceptance of Health Care; Patient Compliance; PC-3 Cells; Peptide Fragments; Peptides; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Peroxides; Peru; Pest Control, Biological; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phylogeny; Pilot Projects; Piperidines; Plant Bark; Plant Extracts; Plant Leaves; Plasmids; Platelet Function Tests; Pneumonia, Viral; Podocytes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Polyethylene Terephthalates; Polymers; Polymorphism, Single Nucleotide; Porosity; Portugal; Positron-Emission Tomography; Postoperative Complications; Postural Balance; Potassium Channels, Inwardly Rectifying; Povidone; Powders; Precancerous Conditions; Precision Medicine; Predictive Value of Tests; Pregnancy; Prenatal Care; Prognosis; Promoter Regions, Genetic; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Proteasome Inhibitors; Protective Agents; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein Transport; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-akt; Psychiatric Nursing; PTEN Phosphohydrolase; Pulmonary Embolism; Pyrimethamine; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reactive Oxygen Species; Receptor, ErbB-2; Receptor, IGF Type 1; Receptors, Estrogen; Receptors, G-Protein-Coupled; Recombinational DNA Repair; Recovery of Function; Regional Blood Flow; Renal Dialysis; Renin; Renin-Angiotensin System; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Distress Syndrome; Retrospective Studies; Rhodamines; Risk Assessment; Risk Factors; RNA, Long Noncoding; RNA, Messenger; Running; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salinity; Salmeterol Xinafoate; Sarcoma; Seasons; Shoulder Injuries; Signal Transduction; Silicon Dioxide; Silver; Sirtuin 1; Sirtuins; Skull Fractures; Social Determinants of Health; Sodium; Sodium Fluoride; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Soil; Soil Pollutants; Spain; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Staphylococcal Protein A; Staphylococcus aureus; Stem Cells; Stereoisomerism; Stomach Neoplasms; Streptomyces; Strontium; Structure-Activity Relationship; Students, Nursing; Substance-Related Disorders; Succinic Acid; Sulfur; Surface Properties; Survival Rate; Survivin; Symporters; T-Lymphocytes; Temozolomide; Tensile Strength; Thiazoles; Thiobacillus; Thiohydantoins; Thiourea; Thrombectomy; Time Factors; Titanium; Tobacco Mosaic Virus; Tobacco Use Disorder; Toll-Like Receptor 4; Toluene; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Toxicity Tests, Acute; Toxicity Tests, Subacute; Transcriptional Activation; Treatment Outcome; Troponin I; Tumor Cells, Cultured; Tumor Escape; Tumor Hypoxia; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Tyrosine; Ubiquitin-Protein Ligases; Ubiquitination; Ultrasonic Waves; United Kingdom; United States; United States Department of Veterans Affairs; Up-Regulation; Urea; Uric Acid; Urinary Bladder Neoplasms; Urinary Bladder, Neurogenic; Urine; Urodynamics; User-Computer Interface; Vemurafenib; Verbenaceae; Veterans; Veterans Health; Viral Load; Virtual Reality; Vitiligo; Water Pollutants, Chemical; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Xylenes; Young Adult; Zinc; Zinc Oxide; Zinc Sulfate; Zoonoses | 2021 |
Effect of physical activity promotion on adiponectin, leptin and other inflammatory markers in prediabetes: a systematic review and meta-analysis of randomized controlled trials.
Inflammatory stage in prediabetes is associated with increase in level of adipokines and pro-inflammatory cytokines. Physical activity promotion considered as a first-line therapeutic strategy to treat prediabetes. We have conducted the systematic review and meta-analysis to strengthen the evidence on the impact of physical activity promotion on inflammatory markers in prediabetes.. Studies were identified using electronic search and manual search techniques by choosing keywords for prediabetes, physical activity and inflammatory marker. Randomized controlled trials on individuals diagnosed with prediabetes and provided intervention in the form of physical activity were included in this review. Adiponectin, leptin, C-reactive protein, interleukin-6 and tumour necrosis factor-α were the considered outcome measures.. Our search retrieved 1,688 citations, 31 full-text articles assessed for eligibility of inclusion. Nine studies satisfied the pre-specified criteria for inclusion. Meta-analysis found that physical activity with or without dietary or lifestyle modification reduces level of leptin (MD-2.11 ng/mL, 95% CI -3.81 - -0.42) and interleukin-6 (MD -0.15 pg/mL, 95% CI -0.25--0.04). It has no effect on level of adiponectin (MD 0.26 µg/mL, 95% CI -0.42- 0.93), C-reactive protein (MD -0.05 mg/L, 95% CI -0.33-0.23) and tumour necrosis factor-α (MD 0.67 pg/mL, 95% CI -2.56-3.89).. This review suggests that physical activity promotion with dietary and lifestyle modification may reduce the level of leptin and interleukin-6 but are uncertain if there is any effect on levels of adiponectin, C-reactive protein and tumour necrosis factor-α in the individuals with prediabetes. Topics: Adipokines; Adiponectin; Adult; Aged; Biomarkers; C-Reactive Protein; Cytokines; Exercise; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Middle Aged; Prediabetic State; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha; Young Adult | 2021 |
Nutritional modulation of leptin expression and leptin action in obesity and obesity-associated complications.
In obesity, an elevated accumulation and dysregulation of adipose tissue, due to an imbalance between energy intake and energy expenditure, usually coexists with the loss of responsiveness to leptin in central nervous system, and subsequently with hyperleptinemia. Leptin, a peptide hormone mainly produced by white adipose tissue, regulates energy homeostasis by stimulating energy expenditure and inhibiting food intake. Human obesity is characterized by increased plasma leptin levels, which have been related with different obesity-associated complications, such as chronic inflammatory state (risk factor for diabetes, cardiovascular and autoimmune diseases), as well as infertility and different types of cancer. Besides, leptin is also produced by placenta, and high leptin levels during pregnancy may be related with some pathological conditions such as gestational diabetes. This review focuses on the current insights and emerging concepts on potentially valuable nutrients and food components that may modulate leptin metabolism. Notably, several dietary food components, such as phenols, peptides, and vitamins, are able to decrease inflammation and improve leptin sensitivity by up- or down-regulation of leptin signaling molecules. On the other hand, some food components, such as saturated fatty acids may worsen chronic inflammation increasing the risk for pathological complications. Future research into nutritional mechanisms that restore leptin metabolism and signals of energy homeostasis may inspire new treatment options for obesity-related disorders. Topics: Adipose Tissue; Adipose Tissue, White; Animals; Autoimmune Diseases; Diabetes Mellitus; Energy Intake; Energy Metabolism; Fatty Acids; Female; Humans; Infertility; Inflammation; Leptin; Male; Neoplasms; Nutritional Physiological Phenomena; Obesity | 2021 |
Contribution of RAGE axis activation to the association between metabolic syndrome and cancer.
Far beyond the compelling proofs supporting that the metabolic syndrome represents a risk factor for diabetes and cardiovascular diseases, a growing body of evidence suggests that it is also a risk factor for different types of cancer. However, the involved molecular mechanisms underlying this association are not fully understood, and they have been mainly focused on the individual contributions of each component of the metabolic syndrome such as obesity, hyperglycemia, and high blood pressure to the development of cancer. The Receptor for Advanced Glycation End-products (RAGE) axis activation has emerged as an important contributor to the pathophysiology of many clinical entities, by fueling a chronic inflammatory milieu, and thus supporting an optimal microenvironment to promote tumor growth and progression. In the present review, we intend to highlight that RAGE axis activation is a crosswise element on the potential mechanistic contributions of some relevant components of metabolic syndrome into the association with cancer. Topics: Adiponectin; Adipose Tissue; Animals; Disease Progression; Gene Expression Regulation; Humans; Hyperglycemia; Hypertension; Inflammation; Insulin-Like Growth Factor I; Leptin; Ligands; Metabolic Syndrome; Mice; Neoplasms; Obesity; Peroxisome Proliferator-Activated Receptors; Rats; Receptor for Advanced Glycation End Products; Signal Transduction; Vascular Endothelial Growth Factor A; Wnt Proteins | 2021 |
Leptin levels in patients with Parkinson's disease: A systematic review and meta-analysis.
The exact mechanism of Parkinson's disease (PD) is not fully understood yet, but it is suggested that inflammation is one of its contributing factors. Among several inflammatory factors, adipokines, especially leptin may have a great role in this mechanism; since it is not only causing inflammation, but it can also play other roles in the body that may contribute to the symptoms described for PD. Regarding the contradictions in the association of serum leptin levels with Parkinson's disease, a systematic review and meta-analysis was performed to have a more accurate estimation of this relationship.. Published literature was obtained by searching PubMed, Embase, Cochrane Library, Scopus, Ovid, ProQuest and Google Scholar. Random-effect model analysis was used to calculate pooled standard mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was tested with the heterogeneity statistic Q and quantified using I. Six studies including a total number of 198 PD patients and 182 controls were finally included in the meta-analysis. Serum leptin levels in PD patients were non-significantly lower than those in control group (SMD = -0.40 ng/ml, 95% CI -2.33-1.53). Subgroup analyses revealed that serum leptin levels of PD patients and controls in either females or males didn't show any significant difference.. This meta-analysis revealed that leptin level doesn't show any significant difference between PD patients and healthy controls, even when taking the participants' gender into consideration. Topics: Female; Humans; Inflammation; Leptin; Male; Parkinson Disease | 2021 |
Tumor Metabolic Reprogramming by Adipokines as a Critical Driver of Obesity-Associated Cancer Progression.
Adiposity is associated with an increased risk of various types of carcinoma. One of the plausible mechanisms underlying the tumor-promoting role of obesity is an aberrant secretion of adipokines, a group of hormones secreted from adipose tissue, which have exhibited both oncogenic and tumor-suppressing properties in an adipokine type- and context-dependent manner. Increasing evidence has indicated that these adipose tissue-derived hormones differentially modulate cancer cell-specific metabolism. Some adipokines, such as leptin, resistin, and visfatin, which are overproduced in obesity and widely implicated in different stages of cancer, promote cellular glucose and lipid metabolism. Conversely, adiponectin, an adipokine possessing potent anti-tumor activities, is linked to a more favorable metabolic phenotype. Adipokines may also play a pivotal role under the reciprocal regulation of metabolic rewiring of cancer cells in tumor microenvironment. Given the fact that metabolic reprogramming is one of the major hallmarks of cancer, understanding the modulatory effects of adipokines on alterations in cancer cell metabolism would provide insight into the crosstalk between obesity, adipokines, and tumorigenesis. In this review, we summarize recent insights into putative roles of adipokines as mediators of cellular metabolic rewiring in obesity-associated tumors, which plays a crucial role in determining the fate of tumor cells. Topics: Adipokines; Adipose Tissue; Adiposity; Animals; Disease Progression; Glucose; Glycolysis; Humans; Inflammation; Leptin; Lipid Metabolism; Mice; Mitochondria; Neoplasms; Nicotinamide Phosphoribosyltransferase; Obesity; Oxidation-Reduction; Phenotype; Reactive Oxygen Species; Resistin; Tumor Microenvironment | 2021 |
Effects of Diet and Exercise-Induced Weight Loss on Biomarkers of Inflammation in Breast Cancer Survivors: A Systematic Review and Meta-analysis.
Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy balance through exercise and/or caloric restriction, decreases risk of breast cancer recurrence.. We investigated the effects of lifestyle modifications (exercise only, or combined caloric restriction and exercise) on adipokines, IL2, IL6, IL8, IL10, C-reactive protein (CRP), and TNFα biomarkers in breast cancer survivors. Searches were completed in June and July of 2019 to identify randomized controlled trials that met inclusion criteria. Weighted mean difference was calculated using random- or fixed-effects models based on the heterogeneity of the studies.. 2501 records were identified, with 30 ultimately meeting inclusion criteria of the systematic review; 21 studies provided data suitable for meta-analysis. We observed leptin levels were significantly reduced in the exercise-only group compared with sedentary control [WMD -5.66; 95% confidence interval (CI), -11.0 to -0.33;. Leptin may be a primary mediator of exercise-induced improvements in breast cancer recurrence.. This is the first review and meta-analysis to examine combined exercise and caloric restriction programs in breast cancer survivors. Future studies should further examine combined programs and their efficacy for altering leptin. Topics: Biomarkers; Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; Cancer Survivors; Diet, Healthy; Exercise; Female; Humans; Inflammation; Leptin; Neoplasm Recurrence, Local; Weight Loss | 2021 |
The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections.
Obesity is a globally increasing health problem, entailing diverse comorbidities such as infectious diseases. An obese weight status has marked effects on lung function that can be attributed to mechanical dysfunctions. Moreover, the alterations of adipocyte-derived signal mediators strongly influence the regulation of inflammation, resulting in chronic low-grade inflammation. Our review summarizes the known effects regarding pulmonary bacterial and viral infections. For this, we discuss model systems that allow mechanistic investigation of the interplay between obesity and lung infections. Overall, obesity gives rise to a higher susceptibility to infectious pathogens, but the pathogenetic process is not clearly defined. Whereas, viral infections often show a more severe course in obese patients, the same patients seem to have a survival benefit during bacterial infections. In particular, we summarize the main mechanical impairments in the pulmonary tract caused by obesity. Moreover, we outline the main secretory changes within the expanded adipose tissue mass, resulting in chronic low-grade inflammation. Finally, we connect these altered host factors to the influence of obesity on the development of lung infection by summarizing observations from clinical and experimental data. Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Animals; Anti-Inflammatory Agents; Bacterial Infections; Cells, Cultured; Comorbidity; Female; Humans; Inflammation; Leptin; Lung; Macrophages; Male; Mice; Obesity; Risk Factors; Virus Diseases | 2021 |
The pleiotropic roles of leptin in metabolism, immunity, and cancer.
The discovery of the archetypal adipocytokine leptin and how it regulates energy homeostasis have represented breakthroughs in our understanding of the endocrine function of the adipose tissue and the biological determinants of human obesity. Investigations on leptin have also been instrumental in identifying physio-pathological connections between metabolic regulation and multiple immunological functions. For example, the description of the promoting activities of leptin on inflammation and cell proliferation have recognized the detrimental effects of leptin in connecting dysmetabolic conditions with cancer and with onset and/or progression of autoimmune disease. Here we review the multiple biological functions and complex framework of operations of leptin, discussing why and how the pleiotropic activities of this adipocytokine still pose major hurdles in the development of effective leptin-based therapeutic opportunities for different clinical conditions. Topics: Animals; Energy Metabolism; Gene Expression Regulation; Homeostasis; Humans; Inflammation; Leptin; Mutation; Neoplasms; Obesity | 2021 |
The bifurcated role of adiponectin in colorectal cancer.
The association of adiponectin with metabolism and cancer is well established. Since its discovery in 1990, adiponectin, as one of the adipose tissue-secreted adipokines, has been very widely studied in biomedical research. Low levels of circulatory adiponectin have been reported in obesity, inflammatory diseases and various types of cancers including colorectal cancer (CRC), which is highly linked with obesity and gut inflammation. However, the function and underlying mechanisms of adiponectin in CRC is not well understood. In addition, there are contradictory reports on the role of adiponectin in cancer. Therefore, further investigation is needed. In this review, we explore the information available on the relationship between adiponectin and CRC with respect to proliferation, cell survival, angiogenesis and inflammation. We also highlighted the knowledge gaps, filling in which could help us better understand the function and mechanisms of adiponectin in CRC. Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Biomarkers, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Leptin; Mice; Neoplasm Metastasis; Neovascularization, Pathologic; Obesity; Tumor Microenvironment | 2021 |
Leptin: an unappreciated key player in SLE.
Leptin is the forerunner of the adipokine superfamily and plays a key role in regulating energy expenditure and neuroendocrine function. Researches into leptin put emphasize not only on the metabolic role but also its immunoregulatory effect on immune response through immunocyte activation and cytokine secretion. Leptin acts on receptors that are widespread throughout the body and that are expressed across many tissue types. As a consequence, the abnormal expression of leptin has been found to correlate with a number of diseases, including cancers, autoimmune diseases, and cardiovascular diseases. The significance of leptin in the development of autoimmune diseases is becoming increasingly prominent. Systemic lupus erythematosus (SLE) is a severe atypical autoimmune disease that causes damage to multiple organ systems. It is characterised by the following: impaired clearance of apoptotic cells, loss of tolerance to self-antigens, aberrant activation of T cells and B cells, and chronic inflammation. The heightened immunocyte response in SLE means that these physiological systems are particularly vulnerable to regulation by leptin in addition to being of great significance to the research field. Our current review provides insight into the regulatory roles that leptin plays on immune effector cells in SLE. Topics: B-Lymphocytes; Cytokines; Humans; Inflammation; Leptin; Lupus Erythematosus, Systemic; Macrophages; Neutrophils; T-Lymphocytes, Regulatory; Th17 Cells | 2020 |
An update on the association between metabolic syndrome and osteoarthritis and on the potential role of leptin in osteoarthritis.
Metabolic syndrome (MetS) has been associated with osteoarthritis (OA). Leptin, which is one of the markers of MetS, has been associated with OA pathophysiology. This study aimed to provide an update on the association between MetS and OA and on the potential role of leptin in OA. In this review, we summarized the current knowledge of the association between MetS and OA and updated the evidence on the potential role of leptin in OA. Clinical studies have investigated the epidemiologic association between MetS or its components and OA. Results suggested strong epidemiologic associations between MetS and OA, especially in the Asian population. Animal studies also indicated that metabolic dysregulation may lead to OA pathogenesis. The systemic role of MetS in OA pathophysiology is associated with obesity-related inflammation, the beneficial role of n-3 polyunsaturated fatty acids and deleterious role of cholesterol, physical inactivity, hypertension-induced subchondral ischemia, dyslipidemia-induced ectopic lipid deposition in chondrocytes, hyperglycemia-induced local effects of oxidative stress and advanced glycation end-products, low-grade systemic inflammation, and obesity-related adipokines by inducing the expression of proinflammtory factors. Leptin levels in serum/plasma and synovial fluid were associated with joint pain, radiographic progression, bone formation biomarkers, cartilage volume, knee OA incidence, and total joint arthroplasty in OA patients. Elevated leptin expression and increased effect of leptin on infrapatellar fat pad, synovium, articular cartilage, and bone were also involved in the pathogenesis of OA. Current knowledge indicates a convincing epidemiologic association between MetS and OA, especially in the Asian population. Animal studies have also shown that metabolic dysregulation may lead to OA pathogenesis. Accumulating evidence suggests that leptin may play a potential role in OA pathogenesis. Therefore, leptin and its receptor may be an emerging target for intervention in metabolic-associated OA. Topics: Adipokines; Animals; Chondrocytes; Humans; Inflammation; Leptin; Metabolic Syndrome; Obesity; Osteoarthritis | 2020 |
The impact of high-intensity interval training on inflammatory markers in metabolic disorders: A meta-analysis.
High-intensity interval training (HIIT) is considered a time-efficient strategy to improve metabolic health. We performed a systematic meta-analysis to assess the effects of HIIT on inflammatory markers and adipo-cytokines compared with control conditions (CON) or moderate-intensity continuous training (MICT) in individuals with metabolic disorders.. Up to January 2020, electronic databases were searched for HIIT interventions based on populations with metabolic disorders including diabetes, metabolic syndrome, polycystic ovary syndrome, non-alcoholic fatty liver disease or overweight/obesity, with outcome measurements that included IL-6, TNF-α, CRP, leptin or adiponectin and training ≥2 weeks. Random-effects models were used to aggregate a mean effect size (ES), 95% confidence intervals (Cis), and potential moderators were explored.. Twenty-nine studies involving 841 participants were included in the meta-analysis. HIIT improved circulating adiponectin (P = .02), leptin (P = .02), and TNF-α (P = .003) when compared to CON. There were no differences between groups in IL-6 and CRP. Intervention duration was a significant moderator for the effect of HIIT on IL-6, and leptin (P < .05).. High-intensity interval training improves circulating TNF-α, leptin and adiponectin, thereby indicating that it may be an effective and time-efficient intervention for controlling low-grade inflammation in individuals with metabolic disorders. Topics: Adipokines; Adiponectin; Biomarkers; C-Reactive Protein; Cytokines; High-Intensity Interval Training; Humans; Inflammation; Leptin; Metabolic Diseases; Receptors, Interleukin-6; Tumor Necrosis Factor-alpha | 2020 |
Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression.
Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations. Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Biomarkers; Digestive System; Digestive System Diseases; Homeostasis; Humans; Inflammation; Leptin; Liver; Non-alcoholic Fatty Liver Disease; Obesity | 2020 |
An Overview of the Role of Adipokines in Cardiometabolic Diseases.
Obesity as an independent risk factor for cardiovascular diseases (CVDs) leads to an increase in morbidity, mortality, and a shortening of life span. The changes in heart structure and function as well as metabolic profile are caused by obese people, including those free of metabolic disorders. Obesity alters heart function structure and affects lipid and glucose metabolism, blood pressure, and increase inflammatory cytokines. Adipokines, specific cytokines of adipocytes, are involved in the progression of obesity and the associated co-morbidities. In the current study, we review the scientific evidence on the effects of obesity on CVDs, focusing on the changes in adipokines. Several adipokines have anti-inflammatory and cardioprotective effects comprising omentin, apelin, adiponectin, and secreted frizzled-related protein (Sfrp-5). Other adipokines have pro-inflammatory impacts on the cardiovascular system and obesity including leptin, tumor necrosis factor (TNF), retinol-binding protein4 (RBP-4), visfatin, resistin, and osteopontin. We found that obesity is associated with multiple CVDs, but can only occur in unhealthy metabolic patients. However, more studies should be designed to clarify the association between obesity, adipokine changes, and the occurrence of CVDs. Topics: Adipokines; Adiponectin; Animals; Biomarkers; Cardiovascular Diseases; Genome; Humans; Inflammation; Leptin; Metabolic Syndrome; Obesity; Resistin; Risk Factors | 2020 |
Potential role of adipose tissue and its hormones in burns and critically III patients.
Obesity has become a world-wide pandemic and is considered a major risk factor for various diseases. Despite this, recent intriguing clinical observations have been made suggesting that being overweight has some advantages. Overweight and some obese patients were reported to have significantly lower all-cause mortality, described as the 'obesity paradox'. This phenomenon resulted in increased research aimed at investigating the influence of adipose tissue on outcomes of various clinical states including critical illness. In this review, we summarise research findings on the effect burn injury and trauma-related critical illness have on adipose tissue and discuss potential mechanisms by which adipose tissue influences outcomes in burn and other critically ill patients. Burn injury and critical illness influence adipose tissue functionally and morphologically, with circulating levels of fat derived hormones, adipokines, altered in patients following injury and/or critical illness. As adipokines regulate a variety of processes including inflammation and metabolism, this disruption in the adipokine axis may explain the obesity paradox phenomenon observed in critically ill patients. We conclude that further research on the influence of individual adipokines on prognosis in burn and critically ill patients and the mechanisms involved is required to increase understanding of their therapeutic potential. Topics: Adipokines; Adiponectin; Adipose Tissue; Burns; Critical Illness; Fibrosis; Ghrelin; Humans; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Overweight; Resistin; Skin; Wound Healing | 2020 |
The Role of Adipokines in Breast Cancer: Current Evidence and Perspectives.
The current review shows evidence for the role of adipokines in breast cancer (BC) pathogenesis summarizing the mechanisms underlying the association between adipokines and breast malignancy. Special emphasis is given also on intriguing insights into the relationship between obesity and BC as well as on the role of novel adipokines in BC development.. Recent evidence has underscored the role of the triad of obesity, insulin resistance, and adipokines in postmenopausal BC. Adipokines exert independent and joint effects on activation of major intracellular signal networks implicated in BC cell proliferation, growth, survival, invasion, and metastasis, particularly in the context of obesity, considered a systemic endocrine dysfunction characterized by chronic inflammation. To date, more than 10 adipokines have been linked to BC, and this catalog is continuously increasing. The majority of circulating adipokines, such as leptin, resistin, visfatin, apelin, lipocalin 2, osteopontin, and oncostatin M, is elevated in BC, while some adipokines such as adiponectin and irisin (adipo-myokine) are generally decreased in BC and considered protective against breast carcinogenesis. Further evidence from basic and translational research is necessary to delineate the ontological role of adipokines and their interplay in BC pathogenesis. More large-scale clinical and longitudinal studies are awaited to assess their clinical utility in BC prognosis and follow-up. Finally, novel more effective and safer adipokine-centered therapeutic strategies could pave the way for targeted oncotherapy. Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Apelin; Breast Neoplasms; Cell Proliferation; Cytokines; Female; Fibronectins; Humans; Inflammation; Leptin; Lipocalin-2; Nicotinamide Phosphoribosyltransferase; Obesity; Oncostatin M; Osteopontin; Resistin | 2019 |
Molecular Links between Central Obesity and Breast Cancer.
Topics: Adiponectin; Adipose Tissue; Breast Neoplasms; Cell Transformation, Neoplastic; Estrogens; Exosome Multienzyme Ribonuclease Complex; Female; Humans; Inflammation; Leptin; Menopause; MicroRNAs; Obesity, Abdominal; Signal Transduction; Tumor Microenvironment | 2019 |
Depression and obesity: evidence of shared biological mechanisms.
Depression and obesity are common conditions with major public health implications that tend to co-occur within individuals. The relationship between these conditions is bidirectional: the presence of one increases the risk for developing the other. It has thus become crucial to gain a better understanding of the mechanisms responsible for the intertwined downward physiological spirals associated with both conditions. The present review focuses specifically on shared biological pathways that may mechanistically explain the depression-obesity link, including genetics, alterations in systems involved in homeostatic adjustments (HPA axis, immuno-inflammatory activation, neuroendocrine regulators of energy metabolism including leptin and insulin, and microbiome) and brain circuitries integrating homeostatic and mood regulatory responses. Furthermore, the review addresses interventional opportunities and questions to be answered by future research that will enable a comprehensive characterization and targeting of the biological links between depression and obesity. Topics: Brain; Depression; Depressive Disorder; Depressive Disorder, Major; Energy Metabolism; Female; Homeostasis; Humans; Hypothalamo-Hypophyseal System; Inflammation; Insulin; Leptin; Male; Melanocortins; Microbiota; Obesity; Pituitary-Adrenal System | 2019 |
Misdistribution of iron and oxidative stress in chronic kidney disease.
Chronic kidney disease (CKD) patients have an extremely high risk of developing cardiovascular diseases (CVD) compared to the general population. Systemic inflammation associated with oxidative stress could be an important determinant of morbidity and mortality associated with CVD. We suspected that dysregulation of iron metabolism should be considered in these patients. Anemia is prevalent in CKD patients and is often treated with erythropoiesis-stimulating agents (ESAs) and iron. In addition, iron administration sometimes causes iron overdose. Excessive iron in the cytosol and mitochondria can accelerate the formation of a highly toxic reactive oxygen species, hydroxyl radicals, which damage lipids, proteins, and DNA. In this review, we propose the following four major reasons for oxidative stress in CKD patients: 1) iron is sequestered in cells by proinflammatory cytokines and hepcidin; 2) the reduction in frataxin increases "free" iron in mitochondria; 3) the accumulation of 5-aminolevulinic acid, a heme precursor, has toxic effects on iron and mitochondrial metabolism; and 4) the elevated levels of the metabolic hormone, leptin, promote hepatic hepcidin production. Although an efficient therapy for preventing oxidative stress in these patients has not yet been well defined, we propose that ESAs for renal anemia may ameliorate these causes of oxidative stress. Further clinical trials are necessary to clarify the effectiveness of ESAs on oxidative stress in CKD patients. Topics: Aminolevulinic Acid; Anemia; Hematinics; Heme; Hepcidins; Humans; Inflammation; Iron; Iron Overload; Leptin; Mitochondria; Oxidative Stress; Renal Insufficiency, Chronic | 2019 |
Sympathetic nervous system as a target for aging and obesity-related cardiovascular diseases.
Chronic sympathetic nervous system overactivity is a hallmark of aging and obesity and contributes to the development of cardiovascular diseases including hypertension and heart failure. The cause of this chronic sympathoexcitation in aging and obesity is multifactorial and centrally mediated. In this mini-review, we have provided an overview of the key and emerging central mechanisms contributing to the pathogenesis of sympathoexcitation in obesity and healthy aging, specifically focusing on hypertension. A clear understanding of these mechanisms will pave way for targeting the sympathetic nervous system for the treatment of cardiovascular diseases in obesity and aging. Topics: Aging; Animals; Cardiovascular Diseases; Cellular Senescence; Humans; Hypertension; Inflammation; Leptin; Obesity; Oxidative Stress; Renin-Angiotensin System; Sympathetic Nervous System | 2019 |
The role of adipokines in systemic sclerosis: a missing link?
Systemic sclerosis is a multiorgan autoimmune disease characterized by vasculopathy and tissue fibrosis of unknown etiology. Recently, adipokines (cell signaling proteins secreted by adipose tissue) have attracted much attention as a cytokine family contributing to the various pathological processes of systemic sclerosis. Adipokines, such as leptin, adiponectin, resistin, adipsin, visfatin or chemerin are a heterogenic group of molecules. Adiponectin exhibits anti-fibrotic features and affects inflammatory reactions. Leptin promotes fibrosis and inflammation. Resistin was linked to vascular involvement in systemic sclerosis. Visfatin was associated with regression of skin lesions in late-stage systemic sclerosis. Chemerin appears as a marker of increased risk of impaired renal function and development of skin sclerosis in the early stage of systemic sclerosis. Vaspin was indicated to have a protective role in digital ulcers development. Novel adipokines-adipsin, apelin, omentin and CTRP-3-are emerging as molecules potentially involved in SSc pathogenesis. Serum adipokine levels may be used as predictive and diagnostic factors in systemic sclerosis. However, further investigations are required to establish firm correlations between distinct adipokines and systemic sclerosis. Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Biomarkers; Humans; Inflammation; Leptin; Resistin; Scleroderma, Systemic; Signal Transduction; Vascular Diseases | 2019 |
Mechanisms of obesity-induced metabolic and vascular dysfunctions.
Obesity has reached epidemic proportions and its prevalence is climbing. Obesity is characterized by hypertrophied adipocytes with a dysregulated adipokine secretion profile, increased recruitment of inflammatory cells, and impaired metabolic homeostasis that eventually results in the development of systemic insulin resistance, a phenotype of type 2 diabetes. Nitric oxide synthase (NOS) is an enzyme that converts L-arginine to nitric oxide (NO), which functions to maintain vascular and adipocyte homeostasis. Arginase is a ureohydrolase enzyme that competes with NOS for L-arginine. Arginase activity/expression is upregulated in obesity, which results in diminished bioavailability of NO, impairing both adipocyte and vascular endothelial cell function. Given the emerging role of NO in the regulation of adipocyte physiology and metabolic capacity, this review explores the interplay between arginase and NO, and their effect on the development of metabolic disorders, cardiovascular diseases, and mitochondrial dysfunction in obesity. A comprehensive understanding of the mechanisms involved in the development of obesity-induced metabolic and vascular dysfunction is necessary for the identification of more effective and tailored therapeutic avenues for their prevention and treatment. Topics: Adipogenesis; Adipokines; Adiponectin; Adipose Tissue; Angiopoietin-Like Protein 2; Angiopoietin-like Proteins; Animals; Arginase; Cellular Senescence; Cytokines; Endoplasmic Reticulum Stress; Glucose; GPI-Linked Proteins; Humans; Inflammation; Insulin; Lectins; Leptin; Lipid Metabolism; Lipocalin-2; Metabolic Diseases; Mice; Mitochondria; Nicotinamide Phosphoribosyltransferase; Nitric Oxide; Obesity; Rats; Resistin; Retinol-Binding Proteins, Plasma; Tumor Necrosis Factor-alpha; Vascular Diseases | 2019 |
Metabolic syndrome and systemic lupus erythematosus: the connection.
Topics: Adiponectin; Animals; Atherosclerosis; Humans; Inflammation; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome; Risk Factors | 2019 |
Biomarkers of Inflammation in Obesity-Psoriatic Patients.
Psoriasis is a common chronic inflammatory multisystemic disease with a complex pathogenesis consisting of genetic, immunological, and environmental components. It is associated with a number of comorbidities, including diabetes, metabolic syndrome, obesity, and myocardial infarction. In addition, the severity of psoriasis seems to be related to the severity of obesity. Patients with higher levels of obesity show poorer response to systemic treatments of psoriasis. Several studies have demonstrated that white adipose tissue is a crucial site of the formation of proinflammatory adipokines such as leptin, adiponectin, and resistin and classical cytokines such as interleukin- (IL-) 6 and tumour necrosis factor- Topics: Biomarkers; Humans; Inflammation; Leptin; Obesity; Psoriasis; Resistin | 2019 |
Innate Immune Dysregulation in the Development of Cardiovascular Disease in Lupus.
The systemic inflammatory nature of systemic lupus erythematosus (SLE) is patent not only in the diverse clinical manifestations of the disease but also in the increased risk of premature cardiovascular diseases (CVD). In this review, we discuss the latest findings on the key factors of the innate immune system known to play critical roles in the pathogenesis of accelerated CVD in patients with SLE and discuss the potential that immunometabolism may play a key role in this respect.. Recent studies exploring the association between SLE and premature CVD clearly showed that alterations of specific immune functions play a pivotal role in the increased cardiovascular morbidity and mortality in the SLE patients. Novel molecular factors such as type I interferons (IFN), dysregulated neutrophil function, and changes to cellular metabolism and metabolites are emerging as important regulators of systemic immune dysfunction and as strong risk factors for premature CVD in SLE. Although corticosteroids and cytotoxic agents can be used to effectively manage and control various lupus-related complications, to date, no drug has been proven to prevent the development of premature atherosclerosis in SLE. However, as new mechanisms underlying this complication of SLE are uncovered, such as the role of metabolism and neutrophil-driven inflammation, new avenues for therapeutic intervention are being discovered. Topics: Atherosclerosis; Cardiovascular Diseases; Chemokine CCL2; Endothelial Cells; Humans; Immunity, Innate; Inflammation; Interferon Type I; Leptin; Lupus Erythematosus, Systemic; Macrophages; Metabolic Syndrome; Neutrophils; Reactive Oxygen Species | 2019 |
Leptin and Its Derivatives: A Potential Target for Autoimmune Diseases.
Leptin is an adipocyte-derived hormone product of the obese (ob) gene. Leptin plays an important regulatory role as an immunomodulatory factor in the maintenance and homeostasis of immune functions. Indeed, the role of leptin as an immunomodulator in inflammatory and immune responses has attracted increasing attention in recent years. Leptin mostly affects responses through the immunomodulation of monocytes, dendritic cells, neutrophils, NK cells, and dendritic cells in addition to modulating T and B cell development and functions. Leptin is also an important inflammatory regulator, wherein higher expression influences the secretion rates of IL-6, C-reactive proteins, and TNF-α. Moreover, leptin is highly involved in processes related to human metabolism, inflammatory reactions, cellular development, and diseases, including hematopoiesis. Owing to its diverse immunerelated functions, leptin has been explored as a potential target for therapeutic development in the treatment of autoimmune diseases. Topics: Adipocytes; Autoimmune Diseases; Dendritic Cells; Hematopoiesis; Homeostasis; Humans; Immune System; Immunologic Factors; Inflammation; Inflammation Mediators; Killer Cells, Natural; Leptin; Monocytes; Neutrophils; Signal Transduction | 2019 |
The role of diet in multiple sclerosis: A review.
Multiple sclerosis (MS) is a multifactorial, inflammatory, and neurodegenerative disease of the central nervous system, where environmental factors interact with genetic susceptibility. The role of diet on MS has not been comprehensively elucidated; therefore, through an extensive search of relevant literature, this review reports the most significant evidence regarding nutrition as a possible co-factor influencing the inflammatory cascade by acting on both its molecular pathways and gut microbiota. Since nutritional status and dietary habits in MS patients have not been extensively reported, the lack of a scientific-based consensus on dietary recommendation in MS could encourage many patients to experiment alternative dietetic regimens, increasing the risk of malnutrition. This work investigates the health implications of an unbalanced diet in MS, and collects recent findings on nutrients of great interest among MS patients and physicians. The aim of this review is to elucidate the role of an accurate nutritional counseling in MS to move toward a multidisciplinary management of the disease and to encourage future studies demonstrating the role of a healthy diet on the onset and course of MS. Topics: Animals; Antioxidants; Body Composition; Complementary Therapies; Diet; Disease Models, Animal; Dysbiosis; Fatty Acids; Fatty Acids, Unsaturated; Humans; Inflammation; Leptin; Lipopolysaccharides; Malnutrition; Micronutrients; Multiple Sclerosis; Nutritional Status; Obesity; Osteoporosis; Randomized Controlled Trials as Topic; Recommended Dietary Allowances; Risk Factors; Vitamin D | 2018 |
Immunologic and endocrine functions of adipose tissue: implications for kidney disease.
Excess adiposity can induce adverse sequelae in multiple cell types and organ systems. The transition from the lean to the obese state is characterized by fundamental cellular changes at the level of the adipocyte. These changes affect the local microenvironment within the respective adipose tissue but can also affect nonadipose systems. Adipocytes within fat pads respond to chronic nutrient excess through hyperplasia or hypertrophy, which can differentially affect interorgan crosstalk between various adipose depots and other organs. This crosstalk is dependent on the unique ability of the adipocyte to coordinate metabolic adjustments throughout the body and to integrate responses to maintain metabolic homeostasis. These actions occur through the release of free fatty acids and metabolites during times of energy need - a process that is altered in the obese state. In addition, adipocytes release a wide array of signalling molecules, such as sphingolipids, as well as inflammatory and hormonal factors (adipokines) that are critical for interorgan crosstalk. The interactions of adipose tissue with the kidney - referred to as the adipo-renal axis - are important for normal kidney function as well as the response of the kidney to injury. Here, we discuss the mechanistic basis of this interorgan crosstalk, which clearly has great therapeutic potential given the increasing rates of chronic kidney disease secondary to obesity and type 2 diabetes mellitus. Topics: Adipokines; Adiponectin; Adipose Tissue; AMP-Activated Protein Kinases; Angiotensin II; Angiotensinogen; Ceramidases; Diabetes Mellitus, Type 2; Humans; Inflammation; Kidney Diseases; Leptin; Macrophages; Obesity; Receptors, Adiponectin; Signal Transduction | 2018 |
Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk.
Obesity is currently the most extended metabolic disturbance worldwide favoring the development of cardiometabolic alterations such as type 2 diabetes, hypertension, and dyslipidemia. Obesity and the metabolic syndrome (MS) are characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Consequently, the adiponectin/leptin ratio has been suggested as a maker of adipose tissue dysfunction. This emerging biomarker correlates with insulin resistance better than adiponectin or leptin alone, or even HOMA and is decreased with increasing number of metabolic risk factors having been proposed as a predictive marker for the MS. Moreover, the adiponectin/leptin ratio is negatively correlated with markers of low-grade chronic inflammation. In this sense, an increase in this ratio has been related with reduced atherosclerosis risk as well as with a decreased risk of some types of cancer in epidemiological studies. In this commentary we propose new cutoffs to estimate obesity- and MS-associated cardiometabolic risk according to the adiponectin/leptin ratio and discuss different therapeutic strategies to increase this promising biomarker of metabolic risk. Topics: Adiponectin; Adipose Tissue; Animals; Humans; Inflammation; Leptin; Metabolic Syndrome; Obesity | 2018 |
Cardiovascular Autonomic Dysfunction: Link Between Multiple Sclerosis Osteoporosis and Neurodegeneration.
The high prevalence of osteoporosis, observed in multiple sclerosis (MS) patients, has been attributed to reduced mobility and or the use of disease-modifying drugs. However, MS-impaired cardiovascular autonomic nervous system (ANS) function has the potential of reducing bone mass density (BMD) by altering the expression and/or function of the neuronal, systemic, and local mediators of bone remodeling. This review describes the complex regulation of bone homeostasis with a focus on MS, providing evidence that ANS dysfunction and low BMD are intertwined with MS inflammatory and neurodegenerative processes, and with other MS-related morbidities, including depression, fatigue, and migraine. Strategies for improving ANS function could reduce the prevalence of MS osteoporosis and slow the rate of MS progression, with a significant positive impact on patients' quality of life. Topics: Adiponectin; Autonomic Nervous System; Bone Density; Bone Remodeling; Brain; Cardiovascular System; Depression; Endocannabinoids; Fatigue; Humans; Inflammation; Leptin; Migraine Disorders; Multiple Sclerosis; Nerve Degeneration; Neuropeptide Y; Osteocalcin; Osteopontin; Osteoporosis; Osteoprotegerin; Parathyroid Hormone; RANK Ligand; Serotonin; Vitamin D | 2018 |
Myeloid derived-suppressor cells: their role in cancer and obesity.
Myeloid-derived suppressor cells (MDSC) are present in most individuals with cancer where they inhibit adaptive and innate antitumor immunity and are an obstacle to cancer immunotherapies. Chronic inflammation is characteristic of adipose tissue and is a risk factor for the onset and progression of cancer in obese individuals. Because MDSC accumulate in response to inflammation, it has been hypothesized that one of the mechanisms by which obesity promotes malignancy is through the induction of MDSC. This article reviews the data supporting this hypothesis, the role of leptin and fatty acid metabolism in the induction of MDSC, and the surprising finding that although MDSC promote tumor progression, they are protective against some of the metabolic dysfunction associated with obesity. Topics: Adipokines; Adipose Tissue; Animals; Cell Communication; Cellular Microenvironment; Chronic Disease; Disease Progression; Disease Susceptibility; Fatty Acids; Humans; Immune System; Immunomodulation; Inflammation; Leptin; Myeloid-Derived Suppressor Cells; Neoplasms; Obesity | 2018 |
The Impact of Obesity on Breast Cancer.
The rates of obesity are increasing worldwide and this condition is now recognized as a leading preventable cause of cancer. Several diseases are directly related to obesity, including diabetes, hypertension, atherosclerosis, stroke, musculoskeletal disorders, and a diverse range of malignances-such as breast cancer. Obesity is associated with an increased risk of postmenopausal estrogen receptor-positive breast cancer and worse cancer-related outcomes for all breast tumor subtypes. Several mechanisms have been proposed to contribute to the obesity-cancer link, including high levels of circulating and local estrogens, altered amounts of adipokines (leptin and adiponectin), disrupted insulin/IGF signaling, modifications within the microbiome, and local and systemic effects of inflammation. Here we will review recent advances in our understanding of the complex signaling pathways underlying the obesity-cancer link. An improved understanding of these processes is anticipated to propel novel and effective intervention strategies to reduce the global obesity-cancer burden. Topics: Adipokines; Adiponectin; Breast Neoplasms; Estrogens; Female; Humans; Inflammation; Leptin; Metabolic Networks and Pathways; Obesity; Receptors, Estrogen; Risk Factors | 2018 |
Central Regulation of Glucose Homeostasis.
The ability of the brain to directly control glucose levels in the blood independently of its effects on food intake and body weight has been known ever since 1854 when Claude Bernard, a French physiologist, discovered that lesioning the floor of the fourth ventricle in rabbits led to a rise of sugar in the blood. Despite this outstanding discovery at that time, it took more than 140 years before progress started to be made in identifying the underlying mechanisms of brain-mediated control of glucose homeostasis. Technological advances including the generation of brain insulin receptor null mice revealed that insulin action specifically in the central nervous system is required for the regulation of glucose metabolism, particularly in the modulation of hepatic glucose production. Furthermore, it was established that the hormone leptin, known for its role in regulating food intake and body weight, actually exerts its most potent effects on glucose metabolism, and that this function of leptin is mediated centrally. Under certain circumstances, high levels of leptin can replicate the actions of insulin, thus challenging the idea that life without insulin is impossible. Disruptions of central insulin signaling and glucose metabolism not only lead to impairments in whole body glucose homeostasis, they also have other serious consequences, including the development of Alzheimer's disease which is sometimes referred to as type 3 diabetes reflecting its common etiology with type 2 diabetes. © 2017 American Physiological Society. Compr Physiol 7:471-764, 2017. Topics: Alzheimer Disease; Animals; Blood Glucose; Diet, High-Fat; Fatty Acids; Homeostasis; Humans; Hypothalamic Diseases; Inflammation; Insulin; Leptin; Receptor, Insulin; Wnt Signaling Pathway | 2017 |
Influence of Antioxidants on Leptin Metabolism and its Role in the Pathogenesis of Obesity.
Obesity is associated with low-grade inflammation. Leptin, a hormone made by fat cells regulates appetite and hunger and thus food intake behavior. Interestingly, , food preservatives like sodium sulfite and sodium benzoate and also natural colorant and spice compounds such as curcumin were found to decrease the release of leptin in murine 3T3-L1 adipocytes, after co-incubation with LPS, which was added to mimic the pro-inflammatory status in obesity. Several of these compounds are well known food antioxidants.Whilst reducing oxidation events is beneficial in states of elevated oxidative stress, overexposure to food antioxidant can lead to adverse effects. There are hints from in vivo data, that antioxidant stress in younger age plays a role in the development of adiposity in later life. The insufficient exposure to oxidizing compounds like reactive oxygen species (ROS) cannot only cause an insufficient burning of calories but there is also a link to the regulation of food intake behavior. If the in vitro findings can be extrapolated to the in vivo situation, consumption of antioxidant supplemented food could lead to decreased leptin release and contribute to an obesogenic environment. This aspect sheds some new critical light on the potential role of an antioxidant-enriched nutrition in the obesity epidemic during the past few centuries. Doing sports could represent not only a proper strategy to initiate physiological ROS production and burning of calories, but also may shift the hormone milieu towards a reduction of hunger feelings and thus reduce appetite and food intake. Topics: Adipocytes; Animals; Antioxidants; Humans; Inflammation; Leptin; Obesity; Oxidative Stress | 2017 |
Glycolipids: Essential regulator of neuro-inflammation, metabolism and gliomagenesis.
Gene knockout mice of glycosyltransferases have clearly showed roles of their products in the bodies, while there are examples where phenotype of knockout was much less severe than expected probably due to functional redundancy. The most striking novel finding obtained from ganglioside-deficient mice was that progressive inflammatory reaction took place, leading to neurodegeneration. In particular, dysfunction of complement-regulatory proteins due to deteriorated architecture of lipid rafts seemed to be essential mechanisms for the inflammation. Furthermore, roles of gangliosides in neurons were demonstrated by neuron-specific transgenic of B4galnt1 with genetic background of B4galnt1 deficiency. From study of gene knockout mice of St8sia1, new roles of b-series gangliosides in leptin secretion from adipocytes, and roles of a-series gangliosides in leptin receptor, ObR in hypothalamus were demonstrated, leading to apparent intact balance of energy. Essential roles of b-series gangliosides in malignant properties of gliomas were also shown, suggesting their roles in the regulation of inflammation and proliferation in nervous tissues. How to apply these findings for the control of newly discovered patients with ganglioside deficiency remains to be investigated. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa. Topics: Animals; Complement System Proteins; Gangliosides; Gene Expression Regulation, Neoplastic; Glioma; Humans; Inflammation; Leptin; Membrane Microdomains; Mice; Mice, Knockout; N-Acetylgalactosaminyltransferases; Neoplasms, Nerve Tissue; Nerve Tissue; Neurons; Receptors, Leptin; Sialyltransferases | 2017 |
Searching for Evidence of an Anti-Inflammatory Diet in Children: A Systematic Review of Randomized Controlled Trials for Pediatric Obesity Interventions With a Focus on Leptin, Ghrelin, and Adiponectin.
To address the complex phenomenon of pediatric obesity, one must understand the physiological mechanisms regulating energy intake and inflammation. The peptide hormones leptin, ghrelin, and adiponectin are involved in both, but their functions are dysregulated in obesity. The purpose of this systematic review is (1) to characterize studies of nutrition interventions for weight management in children who measure these peptides as outcomes, (2) to assess risk of bias in the studies, and (3) to determine the relationships between these peptides and body mass index (BMI). Eligibility Criteria: Peer-reviewed articles written in English, published in 2001-2016, and describing randomized controlled trials of pediatric interventions involving a nutrition component with the outcome measures leptin, ghrelin, and/or adiponectin were included. Articles were excluded if the intervention involved pharmaceuticals, supplements, infant formula, breastfeeding, or surgery.. The 25 international studies represented 2,153 obese children.. Ten diets were identified. Successful interventions included both structured exercise and hypocaloric dietary components, with or without counseling, resistance training, or medical components. Direct measures of adiposity were used in 69% of studies. Comparison group designs were disparate. Leptin levels decreased as BMI decreased. Evidence regarding the relationships of ghrelin and adiponectin with BMI was inconclusive.. Despite known effects of maturation on hormones, studies did not consistently differentiate findings by maturational stage. Common anti-inflammatory and disease risk modification diets were missing or underrepresented. Studies that include children with comorbidities are needed. BMI and leptin levels have a positive relationship, but evidence on ghrelin and adiponectin was inconclusive. Topics: Adiponectin; Adolescent; Anti-Inflammatory Agents; Child; Child, Preschool; Diet Therapy; Female; Ghrelin; Humans; Inflammation; Leptin; Male; Pediatric Obesity; Randomized Controlled Trials as Topic | 2017 |
Hypothalamic Dysfunction in Obesity and Metabolic Disorders.
The hypothalamus is the brain region responsible for the maintenance of energetic homeostasis. The regulation of this process arises from the ability of the hypothalamus to orchestrate complex physiological responses such as food intake and energy expenditure, circadian rhythm, stress response, and fertility. Metabolic alterations such as obesity can compromise these hypothalamic regulatory functions. Alterations in circadian rhythm, stress response, and fertility further contribute to aggravate the metabolic dysfunction of obesity and contribute to the development of chronic disorders such as depression and infertility.At cellular level, obesity caused by overnutrition can damage the hypothalamus promoting inflammation and impairing hypothalamic neurogenesis. Furthermore, hypothalamic neurons suffer apoptosis and impairment in synaptic plasticity that can compromise the proper functioning of the hypothalamus. Several factors contribute to these phenomena such as ER stress, oxidative stress, and impairments in autophagy. All these observations occur at the same time and it is still difficult to discern whether inflammatory processes are the main drivers of these cellular dysfunctions or if the hypothalamic hormone resistance (insulin, leptin, and ghrelin) can be pinpointed as the source of several of these events.Understanding the mechanisms that underlie the pathophysiology of obesity in the hypothalamus is crucial for the development of strategies that can prevent or attenuate the deleterious effects of obesity. Topics: Animals; Autophagy; Circadian Rhythm; Eating; Energy Metabolism; Fertility; Ghrelin; Homeostasis; Humans; Hypothalamus; Inflammation; Insulin; Leptin; Metabolic Diseases; Neuronal Plasticity; Obesity; Overnutrition; Oxidative Stress; Stress, Physiological | 2017 |
Cerebrovascular Disease: Consequences of Obesity-Induced Endothelial Dysfunction.
Despite the well-known global impact of overweight and obesity in the incidence of cerebrovascular disease, many aspects of this association are still inconsistently defined. In this chapter we aim to present a critical review on the links between obesity and both ischemic and hemorrhagic stroke and discuss its influence on functional outcomes, survival, and current treatments to acute and chronic stroke. The role of cerebrovascular endothelial function and respective modulation is also described as well as its laboratory and clinical assessment. In this context, the major contributing mechanisms underlying obesity-induced cerebral endothelial function (adipokine secretion, insulin resistance, inflammation, and hypertension) are discussed. A special emphasis is given to the participation of adipokines in the pathophysiology of stroke, namely adiponectin, leptin, resistin, apelin, and visfatin. Topics: Adipokines; Adiponectin; Apelin; Brain Ischemia; Cerebrovascular Disorders; Endothelium, Vascular; Humans; Hypertension; Inflammation; Insulin Resistance; Intracranial Hemorrhages; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin; Stroke | 2017 |
Physiological functions of Vitamin D in adipose tissue.
Adipose tissue has long been identified as the major site of vitamin D storage. Recent studies have demonstrated that VDR and vitamin D metabolizing enzymes are expressed in adipocytes. Furthermore, it has been shown that vitamin D regulates adipogenic gene expression as well as adipocyte apoptosis. Vitamin D is active in adipocytes at all levels. It interacts with membrane receptors, adaptor molecules, and nuclear coregulator proteins. Several functions of unliganded nVDR were discovered by studying human samples from patients having hereditary vitamin D resistant rickets, transgenic mice overexpressing the VDR and VDR knockout mice. Through its genomic action, vitamin D participates in the regulation of energy metabolism by controlling the expression of uncoupling proteins. In vitro, vitamin D stimulates lipogenesis and inhibits lipolysis by interacting with mVDR. mVDR is present in caveolae of the plasma membrane and is the same as the classic nVDR. In addition, vitamin D affects directly the expression of the appetite regulating hormone, leptin. Some researchers reported also that vitamin D regulates the expression of the insulin sensitizing hormone, adiponectin. Vitamin D reduced cytokine release and adipose tissue inflammation through the inhibition of NF-κB signaling. Scientific research investigating the role of adipose tissue resident immune cells in the pathogenesis of obesity-associated inflammation is scarce. Obesity is associated with vitamin D deficiency. However there is no scientific evidence to prove that vitamin D deficiency predispose to obesity. Vitamin D supplementation may prevent obesity but it does not lead to weight loss in obese subjects. Topics: Active Transport, Cell Nucleus; Adipocytes; Adipogenesis; Adipose Tissue; Adolescent; Adult; Aged; Animals; Apoptosis; Calcitriol; Cell Membrane; Female; Gene Expression Regulation; Genomics; Humans; Inflammation; Leptin; Male; Mice; Middle Aged; Mitochondrial Uncoupling Proteins; Obesity; Receptors, Calcitriol; Vitamin D; Young Adult | 2017 |
Leptin in inflammation and autoimmunity.
After its discovery as a key controller of metabolic function, leptin has been later extensively implicated in additional functions including important modulatory activities on the innate and adaptive immune response. This review analyzes the known implications of leptin in multiple inflammatory conditions, including autoimmune diseases, and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses. Topics: Adaptive Immunity; Animals; Autoimmunity; Humans; Immunity, Innate; Inflammation; Leptin; Mice; Obesity | 2017 |
Leptin in the interplay of inflammation, metabolism and immune system disorders.
Leptin is one of the most relevant factors secreted by adipose tissue and the forerunner of a class of molecules collectively called adipokines. Initially discovered in 1994, its crucial role as a central regulator in energy homeostasis has been largely described during the past 20 years. Once secreted into the circulation, leptin reaches the central and peripheral nervous systems and acts by binding and activating the long form of leptin receptor (LEPR), regulating appetite and food intake, bone mass, basal metabolism, reproductive function and insulin secretion, among other processes. Research on the regulation of different adipose tissues has provided important insights into the intricate network that links nutrition, metabolism and immune homeostasis. The neuroendocrine and immune systems communicate bi-directionally through common ligands and receptors during stress responses and inflammation, and control cellular immune responses in several pathological situations including immune-inflammatory rheumatic diseases. This Review discusses the latest findings regarding the role of leptin in the immune system and metabolism, with particular emphasis on its effect on autoimmune and/or inflammatory rheumatic diseases, such as rheumatoid arthritis and osteoarthritis. Topics: Adaptive Immunity; Animals; Arthritis, Rheumatoid; Humans; Immune System Diseases; Immunity, Innate; Inflammation; Killer Cells, Natural; Leptin; Neutrophils; Osteoarthritis; Receptors, Leptin | 2017 |
Nutritional effects on T-cell immunometabolism.
T cells are highly influenced by nutrient uptake from their environment, and changes in overall nutritional status, such as malnutrition or obesity, can result in altered T-cell metabolism and behavior. In states of severe malnutrition or starvation, T-cell survival, proliferation, and inflammatory cytokine production are all decreased, as is T-cell glucose uptake and metabolism. The altered T-cell function and metabolism seen in malnutrition is associated with altered adipokine levels, most particularly decreased leptin. Circulating leptin levels are low in malnutrition, and leptin has been shown to be a key link between nutrition and immunity. The current view is that leptin signaling is required to upregulate activated T-cell glucose metabolism and thereby fuel T-cell activation. In the setting of obesity, T cells have been found to have a key role in promoting the recruitment of inflammatory macrophages to adipose depots along with the production of inflammatory cytokines that promote the development of insulin resistance leading to diabetes. Deletion of T cells, key T-cell transcription factors, or pro-inflammatory T-cell cytokines prevents insulin resistance in obesity and underscores the importance of T cells in obesity-associated inflammation and metabolic disease. Altogether, T cells have a critical role in nutritional immunometabolism. Topics: Animals; Cytokines; Food; Glucose; Humans; Inflammation; Insulin Resistance; Leptin; Lymphocyte Activation; Malnutrition; Nutritional Status; Obesity; Signal Transduction; T-Lymphocytes | 2017 |
[Biomarkers for anorexia nervosa].
Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization in many aspects is seen at recovery from undernutrition. Recent genome-wide association studies support that genetic factors play a role in the pathophysiology of AN, of which some are independent of BMI-related mechanisms. In this review, an update on blood-based biomarkers of AN is presented. Topics: Anorexia Nervosa; Biomarkers; Brain-Derived Neurotrophic Factor; Ghrelin; Humans; Inflammation; Leptin; Oxytocin | 2017 |
Leptin and adiponectin: pathophysiological role and possible therapeutic target of inflammation in ischemic stroke.
Stroke is a multifactorial disease contributing to significant noncommunicable disease burden in developing countries. Risk of stroke is largely a consequence of morbidities of diabetes, obesity, hypertension, and heart diseases. Incidence of stroke is directly proportional to body mass index. Adipose tissue stores energy as well as acts as an active endocrine organ, which secretes numerous humoral factors. Adiponectin and leptin are the commonest adipocytokines and have been invariably linked to the development of coronary heart disease and may be involved in the underlying biological mechanism of stroke. Leptin and adiponectin mediate proatherogenic and antiatherogenic responses, respectively, and hence, determining the plasma or serum levels of leptin and adiponectin alone or in combination may act as a novel prognostic biomarker for inflammation and atherosclerosis in stroke. This review addresses leptin- and adiponectin-mediated inflammatory mechanism in ischemic stroke and their potential as therapeutic targets. Topics: Adiponectin; Animals; Humans; Inflammation; Ischemia; Leptin; Obesity; Stroke | 2017 |
Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases.
Microglial cells are responsible for immune surveillance within the CNS. They respond to noxious stimuli by releasing inflammatory mediators and mounting an effective inflammatory response. This is followed by release of anti-inflammatory mediators and resolution of the inflammatory response. Alterations to this delicate process may lead to tissue damage, neuroinflammation, and neurodegeneration. Chronic pain, such as inflammatory or neuropathic pain, is accompanied by neuroimmune activation, and the role of glial cells in the initiation and maintenance of chronic pain has been the subject of increasing research over the last two decades. Neuropeptides are small amino acidic molecules with the ability to regulate neuronal activity and thereby affect various functions such as thermoregulation, reproductive behavior, food and water intake, and circadian rhythms. Neuropeptides can also affect inflammatory responses and pain sensitivity by modulating the activity of glial cells. The last decade has witnessed growing interest in the study of microglial activation and its modulation by neuropeptides in the hope of developing new therapeutics for treating neurodegenerative diseases and chronic pain. This review summarizes the current literature on the way in which several neuropeptides modulate microglial activity and response to tissue damage and how this modulation may affect pain sensitivity. Topics: Adrenomedullin; Animals; Calcitonin Gene-Related Peptide; Ghrelin; Humans; Inflammation; Inflammation Mediators; Leptin; Macrophage Activation; Microglia; Neuralgia; Neurodegenerative Diseases; Neuroglia; Neuropeptide Y; Neuropeptides; Pain; Pro-Opiomelanocortin; Tachykinins; Vasoactive Intestinal Peptide | 2017 |
Leptin, Neuroinflammation and Obesity.
Hypothalamic resistance to adipostatic actions of leptin is a hallmark of obesity. Studies have revealed that hypothalamic inflammation, triggered in response to the consumption of large amounts of dietary fat, is an important mechanism in the development of leptin resistance. In this chapter, we will review the work that paved the way linking neuroinflammation of the hypothalamus and defective leptin action in obesity. Topics: Animals; Humans; Hypothalamus; Inflammation; Leptin; Neuroimmunomodulation; Obesity | 2017 |
Role of leptin as a link between metabolism and the immune system.
Leptin is an adipocyte-derived hormone not only with an important role in the central control of energy metabolism, but also with many pleiotropic effects in different physiological systems. One of these peripheral functions of leptin is a regulatory role in the interplay between energy metabolism and the immune system, being a cornerstone of the new field of immunometabolism. Leptin receptor is expressed throughout the immune system and the regulatory effects of leptin include cells from both the innate and adaptive immune system. Leptin is one of the adipokines responsible for the inflammatory state found in obesity that predisposes not only to type 2 diabetes, metabolic syndrome and cardiovascular disease, but also to autoimmune and allergic diseases. Leptin is an important mediator of the immunosuppressive state in undernutrition status. Placenta is the second source of leptin and it may play a role in the immunomodulation during pregnancy. Finally, recent work has pointed to the participation of leptin and leptin receptor in the pathophysiology of inflammation in oral biology. Therefore, leptin and leptin receptor should be considered for investigation as a marker of inflammation and immune activation in the frontier of innate-adaptive system, and as possible targets for intervention in the immunometabolic mediated pathophysiology. Topics: Adaptive Immunity; Animals; Biomarkers; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Immune System; Immunity, Innate; Immunomodulation; Inflammation; Leptin; Mice; Obesity; Receptors, Leptin | 2017 |
Systematic Review of Metabolic Syndrome Biomarkers: A Panel for Early Detection, Management, and Risk Stratification in the West Virginian Population.
Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic syndrome and this panel can aid in early detection and management of metabolic syndrome in high risk populations, such as in West Virginia.. A literature review was conducted using PubMed, Science Direct, and Google Scholar to search for markers related to metabolic syndrome. Biomarkers searched included adipokines (leptin, adiponectin), neuropeptides (ghrelin), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-10), markers of antioxidant status (OxLDL, PON-1, uric acid), and prothrombic factors (PAI-1).. According to the literature, the concentrations of pro-inflammatory cytokines (IL-6, TNF-α), markers of pro-oxidant status (OxLDL, uric acid), and prothrombic factors (PAI-1) were elevated in metabolic syndrome. Additionally, leptin concentrations were found to be elevated in metabolic syndrome as well, likely due to leptin resistance. In contrast, concentrations of anti-inflammatory cytokines (IL-10), ghrelin, adiponectin, and antioxidant factors (PON-1) were decreased in metabolic syndrome, and these decreases also correlated with specific disorders within the cluster.. Based on the evidence presented within the literature, the aforementioned biomarkers correlate significantly with metabolic syndrome and could provide a minimally-invasive means for early detection and specific treatment of these disorders. Further research is encouraged to determine the efficacy of applying these biomarkers to diagnosis and treatment in a clinical setting. Topics: Adipokines; Adiponectin; Biomarkers; Humans; Inflammation; Interleukin-10; Leptin; Metabolic Syndrome; Plasminogen Activator Inhibitor 1; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; West Virginia | 2016 |
New therapeutic approaches for the treatment of obesity.
This review discusses current and future pharmacological approaches to the treatment of obesity, with a focus on the biological control of energy balance. Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Bile Acids and Salts; Body Weight; Diabetes Mellitus, Type 2; Drug Discovery; Energy Metabolism; Feeding Behavior; Homeostasis; Humans; Hypothalamus; Inflammation; Leptin; Obesity; Oxidative Phosphorylation; Pediatric Obesity | 2016 |
Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression.
The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. Topics: Adiponectin; Adipose Tissue, White; Androgens; Estrogens; Humans; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Neoplasms; Obesity | 2016 |
Maternal pre-pregnancy obesity and childhood physical and cognitive development of children: a systematic review.
Maternal obesity, usually associated with the adverse birth outcomes, has been a serious public health concern. Studies examining its effect on the physical and cognitive development of children have only recently emerged and the findings are inconsistent. This review aimed to systematically examine the role of maternal obesity on children's physical and cognitive development using the available evidence.. The CINAHL, EMBASE, PSYCINFO, PUBMED and SCOPUS databases were searched. Studies addressing children's (⩽12 years) physical and cognitive development as outcome and maternal pre-pregnancy body mass index as an exposure were included. Data were extracted and evaluated for quality by two independent reviewers.. A total of 17 articles were eligible for this systematic review; 10 of them were birth cohorts from the USA. Nine of the 14 studies supported an adverse association between maternal pre-pregnancy obesity and childhood cognitive development. A few studies also demonstrated a negative association between the maternal obesity and gross motor function in children (5 of 10), but not with fine motor function (none out of five studies). Whether the observed negative association between the maternal obesity and children's cognitive and gross motor abilities is casual or due to residual confounding effects is unclear. The current evidence is based on a limited number of studies with heterogeneous measurement scales and obesity definition.. From the available evidence, it seems that exposure to maternal pre-pregnancy obesity in the intrauterine environment has a detrimental effect on children's cognitive development. However, evidence of the association between the maternal obesity and physical development of children is too scarce to offer a conclusion. More research work is required to delineate the intrauterine effect of the maternal obesity from the residual confounding effects. Topics: Blood Glucose; Body Mass Index; Child; Child Development; Cognition; Fatty Acids; Female; Fetal Development; Humans; Inflammation; Leptin; Obesity; Observational Studies as Topic; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk Factors; Women's Health | 2016 |
Multiple Sclerosis and Obesity: Possible Roles of Adipokines.
Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS. Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Animals; Astrocytes; Autoimmune Diseases; CD8-Positive T-Lymphocytes; Complement Factor D; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Humans; Immune System; Inflammation; Interleukin-17; Leptin; Mesenchymal Stem Cells; Mice; Microglia; Multiple Sclerosis; Nicotinamide Phosphoribosyltransferase; Obesity; Oligodendroglia; Prevalence; Resistin; Risk; Th1 Cells; Th2 Cells | 2016 |
Obesity, adipokines and cancer: an update.
Obesity causes dysfunction of adipose tissue, with resultant chronic inflammation and adverse interplay of various adipokines, sex steroids and endocrine hormones. All these drive tumourigenesis and explain the epidemiological link between obesity and cancer. Over the past decade, the associations among obesity, adipokines and cancer have been increasingly recognized. Adipokines and their respective signalling pathways have drawn much research attention in the field of oncology and cancer therapeutics. This review will discuss the recent advances in the understanding of the association of several adipokines with common obesity-related cancers and the clinical therapeutic implications. Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Female; Hormones; Humans; Inflammation; Interleukin-6; Leptin; Male; Neoplasms; Obesity; Signal Transduction; Tumor Necrosis Factor-alpha | 2015 |
Metabolic mysteries of the inflammatory response: T cell polarization and plasticity.
While simultaneously maintaining homeostasis and reducing further harm to the host, the immune system is equipped to eliminate both tumors and pathogenic microorganisms. Bifurcated into cell-mediated and humoral immunity, the adaptive immune system requires a series of complex and coordinated signals to drive the proliferation and differentiation of appropriate subsets. These include signals that modulate cellular metabolism. When first published in the 1920s, "the Warburg effect" was used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis to meet their biosynthetic demands. Despite the early observations of Warburg and his colleagues, targeting cancer cell metabolism for therapeutic purposes still remains theoretical. Notably, many T cells exhibit the same Warburg metabolism as cancer cells and the therapeutic benefit of targeting their metabolic pathways has since been reexamined. Emerging evidence suggests that specific metabolic alterations associated with T cells may be ancillary to their subset differentiation and influential in their inflammatory response. Thus, T cell lymphocyte activation leads to skewing in metabolic plasticity, and issue that will be the subject of this review. Topics: Cell Differentiation; Cell Proliferation; Gene Expression Regulation; Glucose; Glucose Transporter Type 1; Glycolysis; Humans; Immunity, Cellular; Immunity, Humoral; Inflammation; Leptin; Lymphocyte Activation; Oxidative Phosphorylation; Signal Transduction; T-Lymphocyte Subsets; T-Lymphocytes | 2015 |
PI3K signaling in the pathogenesis of obesity: The cause and the cure.
With the steady rise in the incidence of obesity and its associated comorbidities, in the last decades research aimed at understanding molecular mechanisms that control body weight has gained new interest. Fat gain is frequently associated with chronic adipose tissue inflammation and with peripheral as well as central metabolic derangements, resulting in an impaired hypothalamic regulation of energy homeostasis. Recent attention has focused on the role of phosphatidylinositol 3-kinase (PI3K) in both immune and metabolic response pathways, being involved in the pathophysiology of obesity and its associated metabolic diseases. In this review, we focus on distinct PI3K isoforms, especially class I PI3Ks, mediating inflammatory cells recruitment to the enlarged fat as well as intracellular responses to key hormonal regulators of fat storage, both in adipocytes and in the central nervous system. This integrated view of PI3K functions may ultimately help to develop new therapeutic interventions for the treatment of obesity. Topics: Adipocytes; Adipose Tissue; Animals; Class I Phosphatidylinositol 3-Kinases; Energy Metabolism; Gene Expression Regulation; Homeostasis; Humans; Hypothalamus; Immunity, Innate; Inflammation; Insulin Resistance; Leptin; Obesity; Receptor, Melanocortin, Type 4; Signal Transduction | 2015 |
Obesity, adipokines and neuroinflammation.
Global levels of obesity are reaching epidemic proportions, leading to a dramatic increase in incidence of secondary diseases and the significant economic burden associated with their treatment. These comorbidities include diabetes, cardiovascular disease, and some psychopathologies, which have been linked to a low-grade inflammatory state. Obese individuals exhibit an increase in circulating inflammatory mediators implicated as the underlying cause of these comorbidities. A number of these molecules are also manufactured and released by white adipose tissue (WAT), in direct proportion to tissue mass and are collectively known as adipokines. In the current review we focused on the role of two of the better-studied members of this family namely, leptin and adiponectin, with particular emphasis on their role in neuro-immune interactions, neuroinflammation and subsequent brain diseases. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. Topics: Adipokines; Adiponectin; Animals; Encephalitis; Humans; Inflammation; Leptin; Obesity | 2015 |
Leptin resistance in diet-induced obesity: the role of hypothalamic inflammation.
The consumption of Western diets, high in sugar and saturated fat, is a crucial contributor to the alarming incidence of obesity and its associated morbidities. These diets have been reported to induce an inflammatory response in the hypothalamus, which promotes the development of central leptin resistance and obesity. This inflammatory signalling involves dynamic changes in the expression and activity of several mediators of the innate immune system, including toll-like receptor 4, IκB kinase-β/nuclear factor-κB, c-Jun N-terminal kinase, suppressor of cytokine signalling 3 and pro-inflammatory cytokines, as well as the induction of endoplasmic reticulum stress and autophagy defect. Although the exact cellular mechanisms remain incompletely understood, recent evidence suggests that the inflammatory response is at least mediated by interactions between neurons and non-neuronal cells such as microglia and astrocytes. Current evidence of the contribution of each inflammatory mediator to leptin resistance and diet-induced obesity (DIO), including their reciprocal interactions and cell-type-specific effects, is reviewed and integrated in a conceptual model. Based upon this model and pharmacological intervention studies, several inflammatory mediators are proposed to be promising therapeutic targets for the treatment of DIO. Topics: Animals; Diet, High-Fat; Energy Metabolism; Humans; Hypothalamus; Inflammation; Leptin; Mice; Obesity; Oxidative Stress; Rats; Signal Transduction | 2015 |
Leptin signaling as a therapeutic target of obesity.
Leptin is a hormone with a key role in food intake and body weight homeostasis. Congenital leptin deficiency (CLD) is a rare disease that causes hyperphagia and early severe obesity. However, common obesity conditions are associated with hyperleptinemia and leptin resistance.. The main signaling pathways activated by leptin as well as the mechanisms underlying the regulatory actions of leptin on food intake and on lipid and glucose metabolism are reviewed. The potential mechanisms involving leptin resistance and the main regulatory hormonal and nutritional factors controlling leptin production/functions are also analyzed. The pathophysiology of leptin in human obesity, and especially the trials analyzing effects of leptin replacement therapy in patients with CLD or in subjects with common obesity and in post-obese weight-reduced subjects are also summarized.. The use of drugs or specific bioactive food components with anti-inflammatory properties to reduce the inflammatory state associated with obesity, especially at the hypothalamus, may help to overcome leptin resistance. Research should also be focused on investigating dietary strategies, food supplements or drugs capable of avoiding or reversing the leptin fall during weight management, in order to promote sustained body weight lowering and weight loss maintenance. Topics: Animals; Anti-Inflammatory Agents; Anti-Obesity Agents; Body Weight; Humans; Hypothalamus; Inflammation; Leptin; Molecular Targeted Therapy; Obesity; Signal Transduction | 2015 |
How effective are antioxidant supplements in obesity and diabetes?
Obesity is a central health issue due to its epidemic prevalence and its association with type 2 diabetes and other comorbidities. Obesity is not just being overweight. It is a metabolic disorder due to the accumulation of excess dietary calories into visceral fat and the release of high concentrations of free fatty acids into various organs. It represents a state of chronic oxidative stress and low-grade inflammation whose intermediary molecules may include leptin, adiponectin and cytokines. It may progress to hyperglycemia, leading to type 2 diabetes. Whether or not dietary antioxidant supplements are useful in the management of obesity and type 2 diabetes is discussed in this review. Only the benefits for obesity and diabetes are examined here. Other health benefits of antioxidants are not considered. There are difficulties in comparing studies in this field because they differ in the time frame, participants' ethnicity, administration of antioxidant supplements, and even in how obesity was measured. However, the literature presents reasonable evidence for marginal benefits of supplementation with zinc, lipoic acid, carnitine, cinnamon, green tea, and possibly vitamin C plus E, although the evidence is much weaker for omega-3 polyunsaturated fatty acids, coenzyme Q10, green coffee, resveratrol, or lycopene. Overall, antioxidant supplements are not a panacea to compensate for a fast-food and video-game way of living, but antioxidant-rich foods are recommended as part of the lifestyle. Such antioxidant foods are commonly available. Topics: Adipose Tissue; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Antioxidants; Biomarkers; Body Mass Index; Diabetes Mellitus, Type 2; Dietary Supplements; Fatty Acids, Nonesterified; Genetic Predisposition to Disease; Humans; Inflammation; Leptin; Obesity; Overweight; Oxidative Stress; Proprotein Convertase 1; Proteins; Reactive Oxygen Species; Receptor, Melanocortin, Type 4; Vitamins | 2015 |
Improved fracture healing in patients with concomitant traumatic brain injury: proven or not?
Over the last 3 decades, scientific evidence advocates an association between traumatic brain injury (TBI) and accelerated fracture healing. Multiple clinical and preclinical studies have shown an enhanced callus formation and an increased callus volume in patients, respectively, rats with concomitant TBI. Over time, different substances (cytokines, hormones, etc.) were in focus to elucidate the relationship between TBI and fracture healing. Until now, the mechanism behind this relationship is not fully clarified and a consensus on which substance plays the key role could not be attained in the literature. In this review, we will give an overview of current concepts and opinions on this topic published in the last decade and both clinical and pathophysiological theories will be discussed. Topics: Blood-Brain Barrier; Brain Injuries; Calcitonin Gene-Related Peptide; Cell Death; Fracture Healing; Humans; Inflammation; Interleukin-6; Leptin; Mesenchymal Stem Cells; Transforming Growth Factor beta | 2015 |
Adipokines as drug targets in diabetes and underlying disturbances.
Diabetes and obesity are worldwide health problems. White fat dynamically participates in hormonal and inflammatory regulation. White adipose tissue is recognized as a multifactorial organ that secretes several adipose-derived factors that have been collectively termed "adipokines." Adipokines are pleiotropic molecules that gather factors such as leptin, adiponectin, visfatin, apelin, vaspin, hepcidin, RBP4, and inflammatory cytokines, including TNF and IL-1β, among others. Multiple roles in metabolic and inflammatory responses have been assigned to these molecules. Several adipokines contribute to the self-styled "low-grade inflammatory state" of obese and insulin-resistant subjects, inducing the accumulation of metabolic anomalies within these individuals, including autoimmune and inflammatory diseases. Thus, adipokines are an interesting drug target to treat autoimmune diseases, obesity, insulin resistance, and adipose tissue inflammation. The aim of this review is to present an overview of the roles of adipokines in different immune and nonimmune cells, which will contribute to diabetes as well as to adipose tissue inflammation and insulin resistance development. We describe how adipokines regulate inflammation in these diseases and their therapeutic implications. We also survey current attempts to exploit adipokines for clinical applications, which hold potential as novel approaches to drug development in several immune-mediated diseases. Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Diabetes Mellitus; Humans; Inflammation; Interleukin-1beta; Leptin; Mice; Nicotinamide Phosphoribosyltransferase; Obesity; Retinol-Binding Proteins, Plasma; Tumor Necrosis Factor-alpha | 2015 |
Nonalcoholic Fatty liver disease, diabetes, obesity, and hepatocellular carcinoma.
Diabetes and obesity are associated with nonalcoholic fatty liver disease (NAFLD) and an increased incidence of hepatocellular carcinoma (HCC). NAFLD is the commonest cause of chronic liver disease. HCC can develop in NAFLD patients even without cirrhosis, suggesting an association between the metabolic process and HCC and raising a concern that many cancers could be missed given high NAFLD prevalence and screening limitations. The increasing prevalence of these conditions and lack of effective treatments necessitate a better understanding of their connection. This article defines the known interrelationships and common pathways between NAFLD, diabetes, obesity and HCC and possible chemoprevention strategies. Topics: Carcinoma, Hepatocellular; Chemoprevention; Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Incidence; Inflammation; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Leptin; Liver Neoplasms; Metformin; Non-alcoholic Fatty Liver Disease; Obesity; Risk Factors; S-Adenosylmethionine; Toll-Like Receptors | 2015 |
Role of Obesity in the Pathogenesis and Progression of Barrett's Esophagus.
Central obesity is involved in the pathogenesis and progression of Barrett's esophagus to esophageal adenocarcinoma. Involved are likely both mechanical and nonmechanical effects. Mechanical effects of increased abdominal fat cause disruption of the gastroesophageal reflux barrier leading to increased reflux events. Nonmechanical effects may be mediated by inflammation, via classically activated macrophages, pro-inflammatory cytokines, and adipokines such as Leptin, all of which likely potentiate reflux-mediated inflammation. Insulin resistance, associated with central obesity, is also associated with both Barrett's pathogenesis and progression to adenocarcinoma. Molecular pathways activated in obesity, inflammation and insulin resistance overlap with those involved in Barrett's pathogenesis and progression. Topics: Adiponectin; Barrett Esophagus; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Obesity, Abdominal | 2015 |
Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development.
Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-α (TNF-α). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression). Topics: Adiponectin; Carcinogenesis; Chronic Disease; Colorectal Neoplasms; Cytokines; Female; Humans; Inflammation; Leptin; Male; Obesity; Reactive Oxygen Species | 2015 |
Adipokines influence the inflammatory balance in autoimmunity.
Over the past few decades, our understanding of the role of adipose tissue has changed dramatically. Far from simply being a site of energy storage or a modulator of the endocrine system, adipose tissue has emerged as an important regulator of multiple important processes including inflammation. Adipokines are a diverse family of soluble mediators with a range of specific actions on the immune response. Autoimmune diseases are perpetuated by chronic inflammatory responses but the exact etiology of these diseases remains elusive. While researchers continue to investigate these causes, millions of people continue to suffer from chronic diseases. To this end, an increased interest has developed in the connection between adipose tissue-secreted proteins that influence inflammation and the onset and perpetuation of autoimmunity. This review will focus on recent advances in adipokine research with specific attention on a subset of adipokines that have been associated with autoimmune diseases. Topics: Adipokines; Adiponectin; Adipose Tissue, White; Autoimmunity; Chemokines; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin | 2015 |
New insights in leptin resistance mechanisms in mice.
Leptin resistance is one of the main challenges of obesity. To date, two levels of resistance have been identified, first a decreased rate of leptin uptake into the brain and secondly a diminished central response to leptin. New findings have identified the mechanisms of leptin transport and demonstrated that it can be rescued in obesity, but it did not overcome the problem of central resistance. Alteration in the actions of leptin following diet-induced obesity (DIO) appears to be a multifactorial condition. Several phosphatases are inhibiting leptin signaling pathways in a pathological way. Besides, hypothalamic inflammation alters the neuronal circuits that control metabolism. Recent studies describing both mechanisms (inhibition of leptin signaling and inflammation), have provided key insights to potential new targets for treatment. However, recent data showing that DIO mice may conserve a cellular and physiological response to endogenous leptin, highlights the need to redefine the concept of "leptin resistance". Topics: Animals; Female; Hypothalamus; Inflammation; Leptin; Mice; Obesity; Pregnancy | 2015 |
Cancer as a Proinflammatory Environment: Metastasis and Cachexia.
The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines. Topics: Angiopoietin-Like Protein 4; Angiopoietins; Animals; Cachexia; Cytokines; Ghrelin; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Inflammation; Interleukin-6; Leptin; Myostatin; Neoplasm Metastasis; Neoplasms; Prognosis; Syndrome; Tumor Microenvironment; Tumor Necrosis Factor-alpha | 2015 |
Potential Biomarkers of Fat Loss as a Feature of Cancer Cachexia.
Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may not relate to adipose atrophy. Zinc-α2-glycoprotein may be a local catabolic mediator within adipose tissue rather than serving as a plasma biomarker of fat loss. Plasma glycerol and leptin associate with adipose tissue atrophy and mass, respectively; however, no study has evaluated their potential as a prognostic biomarker of cachexia-associated fat loss. This review confirms the need for further studies to identify valid prognostic biomarkers to identify loss of fat based on changes in plasma levels of biomarkers. Topics: Adipokines; Adipose Tissue; Biomarkers; Cachexia; Carrier Proteins; Cytokines; Glycerol; Glycoproteins; Humans; Inflammation; Leptin; Lipid Metabolism; Lipolysis; Neoplasms; Prognosis; Weight Loss | 2015 |
[The diversity of leptin].
The role of leptin in regulation of energy homeostasis is well established, yet both the diagnostic as well as the therapeutic relevance of leptin in diet-induced obesity remains unresolved. Nevertheless, in the last few years, the substantial impact of leptin substitution in selected forms of monogenic obesity has advanced our knowledge about the neuroendocrine network of body weight regulation. Moreover, leptin seems to play a crucial role in intestinal nutrient reabsorption, regulation of blood pressure, fertility, inflammation and autoimmune diseases. A better understanding of these processes could possibly provide novel diagnostic and therapeutic options in the future. Topics: Autoimmune Diseases; Blood Pressure; Body Composition; Body Weight; Energy Metabolism; Fertility; Homeostasis; Humans; Inflammation; Intestinal Absorption; Leptin; Obesity | 2015 |
Parturition dysfunction in obesity: time to target the pathobiology.
Over a third of women of childbearing age in the United States are obese, and during pregnancy they are at increased risk for delayed labor onset and slow labor progress that often results in unplanned cesarean delivery. The biology behind this dysfunctional parturition is not well understood. Studies of obesity-induced changes in parturition physiology may facilitate approaches to optimize labor in obese women. In this review, we summarize known and proposed biologic effects of obesity on labor preparation, contraction/synchronization, and endurance, drawing on both clinical observation and experimental data. We present evidence from human and animal studies of interactions between obesity and parturition signaling in all elements of the birth process, including: delayed cervical ripening, prostaglandin insensitivity, amniotic membrane strengthening, decreased myometrial oxytocin receptor expression, decreased myocyte action potential initiation and contractility, decreased myocyte gap junction formation, and impaired myocyte neutralization of reactive oxygen species. We found convincing clinical data on the effect of obesity on labor initiation and successful delivery, but few studies on the underlying pathobiology. We suggest research opportunities and therapeutic interventions based on plausible biologic mechanisms. Topics: Adipokines; Body Mass Index; Cesarean Section; Cholesterol; Dystocia; Female; Humans; Inflammation; Leptin; Myometrium; Obesity; Obstetric Labor Complications; Parturition; Phenotype; Pregnancy; Pregnancy Complications; Prostaglandins; Receptors, Oxytocin; Signal Transduction; Uterine Contraction; Uterus | 2015 |
Adiponectin and leptin: new targets in inflammation.
Inflammation is a complex mechanism of cell/tissue responses to injuries triggered by multiple causes, including trauma, pathogens or autoimmune abnormal responses. In the last years, a novel line of thought is emerging by giving a more holistic vision of chronic arthropathies through a recently identified group of molecules, called adipokines. Actually, most of these recently identified factors, produced prevalently by white adipose tissue but also by cells of the joints (chondrocytes and synovial fibroblasts) and immune cells, play a significant role in chronic inflammation. Adipokines dysregulation has emerged as a common characteristic of chronic inflammation in rheumatic diseases in particular when obesity or, more precisely, adipose tissue dysfunction is associated with common rheumatic diseases, such as osteoarthritis and rheumatoid arthritis. In this MiniReview, we discuss the role of adipokines in osteoarthritis and rheumatoid arthritis providing an updated overview of their pathophysiological role and potential use as therapeutic targets. Topics: Adiponectin; Adipose Tissue, White; Animals; Arthritis, Rheumatoid; Humans; Inflammation; Leptin; Osteoarthritis | 2014 |
Regulatory T cells, leptin and angiogenesis.
Regulatory T cells (Treg cells) are crucial in mediating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Excess body weight and obesity are typified by 'low-degree' chronic inflammation and are associated with an increased risk of atherosclerosis, diabetes, fatty liver disease, autoimmune diseases and cancer. All these pathological conditions are characterized by chronic inflammation, abnormal cytokine production, elevated acute-phase reactants, and the activation of several inflammatory signaling pathways. In this context, the discovery of the adipose tissue-derived hormone leptin has shed fundamental insights on how these processes might occur. Leptin represents a link among metabolic disorders and immune tolerance; indeed, leptin can negatively affect the generation and proliferation of Treg cells, key players in this context. Treg cells play also a central role in tumor progression; different reports have proposed that tumor microenvironment can induce the recruitment of Treg cells which can promote tumor tolerance and angiogenesis through expression of suppressive molecules, cytokines and angiogenic factors (i.e. vascular endothelial growth factor, leptin). This work aims to discuss some of the most recent advances on the relationship between angiogenesis, leptin and immune tolerance, focusing on the role of Treg cell function in this context. Topics: Acute-Phase Proteins; Adipose Tissue; Autoimmune Diseases; Cytokines; Gene Expression Regulation; Humans; Immune Tolerance; Inflammation; Leptin; Neovascularization, Pathologic; Neovascularization, Physiologic; Obesity; Signal Transduction; T-Lymphocytes, Regulatory | 2014 |
Obesity related adipokines and colorectal cancer: a review and meta-analysis.
Obesity has been considered as an important risk factor for the development of colorectal cancer (CRC), but the association has not been fully elucidated. Obesity is linked significantly to adipose tissue dysfunction and to alteration of adipokines in blood; in particular, obesity-induced inflammation is thought to be an important link between obesity and colorectal cancer. Based on epidemiological studies, we undertook a systematic review to understand the association of circulating levels of selected adipokines, including adiponectin, leptin, resistin, IL-6 and TNF-α, with the level of CRC risk. Most prospective studies suggested protective effects of adiponectin, but these were attenuated by body mass index (BMI) and waist circumference (WC) data in our meta-analysis. On the other hand, meta-analyses for leptin and CRC did not demonstrate any association, similar to the results of systematic review. Although it proved difficult to determine whether other selected adipokines (resistin, IL-6 and TNF-α) were related to CRC risk due to small number of reports, the present systematic review suggested a positive association with elevated resistin levels but null associations with IL-6 and TNF-α. Topics: Adiponectin; Body Mass Index; Colorectal Neoplasms; Humans; Inflammation; Interleukin-6; Leptin; Obesity; Resistin; Risk Factors; Tumor Necrosis Factor-alpha; Waist Circumference | 2014 |
Bacteria, viruses, and hypothalamic inflammation: potential new players in obesity.
Being overweight and obese has become an increasingly serious clinical and socioeconomic problem worldwide. The rapidly rising prevalence of obesity has prompted studies on modifiable, causative factors and novel treatment options for this disorder. Recent evidence indicates that excessive weight gain that leads to being overweight and obese may result from alterations in gut microflora. Studies in humans and animals demonstrated that the composition of gut microbiota may differ in lean and obese subjects, suggesting that these differences result in the increased efficiency of caloric extraction from food, enhanced lipogenesis, and impaired central and peripheral regulation of energy balance. Other studies revealed an excessive increase in body weight in a significant percentage of people infected with human adenoviruses SMAM-1 and Ad-36. Dysregulation of adipocyte function by viruses appears to be the most likely cause of excessive fat accumulation in these individuals. Studies on the pathomechanisms related to the pathogenesis of obesity indicated that a high-fat diet triggers the inflammatory response in the hypothalamus, an event that promotes weight gain and further defends elevated body weight through the initiation of central leptin and insulin resistance and impairment of regenerative capacity of hypothalamic neurons. Exposure to a high-calorie diet appears to predispose individuals to obesity not only because of excessive caloric intake but also because of the induction of microbiota- and central inflammatory response-dependent changes that lead to a dysregulation of energy balance. Topics: Animals; Bacterial Infections; Body Weight; Energy Intake; Energy Metabolism; Gastrointestinal Tract; Humans; Hypothalamus; Inflammation; Insulin Resistance; Leptin; Obesity; Virus Diseases | 2014 |
Novel molecular aspects of ghrelin and leptin in the control of adipobiology and the cardiovascular system.
Ghrelin and leptin show opposite effects on energy balance. Ghrelin constitutes a gut hormone that is secreted to the bloodstream in two major forms, acylated and desacyl ghrelin. The isoforms of ghrelin not only promote adiposity by the activation of hypothalamic orexigenic neurons but also directly stimulate the expression of several fat storage-related proteins in adipocytes, including ACC, FAS, LPL and perilipin, thereby stimulating intracytoplasmic lipid accumulation. Moreover, both acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in adipocytes, suggesting an anti-inflammatory role of ghrelin in human adipose tissue. On the other hand, leptin is an adipokine with lipolytic effects. In this sense, leptin modulates via PI3K/Akt/mTOR the expression of aquaglyceroporins such as AQP3 and AQP7 that facilitate glycerol efflux from adipocytes in response to the lipolytic stimuli via its translocation from the cytosolic fraction (AQP3) or lipid droplets (AQP7) to the plasma membrane. Ghrelin and leptin also participate in the homeostasis of the cardiovascular system. Ghrelin operates as a cardioprotective factor with increased circulating acylated ghrelin concentrations in patients with left ventricular hypertrophy (LVH) causally related to LV remodeling during the progression to LVH. Additionally, leptin induces vasodilation by inducible NO synthase expression (iNOS) in the vascular wall. In this sense, leptin inhibits the angiotensin II-induced Ca(2+) increase, contraction and proliferation of VSMC through NO-dependent mechanisms. Together, dysregulation of circulating ghrelin isoforms and leptin resistance associated to obesity, type 2 diabetes, or the metabolic syndrome contribute to cardiometabolic derangements observed in these pathologies. Topics: Adipose Tissue; Adiposity; Cardiovascular Diseases; Cardiovascular System; Ghrelin; Humans; Inflammation; Leptin; Lipid Metabolism; Obesity | 2014 |
[Metabolic pro-inflammatory stress, adipokines and respiratory diseases].
Topics: Adipokines; Adiponectin; Humans; Inflammation; Leptin; Obesity; Respiratory Tract Diseases; Stress, Physiological | 2014 |
Hypothalamic inflammation and the central nervous system control of energy homeostasis.
The control of energy homeostasis relies on robust neuronal circuits that regulate food intake and energy expenditure. Although the physiology of these circuits is well understood, the molecular and cellular response of this program to chronic diseases is still largely unclear. Hypothalamic inflammation has emerged as a major driver of energy homeostasis dysfunction in both obesity and anorexia. Importantly, this inflammation disrupts the action of metabolic signals promoting anabolism or supporting catabolism. In this review, we address the evidence that favors hypothalamic inflammation as a factor that resets energy homeostasis in pathological states. Topics: Animals; Anorexia; Central Nervous System; Energy Metabolism; Homeostasis; Humans; Hypothalamus; Inflammation; Insulin; Leptin; Models, Biological; Obesity; Signal Transduction | 2014 |
Leptin as an uremic toxin: Deleterious role of leptin in chronic kidney disease.
White adipose tissue secretes a large variety of compounds named adipokines amongst which, leptin exhibits pleiotropic metabolic actions. Leptin is an anorexigenic hormone, secreted in proportion of fat mass, with additional effects on the regulation of inflammation, cardiovascular system, immunity, hematopoiesis and bone metabolism. Chronic kidney disease (CKD) is characterized by an increase of plasma leptin concentration that may be explained by a lack of renal clearance. Hyperleptinemia plays a key role in the pathogenesis of complications associated with CKD such as cachexia, protein energy wasting, chronic inflammation, insulin resistance, cardiovascular damages and bone complications. Leptin is also involved in the progression of renal disease through its pro-fibrotic and pro-hypertensive actions. Most of the adverse effects of leptin have been documented both experimentally and clinically. Leptin may therefore be considered as an uremic toxin in CKD. The aim of this review is to summarize the pathophysiological and clinical role of leptin in in vitro studies, experimental models, as well as in patients suffering from CKD. Topics: Adipose Tissue; Cachexia; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Receptors, Leptin; Renal Insufficiency, Chronic; Toxins, Biological | 2014 |
An update on leptin as immunomodulator.
Until the discovery of leptin 20 years ago, adipose tissue was considered only as a fat storage organ, involved in the regulation of energy homeostasis. At present, it is well known that adipokines, being leptin the forerunner of this superfamily, may act in different biological processes, including inflammation and immunity. In this review, we have explored the recent evidence about the relationship between leptin and immune system, summarizing the most important findings related to the involvement of leptin in both innate and adaptive immune response. Topics: Adaptive Immunity; Adipose Tissue; Animals; Energy Metabolism; Humans; Immunity, Innate; Immunomodulation; Inflammation; Leptin; Obesity | 2014 |
Role of fat and adipokines in intestinal inflammation.
This review summarizes current knowledge on the contribution of mesenteric adipose tissue in intestinal inflammation. We will describe the cellular and humoral characteristics of creeping fat, their potential impact for Crohn's disease and propose a working model for the critical interplay between the creeping fat and the inflamed intestine.. Creeping fat can be distinguished from healthy adipose tissue by its distinctively small adipocytes, by a specific microenvironment defined by high levels of adipokines and by a dominant immune cell infiltration. In Crohn's disease transmural inflammation facilitates increased bacterial translocation into the creeping fat. Translocalizing antigens can directly activate (pre)adipocytes via innate receptors. Adipocyte-derived mediators modulate phenotype and function of innate and adaptive immune cells. Activated (pre)adipocytes and adipokine-modulated immune cells might support a degree of inflammatory activation within the creeping fat that allows competent immune defense against exogenous factors while preventing systemic inflammation.. Fat tissue as an active organ in health and disease has been ignored for too long. The last few years of research provided evidence for the complex metabolic and immunological functions of adipose tissue. On the basis of the available data, creeping fat in Crohn's disease exerts a protective function by a localized anti-inflammatory effect, thus preventing a systemic inflammatory response. Topics: Adipokines; Adipose Tissue; Biomarkers; Humans; Inflammation; Inflammation Mediators; Inflammatory Bowel Diseases; Intestinal Mucosa; Leptin; Lipid Metabolism; Mesentery; Receptors, Adiponectin; Receptors, Cell Surface; Receptors, Leptin; Resistin | 2014 |
n-3 polyunsaturated fatty acids and mechanisms to mitigate inflammatory paracrine signaling in obesity-associated breast cancer.
Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA) may have utility in mitigating the severity of obesity-associated inflammation and breast cancer. Topics: Adiponectin; Aromatase; Breast Neoplasms; Cytokines; Estrogens; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Inflammation; Intra-Abdominal Fat; Leptin; Obesity; Paracrine Communication; Prevalence | 2014 |
Estrogen signaling in metabolic inflammation.
There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions. Topics: Adiposity; Animals; Aromatase; Energy Metabolism; Estrogen Replacement Therapy; Estrogens; Female; Glucocorticoids; Humans; Inflammation; Leptin; Male; Ovariectomy; Receptors, Estrogen; Signal Transduction | 2014 |
Hypercholesterolemia induces adipose dysfunction in conditions of obesity and nonobesity.
It is well known that hypercholesterolemia can lead to atherosclerosis and coronary heart disease. Adipose tissue represents an active endocrine and metabolic site, which might be involved in the development of chronic disease. Because adipose tissue is a key site for cholesterol metabolism and the presence of hypercholesterolemia has been shown to induce adipocyte cholesterol overload, it is critical to investigate the role of hypercholesterolemia on normal adipose function. Studies in preadipocytes revealed that cholesterol accumulation can impair adipocyte differentiation and maturation by affecting multiple transcription factors. Hypercholesterolemia has been observed to cause adipocyte hypertrophy, adipose tissue inflammation, and disruption of endocrine function in animal studies. Moreover, these effects can also be observed in obesity-independent conditions as confirmed by clinical trials. In humans, hypercholesterolemia disrupts adipose hormone secretion of visfatin, leptin, and adiponectin, adipokines that play a central role in numerous metabolic pathways and regulate basic physiologic responses such as appetite and satiety. Remarkably, treatment with cholesterol-lowering drugs has been shown to restore adipose tissue endocrine function. In this review the role of hypercholesterolemia on adipose tissue differentiation and maturation, as well as on hormone secretion and physiologic outcomes, in obesity and non–obesity conditions is presented. Topics: Adipocytes; Adiponectin; Adipose Tissue; Adiposity; Animals; Anticholesteremic Agents; Cell Differentiation; Clinical Trials as Topic; Disease Models, Animal; Humans; Hypercholesterolemia; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity | 2014 |
Insulin resistance, selfish brain, and selfish immune system: an evolutionarily positively selected program used in chronic inflammatory diseases.
Insulin resistance (IR) is a general phenomenon of many physiological states, disease states, and diseases. IR has been described in diabetes mellitus, obesity, infection, sepsis, trauma, painful states such as postoperative pain and migraine, schizophrenia, major depression, chronic mental stress, and others. In arthritis, abnormalities of glucose homeostasis were described in 1920; and in 1950 combined glucose and insulin tests unmistakably demonstrated IR. The phenomenon is now described in rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, polymyalgia rheumatica, and others. In chronic inflammatory diseases, cytokine-neutralizing strategies normalize insulin sensitivity. This paper delineates that IR is either based on inflammatory factors (activation of the immune/ repair system) or on the brain (mental activation via stress axes). Due to the selfishness of the immune system and the selfishness of the brain, both can induce IR independent of each other. Consequently, the immune system can block the brain (for example, by sickness behavior) and the brain can block the immune system (for example, stress-induced immune system alterations). Based on considerations of evolutionary medicine, it is discussed that obesity per se is not a disease. Obesity-related IR depends on provoking factors from either the immune system or the brain. Chronic inflammation and/or stress axis activation are thus needed for obesity-related IR. Due to redundant pathways in stimulating IR, a simple one factor-neutralizing strategy might help in chronic inflammatory diseases (inflammation is the key), but not in obesity-related IR. The new considerations towards IR are interrelated to the published theories of IR (thrifty genotype, thrifty phenotype, and others). Topics: Brain; Chronic Disease; Cytokines; Endocrinology; Energy Metabolism; Fasting; Humans; Inflammation; Insulin Resistance; Leptin; Models, Biological; Neuroimmunomodulation; Obesity; Selection, Genetic; Starvation; Stress, Psychological | 2014 |
Antioxidant food supplements and obesity-related inflammation.
The obesity prevalence is growing worldwide and largely responsible for the increased incidence of cardiovascular disease, the most common cause of death in the western world. Excessive food intake along with insufficient physical exercise is the basic impetus for this development. The obese state is commonly associated with an increase in leptin levels and chronic immune-mediated inflammation. Despite high leptin levels, the leptin response, normally associated with satiety and satiation, seems to be impaired and individuals continue to consume calorie-rich food. Antioxidant food additives such as sodium sulphite, sodium benzoate and curcumin were shown to suppress the leptin release in lipopolysaccharide- treated murine adipocytes. Based on this, we hypothesize that the insufficient leptin release, caused by excessive consumption of food additives, may lead to a reduced exposure of the central nervous system to leptin and ultimately propagate obesity. On the other hand, leptin has been shown to favor Th1-type activity, which ultimately decreases tryptophan levels. Tryptophan derivatives, serotonin and melatonin, induce satiety/satiation through several mechanisms. In this context, the antioxidant suppression of leptin release and Th1-type activity is beneficial to increase serotonin and melatonin levels. The molecules in the mechanism described in this review are highly integrated in the reward system, and have been implicated in the addiction behavior of obesity. Based on these facts, the involvement of antioxidant food supplements in the mechanisms of the reward-deficiency syndrome which perpetuates obesity will be discussed. Topics: Adaptive Immunity; Animals; Antioxidants; Food Additives; Humans; Inflammation; Leptin; Obesity | 2013 |
Leptin as regulator of pulmonary immune responses: involvement in respiratory diseases.
Leptin is an adipocyte-derived hormone, recognized as a critical mediator of the balance between food intake and energy expenditure by signalling through its functional receptor (Ob-Rb) in the hypothalamus. Structurally, leptin belongs to the long-chain helical cytokine family, and is now known to have pleiotropic functions in both innate and adaptive immunity. The presence of the functional leptin receptor in the lung together with evidence of increased airspace leptin levels arising during pulmonary inflammation, suggests an important role for leptin in lung development, respiratory immune responses and eventually pathogenesis of inflammatory respiratory diseases. The purpose of this article is to review our current understanding of leptin and its functional role on the different resident cell types of the lung in health as well as in the context of three major respiratory conditions being chronic obstructive pulmonary disease (COPD), asthma, and pneumonia. Topics: Adaptive Immunity; Animals; Asthma; Humans; Immunity, Innate; Inflammation; Leptin; Lung; Pneumonia; Pulmonary Disease, Chronic Obstructive | 2013 |
Leptin, resistin and visfatin: the missing link between endocrine metabolic disorders and immunity.
Adipose tissue is still regarded as a principle site for lipid storage and mobilizing tissue with an important role in the control of energy homeostasis. Additionally, adipose tissue-secreted hormones such as leptin, visfatin, resistin, apelin, omentin, sex steroids, and various growth factors are now regarded as a functional part of the endocrine system. These hormones also play an important role in the immune system. Several in vitro and in vivo studies have suggested the complex role of adipocyte-derived hormones in immune system and inflammation. Adipokines mediate beneficial and detrimental effects in immunity and inflammation. Many of these adipocytokines have a physiological role in metabolism. The uncontrolled secretions of several adipocytokines were associated with the stimulation of inflammatory processes leading to metabolic disorders including obesity, atherosclerosis, insulin resistance and type 2 diabetes. Obesity leads to the dysfunction of adipocytes andcorrelated with the imbalance of adipokines levels. In obese and diabetic conditions, leptin deficiency inhibited the Jak/Stat3/PI3K and insulin pathways. In this review, ample evidence exists to support the recognition of the adipocyte's role in various tissues and pathologies. New integral insights may add dimensions to translate any potential agents into the future clinical armamentarium of chronic endocrine metabolic and inflammatory diseases. Functional balance of both adipocytes and immune cells is important to exert their effects on endocrine metabolic disorders; furthermore, adipose tissue should be renamed not only as a functional part of the endocrine system but also as a new part of the immune system. Topics: Adipocytes; Adipokines; Adipose Tissue; Endocrine System Diseases; Energy Metabolism; Hormones; Humans; Immunity; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Resistin | 2013 |
Linking obesity to colorectal cancer: recent insights into plausible biological mechanisms.
This review will examine the recent scientific literature on the mechanisms that are thought to link obesity to colorectal cancer (CRC) risk.. Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully elucidated. Recent literature has focused on inflammatory processes, adipokines, and estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of inflammatory cytokines including tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, whereas leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although its role remains controversial; some studies have implicated estrogen as being protective, whereas others have suggested it to be a risk factor. We highlight the most important recent advances that have been made on the aforementioned mechanisms that are thought to link obesity to CRC.. A better understanding of the mechanisms linking obesity to CRC risk is necessary for the design of effective treatment approaches in future clinical trials. Topics: Adiponectin; Adipose Tissue; Chemokine CCL2; Colorectal Neoplasms; Estrogens; Humans; Inflammation; Interleukin-6; Leptin; Macrophages; Obesity; Tumor Necrosis Factor-alpha | 2013 |
Adipo-myokines: two sides of the same coin--mediators of inflammation and mediators of exercise.
This review summarizes the current literature regarding the most discussed contraction-regulated moykines like IL-6, IL-15, irisin, BDNF, ANGPTL4, FGF21, myonectin and MCP-1. It is suggested that the term myokine is restricted to proteins secreted from skeletal muscle cells, excluding proteins that are secreted by other cell types in skeletal muscle tissue and excluding proteins which are only described on the mRNA level. Interestingly, many of the contraction-regulated myokines described in the literature are additionally known to be secreted by adipocytes. We termed these proteins adipo-myokines. Within this review, we try to elaborate on the question why pro-inflammatory adipokines on the one hand are upregulated in the obese state, and have beneficial effects after exercise on the other hand. Both, adipokines and myokines do have autocrine effects within their corresponding tissues. In addition, they are involved in an endocrine crosstalk with other tissues. Depending on the extent and the kinetics of adipo-myokines in serum, these molecules seem to have a beneficial or an adverse effect on the target tissue. Topics: Adipokines; Adipose Tissue; Angiopoietin-Like Protein 4; Angiopoietins; Animals; Brain-Derived Neurotrophic Factor; Chemokine CCL2; Endocrine System; Exercise; Fibroblast Growth Factors; Follistatin-Related Proteins; Gene Expression Regulation; Humans; Inflammation; Interleukin-15; Interleukin-6; Leptin; Muscle, Skeletal; RNA, Messenger | 2013 |
Biomarkers in pediatric depression.
Topics: Biomarkers; Brain; Brain-Derived Neurotrophic Factor; Child; Depressive Disorder; Ghrelin; Humans; Hypothalamo-Hypophyseal System; Inflammation; Leptin; Models, Biological; Neural Pathways; Pituitary-Adrenal System; Sleep Wake Disorders | 2013 |
Systematic review of saturated fatty acids on inflammation and circulating levels of adipokines.
Diet is one factor that plays a part in coronary heart disease risk through multiple biological mechanisms including subclinical inflammation. In this review, we aimed to systematically assess and summarize evidence regarding the association of saturated fatty acids (SFAs) with inflammatory markers and adipokines. An electronic search of the literature was conducted up to September 2010 using Medline, Scopus, Web of Science, and Science Direct (updated from September 2010 to August 2011 through Medline). Original studies that were written in Portuguese, English, Spanish, or French, and addressed the effects of SFA (not dietary sources or SFA-rich diets) on inflammatory markers or adipokines in adult populations were considered eligible. Data from 15 studies providing adjusted estimates were extracted. The publication year varied from 1995 to 2010 and the sample size from 54 to 4900. Most studies were cross sectional, with 3 studies using a prospective design. Twelve studies assessed total SFA, and 3 studies considered their subtypes, which were measured through dietary assessments (11 studies) or in blood samples (4 studies). Significant positive associations were observed between SFA and soluble intercellular adhesion molecule-1 and interleukin-6, whereas no significant associations were observed with E-selectin, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, fibrinogen, and adiponectin. For high-sensitivity C-reactive protein, 2 studies showed significant positive associations, whereas 3 studies reported no significant associations. One study reported a significant inverse association of SFA with leptin, although the other 3 found no significant associations. Based on this systematic review, a potential positive association of SFA with high-sensitivity C-reactive protein but not with adipokines is suggested, which should be confirmed by future research. Topics: Adipokines; Biomarkers; C-Reactive Protein; Cell Adhesion; Diet; E-Selectin; Fatty Acids; Feeding Behavior; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Tumor Necrosis Factor-alpha | 2013 |
Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management.
An increase in adiposity is associated with altered levels of biologically active proteins. These include the hormones adiponectin and leptin. The marked change in circulating concentrations of these hormones in obesity has been associated with the development of insulin resistance and metabolic syndrome. Variations in dietary lipid consumption have also been shown to impact obesity. Specifically, omega-3 fatty acids have been correlated with the prevention of obesity and subsequent development of chronic disease sequalae. This review explores animal and human data relating to the effects of omega-3 fatty acids (marine lipids) on adiponectin and leptin, considering plausible mechanisms and potential implications for obesity management. Current evidence suggests a positive, dose-dependent relationship between omega-3 fatty acid intake and circulating levels of adiponectin. In obese subjects, this may translate into a reduced risk of developing cardiovascular disease, metabolic syndrome and diabetes. In non-obese subjects, omega-3 is observed to decrease circulating levels of leptin; however, omega-3-associated increases in leptin levels have been observed in obese subjects. This may pose benefits in the prevention of weight regain in these subjects following calorie restriction. Topics: Adiponectin; Animals; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Health Promotion; Humans; Inflammation; Leptin; Metabolic Syndrome; Obesity; Randomized Controlled Trials as Topic | 2013 |
Focus on adipokines.
Once considered a passive reservoir for lipid storage and an inert provider of thermal/mechanical insulation, white adipose tissue (WAT) is presently seen as a highly dynamic endocrine organ that actively modulates a variety of physiologic processes, including energy balance, food intake, inflammation, immunity, metabolism, as well as cardio-vascular (CV) and neuroendocrine homeostasis. Actually, other than fatty acids and lipid moieties, WAT secretes a wide range of bioactive factors, considerably different in therms of structure and functions, including cytokines, chemokines, growth factors, complement system molecules, acute phase reactants, and hormones, among which the products predominantly or exclusively synthesized by and released from adipocytes are categorized as "adipokines". The adipokine expression is intimately linked to various parameters of adiposity (such as total body fat, percentage of body fat, and fat distribution), resulting generally (with very few exceptions, such as adiponectin, omentin, and Zinc-alpha2-glycoprotein) in positive correlation with WAT mass. The adipokine profiles undergo opposite changes in WAT excess or deficiency/dystrophy. In obese subjects, the altered adipokine network strikingly contributes to the development of systemic low-grade inflammation, as well as of obesity-related metabolic/CV comorbidities, that collectively define the so called metabolic syndrome. Adipokine dysregulation has been also observed in patients with chronic inflammatory/autoimmune disorders, such as connective tissue diseases, and adipokine pathway targeting has been thought to represent a potential innovative therapeutic perspective. Comprehensive advances in understanding the WAT biology and signaling may provide crucial insights into the physiopathology of the whole body homeostasis. Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Apelin; Cardiovascular System; Chemokines; Cytokines; Gene Expression Regulation; GPI-Linked Proteins; Homeostasis; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Lectins; Leptin; Lipocalins; Models, Biological; Nicotinamide Phosphoribosyltransferase; Obesity; Retinol-Binding Proteins, Plasma; Seminal Plasma Proteins; Serpins; Signal Transduction; Zn-Alpha-2-Glycoprotein | 2013 |
Ghrelin and leptin pathophysiology in chronic kidney disease.
Ghrelin is an orexigenic hormone with additional effects on the regulation of inflammation and the cardiovascular system. It may play an important role in the pathogenesis of cachexia/protein-energy wasting (PEW), inflammation and cardiovascular complications in chronic kidney disease (CKD). There are three circulating gene products of ghrelin, namely, acyl ghrelin, des-acyl ghrelin and obestatin, each with individual distinct functions. Perturbations of these circulating ghrelin proteins impact the overall milieu of CKD. Leptin is an anorexigenic hormone which is secreted from the adipocytes and interacts with ghrelin and other appetite-regulating hormones. Leptin also plays a role in regulating inflammation and the cardiovascular system. Indeed, ghrelin and leptin may play yin-and-yang roles in CKD pathophysiology. Clinical trials involving the use of the mimetics or antagonists of these hormones are limited to short-term phase I/II studies. Further understanding of their interactions in CKD pathophysiology is needed for potential large-scale clinical trials, which may impact the quality of life and survival of patients with CKD. Topics: Animals; Appetite Regulation; Body Weight; Cardiovascular Diseases; Disease Progression; Ghrelin; Humans; Inflammation; Kidney; Leptin; Malnutrition; Prognosis; Renal Insufficiency, Chronic; Signal Transduction | 2013 |
Stress and obesity as risk factors in cardiovascular diseases: a neuroimmune perspective.
Obesity is now growing at an alarming rate reaching epidemic proportions worldwide thus increasing morbidity and mortality rates for chronic disease. But although we have ample information on the complications associated with obesity, precisely what causes obesity remains poorly understood. Some evidence attributes a major role to a low-grade chronic inflammatory state (neurogenic inflammation) induced in obesity by inflammatory mediators produced and secreted within the expanded activated adipocyte pool. Adipose tissue is an endocrine organ that secretes numerous adipose tissue-specific or enriched hormones, known as adipokines, cytokine-like molecules thought to play a pathogenic role in cardiovascular diseases. The imbalance between increased inflammatory stimuli and decreased anti-inflammatory mechanisms may depend on chronic stress. Hence the positive correlation found between stress, obesity and cardiovascular diseases. The chronic inflammatory state associated with insulin resistance and endothelial dysfunction is highly deleterious for vascular function. This review focuses on the proposed neuroimmunodulatory mechanisms linking chronic (psychological) stress, obesity and cardiovascular diseases. Topics: Allostasis; Cardiovascular Diseases; Comorbidity; Extracellular Matrix; Humans; Inflammation; Leptin; Macrophages; Neuroimmunomodulation; Obesity; Risk Factors; Stress, Psychological | 2013 |
Influence of inflammatory disorders and infection on iron absorption and efficacy of iron-fortified foods.
The provision of iron- fortified foods is a common strategy to prevent iron deficiency; however, ensuring adequate iron absorption is a challenge. Iron bioavailability depends on the choice of iron compound, the presence enhancers and inhibitors of absorption in the food matrix, and the physiological state of the consumer, including iron status, other nutritional deficiencies and inflammatory disorders. Inflammation associated with infections and inflammatory disorders would be expected to decrease iron absorption and reduce the efficacy of iron- fortified foods. The decreased absorption is due to an increase in circulating hepcidin in response to inflammatory cytokines. Hepcidin degrades ferroportin and blocks the passage of iron from the intestinal cell to the plasma. This is the innate immune response to infections and aims to restrict pathogen growth by restricting iron supply. Stable isotope studies have reported women and children with chronic malaria parasitemia or febrile malaria to have increased inflammatory cytokines, increased hepcidin and much decreased iron absorption. No studies have specifically investigated the efficacy of iron- fortified foods in the absence and presence of infections. In contrast, inflammation and increased hepcidin associated with adiposity in overweight have been linked to both lower iron absorption and the decreased efficacy of iron- fortified foods. Topics: Adiposity; Biological Availability; Food, Fortified; Hepcidins; Humans; Inflammation; Intestinal Absorption; Iron, Dietary; Leptin; Malaria; Nutritional Status | 2012 |
Adipokines as uremic toxins.
The adipose tissue has pleiotropic functions far beyond the mere storage of energy, and it secretes a number of hormones and cytokines, called adipokines, which have biological effects that impact heath and disease. Adipokines are markedly elevated in the plasma of uremic patients, mainly due to decreased renal excretion. They have pluripotent signaling effects on inflammation/oxidative stress (leptin, adiponectin, resistin), protein-energy wasting (leptin, adiponectin), insulin signaling (adiponectin, leptin, visfatin), endothelial dysfunction (visfatin), and vascular damage (adiponectin, leptin, resistin), which are prevalent in uremic patients. Obesity superimposed to uremia may further aggravate hyperadipokinemia, with the exception of adiponectinemia, which is mitigated by adiposity. Among adipokines and until more data become available, only leptin may be considered as a full uremic toxin owing to adverse effects on protein-energy wasting, cardiovascular damage, inflammation, and the immune system, which have been documented both clinically and experimentally. Resistin and visfatin display some features of uremic toxins, but more data are needed to consider these adipokines as true uremic toxins. In contrast, high levels of adiponectin and chemerin seen in uremia appear to be beneficial. Further research is needed to investigate whether selective removal of leptin, resistin, and visfatin and increments of adiponectin and chemerin levels may have clinical relevance in uremic patients. Topics: Adipokines; Adiponectin; Adipose Tissue; Drug-Related Side Effects and Adverse Reactions; Humans; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Oxidative Stress; Resistin; Signal Transduction; Uremia | 2012 |
[Obesity and gastrointestinal cancer-related factor].
Despite a higher incidence and less favorable outcome of malignant tumors in obese patients, much less recognized is the link between obesity and cancer. The mechanism of the association of obesity with carcinogenesis remains incompletely understood. Postulated mechanisms include insulin resistance, insulin-like growth factor signaling, chronic inflammation, immunomodulation, hyperglycemia-induced oxidative stress, and changes of intestinal microbiome. Insulin resistance leads to direct mitogenic and antiapoptotic signaling by insulin and the insulin-like growth factor axis. Obesity can be considered to be a state of chronic low-grade inflammation. In obesity, numerous proinflammatory cytokines are released from adipose tissue which may involve in carcinogenesis. Hyperglycemia in susceptible cells results in the overproduction of superoxide and this process is the key to initiating all damaging pathways related to diabetes. This hyperglycemia-induced oxidative stress could be one possible link among obesity, diabetes, and cancer development. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention. Topics: Adipokines; Gastrointestinal Neoplasms; Humans; Inflammation; Insulin; Leptin; Obesity; Oxidative Stress; Somatomedins | 2012 |
Proinflammatory activities of leptin in non-autoimmune conditions.
Leptin is an adipokine whose proinflammatory properties contribute to the pathogenesis of several autoimmune diseases but also to the development and progression of inflammation in several non-autoimmune inflammatory conditions of the kidney, liver, lung, endometrium, blood vessels and endothelia. Here we review the influences of leptin in those conditions and the pertinent experimental work that has defined some mechanisms of action and/or suggested a therapeutic potential for leptin-based modulation of inflammation in non-autoimmune conditions. Topics: Adipokines; Animals; Autoimmune Diseases; Humans; Inflammation; Leptin | 2012 |
Leptin, a neuroendocrine mediator of immune responses, inflammation, and sickness behaviors.
Effective immune responses are coordinated by interactions among the nervous, endocrine, and immune systems. Mounting immune, inflammatory, and sickness responses requires substantial energetic investments, and as such, an organism may need to balance energy allocation to these processes with the energetic demands of other competing physiological systems. The metabolic hormone leptin appears to be mediating trade-offs between the immune system and other physiological systems through its actions on immune cells and the brain. Here we review the evidence in both mammalian and non-mammalian vertebrates that suggests leptin is involved in regulating immune responses, inflammation, and sickness behaviors. Leptin has also been implicated in the regulation of seasonal immune responses, including sickness; however, the precise physiological mechanisms remain unclear. Thus, we discuss recent data in support of leptin as a mediator of seasonal sickness responses and provide a theoretical model that outlines how seasonal cues, leptin, and proinflammatory cytokines may interact to coordinate seasonal immune and sickness responses. Topics: Animals; Illness Behavior; Immune System; Inflammation; Leptin; Neurosecretory Systems | 2012 |
Obesity and eosinophilic inflammation: does leptin play a role.
It has been pointed out that obesity is a risk factor for, and is involved in the exacerbation of asthma. Mounting evidence about adipose tissue-derived proteins (adipokines) gave rise to the current understanding of obesity as a systemic inflammatory disorder. In this review, we summarized the involvement of leptin, focusing on eosinophil functions. Several studies have indicated that leptin can restrain eosinophil apoptosis, enhance migration, increase adhesion molecules and induce cytokine production. Since leptin also acts on a variety of immune cells related to allergic response, increased leptin in obese individuals potentially explains the mechanism by which obesity leads to an exacerbation of asthma. Further studies targeting adipokines will delineate the association between obesity and eosinophil-associated diseases. Topics: Adipose Tissue; Eosinophilia; Humans; Inflammation; Leptin; Obesity | 2012 |
Obesity and gastric cancer.
Obesity is an important public health problem worldwide. It increases the risk of many chronic diseases such as diabetes and cardiovascular diseases. Meanwhile, obesity is a major risk factor for several types of cancer including gastric cancer. Possible mechanisms linking obesity with gastric cancer may include obesity associated gastro-oesophageal reflux, insulin resistance, altered levels of adiponectin, leptin, ghrelin, and an abnormally increased blood level of insulin-like growth factor (IGF). Helicobacter pylori (H. pylori) infection is a well-recognized risk factor for peptic ulcer and gastric cancer. Recent studies have revealed an increased prevalence of H. pylori infection in obese patients, providing another clue for the increased incidence of gastric cancer in obese population. If this connection can be confirmed in animal models and a large cohort of patients, then eradicating H. pylori together with life style modification in obese individuals may help prevent the development of gastric cancer in the increasingly obese population. Topics: Adiponectin; Animals; Gastroenteritis; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Obesity; Risk Factors; Signal Transduction; Stomach Neoplasms | 2012 |
Lymphocytes in obesity-related adipose tissue inflammation.
Inflammation in the white adipose tissue (WAT) is considered a major player in the development of insulin resistance. The role of macrophages accumulating in the WAT during obesity, promoting WAT inflammation and insulin resistance is well established. In contrast, less is known about the role of lymphocytes. Recent studies have implicated different lymphocyte subsets in WAT inflammation. For instance, cytotoxic CD8(+) T cells infiltrating the WAT may contribute to the recruitment, differentiation and activation of macrophages. On the other hand, a differential role for CD4(+) Th1 and CD4(+) Th2 cells has been suggested. Levels of WAT regulatory T cells decrease during the course of obesity and may represent a crucial factor for the maintenance of insulin sensitivity. Moreover, activation of natural killer T cells, an innate-like T cell population, which recognises lipid antigens, promotes insulin resistance and WAT inflammation. Finally, B cells may infiltrate WAT very early in response to high-fat feeding and worsen glucose metabolism through modulation of T cells and the production of pathogenic antibodies. These interesting new findings however bear controversies and introduce novel, yet unanswered, questions. Here, we review and discuss the impact of the different lymphocyte subsets in obesity-related WAT inflammation and attempt to identify the open questions to be answered by future studies. Topics: Adipose Tissue, White; Animals; B-Lymphocyte Subsets; Disease Models, Animal; Humans; Inflammation; Leptin; Lymphocytes; Mice; Obesity; T-Lymphocyte Subsets | 2012 |
Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer.
Nearly 35% of adults and 20% of children in the United States are obese, defined as a body mass index ≥ 30 kg/m(2). Obesity, which is accompanied by metabolic dysregulation often manifesting in the metabolic syndrome, is an established risk factor for many cancers. Within the growth-promoting, proinflammatory environment of the obese state, cross talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, cytokines, and other mediators that may enhance cancer risk and progression. This review synthesizes the evidence on key biological mechanisms underlying the obesity-cancer link, with particular emphasis on obesity-associated enhancements in growth factor signaling, inflammation, and vascular integrity processes. These interrelated pathways represent possible mechanistic targets for disrupting the obesity-cancer link. Topics: Adiponectin; Cell Communication; Humans; Inflammation; Insulin; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Neoplasms; Obesity; Receptor, IGF Type 1; Receptor, Insulin; Signal Transduction; Vascular Endothelial Growth Factor A | 2012 |
At the crossroad of T cells, adipose tissue, and diabetes.
The study of how different intracellular metabolic signaling pathways impact the control of self-immune tolerance and how metabolic dysregulation in overweight, obesity, and diabetes is able to alter self-immune tolerance are topics of intensive investigation. Recent evidence suggests that metabolic and autoimmune diseases, both characterized by chronic inflammation and an altered self-immune tolerance, are more common in affluent countries. The reasons for such phenomena are still not completely understood, but the 'metabolic pressure' induced by nutritional overload, typical of more developed countries, seems to play a role. In this context, the discovery of the adipose tissue-derived hormone leptin has shed fundamental insights on how these processes might occur. We believe that there is a strong relationship among leptin, metabolic state, and immunological self-tolerance. We hypothesize that the leptin-induced metabolic pressure sets the basis for an exaggerated immuno-inflammatory response to altered self or non-self, leading to chronic inflammation, metabolic dysregulation, and autoimmunity in subjects with risk factors (i.e. genetic predisposition, environment, sex, infectious agents, etc). Capitalizing on our joint effort and trans-disciplinary expertise in metabolism, self-tolerance, and autoimmune diseases, this review highlights key questions on the basic mechanisms governing immune tolerance in the context of metabolic and autoimmune disease susceptibility. Topics: Adipose Tissue; Animals; Autoimmune Diseases; Body Weight; Diabetes Mellitus; Energy Metabolism; Humans; Immune Tolerance; Inflammation; Leptin; Self Tolerance; Signal Transduction; T-Lymphocytes | 2012 |
Advances in adipokines.
Topics: Adipokines; Adiponectin; Adipose Tissue; Adult; Aged; Animals; Chronic Disease; Clinical Trials as Topic; Cytokines; Diabetes Mellitus, Type 2; Exercise; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin; Serpins | 2012 |
Value of adipokines in predicting the severity of acute pancreatitis: comprehensive review.
To analyze the prognostic value of adipokines in predicting the course, complications and fatal outcome of acute pancreatitis (AP).. We performed the search of PubMed database and the systemic analysis of the literature for both experimental and human studies on prognostic value of adipokines in AP for period 2002-2012. Only the papers that described the use of adipokines for prediction of severity and/or complications of AP were selected for further analysis. Each article had to contain information about the levels of measured adipokines, diagnosis and verification of AP, to specify presence of pancreatic necrosis, organ dysfunction and/or mortality rates. From the very beginning, study was carried out adhering to the PRISMA checklist and flowchart for systemic reviews. To assess quality of all included human studies, the Quality Assessment of Diagnostic Accuracy Studies tool was used. Because of the high heterogeneity between the studies, it was decided to refrain from the statistical processing or meta-analysis of the available data.. Nine human and three experimental studies were included into review. In experimental studies significant differences between leptin concentrations at 24 and 48 h in control, acute edematous and acute necrotizing pancreatitis groups were found (P = 0.027 and P < 0.001). In human studies significant differences between leptin and resitin concentrations in control and acute pancreatitis groups were found. 1-3 d serum adiponectin threshold of 4.5 μg/mL correctly classified the severity of 81% of patients with AP. This threshold yielded a sensitivity of 70%, specificity 85%, positive predictive value 64%, negative predictive value88% (area under curve 0.75). Resistin and visfatin concentrations differ significantly between mild and severe acute pancreatitis groups, they correlate with severity of disease, need for interventions and outcome. Both adipokines are good markers for parapancreatic necrosis and the cut-off values of 11.9 ng/mL and 1.8 ng/mL respectively predict the high ranges of radiological scores. However, the review revealed that all nine human studies with adipokines are very different in terms of methodology and objectives, so it is difficult to generalize their results. It seems that concentrations of the leptin and resistin increases significantly in patients with acute pancreatitis compared with controls. Serum levels of adiponectin, visfatin and especially resitin (positive correlation with Acute Physiology and Chronic Health Evaluation II, Ranson and C-reactive protein) are significantly different in mild acute pancreatitis and severe acute pancreatitis patients, so, they can serve as a markers for the disease severity prediction. Resistin and visfatin can also be used for pancreatic and parapancreatic necrosis prediction, interventions needs and possible, outcome.. High levels of adipokines could allow for prediction of a severe disease course and outcome even in small pancreatic lesions on computed tomography scans. Topics: Acute Disease; Adipokines; Humans; Inflammation; Leptin; Necrosis; Nicotinamide Phosphoribosyltransferase; Pancreatitis; Pancreatitis, Acute Necrotizing; Prognosis; Resistin; Sensitivity and Specificity; Time Factors; Treatment Outcome | 2012 |
Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications.
Leptin, the adipokine produced mainly by the white adipose tissue, plays important roles not only in the regulation of food intake, but also in controlling immunity and inflammation. It has been widely demonstrated that the absence of leptin leads to immune defects in animal and human models, ultimately increasing mortality. Leptin also regulates inflammation by means of actions on its receptor, that is widely spread across different immune cell populations. The molecular mechanisms by which leptin determines its biological actions have also been recently elucidated, and three intracellular pathways have been implicated in leptin actions: JAK-STAT, PI3K, and ERK 1/2. These pathways are closely regulated by intracellular proteins that decrease leptin biological activity. In this review, we discuss the molecular mechanisms by which leptin regulates immunity and inflammation, and associate those mechanisms with chronic inflammatory disorders. Topics: Adaptive Immunity; Animals; Chronic Disease; Cytokines; Disease Models, Animal; Humans; Immunologic Factors; Inflammation; Inflammation Mediators; Leptin; Receptors, Leptin | 2012 |
Fighting protein-energy wasting in chronic kidney disease: a challenge of complexity.
Chronic uremia is often characterized by wasting of muscle and fat mass, which has been defined as protein-energy wasting (PEW), and is responsible for substantial worsening of patient outcome in terms of morbidity and mortality, mostly from cardiovascular events. Despite major advances in patient treatment, nutritional outcome in patients with end-stage renal disease has not improved substantially in recent years. Extensive research in this field has provided plausible explanations for this limitation by indicating that the pathogenesis of PEW in kidney disease is complex and multifactorial. Complexity involves underlying metabolic alterations, including inflammation, oxidative stress, and insulin resistance. In addition, patient heterogeneity is increasing with large numbers of obese individuals as a result of the ongoing obesity epidemics. Several tissues are involved in cross-talk and contribute to metabolic derangements, including adipose tissue, the gut, and the central nervous system, with novel mediators including the gastric hormone ghrelin. Acknowledging its complex pathogenesis may favor the development of novel and more effective therapeutic tools for PEW. These should ideally be effective in treating the underlying common mechanisms of wasting, which appear to include oxidative stress, inflammation, and insulin resistance. Topics: Animals; Ghrelin; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Leptin; Obesity; Oxidative Stress; Protein-Energy Malnutrition | 2011 |
Inflammatory markers and cardiovascular risk in the metabolic syndrome.
Elevated blood glucose, obesity, high blood pressure, elevated triglycerides and low high density lipoprotein (HDL) cholesterol are well accepted risk factors in the development of coronary artery disease. Clustering of at least three of these factors in an individual is defined as metabolic syndrome (MetS). Obesity is a central pathological mechanism in the disease and it is expected that the incidence of this condition will increase dramatically within the next years. The visceral adipose tissue is not only an energy depot but also an endocrine organ which produces a large number of bioactive molecules, the so called adipokines. In the setting of obesity, the over-production of proinflammatory and pro-thrombotic adipokines is associated with insulin resistance. This mechanism represents the pathophysiological basis for the development of MetS. Inflammation has a central role in the pathogenesis of MetS and in mediating its impact on the development of cardiovascular disease. Knowledge of these mechanisms has relevance in the context of preventive and therapeutic strategies. Topics: Adiponectin; Adolescent; Adult; Angiotensinogen; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Endothelium, Vascular; Humans; Inflammation; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Leptin; Life Style; Metabolic Syndrome; Obesity; Plaque, Atherosclerotic; Plasminogen Activator Inhibitor 1; Prognosis; Resistin; Risk; Tumor Necrosis Factor-alpha | 2011 |
Hypothalamic inflammation and thermogenesis: the brown adipose tissue connection.
Hypothalamic inflammation and dysfunction are common features of experimental obesity. An imbalance between caloric intake and energy expenditure is generated as a consequence of this inflammation, leading to the progressive increase of body adiposity. Thermogenesis, is one of the main functions affected by obesity-linked hypothalamic dysfunction and the complete characterization of the mechanisms involved in this process may offer new therapeutic perspectives for obesity. The brown adipose tissue is an important target for hypothalamic action in thermogenesis. This tissue has been thoroughly studied in rodents and hibernating mammals; however, until recently, its advocated role in human thermogenesis was neglected due to the lack of substantial evidence of its presence in adult humans. The recent demonstration of the presence of functional brown adipose tissue in adult humans has renovated the interest in this tissue. Here, we review some of the work that shows how inflammation and dysfunction of the hypothalamus can control brown adipose tissue activity and how this can impact on whole body thermogenesis and energy expenditure. Topics: Adipose Tissue, Brown; Adult; Humans; Hypothalamus; Inflammation; Insulin; Leptin; Models, Biological; Obesity; Thermogenesis | 2011 |
Toll-like receptors, inflammation, metabolism and obesity.
Obesity is a highly prevalent health problem in Western countries that leads to many important diseases such as type 2 diabetes and metabolic syndrome being now considered an inflammatory chronic disease. Adipocytes are no longer considered passive cells storing fat since they are major producers of inflammatory cytokines during obesity. Adipocytes and macrophages share many biological properties including the synthesis of similar molecules regulating inflammation. Fatty acid levels are elevated in obesity and induce inflammatory pathways by yet a mostly unknown mechanism, leading to the development of insulin and leptin resistance. Recent studies suggest that these effects could be mediated through the activation of toll-like receptors (TLR). TLR signalling pathways might contribute to the development of obesity-associated insulin resistance, thus representing a connection between innate immunity and metabolism. Here, we summarize the recent evidence for the important role that TLRs play in adipose tissue, obesity and insulin resistance. Topics: Adipocytes; Adipose Tissue; Animals; Cytokines; Diabetes Mellitus, Type 2; Humans; Inflammation; Insulin Resistance; Leptin; Macrophages; Metabolic Syndrome; Obesity; Signal Transduction; Toll-Like Receptors | 2011 |
AMP-activated protein kinase: a potential player in Alzheimer's disease.
AMP-activated protein kinase (AMPK) stimulates energy production via glucose and lipid metabolism, whereas it inhibits energy consuming functions, such as protein and cholesterol synthesis. Increased cytoplasmic AMP and Ca(2+) levels are the major activators of neuronal AMPK signaling. Interestingly, Alzheimer's disease (AD) is associated with several abnormalities in neuronal energy metabolism, for example, decline in glucose uptake, mitochondrial dysfunctions and defects in cholesterol metabolism, and in addition, with problems in maintaining Ca(2+) homeostasis. Epidemiological studies have also revealed that many metabolic and cardiovascular diseases are risk factors for cognitive impairment and sporadic AD. Emerging studies indicate that AMPK signaling can regulate tau protein phosphorylation and amyloidogenesis, the major hallmarks of AD. AMPK is also a potent activator of autophagic degradation which seems to be suppressed in AD. All these observations imply that AMPK is involved in the pathogenesis of AD. However, the responses of AMPK activation are dependent on stimulation and the extent of activating stress. Evidently, AMPK signaling can repress and delay the appearance of AD pathology but later on, with increasing neuronal stress, it can trigger detrimental effects that augment AD pathogenesis. We will outline the potential role of AMPK function in respect to various aspects affecting AD pathogenesis. Topics: Alzheimer Disease; AMP-Activated Protein Kinases; Amyloid; Animals; Autophagy; Calcium; Enzyme Activation; Humans; Inflammation; Leptin; Metformin; Neurons; Phosphorylation; tau Proteins | 2011 |
The obesity phenotype in children with asthma.
Asthma and obesity have been increasing in prevalence internationally among children. Evidence points to an association between these chronic morbidities, suggesting the development of an 'obese asthma' phenotype in childhood. This review summarises the evidence that the proinflammatory environment created by excess adiposity may provide a mechanism leading to obese asthma in children and adolescents. Weight loss studies conducted in children without asthma have demonstrated a reduction in systemic inflammation. However, the impact of weight loss in the obese paediatric population with asthma has not been investigated. The paucity of information highlights the need for high quality randomised controlled trials of weight loss in this population that include assessment of systemic and airway inflammation, and clinical asthma outcomes. This will lead to refinements in management approaches for these patients. Topics: Adiponectin; Adolescent; Asthma; C-Reactive Protein; Child; Comorbidity; Humans; Inflammation; Leptin; Obesity; Phenotype; Tumor Necrosis Factor-alpha; Weight Loss | 2011 |
Leptin and cardiovascular diseases.
1. Leptin is a 16-kDa hormone, synthesized primarily by adipocyte, which acts as a key factor for maintenance of energy homeostasis in central and peripheral tissues. In most obese individuals, serum leptin levels are increased and correlate with the individual's body mass index. 2. Abundant investigations ranging from clinical and animal model studies to in vitro analyses show that leptin plays a pivotal role in obesity-related cardiovascular diseases (CVD). Hyperleptinaemia has been confirmed to be a predictor of acute cardiovascular events. However, some studies have shown that leptin has a cardioprotective effect in leptin-deficient models. These data suggest the influences of leptin on the pathophysiology of cardiovascular diseases are complex and not completely understood. 3. In the present review, we summarize the major leptin signalling pathways, including Janus-activated kinase/signal transducers and activators of transcription (Jak/STAT), mitogen-activated protein kinases (MAPK), and phosphatidylinositol 3-kinase (PI-3K) signalling pathways, and analyse the probable mechanisms of selective leptin resistance. We then provide a detailed review of the effects of leptin on the cardiovascular system, including sympathoactivation, oxidative stress, vascular inflammation, endothelial dysfunction, vascular cell proliferation, cardiomyocytes hypertrophy, as well as fatty acid metabolism, all of which contribute to the pathogenesis of cardiovascular diseases (e.g. ischaemic heart disease). The central premise of this review is to elucidate the mechanisms by which leptin affects the cardiovascular function and provide insight into obesity-related CVD. Topics: Animals; Cardiomegaly; Cardiovascular Diseases; Endothelium, Vascular; Extracellular Matrix; Female; Humans; Inflammation; Leptin; Male; Mice; Myocardium; Obesity; Rats; Receptors, Leptin; Risk Factors; Signal Transduction; Thrombosis | 2011 |
Inflammatory mediators: tracing links between obesity and osteoarthritis.
Osteoarthritis (OA), the most common form of arthritis, is associated with joint malfunction and chronic disability in the aged population. It is a multifactorial disorder to which several factors-such as age, sex, trauma, and obesity-contribute significantly. Obesity is one of the most influential but modifiable risk factors because it exerts an increased mechanical stress on the tibiofemoral cartilage. However, the high prevalence of OA in obese individuals in non-weightbearing areas, like finger joints, suggests that the link between being overweight and OA lies with factors other than simple biomechanics. An important correlation has been made between obesity and inflammation. Adipose tissues (and the infrapatellar fat pad) play an important role in this context because they are the major source of cytokines, chemokines, and metabolically active mediators called adipokines (or adipocytokines). These metabolic factors are known to possess catabolic and proinflammatory properties and to orchestrate the pathophysiological processes in OA. This review provides information on the relationship between obesity and OA through biomechanical and biochemical factors and highlights the functions of important obesity-related inflammatory products in the initiation and progression of OA. This information will broaden our thinking in identifying the targets for both prevention and intervention for OA. Topics: Adiponectin; Adipose Tissue; Animals; Cytokines; Disease Models, Animal; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Interleukin-8; Leptin; Obesity; Osteoarthritis; Prevalence; Resistin; Risk Factors; Tumor Necrosis Factor-alpha | 2011 |
Hypothalamic inflammation and energy homeostasis: resolving the paradox.
Determining the effect of hypothalamic inflammatory signals on energy balance presents a paradox. On the one hand, a large body of work has identified inflammatory signaling in the hypothalamus as an essential mediator of the sickness response--the anorexia, cachexia, fever, inactivity, lethargy, anhedonia and adipsia that are triggered by systemic inflammatory stimuli and promote negative energy balance. On the other hand, numerous recent studies implicate inflammatory activation within the hypothalamus as a key factor whereby high-fat diets--and saturated fats in particular--cause central leptin and insulin resistance and thereby promote the defense of elevated body weight. This paradox will likely remain unresolved until several issues have been addressed. Firstly, the hypothalamus--unlike many peripheral inflamed tissues--is an extremely heterogeneous tissue comprised of astrocytes, oligodendrocytes, microglia, endothelial cells, ependymal cells as well as numerous neuronal subgroups. Determining exactly which cells activate defined inflammatory signals in response to a particular stimulus--i.e. sepsis vs. nutrient excess--may yield critical clues. Secondly, for the sake of simplicity many studies evaluate inflammation as an on/off phenomenon. More realistically, inflammatory signaling occurs as a cascade or cycle that changes and progresses over time. Accordingly, even within the same cell type, the low-grade, chronic signal induced by nutrient excess may invoke a different cascade of signals than a strong, acute signal such as sepsis. In addition, because tolerance can develop to certain inflammatory mediators, physiological outcomes may not correlate with early biochemical markers. Lastly, the neuroanatomical location, magnitude, and duration of the inflammatory stimulus can undoubtedly influence the net CNS response. Rigorously evaluating the progression of the inflammatory signaling cascade within specific hypothalamic cell types is a key next step towards resolving the paradox surrounding the effect of inflammatory signaling on energy homeostasis. Topics: Animals; Dietary Fats; Eating; Energy Metabolism; Homeostasis; Humans; Hypothalamus; Inflammation; Insulin Resistance; Leptin; Melanocortins; Obesity; Signal Transduction; Weight Gain | 2010 |
Obesity, airway hyperresponsiveness, and inflammation.
Epidemiological data indicate that obesity is a risk factor for asthma, but the mechanistic basis for this relationship is not established. Here we review data from human subjects and animal models investigating the relationship between obesity and airway hyperresponsiveness, a characteristic feature of asthma. We discuss obesity as a state of chronic systemic inflammation resulting from interactions between adipocytes and adipose tissue macrophages that are recruited to obese adipose tissue. Finally, we focus on the possibility that aspects of this inflammation, particularly obesity-related changes in TNF-alpha, leptin, and adiponectin, may contribute to airway hyperresponsiveness in obesity. Determining how obesity promotes asthma may uncover novel therapeutic strategies that are effective in the obese asthmatic subject. Topics: Adiponectin; Adipose Tissue; Adult; Animals; Asthma; Bronchial Hyperreactivity; Child; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Obesity; Risk Factors; Tumor Necrosis Factor-alpha | 2010 |
Cardiovascular effects of leptin.
A wealth of investigations, ranging from clinical and animal model studies to in vitro analyses, have generated great interest in the cardiovascular effects of leptin. Accordingly, many studies have examined the contribution of leptin to cardiac remodeling in heart failure and whether the effects of leptin on metabolism, apoptosis, extracellular matrix remodeling, and hypertrophy could explain the so-called obesity paradox. Furthermore, obesity and hyperleptinemia have often been associated with hypertension, and regulation of sympathetic tone or direct effects of leptin on contributors such as atherosclerosis, endothelial dysfunction, and thrombosis have been documented. Unfortunately, translating basic research studies in vitro, or in animal models, to human physiology has proven difficult. The degree of leptin resistance in obesity is one intriguing issue that must be resolved. Furthermore, the importance of autocrine and paracrine effects of leptin derived from the heart and perivascular adipose tissue must be further studied. Carefully planned and executed research to conclusively establish distinct effects of leptin on the cardiovascular system in normal and diseased states will be essential to harness any therapeutic potential associated with leptin's effects. Topics: Adipose Tissue; Animals; Apoptosis; Atherosclerosis; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Endothelium, Vascular; Extracellular Matrix; Humans; Hypertension; Inflammation; Leptin; Myocardium; Obesity | 2010 |
Inflammation and cachexia in chronic kidney disease.
Chronic inflammation is associated with cachexia and increased mortality risk in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Inflammation suppresses appetite and causes the loss of protein stores. In CKD patients, increased serum levels of pro-inflammatory cytokines may be caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions. Cachexia is brought about by the synergistic combination of a dramatic decrease in appetite and an increase in the catabolism of fat and lean body mass. Pro-inflammatory cytokines act on the central nervous system to alter appetite and energy metabolism and to provide a signal-through the nuclear factor-kappaB and ATP-ubiquitin-dependent proteolytic pathways-that causes muscle wasting. Further research into the molecular pathways leading to inflammation and cachexia may lead to novel therapeutic therapies for this devastating and potentially fatal complication of chronic disease. Topics: Cachexia; Cardiovascular Diseases; Chronic Disease; Cytokines; Feeding and Eating Disorders; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Muscular Atrophy; Neuropeptides | 2010 |
The role of insulin resistance in the pathogenesis of atherosclerotic cardiovascular disease: an updated review.
Insulin resistance is the main pathologic mechanism that links the constellation of clinical, metabolic and anthropometric traits with increased risk for cardiovascular disease and type II diabetes mellitus. These traits include hyperinsulinemia, impaired glucose intolerance, endothelial dysfunction, dyslipidemia, hypertension, and generalized and upper body fat redistribution. This cluster is often referred to as insulin resistance syndrome. The progression of insulin resistance to diabetes mellitus parallels the progression of endothelial dysfunction to atherosclerosis leading to cardiovascular disease and its complications. In fact, insulin resistance assessed by homeostasis model assessment (HOMA) has shown to be independently predictive of cardiovascular disease in several studies and one unit increase in insulin resistance is associated with a 5.4% increase in cardiovascular disease risk. This review article addresses the role of insulin resistance as a main causal factor in the development of metabolic syndrome and endothelial dysfunction, and its relationship with cardiovascular disease. In addition to this, we review the type of lifestyle modification and pharmacotherapy that could possibly ameliorate the effect of insulin resistance and reverse the disturbances in insulin, glucose and lipid metabolism. Topics: Adiponectin; Animals; Atherosclerosis; Blood Glucose; Blood Pressure; Endothelium, Vascular; Humans; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Risk Factors; Risk Reduction Behavior | 2010 |
Inflammation accelerates atherosclerotic processes in obstructive sleep apnea syndrome (OSAS).
Obstructive sleep apnea syndrome (OSAS) is an often underestimated sleep disorder that has been associated with cardiovascular disease. OSAS is characterized by cycles of apnea and/or hypopnea during sleep caused by the collapse of the upper airways. Intermittent hypoxia deriving from the cycles of apnea/arousals (to retrieve the ventilation) plays a pivotal role in the pathogenesis of the disease. Obesity is the most frequent predisposing condition of OSAS. Recent evidence suggests that OSAS could be considered as a pro-atherosclerotic disease, independently of visceral fat amount. Oxidative stress, cardiovascular inflammation, endothelial dysfunction, and metabolic abnormalities in OSAS could accelerate atherogenesis. The present review is focused on the possible pathophysiological mediators which could favor atherosclerosis in OSAS. Topics: Atherosclerosis; Cytokines; Disease Progression; Humans; Hypoxia; Inflammation; Leptin; Oxidative Stress; Platelet Aggregation; Risk Factors; Sleep Apnea, Obstructive | 2010 |
Diabetes mellitus, inflammation, obesity: proposed treatment pathways for current and future therapies.
To review the pathophysiology, pharmacology, and current or future therapies under study for use in treating diabetes mellitus, inflammation associated with diabetes mellitus, and/or obesity related to diabetes mellitus, through 1 of 4 investigational pathways: adiponectin, ghrelin, resveratrol, or leptin.. A literature search using MEDLINE (1966-December 12, 2009), PubMed (1950-December 12, 2009), Science Direct (1994-December 12, 2009), and International Pharmaceutical Abstracts (1970-December 12, 2009) was performed using the terms adiponectin, ghrelin, resveratrol, leptin, inflammation, obesity, and diabetes mellitus. English-language, original research, and review articles were examined, and citations from these articles were assessed as well.. Clinical studies and in vitro studies were included in addition to any Phase 1, 2, or 3 clinical trials.. Mechanistic pathways regarding adiponectin, ghrelin, resveratrol, and leptin are of interest as future treatment options for diabetes mellitus. Each of these pathways has produced significant in vitro and in vivo clinical data warranting further research as a possible treatment pathway for diabetes-related inflammation and/or obesity reduction. While research is still underway to determine the exact effects these pathways have on metabolic function, current data suggest that each of these compounds may be of interest for future therapies.. While several pathways under investigation may offer additional benefits in the treatment of diabetes mellitus and associated impairments, further investigation is necessary for both investigational and approved therapies to ensure that the impact in new pathways does not increase risks to patient safety and outcomes. Topics: Adiponectin; Animals; Anti-Inflammatory Agents; Anti-Obesity Agents; Antioxidants; Diabetes Mellitus; Ghrelin; Humans; Hypoglycemic Agents; Inflammation; Leptin; Obesity; Resveratrol; Stilbenes | 2010 |
Role of leptin in the activation of immune cells.
Adipose tissue is an active endocrine organ that secretes various humoral factors (adipokines), and its shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that may be present in metabolic syndrome-associated chronic pathologies such as atherosclerosis. Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone leptin has been shown to regulate the immune response, innate and adaptive response, both in normal and pathological conditions. The role of leptin in regulating immune response has been assessed in vitro as well as in clinical studies. It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune diseases are associated with increased secretion of leptin and production of proinflammatory pathogenic cytokines. Thus, leptin is a mediator of the inflammatory response. Topics: Adaptive Immunity; Adipokines; Adipose Tissue; Animals; Humans; Immunity, Innate; Inflammation; Leptin; Lymphocyte Activation; Obesity | 2010 |
Leptin: the prototypic adipocytokine and its role in NAFLD.
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, whose pathogenesis begins with the accumulation of liver fat and is followed by the development of necro-inflammation and fibrosis. Recent evidence indicates that adipocytokines, polypeptides secreted by the adispose tissue, might play an important role in the pathogeneic process and progression of NAFLD. In this review, we explore the role of leptin, and in part of other adipocytokines, in the interference with hepatic injury associated with fatty infiltration, in the modulation of steatosis and fibrosis, in both experimental models of the disease and in the clinical practice. We also discuss the potential use of leptin as non-invasive marker for differentiating simple fatty liver from NAFLD, and the possible novel therapeutic strategies aimed at interfering with the leptin axis to dampen chronic liver inflammation and NAFLD. Topics: Adipokines; Animals; Biomarkers; Drug Delivery Systems; Fatty Liver; Humans; Inflammation; Leptin; Liver Cirrhosis; Metabolic Syndrome | 2010 |
Central adiposity, systemic inflammation, and the metabolic syndrome.
Metabolic syndrome (MetS) is a constellation of metabolic derangements and underlying factors that significantly increases the risk for developing type 2 diabetes and cardiovascular diseases. MetS is a low-grade inflammatory condition, with systemic inflammation and inflammation of central abdominal fat as contributors. Systemic inflammation in MetS is thought to involve C-reactive protein and some proinflammatory cytokines; the nuclear factor-kappaB pathway also is believed to play a role. Inflammation of central adipose tissue leads to adipokine production, followed by secretion of adipokines into the general circulation to contribute to the overall inflammatory condition. The molecular mechanisms that contribute to this inflammation are still somewhat unclear, but several serine/threonine kinases are known to be involved. Dietary components may also contribute to central adiposity and the inflammation seen in MetS. Topics: Abdominal Fat; Adipokines; Adiponectin; Adiposity; C-Reactive Protein; Cytokines; Diet; Humans; Inflammation; Insulin Resistance; Interleukins; Leptin; Life Style; Metabolic Syndrome; NF-kappa B; Nutritional Status; Oxidative Stress; Risk Factors; Serine; Threonine; Tumor Necrosis Factor-alpha | 2010 |
Peritoneal adipocytes and their role in inflammation during peritoneal dialysis.
Adipose tissue is a major site of chronic inflammation associated with peritoneal dialysis (PD) frequently complicating peritonitis. Adiposity-associated inflammation plays a significant contributory role in the development of chronic inflammation in patients undergoing maintenance PD. However, the molecular and cellular mechanisms of this link remain uncertain. Adipose tissue synthesizes different adipokines and cytokines that orchestrate and regulate inflammation, insulin action, and glucose metabolism locally and systemically. In return, inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation. An understanding of the inflammatory roles played by adipose tissue during PD and the healing mechanism of injured mesothelium will help to devise new therapeutic approach to slow the progression of peritoneal damage during peritoneal dialysis. This article reviews the roles of peritoneal adipose tissue in chronic peritoneal inflammation under PD and in serosal repair during PD. Topics: Adipocytes; Adipokines; Adipose Tissue; Antigens, CD; Endothelial Cells; Humans; Inflammation; Leptin; Peritoneal Dialysis; Peritonitis; Polymerase Chain Reaction; Regeneration; RNA, Messenger; Stem Cells | 2010 |
Minireview: Inflammation and obesity pathogenesis: the hypothalamus heats up.
Obesity induced by high-fat (HF) feeding is associated with low-grade inflammation in peripheral tissues that predisposes to insulin resistance. Recent evidence suggests the occurrence of a similar process in the hypothalamus, which favors weight gain through impairment of leptin and insulin signaling. In addition to its implications for obesity pathogenesis, this hypothesis suggests that centrally targeted antiinflammatory therapies may prove effective in prevention and treatment of this disorder. This article highlights molecular and cellular mechanisms by which hypothalamic inflammation predisposes to diet-induced obesity. Topics: Animals; Glucose Intolerance; Humans; Hypothalamus; Inflammation; Insulin Resistance; Leptin; Models, Biological; Obesity; Weight Gain | 2010 |
Energy balance, host-related factors, and cancer progression.
Obesity is associated with an increased risk and worsened prognosis for many types of cancer, but the mechanisms underlying the obesity-cancer progression link are poorly understood. Several energy balance-related host factors are known to influence tumor progression and/or treatment responsiveness after cancer develops, and these have been implicated as key contributors to the complex effects of obesity on cancer outcome. These host factors include leptin, adiponectin, steroid hormones, reactive oxygen species associated with inflammation, insulin, insulin-like growth factor-1, and sirtuins. Each of these host factors is considered in this article in the context of energy balance and cancer progression. In addition, future research directions in this field are discussed, including the importance of study designs addressing energy balance across the life course, the development and application of highly relevant animal models, potential roles of cancer stem cells in the response to energy balance modulation, and emerging pharmacologic approaches that target energy balance-related pathways. Topics: Adiponectin; Adrenal Cortex Hormones; Disease Progression; Energy Metabolism; Gonadal Steroid Hormones; Humans; Inflammation; Insulin; Insulin-Like Growth Factor I; Leptin; Metabolic Syndrome; Neoplasms; Oxidative Stress; Sirtuin 1 | 2010 |
Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis.
Whereas in most cases a fatty liver remains free of inflammation, 10%-20% of patients who have fatty liver develop inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Inflammation may precede steatosis in certain instances. Therefore, NASH could reflect a disease where inflammation is followed by steatosis. In contrast, NASH subsequent to simple steatosis may be the consequence of a failure of antilipotoxic protection. In both situations, many parallel hits derived from the gut and/or the adipose tissue may promote liver inflammation. Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH. Topics: Animals; Diet; Disease Progression; Fatty Liver; Humans; Inflammation; Interleukin-5; Leptin; Metabolic Diseases; Models, Biological; Obesity; Trans Fatty Acids; Tumor Necrosis Factor-alpha | 2010 |
Three questions about leptin and immunity.
Leptin is a protein produced by adipocytes (and other cell types) that acts in the brain to regulate appetite and energy expenditure according to the amount of energy stored in adipose tissue. Leptin also exerts a variety of other functions, including important roles as a regulator of immune and inflammatory reactions. The present article is not meant to be a comprehensive review on leptin and immunity, but rather highlights a few controversial issues about leptin's place in the complex network of mediators regulating immune and inflammatory responses. Three issues are discussed: (1) Where am I going, or What is the cellular target of leptin for modulation of immune responses?; (2) Where am I coming from, or Is the cellular source important in determining leptin's effects on immune responses? and (3) What am I doing, or What are leptin's effects on immune and inflammatory responses? Topics: Adipocytes; Adipose Tissue; Animals; Cytokines; Feeding Behavior; Humans; Inflammation; Leptin; Lymphocytes | 2009 |
Emerging role of adipose tissue hypoxia in obesity and insulin resistance.
Recent studies consistently support a hypoxia response in the adipose tissue in obese animals. The observations have led to the formation of an exciting concept, adipose tissue hypoxia (ATH), in the understanding of major disorders associated with obesity. ATH may provide cellular mechanisms for chronic inflammation, macrophage infiltration, adiponectin reduction, leptin elevation, adipocyte death, endoplasmic reticulum stress and mitochondrial dysfunction in white adipose tissue in obesity. The concept suggests that inhibition of adipogenesis and triglyceride synthesis by hypoxia may be a new mechanism for elevated free fatty acids in the circulation in obesity. ATH may represent a unified cellular mechanism for a variety of metabolic disorders and insulin resistance in patients with metabolic syndrome. It suggests a new mechanism of pathogenesis of insulin resistance and inflammation in obstructive sleep apnea. In addition, it may help us to understand the beneficial effects of caloric restriction, physical exercise and angiotensin II inhibitors in the improvement of insulin sensitivity. In this review article, literatures are reviewed to summarize the evidence and possible cellular mechanisms of ATH. The directions and road blocks in the future studies are analyzed. Topics: Adiponectin; Adipose Tissue; Animals; Humans; Hypoxia; Inflammation; Insulin Resistance; Leptin; Mice; Neovascularization, Physiologic; Obesity; Signal Transduction | 2009 |
Obstructive sleep apnea syndrome and asthma: what are the links?
Recent data suggest that obstructive sleep apnea syndrome (OSAS) is an independent risk factor for asthma exacerbations. Neuromechanical reflex bronchoconstriction, gastroesophageal reflux, inflammation (local and systemic), and the indirect effect on dyspnea of OSAS-induced cardiac dysfunction have been suggested as mechanisms that lead to worsening asthma control in patients with concomitant OSAS. Vascular endothelial growth factor-induced airway angiogenesis, leptin-related airway changes, and OSAS-induced weight gain also may play a common mechanistic role linking both disorders. Several studies have confirmed that asthmatic patients are more prone to develop OSAS symptoms than are members of the general population. The common asthmatic features that promote OSAS symptoms are nasal obstruction, a decrease in pharyngeal cross sectional area, and an increase in upper airway collapsibility. Clarifying the nature of the relationship between OSAS and asthma is a critical area with important therapeutic implications. Topics: Animals; Asthma; Bronchi; Bronchoconstriction; Comorbidity; Dyspnea; Gastroesophageal Reflux; Glottis; Heart Failure; Humans; Inflammation; Laryngeal Nerves; Leptin; Neovascularization, Pathologic; Reflex, Abnormal; Risk Factors; Sleep Apnea, Obstructive; Vagus Nerve; Vascular Endothelial Growth Factor A; Weight Gain | 2009 |
Leptin in non-autoimmune inflammation.
Leptin is an adipokine that modulates multiple functions including energy homeostasis, thermoregulation, bone metabolism, endocrine and pro-inflammatory immune responses. Several studies have implicated leptin in the pathogenesis of chronic autoimmune inflammatory conditions such as autoimmune encephalomyelitis, intestinal bowel inflammation and type-1 diabetes. This review focuses on the role of leptin in non-autoimmune inflammatory diseases that include renal, liver and lung inflammation, atherosclerosis and metabolic syndrome, Behçet's disease and endometriosis. Topics: Animals; Humans; Inflammation; Leptin; Lipid Metabolism; Metabolic Diseases; Oxidative Stress; Recombinant Proteins | 2009 |
Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity.
There is a growing evidence that both overnutrition and undernutrition negatively interfere with immune system. The overnutrition has been found to increase susceptibility to the development of inflammatory or autoimmune diseases. On the other hand, starvation or malnutrition has been more associated with increased susceptibility to infections. In the regulation of immune and inflammatory processes, white adipose tissue plays a critical role as an endocrine organ which produces number of active peptides, called adipokines. The adipokines, leptin and adiponectin represent a critical link among nutritional status, metabolism and immunity. Leptin is primarily known as a satiety factor regulating body weight by suppression of appetite and stimulation of energy expenditure, and its serum levels and gene expression in adipocytes strongly correlate with proportion of body fat stores. On the other hand, leptin is a pro-inflammatory adipokine inducing T helper 1 cells and may contribute to the development and progression of autoimmune responses. Adiponectin plays an important role as an insulin-sensitizing adipokine which production is decreased in obesity and in conditions associated with insulin resistance. Adiponectin also acts as an anti-inflammatory factor especially with regard to atherosclerosis, but in some chronic inflammatory/autoimmune diseases adiponectin may have pro-inflammatory effects and its production correlates with inflammatory markers and disease activity. This review discusses the main biological activities of leptin and adiponectin as well as their contribution to inflammatory and autoimmune processes with particular focus on rheumatoid arthritis and its experimental models. Topics: Adiponectin; Adipose Tissue; Animals; Arthritis, Rheumatoid; Autoimmunity; Energy Metabolism; Humans; Inflammation; Leptin; Nutritional Physiological Phenomena | 2009 |
Obesity and cancer.
Epidemiological studies have suggested that obesity is associated with increased risk of several cancer types including colon, esophagus, breast (in postmenopausal women), endometrium, kidney, liver, gallbladder and pancreas. Suggested mechanisms include increased intake of potentially carcinogenic food ingredients along with excessive amount of calories, loss of cancer protective effects due to reduced physical activity, carcinogenic factors released from increased adipose tissue mass and "secondary" associations via "precursor" condition such as gallstones. The increased cancer risk in patients with obesity is a neglected topic which deserves more scientific attention. Because of its extreme chronicity and co-association with numerous other conditions true causality and underlying mechanisms are difficult to study. Nevertheless, a large body of literature is already available which provides concepts for future research. Topics: Adiposity; Comorbidity; Energy Intake; Humans; Inflammation; Insulin; Leptin; Neoplasms; Obesity; Risk Factors | 2009 |
[Resistin: a pathogenic factor or a biomarker of metabolic disorders and inflammation?].
Cardiovascular diseases are currently the most frequent cause of death in Poland and their incidence continually rises. This is related to the high incidence of obesity associated with insulin resistance, which is present in type 2 diabetes mellitus. Adipose tissue produces multiple cytokines(TNF-alpha, IL-6, PAI-1, CRP, angiotensinogen, leptin, adiponectin, visfatin, apelin, resistin)which decrease insulin sensitivity and induce inflammatory processes, endothelial dysfunction,and atherosclerosis. This article presents the link between obesity, insulin resistance, and type 2 diabetes mellitus according to studies conducted in vitro and in animal models. In human studies, the influence of resistin on the development of insulin resistance is controversial. The article underlines the role of resisitin in the development of inflammatory processes and endothelial dysfunction in humans. In clinical studies, resistin was shown to be a predictive factor of coronary artery disease and mortality connected with cardiovascular diseases. Topics: Adipose Tissue; Animals; Biomarkers; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Inflammation; Inflammation Mediators; Leptin; Metabolic Diseases; Metabolic Syndrome; Obesity; Resistin | 2009 |
The implication of proinflammatory cytokines in type 2 diabetes.
The incidence of type 2 diabetes (T2D) is rapidly expanding. Some of the more obvious pathologies associated with it include: defective glucose metabolism, obesity, cardiovascular disease and an inability to mount an effective immune response to infection by certain pathogenic organisms, leading to sepsis and death. A common tie linking these seemingly disparate complications is chronic inflammation. Today we know that inflammation is regulated locally and systemically by numerous biochemical signals. One of the most important of these signals is a class of molecules called cytokines. Cytokines can be generally classified as proinflammatory or anti-inflammatory and allow an organism to respond rapidly to an immune challenge by coordinating an appropriate immune response. In T2D, the balance between proinflammatory and anti-inflammatory cytokines is shifted toward proinflammation, potentially causing or exacerbating the health complications found in T2D. Over-nutrition has been shown to trigger the innate immune system but activation of the innate immune system, itself, induces hyperglycemia and insulin resistance. In all likelihood, diabetes and chronic inflammation are inseparable and act as a reciprocal feed-forward loop. Topics: Anti-Inflammatory Agents; Cytokines; Diabetes Mellitus, Type 2; Humans; Incidence; Inflammation; Interleukin-1beta; Interleukin-6; Leptin; Tumor Necrosis Factor-alpha | 2008 |
[Obesity as inflammatory disease].
Studies of the role of immune system activation in the pathogenesis of obesity and its concomitant diseases have been conducted for some years. Numerous recent studies revealed an association between increased immune activation in obesity and the development of insulin resistance. On the other hand there is the hypothesis that immune activation in obesity is a homeostatic mechanism to protect the organism from reaching the point at which the over-accumulation of fat decreases the possibility to move. The aim of the present study was to review the current literature on immune activation in obesity and the participation of adipokines produced by adipose tissue in the development of insulin resistance. Attention is drawn to the similarities in function and gene expression of adipocytes and macrophages. Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Gene Expression; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Macrophages; Obesity; Resistin; Tumor Necrosis Factor-alpha | 2008 |
The intricate interface between immune and metabolic regulation: a role for leptin in the pathogenesis of multiple sclerosis?
Over the last few years, a series of molecules known to play a function in metabolism has also been shown to play an important role in the regulation of the immune response. In this context, the adipocyte-derived hormone leptin has been shown to regulate the immune response in normal as well as in pathological conditions. More specifically, it has been shown that conditions of reduced leptin production (i.e., genetic leptin deficiency, anorexia nervosa, malnutrition) are associated with increased susceptibility to infections. Conversely, immune-mediated disorders such as autoimmune disorders are associated with increased secretion of leptin and production of proinflammatory, pathogenic cytokines. Leptin could represent the "missing link" among immune response, metabolic function, and nutritional status. Indeed, more recently, leptin-deficient mice have been shown to be resistant to a series of experimentally induced autoimmune disorders including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Normal wild-type mice show increased secretion of leptin in serum upon EAE induction, and brain inflammatory infiltrates stain positive for leptin. Finally, leptin neutralization with leptin antagonists improves the EAE course by profoundly altering intracellular signaling of myelin-reactive T cells and increasing the number of regulatory forkhead/winged helix transcription factor 3(+)CD4(+) T cells. These data suggest that leptin can be considered as a link among immune tolerance, metabolic state, and autoimmunity and that strategies aimed at interfering with the leptin axis could represent innovative, therapeutic tools for autoimmune disorders. Topics: Animals; Autoimmune Diseases; Brain; CD4-Positive T-Lymphocytes; Encephalomyelitis, Autoimmune, Experimental; Homeostasis; Humans; Immunity; Inflammation; Leptin; Metabolism; Multiple Sclerosis; Obesity; T-Lymphocytes, Regulatory | 2008 |
Leptin and mTOR: partners in metabolism and inflammation.
Leptin is both a hormone/cytokine that plays a major role in the regulation of feeding and energy expenditure. Beyond its central role in the hypothalamus, leptin modulates peripheral tissues' responses to growth and storage based on nutrient availability, and it regulates the innate and adaptive immune responses. mTOR (mammalian Target of Rapamycin) is a core component of intracellular signaling for cellular growth, mRNA translation, and metabolism. Here, we review recent findings on the cross talk between mTOR and leptin signaling. Important roles for mTOR on leptin signaling have been established both in hypothalamic centers to control food intake and in peripheral cells to regulate lipid metabolism and inflammation. Leptin directly activates resident macrophages to form ADRP-enriched lipid droplets and enhances eicosanoid production via a mechanism that is dependent on activation of the PI3K/mTOR pathway. Leptin-induced mTOR activation may have implications for obesity-related pathophysiological conditions such as diabetes, cardiovascular disease and cancer. Topics: Humans; Hypothalamus; Immunity; Inflammation; Leptin; Lipid Metabolism; Macrophage Activation; Macrophages; Protein Kinases; Signal Transduction; TOR Serine-Threonine Kinases | 2008 |
Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease.
The metabolic syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is a primary risk factor for diabetes and cardiovascular disease. We showed for the first time that the metabolic syndrome is associated with a higher fraction of oxidized LDL and thus with higher levels of circulating oxidized LDL. Hyperinsulinemia and impaired glycaemic control, independent of lipid levels, were associated with increased in vivo LDL oxidation, as reflected by the higher prevalence of high oxidized LDL. High levels of oxidized LDL were associated with increased risk of future myocardial infarction, even after adjustment for LDL-cholesterol and other established cardiovascular risk factors. This association is in agreement with the finding that accumulation of oxidized LDL, which activates/induces subsets of smooth muscle cells and macrophages to gelatinase production, was associated with upstream localization of a vulnerable plaque phenotype. Dyslipidemia and insulin resistance in obese LDL receptor-deficient mice were associated with increased oxidative stress and impaired HDL-associated antioxidant defence associated with accelerated atherosclerosis due to increased macrophage infiltration and accumulation of oxidized LDL in the aorta. The accumulation of oxidized LDL was partly due to an impaired HDL-associated antioxidant defence due to a decrease in PON. Our data in this experimental model are thus the more relevant because a decrease in PON activity was found to be associated with a defective metabolism of oxidized phospholipids by HDL from patients with type 2 diabetes. Weight loss in leptin-deficient, obese, and insulin-resistant mice was associated with expressional changes of key genes regulating adipocyte differentiation, glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. We established an important relationship between PPAR-gamma and SOD1 for the prevention of the oxidation of LDL in the arterial wall. For example we showed that rosuvastatin decreased the oxidized LDL accumulation by increasing the expression of PPAR-gamma and SOD1. In addition, we established a relation between increased PPAR-alpha expression in the adipose tissue and a change in the gene expression pattern, which explains the decrease of free fatty acids, triglycerides and the increase in insulin sensitivity. We demonstrated Topics: Animals; Cardiovascular Diseases; Comorbidity; Humans; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Lipoproteins, LDL; Metabolic Syndrome; Mice; Obesity; Oxidation-Reduction; Oxidative Stress; Risk Factors; Weight Loss | 2008 |
Intricacies of fat.
One of the most exciting cell biology fields of study concerns the physiology and pathology of fat. The basic assumptions once held concerning the function of adipose tissue have been shown to be oversimplified or sometimes completely wrong. Fat does more than store excess energy; it is actually the largest endocrine organ in the body, and it may be one of the most active. Adipocytes release hormones and other molecules that act on nearby tissues and travel through the vasculature to distant sites, such as the brain, skeletal muscle, and liver. Under conditions of normal weight, those signals help the body to suppress hunger, utilize glucose, and decrease the risk of cardiovascular disease. However, under conditions of obesity, the hormones (or the proteins that bind the hormones) become abnormal and can result in states of chronic inflammation leading to diabetes and heart disease. In addition, excessive fat can lead to the accumulation of lipid droplets in nonfat cells, including skeletal and cardiac muscle. Although some lipid droplets are used as an immediate source of energy for cells, large numbers of stored droplets can cause cellular damage and cell death. The purposes of this article are to review the normal and deviant signals released by fat cells, to draw a link between those signals and chronic diseases such as diabetes, and to discuss the role of exercise in reversing some of the deviant signaling perpetrated by excess fat. Topics: Adipokines; Adipose Tissue; Exercise; Humans; Inflammation; Leptin; Obesity | 2008 |
Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease.
Leptin is an adipocyte-derived hormone and cytokine that regulates energy balance through a wide range of functions, including several that are important to cardiovascular health. Increased circulating leptin, a marker of leptin resistance, is common in obesity and independently associated with insulin resistance and cardiovascular disease (CVD) in humans. The mechanisms of leptin resistance include genetic mutation, leptin self-regulation, limited tissue access, and cellular or circulating molecular regulation. Evidence suggests that central leptin resistance causes obesity and that obesity-induced leptin resistance injures numerous peripheral tissues, including liver, pancreas, platelets, vasculature, and myocardium. This metabolic- and inflammatory-mediated injury may result from either resistance to leptin's action in selective tissues, or excess leptin action from adiposity-associated hyperleptinemia. In this sense, the term "leptin resistance" encompasses a complex pathophysiological phenomenon. The leptin axis has functional interactions with elements of metabolism, such as insulin, and inflammation, including mediators of innate immunity, such as interleukin-6. Leptin is even purported to physically interact with C-reactive protein, resulting in leptin resistance, which is particularly intriguing, given C-reactive protein's well-studied relationship to cardiovascular disease. Given that plasma levels of leptin and inflammatory markers are correlated and also predict cardiovascular risk, it is conceivable that part of this risk may be mediated through leptin resistance-related insulin resistance, chronic inflammation, type II diabetes, hypertension, atherothrombosis, and myocardial injury. Leptin resistance and its interactions with metabolic and inflammatory factors, therefore, represent potential novel diagnostic and therapeutic targets in obesity-related cardiovascular disease. Topics: Animals; Cardiovascular Diseases; Humans; Inflammation; Leptin; Obesity | 2008 |
Obstructive sleep apnea syndrome and asthma: the role of continuous positive airway pressure treatment.
To review the concept of a possible link between asthma and obstructive sleep apnea syndrome (OSAS) and the impact on asthma symptoms of treatment of OSAS with continuous positive airway pressure (CPAP) in patients with both conditions.. The Ovid, MEDLINE, and PubMed databases from 1950 to the present were searched for relevant articles regarding a possible relationship between asthma and OSAS and the effectiveness of CPAP in treating OSAS.. Articles describing pathophysiologic conditions occurring in OSAS that may be linked to asthma pathogenesis were used for this review.. The data suggest that OSAS is an independent risk factor for asthma exacerbations. CPAP has been shown in prospective clinical studies to have a positive impact on asthma outcome in patients with concomitant OSAS. Ameliorative mechanisms of treatment with CPAP include mechanical and neuromechanical effects, gastroesophageal acid reflux suppression, local and systemic anti-inflammatory effects (including suppression of increased serum levels of inflammatory cytokines, chemokines, and vascular endothelial growth factor), cardiac function improvements, leptin level suppression, weight reduction, and sleep restoration.. Asthma and OSAS are increasingly troublesome public health issues. Mounting evidence implicates OSAS as a risk factor for asthma exacerbations, thereby linking these 2 major epidemics. We describe potential mechanisms whereby CPAP, the first line of therapy for OSAS, might modify airway smooth muscle function and asthma control in patients with both disorders. Despite the ever-increasing population of patients with both disorders, large, prospective, randomized controlled studies are necessary to more fully evaluate CPAP and asthma outcomes. Topics: Asthma; Continuous Positive Airway Pressure; Gastroesophageal Reflux; Heart; Humans; Inflammation; Leptin; Obesity; Respiratory Mechanics; Risk Factors; Sleep; Sleep Apnea, Obstructive | 2008 |
Does obesity play a major role in the pathogenesis of sleep apnoea and its associated manifestations via inflammation, visceral adiposity, and insulin resistance?
Despite the early recognition of the strong association between obstructive sleep apnoea (OSA) and obesity, and OSA and cardiovascular problems, sleep apnoea has been treated as a "local abnormality" of the respiratory track rather than as a "systemic illness". In 1997, we first reported that the pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNFalpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. In subsequent studies, it was shown that IL-6, TNFalpha, and insulin levels were elevated in sleep apnoea independently of obesity and that visceral fat was the primary parameter linked with sleep apnoea. Further studies showed that women with the polycystic ovary syndrome (PCOS) were much more likely than controls to have sleep-disordered breathing (SDB) and daytime sleepiness, suggesting a pathogenetic role of insulin resistance in OSA. Additional accumulated evidence that supports the role of obesity and the associated metabolic aberrations in the pathogenesis of sleep apnoea and related symptoms include: obesity without sleep apnoea is associated with daytime sleepiness; the protective role of gonadal hormones as suggested by the increased prevalence of sleep apnoea in post-menopausal women and the significantly reduced risk for OSA in women on hormonal therapy; partial effects of continuous positive airway pressure (CPAP) in obese patients with apnoea on hypercytokinemia, insulin resistance indices, and visceral fat; and that the prevalence of the metabolic syndrome in the U.S. population from the Third National Health and Nutrition Examination Survey (1988-1994) parallels the prevalence of symptomatic sleep apnoea in general random samples. Furthermore, the beneficial effect of a cytokine antagonist on EDS and apnoea in obese, male apnoeics and that of exercise and weight loss on SDB and EDS in general random or clinical samples, supports the hypothesis that cytokines and insulin resistance are mediators of EDS and sleep apnoea in humans. Finally, our recent finding that in obese, hypothalamic CRH neuron is hypoactive, provides additional evidence on the potential central neural mechanisms for depressed ventilation and consequent development of sleep apnoea in obese individuals. In conclusion, accumulating evidence provides support to our thesis that obesity via inflammation, insulin resistance, visceral adiposity, and Topics: Adiposity; Female; Humans; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Models, Biological; Obesity; Polycystic Ovary Syndrome; Sleep Apnea Syndromes | 2008 |
[The metabolic syndrome and type-2 diabetes mellitus as conditions predisposing for malignant tumors].
Recently more and more evidences have emerged about the oncogenic effect of type 2 diabetes and metabolic syndrome. Among these evidences epidemiological data are in first line. There is a causal relationship according to gender, ethnicity and geographic situation between different tumors and type 2 diabetes/metabolic syndrome as well. Supposed pathomechanisms are obesity, cytokines, secreted excessively in adipose tissue, permanent and postprandial hyperglycemia, hyperinsulinism and insulin resistance, other growth factors, like proinsulin, insulin like growth factor-1, reactive oxygen species, angiogenesis, inflammation, and the multiple effects of inflammatory cytokines. It proved to be evident that both peroxisome-proliferator-activated receptors and the regulatory ubiquitin proteasome system have significant role in insulin sensitivity and in co-ordinating cell proliferation and angiogenesis. These mechanisms in metabolic syndrome are risk factors towards atherosclerosis and cancer diseases as well. This newly emerged knowledge may open new pathways in treating and preventing the above-mentioned pathologic processes. Topics: Adiponectin; Adipose Tissue; Animals; Cell Proliferation; Cytokines; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hyperinsulinism; Inflammation; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Metabolic Syndrome; Neoplasms; Neovascularization, Pathologic; Obesity; Peroxisome Proliferator-Activated Receptors; Reactive Oxygen Species; Risk Factors; Ubiquitins; Vascular Endothelial Growth Factor A | 2008 |
Leptin hormone and other biochemical influences on systemic inflammation.
Over the past 30 years, a sharp rise in the prevalence of overweight and obesity has been noted in both children and adults. Health consequences include biomechanical, biochemical and psychosocial factors, with broad implications toward central adiposity and a number of conditions with which it relates. Substantial new information has surfaced within the last decade that alters previous concepts regarding the role of adipose tissue in health and in disease. This literature review explores the role that white adipose tissue (WAT) plays within a cascade of endocrine interfaces that have significant health consequences. WAT is now known to be an active participant in regulating physiological and pathological processes, including immunity and inflammation and to play a primary role in the development of a triad of hormonal imbalance (leptin resistance, adrenaline resistance, insulin resistance). Particular focus is placed on leptin hormone and its potential influences on inflammation and a host of other metabolic disturbances. Topics: Adipose Tissue, White; Adult; Child; Diet Therapy; Female; Hormones; Humans; Inflammation; Insulin Resistance; Leptin; Male; Obesity; Waist Circumference | 2008 |
Heart failure and cachexia: insights offered from molecular biology.
Chronic heart failure (CHF) is an enormous medical and communal burden. The syndrome is common, carries a grim prognosis and severely impacts quality of life. Those patients who develop cardiac cachexia combat both important disability and a poor outlook. Muscle wasting is a critical component of cachexia. The pathophysiological determinants are numerous and some of them are common to other chronic severe illnesses. There is increasing awareness, however, that heart failure related myopathy is a distinct entity, characterized by specific functional, structural and morphologic changes and the involvement of several neurohormonal pathways, catabolic processes, a pro-inflammatory environment and increased oxidative stress. Although clear-cut evidence based solutions for the problem are not readily available, the modulating effects of regular exercise in CHF patients suggest that physical training should at least be incorporated in the essentially multi-disciplinary approach. Topics: Animals; Cachexia; Catecholamines; Exercise; Ghrelin; Heart Failure; Humans; Inflammation; Leptin; Muscle, Skeletal; Neurosecretory Systems; Oxidative Stress; Physical Conditioning, Animal | 2008 |
Adipokines: the missing link between insulin resistance and obesity.
White adipose tissue was believed to be just an energy-storage organ, but it is now recognized to be an active participant in energy homoeostasis and physiological functions such as immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Adipose tissue is known to express and secrete a variety of products known as 'adipokines', including leptin, adiponectin, resistin and visfatin, as well as cytokines and chemokines such as tumor necrosis factor-alpha, interleukin-6 and monocyte chemoattractant protein-1. The release of adipokines by either adipocytes or adipose tissue-infiltrated macrophages leads to a chronic subinflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes, and the increased risk of cardiovascular disease associated with obesity. Topics: Adipokines; Adiponectin; Endoplasmic Reticulum; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Plasminogen Activator Inhibitor 1; Resistin; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha | 2008 |
Islet inflammation in type 2 diabetes: from metabolic stress to therapy.
Decreases in both mass and secretory function of insulin-producing beta-cells contribute to the pathophysiology of type 2 diabetes. The histology of islets from patients with type 2 diabetes displays an inflammatory process characterized by the presence of cytokines, apoptotic cells, immune cell infiltration, amyloid deposits, and eventually fibrosis. This inflammatory process is probably the combined consequence of dyslipidemia, hyperglycemia, and increased circulating adipokines. Therefore, modulation of intra-islet inflammatory mediators, in particular interleukin-1 beta, appears as a promising therapeutic approach. Topics: Cytokines; Diabetes Mellitus, Type 2; Dyslipidemias; Glucose; Humans; Hypoglycemic Agents; Inflammation; Insulin-Secreting Cells; Interleukin-1beta; Islets of Langerhans; Leptin; Obesity; Pancreatic Diseases | 2008 |
Intra-abdominal adiposity, inflammation, and cardiovascular risk: new insight into global cardiometabolic risk.
Increasing evidence supports the role of adipose tissue in the development of a systemic inflammatory state, which contributes to obesity-associated vasculopathy and cardiovascular risk. In addition to storing calories as triglycerides, adipocytes secrete a large variety of proteins, including cytokines, chemokines, and -hormone-like factors (eg, leptin, adiponectin, resistin). This production of pro chemokines by adipose tissue is of particular interest, because their local secretion by perivascular adipose depots may provide a new mechanistic link between obesity and its associated vascular complications. Insulin resistance, in subjects with or without diabetes, is frequently associated with obesity, particularly with an excess of intra-abdominal fat. Recently, the endocannabinoid system, among others, has been shown to be involved in the pathophysiology of visceral obesity and global cardiometabolic risk, as represented by the overall risk of developing type 2 diabetes or cardiovascular diseases. Topics: Abdominal Fat; Adiponectin; C-Reactive Protein; Cardiovascular Diseases; Humans; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; Resistin; Risk Factors | 2008 |
The role of adiposity as a determinant of an inflammatory milieu.
With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they have been shown increasingly to affect several aspects of the pathogenesis of obesity-related diseases. Until relatively recently, the role of adipose tissue itself in the development of obesity and its consequences was considered to be a passive one. It is now clear that, in addition to storing energy in the form of triglycerides, adipocytes also secrete a large variety of proteins, including cytokines, chemokines and hormone-like factors. This production of proatherogenic chemokines by adipose tissue is of particular interest, since their local secretion, for example by perivascular adipose depots, may provide a novel mechanistic link between obesity and associated vascular complications. Topics: Acute-Phase Proteins; Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Cardiovascular Diseases; Humans; Inflammation; Inflammation Mediators; Leptin; Obesity; Resistin | 2008 |
An integrated and unifying hypothesis for the metabolic basis of sporadic Alzheimer's disease.
Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SAD). Among these, brain glucose utilization is reduced in the early stages of the disease. Hyperinsulinemia, which is a characteristic finding of insulin resistance, results in a central insulin deficit. Insufficient insulin signaling impairs the intricate balance of nitric oxide regulation of the central nervous system. Reduction in central insulin decreases neuronal nitric oxide synthase and increases inducible synthase activity. This, in turn, decreases astrocytic energy substrates and antioxidant supply of neurons. In addition, an increase in peroxynitrite formation impairs redox balance. Hyperleptinemia and glucose excess, which are the other parameters of insulin resistance, may worsen the reduced astrocytic energy supply and the ongoing inflammation via the inhibition of AMP-activated protein kinase (AMPK). Consequently, energy deficit and inflammation in neuronal tissue may cause neurodegeneration of SAD. Topics: Alzheimer Disease; AMP-Activated Protein Kinases; Antioxidants; Astrocytes; Blood-Brain Barrier; Brain; Cerebral Amyloid Angiopathy; Diabetes Mellitus; Glucose; Humans; Inflammation; Insulin Resistance; Ketones; Leptin; Liver; Mitochondrial Diseases; Multienzyme Complexes; Nerve Degeneration; Oxidation-Reduction; Peroxynitrous Acid; Protein Serine-Threonine Kinases | 2008 |
[Pathogenesis of the metabolic syndrome].
After an initial attempt by the WHO to define metabolic syndrome (MS) on a pathophysiologically oriented approach requiring the assessment of insulin resistance markers, the NCEP-ATPIII and more recently the IDF proposed more clinically oriented criteria to help, toward a preventive medicine goal, to identify patients who are likely to have features of the MS and be at increased risk of type 2 diabetes and cardio vascular disease. The notion of MS is built around abnormalities of the metabolism of lipids and carbon hydrates, a rise of blood pressure, and visceral obesity of abdominal localization. These parameters report only partially on mechanisms leading to the development of the MS. The physiopathology of MS is partially understood even today and likely results from the combination of environmental, genetic and epigenetic factors. Abdominal visceral obesity, a state of low-grade chronic inflammation and insulin resistance are the main processes susceptible to explain the various constituents of this syndrome. Topics: Environment; Exercise; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; Models, Biological; Nutritional Status; Psoriasis | 2008 |
Promising new causal explanations for obesity and obesity-related diseases.
Current explanations for obesity center around a predisposition in genotype and phenotype, possibly triggered by an inflammatory process or event, and exacerbated by environmental and psychological factors. It is likely that a variety of physiologic factors may act in combination to produce clinical obesity. Leptin resistance may be an important neurochemical cause of obesity; elevated leptin levels have been correlated with weight gain over extended time periods. Genetic studies support the postulate that a gene originating with our cave-dwelling ancestors, critical to survival when food was scare, has evolved into a trigger for obesity and related diseases. A variety of biochemical markers are prevalent in obesity and obesity-linked disease states. C-reactive protein, interleukin-6, and others are elevated in obesity, supporting the hypothesis that inflammation plays a role in the condition. Tumor necrosis factor-alpha is overexpressed in obesity and diabetes, suggesting that it may be part of the link between the 2 conditions. Topics: Appetite; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Causality; Cost of Illness; Diabetes Mellitus, Type 2; Dietary Fats; Genetic Predisposition to Disease; Genotype; Humans; Inflammation; Interleukin-6; Leptin; Life Style; Neoplasms; Obesity; Phenotype; Tumor Necrosis Factor-alpha; United States | 2007 |
Diabetes and suppressors of cytokine signaling proteins.
Topics: Cytokines; Diabetes Mellitus; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Obesity; Signal Transduction; Suppressor of Cytokine Signaling Proteins | 2007 |
Leptin: at the crossroads of energy balance and systemic inflammation.
In addition to playing a central role in energy homeostasis, leptin is also an important player in the inflammatory response. Systemic inflammation is accompanied by fever (less severe cases) or hypothermia (more severe cases). In leptin-irresponsive mutants, the hypothermia of systemic inflammation is exaggerated, presumably due to the enhanced production and cryogenic action of tumor necrosis factor (TNF)-alpha. Mechanisms that exaggerate hypothermia can also attenuate fever, particularly in a cool environment. Another common manifestation of systemic inflammation is behavioral depression. Along with the production of interleukin (IL)-1beta, this manifestation is exaggerated in leptin-irresponsive mutants. The enhanced production of TNF-alpha and IL-1beta may be due, at least in part, to insufficient activation of the anti-inflammatory hypothalamo-pituitary-adrenal axis by immune stimuli in the absence of leptin signaling. In experimental animals and humans that are responsive to leptin, suppression of leptin production under conditions of negative energy balance (e.g., fasting) can exaggerate both hypothermia and behavioral depression. Since these manifestations aid energy conservation, exaggeration of these manifestations under conditions of negative energy balance is likely to be beneficial. Topics: Animals; Homeostasis; Humans; Inflammation; Leptin; Models, Genetic; Receptors, Leptin; Temperature | 2007 |
Obesity, metabolic syndrome and sleep apnoea: all pro-inflammatory states.
Obesity is associated with significant morbidity and mortality and is increasing in prevalence worldwide. Associated conditions include insulin resistance (IR), diabetes, hypertension and dyslipidaemia; a clustering of these has recently been termed as metabolic syndrome. Weight gain is a major predictor of the metabolic syndrome with waist circumference being a more sensitive indicator than body mass index as it reflects both abdominal subcutaneous adipose tissue and visceral adipose tissue (VAT). VAT has more metabolic activity and secretes a number of hormones and pro-inflammatory cytokines which are linked with the metabolic abnormalities listed above. Central obesity also increases the risk of obstructive sleep apnoea syndrome (OSAS), where the sleep disordered breathing may also independently lead to/or exacerbate IR, diabetes and cardiovascular risk. The contribution of OSAS to the metabolic syndrome has been under-recognized. The putative mechanisms by which OSAS causes or exacerbates these other abnormalities are discussed. We propose that activation of nuclear factor kappa B by stress hypoxia and/or by increased adipokines and free fatty acids released by excess adipose tissue is the final common inflammatory pathway linking obesity, OSAS and the metabolic syndrome both individually and, in many cases, synergistically. Topics: Adiponectin; Diabetes Mellitus, Type 2; Humans; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; NF-kappa B; Obesity; Risk Factors; Sleep Apnea Syndromes | 2007 |
Adipocyte biology.
Topics: Adipocytes, White; Adiponectin; Adipose Tissue; Biomedical Research; Humans; Inflammation; Leptin; Obesity | 2007 |
[Relationship between obesity and asthma].
The prevalences of both obesity and asthma have clearly increased in recent decades, giving rise to speculation that they may be related. Studies have found that obesity precedes and predicts the onset of asthma (time effect), that increased obesity leads to more severe asthma (dose-response effect), that weight reduction (by diet or gastric bypass) improves asthmatic symptoms, and that obesity co-occurs with intermediate asthma phenotypes (obese young girls undergoing early menarche). In the light of that evidence, we can finally suggest a causal relationship between obesity and asthma. Various biological mechanisms (immunologic and inflammatory, hormonal, genetic, nutritional, mechanical, and others related to physical activity) have been put forth to explain the relationship. However, this relation is complex, involving not only the interaction of genetic and environmental factors in triggering both diseases but also the likely participation of several mechanisms at once. Topics: Adolescent; Adult; Airway Resistance; Asthma; Child; Chromosome Mapping; Cytokines; Diet; Disease Susceptibility; Female; Hormones; Humans; Inflammation; Leptin; Male; Menarche; Motor Activity; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Respiratory Mechanics; Sex Factors; Weight Loss | 2007 |
Is metabolic syndrome X a disorder of the brain with the initiation of low-grade systemic inflammatory events during the perinatal period?
An imbalance between pro- and anti-inflammatory molecules occurs in metabolic syndrome X. High-energy diet, saturated fats and trans-fats during perinatal period could suppress Delta(6) and Delta(5) desaturases both in the maternal and fetal tissues, resulting in a decrease in the concentrations of long-chain polyunsaturated fatty acids (LCPUFAs): arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that have a negative feedback control on inflammation. EPA, DHA and AA augment endothelial nitric oxide synthesis, potentiate insulin action both in the peripheral tissues and brain and alter leptin production. LCPUFAs are essential for brain growth and development and synaptogenesis and modulate the action of several neurotransmitters and hypothalamic peptides. This suggests that metabolic syndrome X could be a disorder of the brain due to suboptimal LCPUFAs during perinatal period that triggers low-grade systemic inflammation, implying that perinatal strategies are needed to prevent its development. Topics: Animals; Appetite Regulation; Arachidonic Acid; Brain; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Dopamine; Eicosapentaenoic Acid; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Aminobutyric Acid; Humans; Hypothalamus, Middle; Infant, Newborn; Inflammation; Insulin; Leptin; Metabolic Syndrome; N-Methylaspartate; Neurons; Qa-SNARE Proteins; Receptor, Insulin; Receptors, Retinoic Acid; Serotonin; Synapses | 2007 |
Type 2 diabetes and cardiovascular disease: getting to the fat of the matter.
The increasing national prevalence of obesity is a major public health concern and a substantial burden on the health care resources of Canada. In addition to the direct health impact of obesity, this condition is a well-established risk factor for the development of various prevalent comorbidities including type 2 diabetes, hypertension, and cardiovascular disease. Historically, adipose tissue has been regarded primarily as an organ for energy storage. However, the discovery of leptin in the mid 1990's revolutionized our understanding of this tissue and has focused attention on the endocrine function of adipose tissue as a source of secreted bioactive peptides. These compounds, collectively termed adipokines, regulate a number of biological functions including appetite and energy balance, insulin sensitivity, lipid metabolism, blood pressure, and inflammation. The physiological importance of adipokines has led to the hypothesis that changes in the synthesis and secretion of these compounds in the obese are a causative factor contributing to the development of obesity and obesity-related diseases in these individuals. Following from this it has been proposed that pharmacologic manipulation of adipokine levels may provide novel effective therapeutic strategies to treat and prevent obesity, type 2 diabetes, and cardiovascular disease. Topics: Adiponectin; Adipose Tissue; Angiotensin II; Animals; Cardiovascular Diseases; Complement Activation; Complement C3a; Complement Factor D; Cytokines; Diabetes Mellitus, Type 2; Fibrinolysis; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Plasminogen Activator Inhibitor 1; Renin-Angiotensin System; Resistin; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Risk Factors; Tumor Necrosis Factor-alpha | 2007 |
[The function of adipose tissue in inflammatory state].
Topics: Adiponectin; Adipose Tissue; Animals; Complement C3; Fatty Acids, Nonesterified; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Obesity | 2007 |
Obesity and inflammation: a new look at an old problem.
Obesity is a highly prevalent disease with multiple implications for cardiovascular morbidity and mortality. The traditional view of obesity is that excessive adipose tissue represents a passive storage depot of excess energy. However, obesity has been demonstrated to be a highly active endocrine organ with multiple metabolic pathways that interact with classic cardiac risk factors. The role of inflammation in atherosclerosis has been clarified by the ready availability of a variety of markers, including C-reactive protein, adiponectin, tumor necrosis factor-alpha, hemostatic markers, resistin, and a variety of emerging markers such as interleukins and adhesion molecules. Adipose tissue has been demonstrated to be the site of synthesis of a variety of proteins that are intimately involved in the regulation of inflammation. The concept that obesity represents an inflammatory state has gained credence over the past decade and has provided insights into the mechanisms of atherosclerosis and risk factor interaction. Topics: Acute-Phase Proteins; Adiponectin; Atherosclerosis; Cardiovascular Diseases; Humans; Inflammation; Inflammation Mediators; Leptin; Obesity; Resistin; Risk Factors; Tumor Necrosis Factor-alpha | 2007 |
Adipokines as emerging mediators of immune response and inflammation.
The scientific interest in the biology of white adipose tissue (WAT) has increased since the discovery of leptin in 1994. The description of the product of the gene obese (ob) demonstrated the role of adipose tissue in the physiopathology of obesity-related diseases, and helped to increase the identification of numerous other adipokines, many of a pro-inflammatory nature. It has become increasingly evident that WAT-derived adipokines can be considered as a hub between obesity-related exogenous factors, such as nutrition and lifestyle, and the molecular events that lead to metabolic syndrome, inflammatory and/or autoimmune conditions, and rheumatic diseases. In this Review, we will discuss the progress in adipokine research, focusing particular attention to the roles of leptin, adiponectin, resistin, visfatin, and other recently identified adipokines in inflammatory, autoimmune and rheumatic diseases. Topics: Adipokines; Adiponectin; Humans; Immune System; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Resistin | 2007 |
Estrogens and glucocorticoid hormones in adipose tissue metabolism.
Women have a higher percentage of body fat than men, and there is a gender-specific difference in fat distribution: Females tend to accumulate fat around the hips, buttocks, and thighs while men have a larger intra-abdominal (visceral) fat mass. After menopause, there is a redistribution of fat depots, and post-menopausal women develop increased amounts of visceral fat. The risk of developing obesity-related diseases is significantly lower in pre-menopausal women compared to men, a difference that is abolished after menopause, suggesting that the female sex steroid estrogen influences adipogenesis and adipose metabolism. Experimentally, estrogen increases the size and number of subcutaneous adipocytes and attenuates lipolysis. Post-menopausal women also develop a more atherogenic lipid pattern and decreased levels of the prothrombotic protein plasminogen activator inhibitor-1, which attenuates fibrinolysis. Pathologically increased circulating cortisol concentration is associated with dysmetabolic features e.g., central obesity, elevated blood pressure, insulin resistance, and dyslipidemia. In "simple obesity," glucocorticoid production is elevated. Peak levels of circulating cortisol are however low or normal, possibly because of increased clearance and/or tissue-specific changes in cortisol production. In addition to the adrenal production of cortisol, cortisol is also generated in adipose tissue by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) which converts inactive cortisone to active cortisol. The enzyme activity in subcutaneous fat increases with increasing body weight. Estrogen seems to have a tissue-specific influence on 11betaHSD1 enzyme activity, attenuating it in liver, kidney, and testis but upregulating 11betaHSD1 mRNA expression in preadipocytes from women. In the present review, we summarize and discuss the interaction between glucocorticoids and sex steroids and their influence on adipocyte metabolism. Topics: Adiponectin; Adipose Tissue; Animals; Estrogens; Female; Glucocorticoids; Humans; Hydrocortisone; Inflammation; Insulin; Leptin; Lipid Metabolism; Male; Receptors, Estrogen | 2007 |
Systemic inflammation in chronic obstructive pulmonary disease: the role of exacerbations.
The systemic manifestations of chronic obstructive pulmonary disease (COPD) exacerbations are recognized, but our understanding of their etiology and importance is lacking largely due to the small number of systematic and longitudinal studies. Most of the systemic manifestations are likely the result of inflammatory processes. Serum biomarkers, such as various cytokines, adipokines, C-reactive protein, and coagulation factors, are elevated during exacerbations. Our understanding of the systemic manifestations can be greatly enhanced if we integrate what is known about the basic science of systemic mediators with the translational science of their role in COPD exacerbations. Many overlapping connections and promising avenues of future research come to light with such a viewpoint. Topics: Adiponectin; C-Reactive Protein; Endothelium, Vascular; Hemostasis; Humans; Immunity, Innate; Inflammation; Leptin; Pulmonary Disease, Chronic Obstructive | 2007 |
Markers of pro-inflammatory and pro-thrombotic state in the diagnosis of metabolic syndrome.
The metabolic syndrome refers to the clustering of upper body obesity, atherogenic dyslipidemia, insulin resistance and elevated blood pressure. Both, obesity and metabolic syndrome, have the potential to influence on the incidence and severity of cardiovascular disease with serious implications for worldwide health care systems. Obesity plays a central role in the development of insulin resistance and dyslipidemia through the mediation of a pro-inflammatory and pro-thrombotic state. Adipose tissue has been shown to exert important endocrine and immune functions. Pathogenesis of obesity associated metabolic syndrome is mediated by disturbed production and release of biologically active molecules by fat cells and other cells infiltrating fat tissue. In obese subjects synthesis of several bioactive compounds--adipokines and cytokines/chemokines by adipose tissue cells is dysregulated. Those bioactive molecules participate in regulation of apetite and energy homeostasis, lipid metabolism (tumour necrosis factor alpha--TNF-alpha), insulin sensitivity (TNF-alpha, adiponectin, resistin, visfatin) immunity (monocyte chemoattractant protein-1--MCP-1, TNF-alpha, IL-6), angiogenesis, blood pressure and hemostasis (plasminogen activator inhibitor--PAI-1). The effects of major pro-/anti-inflammatory and pro-thrombotic adipokines on several physiological processes will be discussed in this review. Also, an evidence-based approach to the laboratory diagnosis and treatment of metabolic syndrome will be presented. Topics: Adiponectin; Cardiovascular Diseases; Complement Factor D; Humans; Inflammation; Interleukin-6; Leptin; Metabolic Syndrome; Models, Biological; Nicotinamide Phosphoribosyltransferase; Obesity; Plasminogen Activator Inhibitor 1; Resistin; Risk; Thrombosis; Tumor Necrosis Factor-alpha | 2007 |
Leptin and adipocytokines: bridging the gap between immunity and atherosclerosis.
The role of the adipose tissue in immunity has recently emerged, and there is now ample evidence that this role is elucidated by a number of cytokine-like hormones produced by adipocytes - called adipokines. The most relevant adipokines are leptin, adiponectin and visfatin, and all have marked effects on metabolic and immune function. The discovery of adipokines has led to the development of a novel concept that the pathogenesis of atherosclerosis can be associated with low-degree inflammation associated with slow (auto)immune attack of the endothelial wall of arteries. This model considers therefore adipokines as the bridge between atherosclerosis, inflammation and immunity. We review here the most recent advances on adipokine research, with a particular emphasis on the model that considers atherosclerotic lesions as effects of the (auto)immune-mediated damage of the endothelium that is sustained by low-degree chronic inflammation typical of obesity and metabolic syndrome. Topics: Adipokines; Adipose Tissue; Animals; Atherosclerosis; Autoimmunity; Endothelium, Vascular; Humans; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Signal Transduction | 2007 |
Obesity, metabolic syndrome, and prostate cancer.
Although obesity has been consistently linked to an increased risk of several malignancies, including cancers of the colon, gallbladder, kidney, and pancreas, its role in prostate cancer etiology remains elusive. Data on the association between obesity and prostate cancer incidence are inconsistent, and in some studies obesity is associated with an increase in risk of high-grade prostate cancer but with a decrease in risk of low-grade tumors. In contrast, obesity has been consistently associated with an increased risk of prostate cancer aggressiveness and mortality. The differential effects of obesity on subtypes of prostate cancer suggest etiologic heterogeneity in these tumors and complex interactions between androgen metabolism and several putative risk factors, including insulin resistance, diabetes, inflammation, and genetic susceptibility, on prostate cancer risk. Data on the role of abdominal obesity, insulin resistance, and metabolic syndrome in prostate cancer etiology are limited. Obesity has been shown to be associated with a state of low-grade chronic inflammation, and insulin resistance and the metabolic syndrome are associated with adverse metabolic profiles and with higher circulating concentrations of inflammation-related markers, including leptin, interleukin-6, and tumor necrosis factor-, many of which have been shown to enhance tumor growth. Thus, whether obesity and metabolic syndrome modulate the risk of prostate cancer through chronic inflammation needs to be investigated further. Given that the prevalence of obesity and metabolic syndrome is increasing worldwide and that the world population is aging, the roles of obesity and metabolic syndrome in prostate carcinogenesis warrant further clarification. Topics: Abdominal Fat; Body Mass Index; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Obesity; Prostatic Neoplasms; Risk Factors; Somatomedins | 2007 |
Obesity and the role of adipose tissue in inflammation and metabolism.
Recent discoveries, notably of the hormones leptin and adiponectin, have revised the notion that adipocytes are simply a storage depot for body energy. Instead, adipocytes are also endocrine organs, with multiple metabolic roles in regulating whole-body physiology. Small adipocytes in lean individuals promote metabolic homeostasis; the enlarged adipocytes of obese individuals recruit macrophages and promote inflammation and the release of a range of factors that predispose toward insulin resistance. Exercise activates the AMP-activated protein kinase (AMPK) in muscle and other tissues, a pathway that increases fat oxidation and glucose transport. Importantly, the adipocyte hormones leptin and adiponectin also activate AMPK; remarkably, the same pathway is activated by certain antidiabetic agents such as thiazolidinediones. Increasingly, our understanding of the adipocyte as an endocrine organ is leading to new insights into obesity and health. Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Energy Metabolism; Humans; Inflammation; Leptin; Obesity | 2006 |
A role for leptin in the systemic inflammatory response syndrome (SIRS) and in immune response, an update.
Leptin was originally identified as an adipocyte-derived cytokine with a key role in the regulation of the energy balance. Subsequent research revealed that leptin's biological action is not restricted to its effects on appetite and food intake, but instead has a much more pleiotropic character. There is now ample evidence that leptin has important functions in reproduction, hematopoiesis, HPA-axis endocrinology and angiogenesis. In this review we have focused on the effects of leptin in the antigen-specific immunity and in the inflammatory effector system. Topics: Adaptation, Physiological; alpha-MSH; Animals; Anorexia; Humans; Immunity; Inflammation; Leptin; Macrophages; Metallothionein; Monocytes; Receptors, Cell Surface; Receptors, Leptin; Starvation; Systemic Inflammatory Response Syndrome; T-Lymphocytes | 2006 |
Leptin and inflammation-associated cachexia in chronic kidney disease.
Leptin is an adipocyte-derived hormone that acts as a major regulator of food intake and energy homeostasis. It circulates both as a free and as a protein-bound entity. Leptin is released into the blood in proportion to the amount of body fat and exerts sustained inhibitory effects on food intake while increasing energy expenditure. The leptin receptor belongs to the class I cytokine receptor superfamily and possesses strong homology to the signal-transducing subunits of the IL-6 receptor. The hypothalamic melanocortin system, and specifically the melanocortin-4 receptor (MC-4R), is critical in mediating leptin's effect on appetite and metabolism. Serum leptin concentrations are elevated in patients with chronic kidney disease (CKD) and correlate with C-reactive protein levels suggesting that inflammation is an important factor that contributes to hyperleptinemia in CKD. Hyperleptinemia may be important in the pathogenesis of inflammation-associated cachexia in CKD. We showed that experimental uremic cachexia was attenuated in db/db mice, a model of leptin receptor deficiency. Nephrectomy in these animals did not result in any change in weight gain, body composition, resting metabolic rate, and efficiency of food consumption. Furthermore, experimental uremic cachexia could be ameliorated by blocking leptin signaling through the hypothalamic MC-4R. MC-4R knockout mice or mice administered the MC-4R and MC-3R antagonist, agouti-related peptide, resisted uremia-induced loss of lean body mass and maintained normal basal metabolic rates. Thus, melanocortin receptor antagonism may provide a novel therapeutic strategy for inflammation-associated cachexia in CKD. Topics: Animals; Appetite; Cachexia; Humans; Inflammation; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Melanocyte-Stimulating Hormones; Mice; Receptors, Cell Surface; Receptors, Leptin; Receptors, Melanocortin; Signal Transduction | 2006 |
Recent advances in the relationship between obesity, inflammation, and insulin resistance.
It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and secretion of a wide range of inflammatory molecules including TNF-alpha and interleukin-6 (IL-6), which may have local effects on WAT physiology but also systemic effects on other organs. Recent data indicate that obese WAT is infiltrated by macrophages, which may be a major source of locally-produced pro-inflammatory cytokines. Interestingly, weight loss is associated with a reduction in the macrophage infiltration of WAT and an improvement of the inflammatory profile of gene expression. Several factors derived not only from adipocytes but also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. Most of them are overproduced during obesity, including leptin, TNF-alpha, IL-6 and resistin. Conversely, expression and plasma levels of adiponectin, an insulin-sensitising effector, are down-regulated during obesity. Leptin could modulate TNF-alpha production and macrophage activation. TNF-alpha is overproduced in adipose tissue of several rodent models of obesity and has an important role in the pathogenesis of insulin resistance in these species. However, its actual involvement in glucose metabolism disorders in humans remains controversial. IL-6 production by human adipose tissue increases during obesity. It may induce hepatic CRP synthesis and may promote the onset of cardiovascular complications. Both TNF-alpha and IL-6 can alter insulin sensitivity by triggering different key steps in the insulin signalling pathway. In rodents, resistin can induce insulin resistance, while its implication in the control of insulin sensitivity is still a matter of debate in humans. Adiponectin is highly expressed in WAT, and circulating adiponectin levels are decreased in subjects with obesity-related insulin resistance, type 2 diabetes and coronary heart disease. Adiponectin inhibits liver neoglucogenesis and promotes fatty acid oxidation in skeletal muscle. In addition, adiponectin counteracts Topics: Adiponectin; Adipose Tissue; Diabetes Mellitus, Type 2; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Lipid Metabolism; Macrophages; Obesity; Resistin; Signal Transduction; Tumor Necrosis Factor-alpha | 2006 |
Obesity and asthma.
Asthma and obesity are prevalent disorders, each with a significant public health impact, and a large and growing body of literature suggests an association between the two. The systemic inflammatory milieu in obesity leads to metabolic and cardiovascular complications, but whether this environment alters asthma risk or phenotype is not yet known. Animal experiments have evaluated the effects of leptin and obesity on airway inflammation in response to both allergic and nonallergic exposures and suggest that airway inflammatory response is enhanced by both endogenous and exogenous leptin. Cross-sectional and prospective cohort studies of humans have shown a modest overall increase in asthma incidence and prevalence in the obese, although body mass index does not appear be a significant modifier of asthma severity. Studying the obesity-asthma relationship in large cohorts, in which self-reports are frequently used to ascertain the diagnosis of asthma, has been complicated by alterations in pulmonary physiology caused by obesity, which may lead to dyspnea or other respiratory symptoms but do not fulfill accepted physiologic criteria for asthma. Recent investigations toward elucidating a shared genetic basis for these two disorders have identified polymorphisms in specific regions of chromosomes 5q, 6p, 11q13, and 12q, each of which contains one or more genes encoding receptors relevant to asthma, inflammation, and metabolic disorders, including the beta(2)-adrenergic receptor gene ADRB2 and the glucocorticoid receptor gene NR3C1. Further research is warranted to synthesize these disparate observations into a cohesive understanding of the relationship between obesity and asthma. Topics: Adipocytes; Animals; Asthma; Body Mass Index; Comorbidity; Compliance; Cytokines; Gonadal Steroid Hormones; Humans; Inflammation; Leptin; Obesity; Polymorphism, Genetic; Respiratory Hypersensitivity; Sex Factors | 2006 |
Adipokine signaling in the peritoneal dialysis patient.
Patients on peritoneal dialysis suffer from an increased incidence of cardiovascular disease, obesity, insulin resistance, as well as a markedly increased mortality rate. In both the general population and in renal patients current research implicates fat tissue as an important factor in modulating many of these complications through the secretion of various signaling peptides, mainly cytokines and adipokines. Whereas hemodialysis patients tend to lose fat mass after initiation of renal replacement therapy, peritoneal dialysis-patients instead gain fat, probably as a result of continuous glucose absorption. In the present overview we summarize some recent findings indicating that fat mass actively contributes to systemic inflammation and metabolic disturbances in chronic kidney disease. We conclude that adipokines are likely to influence several key survival factors in peritoneal dialysis patients, including systemic inflammation, endothelial health and appetite. Topics: Adiponectin; Adipose Tissue; Body Mass Index; Humans; Inflammation; Leptin; Macrophages; Peritoneal Dialysis; Resistin; Signal Transduction | 2006 |
[Cytokines, endothelial dysfunction, and insulin resistance].
Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity. Topics: Adiponectin; Cardiovascular Diseases; Cytokines; Endothelium, Vascular; Fatty Acids; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin | 2006 |
Adipose tissue and adipokines--energy regulation from the human perspective.
There has been a rapid rise in the incidence of obesity, primarily as a result of changes in lifestyle (diet and activity levels). Obesity has provided considerable impetus for the investigation of the fundamental mechanisms involved in the regulation of energy balance. Important developments include the identification of novel factors involved in the control of appetite, such as ghrelin, orexin A, and the endogenous cannabinoids, and the emergence of the concept of "nonexercise activity thermogenesis" (NEAT) provided new perspectives on energy expenditure. Studies on white adipose tissue have led to the recognition that it is an important endocrine organ, communicating with the brain and peripheral tissues through the secretion of leptin and other adipokines. There is a rapidly expanding list of protein factors released by white adipose tissue, including the key hormone, adiponectin. Of particular note is the range of cytokines, chemokines, and other inflammation-related proteins secreted by white fat as tissue mass rises; indeed, obesity is characterized by chronic mild inflammation. The adipokines provide an extensive network of communication both within adipose tissue and with other organs, and some are implicated directly in the pathologies associated with obesity, particularly the metabolic syndrome. Although the focus remains very much on obesity in humans, the disorder and its sequelae are also a growing concern in companion animals. Topics: Adiponectin; Adipose Tissue; Animals; Cytokines; Energy Metabolism; Humans; Inflammation; Leptin; Obesity | 2006 |
Inflammation and adipose tissue in uremia.
Enhanced chronic systemic inflammation and reduced insulin sensitivity are often associated in patients with chronic renal failure, contributing to cardiovascular morbidity and mortality in these patients. Adipose tissue produces several hormones (adipocytokines including leptin, resistin, tumor necrosis factor-alpha, and adiponectin) that modulate both systemic inflammatory response and insulin action. High leptin, resistin, and tumor necrosis factor-alpha and low adiponectin are associated with proinflammatory conditions, whereas opposite patterns are commonly observed in the presence of increased insulin sensitivity, low inflammation, and reduced cardiovascular risk. Oxidative stress has also been shown recently to modulate adipocytokine production, resulting in a proinflammatory profile. Increments of plasma concentrations of both proinflammatory and anti-inflammatory adipocytokines have been reported in chronic renal failure, possibly caused by both passive accumulation from reduced renal excretion and metabolic abnormalities induced by uremia. The potential role of altered adipose tissue adipocytokine production in the onset of renal failure-associated inflammatory and metabolic derangements remains largely to be elucidated and is discussed in the current report. Topics: Adiponectin; Adipose Tissue; Cytokines; Ghrelin; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Leptin; Nutritional Physiological Phenomena; Oxidative Stress; Peptide Hormones; Uremia | 2006 |
Leptin is a link between adipose tissue and inflammation.
Leptin is a hormone of the pluripotent white adipose tissue and confers a multitude of regulatory functions within the organism. It controls the energy storage, lipoprotein metabolism, acute phase reactants, sex hormones and glucocorticoid metabolism, and immune function. In this review, we describe these multiple functions of leptin, the regulation of leptin expression, and how leptin can modulate the immune system via direct and indirect mechanisms. We show how leptin can be a link between the adipose tissue and inflammation. Topics: Adipose Tissue; Animals; Autoimmunity; Humans; Inflammation; Leptin; Steroids | 2006 |
The role of leptin in innate and adaptive immune responses.
Leptin is produced primarily by adipocytes and functions in a feedback loop regulating body weight. Leptin deficiency results in severe obesity and a variety of endocrine abnormalities in animals and humans. Several studies indicated that leptin plays an important role in immune responses. It exerts protective anti-inflammatory effects in models of acute inflammation and during activation of innate immune responses. In contrast, leptin stimulates T lymphocyte responses, thus having rather a proinflammatory role in experimental models of autoimmune diseases. Clinical studies have so far yielded inconsistent results, suggesting a rather complex role for leptin in immune-mediated inflammatory conditions in humans. Topics: Animals; Humans; Immune System; Inflammation; Leptin; T-Lymphocytes | 2006 |
Leptin as a proinflammatory cytokine.
Leptin is a 16-kDa protein produced mainly by adipocytes. Animal models demonstrate that leptin is required for control of bodyweight and reproduction, since mice defective in leptin or the leptin receptor are obese, hyperphagic insulin resistant and infertile. Our initial series of observations lead us to propose that leptin also had significant effects on human type I proinflammatory immune responses. In support of this hypothesis, leptin deficient mice are resistant to a wide range of autoimmune diseases and display features of immune deficiency. Subsequent work has confirmed that leptin has a pleiotrophic role on the immune response and can rightly be considered, both structurally and functionally, as a proinflammatory cytokine. Topics: Animals; Cytokines; Humans; Inflammation; Leptin; Obesity | 2006 |
Adipocytokines: mediators linking adipose tissue, inflammation and immunity.
There has been much effort recently to define the role of adipocytokines, which are soluble mediators derived mainly from adipocytes (fat cells), in the interaction between adipose tissue, inflammation and immunity. The adipocytokines adiponectin and leptin have emerged as the most abundant adipocyte products, thereby redefining adipose tissue as a key component not only of the endocrine system, but also of the immune system. Indeed, as we discuss here, several adipocytokines have a central role in the regulation of insulin resistance, as well as many aspects of inflammation and immunity. Other adipocytokines, such as visfatin, have only recently been identified. Understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases. Topics: Adiponectin; Adipose Tissue; Animals; Cytokines; Humans; Immunity, Innate; Inflammation; Leptin; Resistin; Signal Transduction | 2006 |
Adipose tissue, inflammation and endothelial dysfunction.
During the last decade, white adipose tissue was recognized to be an active endocrine organ and a source of many proinflammatory cytokines, chemokines, growth factors and complement proteins. Many of these adipokines seem to play an important role in the pathogenesis of obesity-related diseases including accelerated atherosclerosis, arterial hypertension and some glomerulopathies. As endothelial dysfunction is one of the early stages of atherosclerosis, it is reasonable to consider that substances secreted by adipose tissue may influence directly or indirectly (for instance by induction of microinflammation) the function of endothelial cells. The aim of this review is to summarize the evidences and hypotheses concerning the role of adipokines in the pathogenesis of endothelial dysfunction. Topics: Adiponectin; Adipose Tissue; Atherosclerosis; Cardiovascular Diseases; Endothelial Cells; Endothelium, Vascular; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Obesity; Plasminogen Activator Inhibitor 1; Renin-Angiotensin System; Tumor Necrosis Factor-alpha | 2006 |
Leptin, from fat to inflammation: old questions and new insights.
Leptin is 16 kDa adipokine that links nutritional status with neuroendocrine and immune functions. Initially thought to be a satiety factor that regulates body weight by inhibiting food intake and stimulating energy expenditure, leptin is a pleiotropic hormone whose multiple effects include regulation of endocrine function, reproduction, and immunity. Leptin can be considered as a pro-inflammatory cytokine that belongs to the family of long-chain helical cytokines and has structural similarity with interleukin-6, prolactin, growth hormone, IL-12, IL-15, granulocyte colony-stimulating factor and oncostatin M. Because of its dual nature as a hormone and cytokine, leptin links the neuroendocrine and the immune system. The role of leptin in the modulation of immune response and inflammation has recently become increasingly evident. The increase in leptin production that occurs during infection and inflammation strongly suggests that leptin is a part of the cytokine network which governs the inflammatory-immune response and the host defense mechanisms. Leptin plays an important role in inflammatory processes involving T cells and has been reported to modulate T-helper cells activity in the cellular immune response. Several studies have implicated leptin in the pathogenesis of autoimmune inflammatory conditions, such as experimental autoimmune encephalomyelitis, type 1 diabetes, rheumatoid arthritis, and intestinal inflammation. Very recently, a key role for leptin in osteoarthritis has been demonstrated: leptin indeed exhibits, in concert with other pro-inflammatory cytokines, a detrimental effect on articular cartilage by promoting nitric oxide synthesis in chondrocytes. Here, we review the recent advances regarding leptin biology with a special focus on those actions relevant to the role of leptin in the pathophysiology of inflammatory processes and immune responses. Topics: Animals; Fats; Humans; Immunologic Factors; Inflammation; Leptin | 2005 |
Adipose tissue cytokines, insulin sensitivity, inflammation, and cardiovascular outcomes in end-stage renal disease patients.
From an evolutionary perspective, Darwinian selection has favored insulin-resistant individuals, ie, those with a trait ensuring brain functioning in situations of extreme fuel deprivation. The ability to mount a powerful inflammatory response to infection was another survival advantage in our ancestors, and we now have solid evidence showing that these 2 traits, insulin resistance and inflammation (as measured by serum C-reactive protein [CRP]), are associated in modern human beings. In an analysis of 192 nondiabetic hemodialysis patients, leptin and adiponectin were related in an opposite fashion with insulin sensitivity in end-stage renal disease (ESRD) and interacted in determining insulin resistance in these patients. The risk of insulin resistance was about 6 times higher in ESRD patients with an unfavorable combination of the 2 adipokines (high leptin and low adiponectin) than in those with a favorable combination (low leptin and high adiponectin). Low adiponectin but not high leptin predicted incident cardiovascular events in this cohort. Neither leptin nor adiponectin were associated with CRP in a cross-sectional analysis, but they were linked in an opposite fashion to CRP in a longitudinal study in 21 patients with acute inflammation secondary to infection. High sympathetic activity predicts adverse cardiovascular outcomes in ESRD. Of note, we found that the risk for cardiovascular events is more than 3 times higher in patients with high sympathetic activity and low adiponectin than in those with high adiponectin and low sympathetic activity. The adipocyte hormones leptin and adiponectin are associated in an opposite fashion to insulin sensitivity and inflammation in ESRD patients. Relatively lower plasma adiponectin levels are associated with a higher rate of incident cardiovascular events. Finally, low adiponectin and high norepinephrine seem to be interacting factors in the dismal cardiovascular outcomes with ESRD. Topics: Adiponectin; Adipose Tissue; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Cytokines; Energy Metabolism; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Leptin; Renal Dialysis; Risk Factors | 2005 |
Adipose tissue and its relation to inflammation: the role of adipokines.
An activated inflammatory response is a common feature of end-stage renal disease (ESRD) patients and predicts outcome. Although various factors related to the dialysis procedure may contribute to inflammation in ESRD, a number of nondialysis-related factors also are of importance. Adipose tissue is a complex organ with functions far beyond the mere storage of energy and secretes a number of proinflammatory adipokines, such as leptin, resistin, tumor necrosis factor-alpha and interleukin-6, as well as one anti-inflammatory adipokine, adiponectin. It has been proposed that adipose tissue may be a significant contributor to increased systemic inflammation in nonrenal patients. In this review, we put forward the hypothesis that a reduction of renal mass will contribute to retention of proinflammatory adipokines, thus generating adipokine imbalance. Such an imbalance may, via effects on the central nervous system and the vasculature, contribute to wasting, atherosclerosis, and insulin resistance--all common features of ESRD. Topics: Adiponectin; Adipose Tissue; Body Composition; Body Mass Index; Cardiovascular Diseases; Cytokines; Humans; Infections; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Obesity; Renal Dialysis; Resistin; Risk Factors; Tumor Necrosis Factor-alpha; Wasting Syndrome | 2005 |
Leptin in immunology.
Leptin is an adipokine which conveys information on energy availability. In humans, leptin influences energy homeostasis and regulates neuroendocrine function primarily in states of energy deficiency. As a cytokine, leptin also affects thymic homeostasis and, similar to other proinflammatory cytokines, leptin promotes Th1 cell differentiation and cytokine production. We review herein recent advances on the role of leptin in the pathophysiology of immune responses. Topics: Adipose Tissue; Animals; Autoimmunity; Energy Metabolism; Humans; Immunity, Innate; Infections; Inflammation; Leptin; Models, Immunological; Signal Transduction | 2005 |
Adipose tissue, adipokines, and inflammation.
White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-alpha, IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified. Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Autoimmune Diseases; Complement Factor D; Cytokines; Hormones, Ectopic; Humans; Inflammation; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Macrophages; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin; Serine Endopeptidases | 2005 |
Obesity, smooth muscle, and airway hyperresponsiveness.
Both asthma and obesity are large and growing public health issues. Mounting evidence now implicates obesity as a major risk factor for asthma, thus linking these 2 major epidemics. Moreover, both in human subjects and in mice, obesity appears to predispose toward airway hyperresponsiveness. This review describes potential mechanisms whereby obesity might modify airway smooth muscle function to explain these observations. These mechanisms include both static and dynamic mechanical factors attributable to decreases in functional residual capacity and decreases in tidal volume that are observed in the obese. They include also obesity-related changes in lung development, chronic systemic inflammation (including increased serum levels of inflammatory cytokines and chemokines), and adipocyte-derived factors, including leptin, adiponectin, and plasminogen activator inhibitor. Topics: Adiponectin; Animals; Asthma; Cytokines; Functional Residual Capacity; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Muscle, Smooth; Obesity; Plasminogen Activators; Respiratory System | 2005 |
Feeding-unrelated factors influencing the plasma leptin level in ruminants.
The triglyceride content of lipid depots associated with the current feeding level is the primary determinant of leptin gene expression and the circulating leptin level. In laboratory rodents and primates the plasma leptin is influenced also by the age, gender and physiological status (puberty, pregnancy, lactation, postpartum period), and by the health condition such as sepsis due to Gram-negative (GN) bacteria. Some pathologic conditions with intensive cytokine release evoke an increase in plasma leptin, which is thought to depress the subsequent feed intake. However, the effect of these secondary factors may be species-dependent, with still unknown clinical relevance in ruminants. In our ovine and bovine models plasma leptin increased after castration and dexamethasone treatment, decreased after experimental administration of synthetic androgens in castrated rams, but remained unchanged throughout the ovarian cycle and after ovariectomy. The circulating leptin level increased temporarily during synthetic progestin (fluorogestone) treatment in ewes, but similar changes were not seen in progesterone-supplemented ewes and norgestomet-treated cows. In a second trial on dairy cows we wanted to study whether elevated plasma leptin levels are induced by experimental endotoxin mastitis, or by natural outbreak of GN mastitis and puerperal metritis. Experimental endotoxin mastitis resulted in some-hour elevation in cortisol and insulin, with a simultaneous decrease in IGF-I and thyroid hormones. In the first 14 days of lactation GN mastitis induced the same endocrine alterations as the experimental endotoxin challenge, but in natural cases these changes varied within a wider range, and were more protracted and robust. Cows with puerperal metritis had more obvious catabolic changes in the early weeks of lactation, than their healthy counterparts. However, both mastitis and puerperal metritis failed to increase the circulating leptin level, showing that in cows the plasma leptin is not responsible for the anorexia associated with these inflammatory diseases. Topics: Animals; Bacterial Infections; Cattle; Cattle Diseases; Eating; Endometritis; Female; Glucocorticoids; Gonadal Steroid Hormones; Humans; Inflammation; Leptin; Male; Mastitis, Bovine; Ruminants | 2005 |
Insulin resistance in type 2 diabetes -- role of the adipokines.
The role of adipocytes as protein secreting cells has been known for almost 15 years. Most of these proteins have known biological activity and are called adipokines. However, only a few of the adipokines have been shown to regulate insulin sensitivity. The latter effects are direct or indirect. The adipokines regulating insulin sensitivity are tumor necrosis factor alpha, adiponectin, interleukin-6, resistin and leptin. This review examines the mechanism how these adipokines influence insulin sensitivity, how the adipocyte production of the adipokines is regulated and if genetic variance in the genes encoding for adipokines is important for the development of type 2 diabetes mellitus. Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Cytokines; Diabetes Mellitus, Type 2; Genetic Variation; Hormones, Ectopic; Humans; Inflammation; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Models, Biological; Nicotinamide Phosphoribosyltransferase; Resistin; Tumor Necrosis Factor-alpha | 2005 |
Endocrine and signalling role of adipose tissue: new perspectives on fat.
White adipose tissue (WAT) is now recognized as a major endocrine and secretory organ, releasing a wide range of protein factors and signals termed adipokines - in addition to fatty acids and other lipid moieties. A paradigm shift came with the discovery of leptin, a pleiotropic hormone which is a critical signal to the hypothalamus in the control of appetite and energy balance. A number of adipokines, including adiponectin, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1, macrophage migration inhibitory factor, nerve growth factor, vascular endothelial growth factor, plasminogen activator inhibitor-1 and haptoglobin, are linked to inflammation and the inflammatory response. Obesity is characterized by a state of mild inflammation, and the expression and release of inflammation-related adipokines generally rises as adipose tissue expands; a notable exception is adiponectin, with its anti-inflammatory action, the levels of which fall. WAT may be the main site of inflammation in obesity, increased circulating levels of inflammatory markers reflecting spillover from an 'inflamed' tissue, leading to the obesity-associated pathologies of type 2 diabetes and the metabolic syndrome. From the wide range of adipokines now identified, it is evident that WAT is highly integrated into overall physiological regulation, involving extensive crosstalk with other organs and multiple metabolic systems. Whether major changes in adipokine production in obesity, particularly of those factors linked to inflammation, are unique to this condition, or are a feature of all situations in which there are substantial increases in adipose mass (such as pregnancy, and pre-hibernatory and pre-migratory fattening) requires consideration. Topics: Adipocytes; Adiponectin; Adipose Tissue; Cold Temperature; Energy Metabolism; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Models, Biological; Obesity; Signal Transduction | 2005 |
[Infective factors in the pathogenesis of obesity].
Topics: Biomarkers; Chlamydia Infections; Fatty Acids, Unsaturated; Humans; Infections; Inflammation; Inflammation Mediators; Leptin; Obesity; Stress, Physiological | 2005 |
Keynote review: the adipocyte as a drug discovery target.
The adipocyte has pleiotropic functions beyond the storage of energy in times of nutrient abundance. Considerable efforts in adipocyte biology within the past ten years have emphasized the important role of adipose tissue in processes as diverse as energy metabolism, inflammation and cancer. Adipocytes are able to communicate with the brain and peripheral tissues implementing metabolic signals such as satiety, food intake and energy expenditure. Despite its huge pharmacological potential, only a small number of clinical applications interfere directly with adipocyte physiology. Here, we want to highlight various areas of adipocyte physiology that have not yet been explored pharmacologically and emphasize some of the limitations associated with these pharmacotherapies. Topics: Adipocytes; Adiponectin; Animals; Apoptosis; Cell Differentiation; Drug Design; Hormones, Ectopic; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Lipid Metabolism; Reactive Oxygen Species; Resistin | 2005 |
Mechanisms of beta-cell death in type 2 diabetes.
A decrease in the number of functional insulin-producing beta-cells contributes to the pathophysiology of type 2 diabetes. Opinions diverge regarding the relative contribution of a decrease in beta-cell mass versus an intrinsic defect in the secretory machinery. Here we review the evidence that glucose, dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may contribute to the maladaptation of beta-cells. With respect to these causal factors, we focus on Fas, the ATP-sensitive K+ channel, insulin receptor substrate 2, oxidative stress, nuclear factor-kappaB, endoplasmic reticulum stress, and mitochondrial dysfunction as their respective mechanisms of action. Interestingly, most of these factors are involved in inflammatory processes in addition to playing a role in both the regulation of beta-cell secretory function and cell turnover. Thus, the mechanisms regulating beta-cell proliferation, apoptosis, and function are inseparable processes. Topics: Animals; Cell Death; Diabetes Mellitus, Type 2; Disease Models, Animal; Dyslipidemias; Humans; Immunity, Innate; Inflammation; Insulin-Secreting Cells; Leptin; Risk Factors | 2005 |
Adipose tissue: a regulator of inflammation.
Adipose tissue is a highly active organ. In addition to storing calories as triglycerides, it also secretes a large variety of proteins, including cytokines, chemokines and hormone-like factors, such as leptin, adiponectin and resistin. Intriguingly, many, if not most, of these adipose-derived proteins have dual actions; cytokines have both immunomodulatory functions and act as systemic or auto-/paracrine regulators of metabolism, while proteins such as leptin and adiponectin are regulators of both metabolism and inflammation. The production of pro-atherogenic chemokines by adipose tissue is of particular interest since their local secretion, e.g. by perivascular adipose depots, may provide a novel mechanistic link between obesity and the associated vascular complications. Topics: Adiponectin; Adipose Tissue; Animals; Chemokines; Cytokines; Glucose; Humans; Inflammation; Leptin; Lipid Metabolism; Mice; Resistin | 2005 |
Unraveling the multiple roles of leptin in inflammation and autoimmunity.
Initially described as an antiobesity hormone, leptin has subsequently been shown also to influence hematopoiesis, thermogenesis, reproduction, angiogenesis, and immune homeostasis. Leptin links nutritional status and proinflammatory T helper 1 immune responses, and the decrease in leptin plasma concentration during food deprivation leads to impaired immune function. This review focuses on the multiple roles of leptin in chronic inflammation and autoimmunity and suggests new possible therapeutic implications for leptin modulators. Topics: Animals; Autoimmunity; CD4-Positive T-Lymphocytes; Endometriosis; Female; Humans; Immune System; Immunotherapy; Inflammation; Leptin; Neurosecretory Systems | 2004 |
Hypertension and obesity.
Obesity is a common problem in much of the western world today in that is linked directly with several disease processes, notably, hypertension. It is becoming clear that the adipocyte is not merely an inert organ for storage of energy but that it also secretes a host of factors that interact with each other and may result in elevated blood pressure. Of particular importance is the putative role of leptin in the causation of hypertension via an activation of the sympathetic nervous system and a direct effect on the kidneys, resulting in increased sodium reabsorption leading to hypertension. Obesity per se may have structural effects on the kidneys that may perpetuate hypertension, leading to an increased incidence of end-stage renal disease that results in further hypertension. Adipose tissue may elaborate angiotensin from its own local renin-angiotensin system. The distribution of body fat is considered important in the genesis of the obesity-hypertension syndrome, with a predominantly central distribution being particularly ominous. Weight loss is the cornerstone in the management of the obesity-hypertension syndrome. It may be achieved with diet, exercise, medications, and a combination of these measures. Anti-obesity medications that are currently undergoing clinical trials may play a promising role in the management of obesity and may also result in lowering of blood pressure. Antihypertensives are considered important components in the holistic approach to the management of this complex problem. Topics: Adipose Tissue; Aldosterone; Animals; Body Mass Index; Humans; Hypertension; Inflammation; Insulin Resistance; Kidney; Leptin; Metabolic Syndrome; Neuropeptides; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Thrombosis | 2004 |
Helicobacter pylori persistence: biology and disease.
Helicobacter pylori are bacteria that have coevolved with humans to be transmitted from person to person and to persistently colonize the stomach. Their population structure is a model for the ecology of the indigenous microbiota. A well-choreographed equilibrium between bacterial effectors and host responses permits microbial persistence and health of the host but confers risk of serious diseases, including peptic ulceration and gastric neoplasia. Topics: Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Leptin; Peptide Hormones; Stomach; Stomach Diseases; Virulence | 2004 |
The delicate balance between fat and muscle: adipokines in metabolic disease and musculoskeletal inflammation.
Adipose tissue has evolved as a complex organ with functions far beyond the mere storage of energy. Chronic oversupply of calories, common to Western-style diets, frequently goes hand-in-hand with an altered secretion pattern of adipokines and elevated plasma free fatty acid levels, known to modulate insulin sensitivity in skeletal muscle. Intramyocellular accumulation of lipids directly attenuates insulin signaling within myocytes via distinct kinases. Obesity is also accompanied by an enhanced basal inflammatory tone, originating from adipocytes and adipose tissue-associated macrophages. In addition, adipocytes accumulate within the skeletal muscle and exert direct paracrine effects on muscle insulin sensitivity. Topics: Adiponectin; Adipose Tissue; Animals; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Humans; Inflammation; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Proteins | 2004 |
Adiposity signals, genetic and body weight regulation in humans.
Numerous signals convey information about body fat status from the periphery to the brain areas that control energy homeostasis so that, throughout life, body weight remains nearly stable. These signals mainly originate, either from the adipose tissue, like leptin and to a lesser extent interleukin 6, or from the pancreas, like insulin and amylin. These factors circulate in proportion to body fat mass and they are referred to as "adiposity signals". It is well established, at least for leptin and insulin, that they enter the brain from the plasma where they induce/repress a network of important neuropeptide regulators of energy intake and expenditure. Beside these endocrine signals, a growing amount of literature show data relative to adipocyte-derived molecules, most of them belonging to the cytokine family, like IL6, TNFalpha, IL8, IL10 whose secretion also correlates with body fat mass and that may locally regulate fat mass expansion. Others, like adiponectin, are negatively correlated with body fat mass. These "adiposity molecules" have already been involved in insulin resistance associated with obesity and inflammatory process. They may participate to a complex inter organ dialogue. In this review, we will synthesize data relative to the role played by insulin, leptin and amylin, either alone or through a cross talk, in "energy level sensing" at the brain level. Furthermore, we will develop how "adiposity molecules" through their paracrin and/or autocrin action may contribute to maintain fat mass expansion, therefore representing new adiposity molecules per se. Lastly, since any distortion in the metabolic circuitry of energy homeostasis is susceptible to lead to a pathological status like obesity, the impact of known genetic polymorphisms in genes encoding the adiposity signals will be discussed. Topics: Adipose Tissue; Animals; Body Weight; Cytokines; Homeostasis; Humans; Inflammation; Insulin; Leptin; Obesity; Signal Transduction | 2004 |
Orexigenic vs. anorexigenic peptides and feeding status in the modulation of fever and hypothermia.
Prevailing changes in the feeding status or the nutritional status, in general, can modify the expression of many orexigenic and anorexigenic peptides, which influence hypothalamic functions. These peptides usually adjust body temperature according to anabolic (increased appetite with suppressed metabolic rate and body temperature) or catabolic (anorexia with enhanced metabolism and temperature) patterns. It was plausible to presume that such peptides contribute to regulated changes of body temperature (either fever or hypothermia) in systemic inflammation, particularly since anorexia is a common feature in inflammatory processes. No consistent, common, or uniform way of action was, however, demonstrated, which could have described the effects of various peptides. With the exception of cholecystokinin (CCK), all investigated peptides were devoid of real thermoregulatory actions: they influenced the metabolic rate (and consequently body temperature), but not the mechanisms of heat loss. Central CCK is indeed catabolic and may participate in febrigenesis. Leptin may activate various cytokines, catabolic peptides and may inhibit anabolic peptides, but it probably has no direct febrigenic effect and it is not indispensable in fever. Melanocortins and corticotropin-releasing factor provide catabolic adaptive mechanisms to food intake (diet induced thermogenesis) and environmental stress, respectively, but they act rather as endogenous antipyretic substances during systemic inflammation, possibly contributing to the mechanisms of limitation of fever. Bacterial lipopolysaccharides enhance the expression of most of these catabolic peptides. In contrast, neuropeptide Y (NPY) expression may not be changed, only its release is decreased at specific nuclei, a defective NPY effect may also contribute to the febrile rise in body temperature. The data provide no clear-cut explanation for the mechanism of hypothermia seen in systemic inflammation. According to speculations, a presumed, overflow,-type release of NPY from the hypothalamic nuclei, as well as a suppression of the activity of catabolic peptides, could possibly cause hypothermia. There are no cues, however, referring to the identity of factors that could trigger such changes during systemic inflammation in order to induce hypothermia. Topics: alpha-MSH; Animals; Body Temperature; Cholecystokinin; Corticotropin-Releasing Hormone; Eating; Endotoxins; Fever; Humans; Hypothermia; Inflammation; Leptin; Mice; Neuropeptide Y; Peptides; Rats | 2004 |
Role of leptin and leptin receptor in inflammation.
Topics: Animals; Humans; Inflammation; Leptin; Receptors, Cell Surface; Receptors, Leptin | 2003 |
Macrophage inflammatory protein-2 levels are associated with changes in serum leptin concentrations following ozone-induced airway inflammation.
Topics: Animals; Chemokine CXCL2; Chemotactic Factors; Disease Models, Animal; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Monokines; Oxidants, Photochemical; Ozone; Respiratory Tract Diseases | 2003 |
Metabolic alterations during inflammation and its modulation by central actions of omega-3 fatty acids.
To discuss the possible relationship between long-chain polyunsaturated fatty acids, cytokines, anandamides, nitric oxide, leptin, various neurotransmitters in the brain, and their role in anorexia of acute and chronic inflammatory conditions and cancer.. Recent studies have shown that long-chain polyunsaturated fatty acids, especially the omega-3 series, have antiinflammatory actions, increase the concentrations of anandamides, enhance the levels of acetylcholine and nitric oxide and modulate the concentrations and actions of various neurotransmitters, including leptin, in the brain. Patients suffering from acute and chronic inflammatory conditions have low tissue concentrations of various long-chain polyunsaturated fatty acids, and high levels of proinflammatory cytokines that can cause anorexia and decrease food intake.. It is suggested that supplementation of long-chain polyunsaturated fatty acids may have a role in the prevention and treatment of acute and chronic inflammatory conditions, improving anorexia associated with these conditions. Topics: Animals; Anorexia; Anti-Inflammatory Agents; Cytokines; Energy Metabolism; Fatty Acids, Omega-3; Humans; Inflammation; Inflammation Mediators; Leptin; Neurotransmitter Agents; Nitric Oxide | 2003 |
[Obesity and inflammation: the adipocytokines].
It is now well documented that obesity is associated with a chronic, low grade, inflammatory state. The serum concentrations of a number of inflammatory markers, such as CRP, fibrinogene or serum amyloids are increased in obese subjects. More importantly, the levels of several pro-inflammatory cytokines, including TNFalpha, IL-6 and leptin are significantly higher in the plasma of obese patients. We will review here the possible role of adipose tissue and the production of adipocyte-derived cytokines in this inflammatory state. The observed increase in the concentrations of these adipocytokines is now suspected to play a determinant role in the development of most of the complications of obesity. Topics: Adipose Tissue; Cytokines; Humans; Inflammation; Interleukin-6; Leptin; Obesity; Tumor Necrosis Factor-alpha | 2003 |
Obesity and hypertension.
This article has discussed some of the mechanisms involved in the causal relation between obesity and hypertension. Obesity causes a constellation of maladaptive disorders that individually and synergistically contribute to hypertension, among other cardiovascular morbidities. Well-designed population-based studies are needed to assess the individual contribution of each of these disorders to the development of hypertension. In addition, because the control of obesity may eliminate 48% of the hypertension in whites and 28% in blacks, this article has offered an up-to-date on the management of this problem. It is hoped that this article will help scientists formulate a thorough understanding of obesity hypertension and form the basis for more research in this field, which has a huge impact on human life. Topics: Adipose Tissue; Aldosterone; Body Mass Index; Cardiovascular System; Genetic Predisposition to Disease; Hormones; Humans; Hypertension; Inflammation; Kidney; Leptin; Neuropeptides; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Thrombosis | 2003 |
Obesity and obstructive sleep apnea.
There is a very high prevalence of OSA in obese individuals and a high prevalence of obesity in patients with OSA. The pathophysiology of OSA is intimately linked to obesity. Anatomic and functional considerations of the pharyngeal airway, the CNS, central obesity, and leptin likely interact in the development of OSA in obese individuals. OSA may itself predispose individuals to worsening obesity because of sleep deprivation, daytime somnolence, and disrupted metabolism. The diagnosis of OSA requires the clinician's awareness of its potential to cause a spectrum of acute and chronic neurocognitive, psychiatric, and nonspecific symptoms in patients who may be unaware that their sleep is disturbed. Symptoms and examination findings help predict which obese individuals have OSA, and polysomnography is the gold standard by which to make the diagnosis and assess the effects of treatment. Numerous disease states are associated with both OSA and obesity, and it is becoming clear that the relationships are mediated by complex interrelated mechanisms. Common diseases and disease mechanisms in OSA and obesity suggest that conditions related to obesity may be better managed if patients, particularly those who are morbidly obese, are evaluated and treated for previously undiagnosed OSA. OSA is cured in only specific cases with craniofacial or upper airway surgery, and the general application of UVP is not efficacious. OSA also can be cured with sufficient lifestyle-mediated or surgical weight loss; however, in the absence of long-term weight maintenance, OSA returns with weight gain. Although not curative, nasal CPAP is the initial treatment of choice for most patients because of its noninvasive approach and technical efficacy. It is limited, however, by patient acceptance and long-term compliance. Advances in mask comfort and use of humidified air should increase its acceptance. Future management strategies include newer generations of positive airway devices that automatically titrate pressures (which are not yet recommended by expert organizations) and multidisciplinary approaches to managing the care of patients with OSA. Topics: Blood Coagulation Disorders; Cardiovascular Diseases; Drug Therapy; Genetic Predisposition to Disease; Humans; Inflammation; Leptin; Life Style; Obesity; Sleep Apnea, Obstructive; Surgical Procedures, Operative | 2003 |
Leptin-based immune intervention: current status and future directions.
Current understanding of the role of leptin has expanded from its narrow association with obesity to a variety of effects on different biological processes including immune function. More specifically, leptin links nutritional status and energy balance to regulation of pro-inflammatory T-helper 1 immune responses. This has prompted several studies of targeted intervention with leptin antagonists in rodents to suppress onset and/or progression of chronic inflammation and autoimmunity. This review presents current preclinical evidence and potential applications for leptin-based immune approaches aimed at improving therapy for chronic and autoimmune conditions. Topics: Animals; Autoimmune Diseases; Humans; Inflammation; Leptin; Nutritional Status; Receptors, Cell Surface; Receptors, Leptin; Signal Transduction; T-Lymphocytes | 2003 |
Inflammatory status and insulin resistance.
The inflammatory response is essential in the response to pathogens. TNF-alpha, IL-1 and IL-6 are key mediators of the response. They initiate metabolic changes to provide nutrients for the immune system, from host tissues. These changes include hyperlipidemia and increased gluconeogenesis. Insulin resistance and disordering of lipid metabolism occur in obesity, diabetes mellitus, atherosclerosis. This review examines recent research that links inflammation to insulin insensitivity.. Population studies show a strong association between indices of inflammation, and abnormal lipid and carbohydrate metabolism, obesity and atherosclerosis. TNF-alpha is produced, by cells of the immune system and by adipocytes. It may provide the link between inflammation and insulin sensitivity. TNF-alpha results in insulin insensitivity, indirectly by stimulating stress hormone production and directly by sustained induction of SOCS-3 which decreases insulin-induced insulin receptor substrate 1 (IRS1) tyrosine phosphorylation and its association with the p85, regulatory subunit of phosphatidylinositol-3 kinase; and by negative regulation of PPAR gamma. Adipose tissue produces both TNF-alpha and leptin. Production of the latter relates positively to adipose tissue mass and through its actions on immune function exerts a pro-inflammatory influence.. Recent studies on diseases which involve insulin insensitivity (e.g. obesity, type 2 diabetes and atherosclerosis) also show increased cytokine production and markers of inflammation. Evidence at present favours chronic inflammation as a trigger for chronic insulin insensitivity, rather than the reverse situation. Topics: Animals; Cytokines; Disease Models, Animal; Glucose; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Tumor Necrosis Factor-alpha | 2002 |
Adiposity and diabetes.
Topics: Adipose Tissue; Diabetes Mellitus; Humans; Inflammation; Leptin; Life Style; Obesity | 2002 |
A role for leptin in the systemic inflammatory response syndrome (SIRS) and in immune response.
Leptin was originally identified as an adipocyte-derived cytokine with a key role in the regulation of the energy balance. Subsequent research has, however, revealed that leptin's biological action is not restricted to its effects on appetite and food intake, but rather has a much more pleiotropic character. Evidence is now accumulating that it has important functions in reproduction, hematopoiesis, HPA-axis endocrinology and angiogenesis. In this review, we have focused on the effects of leptin in the immune system, which can be found in both the antigen-specific immunity and in the inflammatory effector system. Topics: Adaptation, Physiological; Animals; Humans; Immunity; Immunity, Cellular; Inflammation; Leptin; Metallothionein; Neuropeptide Y; Starvation; Systemic Inflammatory Response Syndrome; T-Lymphocytes | 2002 |
Leptin as a novel therapeutic target for immune intervention.
The recent cloning of the leptin (obese, ob) gene has determined fundamental insight into the understanding of the regulation of food intake, basal metabolism and reproductive function. Leptin, mainly secreted by adipocytes, belongs to the helical cytokine family and its plasma concentrations correlate with fat mass and respond to changes in energy balance. Initially, leptin was considered as an anti-obesity hormone, but experimental evidence has also shown pleiotropic effects of this molecule on hematopoiesis, angiogenesis, lymphoid organ homeostasis and T lymphocyte functions. More specifically, leptin links the pro-inflammatory T helper (Th)-1 immune response to the nutritional status and the energy balance. Indeed, decreased leptin concentrations during conditions of food deprivation lead to impaired immune capabilities. This review focuses on the potential therapeutic utilities for agents that manipulate the leptin-adipocyte axis and discusses novel strategies for an immune intervention in pathologic conditions. Topics: Animals; Autoimmunity; Brain; CD4-Positive T-Lymphocytes; Humans; Immune System; Infections; Inflammation; Leptin; Receptors, Cell Surface; Receptors, Leptin | 2002 |
IL-6-like cytokines and cancer cachexia: consequences of chronic inflammation.
An estimated 30% of cancer deaths are attributed to cachexia and its consequences. Cachexia (wasting syndrome) is the hypercatabolism of the body's carbon sources, proteins and lipids, for conversion into energy. It is induced by a variety of pathological conditions, including cancer. Among the inflammatory responses to cancer is the synthesis of cytokines, including IL-6 and related cytokines. These cytokines have been found to induce cachexia by altering metabolism of lipids and proteins. IL-6-like cytokines have been found to inhibit lipid biosynthesis by adipocytes, which increased the rate of lipid catabolism. Others have described the atrophy and increased catabolism of muscle protein due to IL-6. A cytokine closely-related to IL-6 is leptin, which plays a major role in lipid metabolism under normal conditions. The role of leptin in pathological conditions such as cancer cachexia has not yet been fully elucidated. Detailed mechanistic information about the induction of cancer cachexia by IL-6-like cytokines requires more research. Topics: Animals; Cachexia; Humans; Inflammation; Interleukin-6; Leptin; Lipid Metabolism; Lipids; Mice; Muscle Proteins; Neoplasms | 2001 |
[Leptin: physiological aspects and implications in hepato-gastroenterology].
Topics: Animals; Carrier Proteins; Digestive System Physiological Phenomena; Homeostasis; Humans; Inflammation; Leptin; Liver; Liver Diseases; Obesity; Receptors, Cell Surface; Receptors, Leptin; Signal Transduction | 2000 |
Tumor necrosis factor-alpha regulates secretion of the adipocyte-derived cytokine, leptin.
The seminal observation that secretion of the adipocyte-derived hormone leptin was induced by inflammatory challenge has been expanded upon to demonstrate the importance of the pro-inflammatory cytokines, especially tumor necrosis factor (TNF)-alpha, in inflammatory hyperleptinemia. Initially, it was thought that cytokine-induced hyperleptinemia might somehow be involved in the anorexia and cachexia that often accompany chronic infectious, neoplastic, and autoimmune disease. While the role of leptin in disease-associated anorexia and cachexia appears tenuous in light of recent findings, there is evidence that the hyperleptinemia induced by cytokines is an integral part of the acute phase response and necessary for comprehensive immunocompetence. This hints at the existence of an integrated communication network, wherein the energy status of the animal impacts its ability to fight pathogens. Topics: Animals; Cachexia; Humans; Immune System; Inflammation; Leptin; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha | 2000 |
Leptin in the regulation of immunity, inflammation, and hematopoiesis.
Leptin, the product of the ob gene, is a pleiotropic molecule that regulates food intake as well as metabolic and endocrine functions. Leptin also plays a regulatory role in immunity, inflammation, and hematopoiesis. Alterations in immune and inflammatory responses are present in leptin- or leptin-receptor-deficient animals, as well as during starvation and malnutrition, two conditions characterized by low levels of circulating leptin. Both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines. Leptin exerts proliferative and antiapoptotic activities in a variety of cell types, including T lymphocytes, leukemia cells, and hematopoietic progenitors. Leptin also affects cytokine production, the activation of monocytes/macrophages, wound healing, angiogenesis, and hematopoiesis. Moreover, leptin production is acutely increased during infection and inflammation. This review focuses on the role of leptin in the modulation of the innate immune response, inflammation, and hematopoiesis. Topics: Adaptation, Physiological; Adipose Tissue; Animals; Anorexia; Apoptosis; Cachexia; Carrier Proteins; Cell Division; Cytokines; Eating; Endocrine System; Hematopoiesis; Humans; Immune System; Infections; Inflammation; Interleukin-6; Leptin; Lymphopenia; Mice; Mice, Mutant Strains; Multigene Family; Neovascularization, Physiologic; Obesity; Organ Specificity; Phagocytes; Rats; Receptors, Cell Surface; Receptors, Cytokine; Receptors, Leptin; Signal Transduction; Starvation; T-Lymphocyte Subsets | 2000 |
Immune and endocrine regulation of food intake in sick animals.
To understand why sick animals do not eat, investigators have studied how the immune system interacts with the central nervous system (CNS), where motivation to eat is ultimately controlled. The focus has been on the cytokines secreted by activated mononuclear myeloid cells, which include interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Either central or peripheral injection of recombinant IL-1 beta, IL-6, and TNF-alpha reduce food-motivated behavior and food intake in rodents. Moreover, these cytokines and their receptors are present in the endocrine system and brain, and antagonism of this system (i.e., the cytokine network) has been shown to block or abrogate anorexia induced by inflammatory stimuli. Recent studies indicate that the same cytokines act on adipocytes and induce secretion of leptin, a protein whose activity has been neuroanatomically mapped to brain areas involved in regulating food intake and energy expenditure. Therefore, many findings converge to suggest that the reduction of food intake in sick animals is mediated by inflammatory cytokines, which convey a message from the immune system to the endocrine system and CNS. The nature of this interaction is the focus of this short review. Topics: Adaptation, Physiological; Adipose Tissue; Animals; Anorexia; Central Nervous System; Chickens; Cytokines; Eating; Immune System; Inflammation; Leptin; Mice; Neuroimmunomodulation; Poultry Diseases; Proteins; Rats; Swine; Swine Diseases | 1998 |
75 trial(s) available for leptin and Inflammation
Article | Year |
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Metformin versus insulin for gestational diabetes: Adiposity variables and adipocytokines in offspring at age of 9 years.
To compare body composition, visceral adiposity, adipocytokines, and low-grade inflammation markers in prepubertal offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM).. 172 offspring of 311 mothers randomized to receive metformin (n = 82) or insulin (n = 90) for GDMwere studied at 9 years of age (follow-up rate 55%). Measurements included anthropometrics, adipocytokines, markers of the low-grade inflammation, abdominal magnetic resonance imaging (MRI), magnetic liver spectrometry (MRS), and whole body dual-energy X-ray absorptiometry (DXA).. Serum markers of low-grade inflammation, visceral adipose tissue volume, total fat percentage, and liver fat percentage were similar between the study groups. Serum adiponectin concentration was higher in children in the metformin group compared to insulin group (median 10.37 vs 9.50 µg/ml, p = 0.016). This difference between groups was observed in boys only (median 12.13 vs 7.50 µg/ml, p < 0.001). Leptin/adiponectin-ratio was lower in boys in the metformin group than in the insulin group (median 0.30 vs 0.75; p = 0.016).. Maternal metformin treatment for GDM had no effects on adiposity, body composition, liver fat, or inflammation markers in prepubertal offspring compared to maternal insulin treatment but was associated with higher adiponectin concentration and lower leptin/adiponectin-ratio in boys. Topics: Adipokines; Adiponectin; Adiposity; Child; Diabetes, Gestational; Female; Humans; Inflammation; Insulin; Insulin, Regular, Human; Leptin; Male; Metformin; Obesity; Pregnancy | 2023 |
Adherence to a Mediterranean diet may improve serum adiponectin in adults with nonalcoholic fatty liver disease: The MEDINA randomized controlled trial.
Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of adults worldwide, with chronic low-grade inflammation being a key pathophysiological feature of progression. The Mediterranean diet (MedDiet) is recognized for improving metabolic and hepatic outcomes in people with diabetes and NAFLD, in part, via anti-inflammatory properties. The aim of this study was to determine the effect of an ad libitum MedDiet versus low-fat diet (LFD) on inflammatory markers in adults with NAFLD. It was hypothesized that the MedDiet, and its individual components, would improve inflammation. This multicenter, randomized controlled trial, randomized participants to a MedDiet or LFD intervention for 12 weeks. Primary outcomes included change from baseline to 12 weeks for serum high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, adiponectin, leptin, and resistin. Forty-two participants (60% female; age 52.3 ± 12.6 years; body mass index, 32.2 ± 6.2 kg/m²) were randomized to the MedDiet (n = 19) or low-fat diet (n = 23). At 12 weeks, the LFD showed a greater decrease in leptin compared with the MedDiet (-1.20 ± 3.9 ng/mL vs 0.64 ± 3.5 ng/mL, P = .010). Adiponectin significantly improved within the MedDiet (13.7 ± 9.2 µg/mL to 17.0 ± 12.5 µg/mL, P = .016), but not within the LFD group. No statistically significant changes were observed for other inflammatory markers following the MedDiet or LFD. Adherence to the MedDiet significantly improved in both study arms, although greater improvements were seen in the MedDiet group. Adiponectin significantly improved following a Mediterranean diet intervention, in the absence of weight loss. The low-fat diet did not elicit improvements in inflammatory markers. High-quality clinical trials appropriately powered to inflammatory markers are required in this population. Topics: Adiponectin; Adult; Diet, Mediterranean; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Non-alcoholic Fatty Liver Disease | 2023 |
The Impact of Long-term Physical Inactivity on Adipose Tissue Immunometabolism.
Adipose tissue and physical inactivity both influence metabolic health and systemic inflammation, but how adipose tissue responds to chronic physical inactivity is unknown.. This work aimed to characterize the impact of chronic physical inactivity on adipose tissue in healthy, young males.. We collected subcutaneous adipose tissue from 20 healthy, young men before and after 60 days of complete bed rest with energy intake reduced to maintain energy balance and fat mass. We used RNA sequencing, flow cytometry, ex vivo tissue culture, and targeted protein analyses to examine adipose tissue phenotype.. Our results indicate that the adipose tissue transcriptome, stromal cellular compartment, and insulin signaling protein abundance are largely unaffected by bed rest when fat mass is kept stable. However, there was an increase in the circulating concentration of several adipokines, including plasma leptin, which was associated with inactivity-induced increases in plasma insulin and absent from adipose tissue cultured ex vivo under standardized culture conditions.. Physical inactivity-induced disturbances to adipokine concentrations such as leptin, without changes to fat mass, could have profound metabolic implications outside a clinical facility when energy intake is not tightly controlled. Topics: Adult; Basal Metabolism; Bed Rest; Healthy Volunteers; Humans; Inflammation; Leptin; Male; Middle Aged; Sedentary Behavior; Subcutaneous Fat; Young Adult | 2022 |
Psychological distress among health care professionals of the three COVID-19 most affected Regions in Cameroon: Prevalence and associated factors.
The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted. Topics: 3' Untranslated Regions; 5'-Nucleotidase; A549 Cells; Accidental Falls; Acetylcholinesterase; Acrylic Resins; Actinobacillus; Acute Disease; Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Adenosine; Adenosine Triphosphate; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Advance Care Planning; Africa, Northern; Age Factors; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Air Pollution, Indoor; Albendazole; Aluminum Oxide; Anastomosis, Surgical; Ancylostoma; Ancylostomiasis; Androstadienes; Angiogenesis Inhibitors; Angiotensin II; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bispecific; Antibodies, Viral; Anticoagulants; Antihypertensive Agents; Antinematodal Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antiporters; Antiviral Agents; Apoptosis; Aptamers, Nucleotide; Aromatase Inhibitors; Asian People; Astrocytes; Atrial Fibrillation; 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Mitochondrial Proteins; Mitral Valve; Mitral Valve Insufficiency; Models, Anatomic; Molecular Structure; Molybdenum; Monocarboxylic Acid Transporters; Moths; MPTP Poisoning; Multigene Family; Multiparametric Magnetic Resonance Imaging; Multiple Myeloma; Muscle, Skeletal; Mutagens; Mutation; Myeloid Cells; Nanocomposites; Nanofibers; Nanomedicine; Nanoparticles; Nanowires; Neoadjuvant Therapy; Neomycin; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Stem Cells; Neostriatum; Neovascularization, Pathologic; Netherlands; Neuromuscular Agents; Neurons; NF-E2-Related Factor 2; NF-kappa B; Nickel; Nitrogen Oxides; Non-alcoholic Fatty Liver Disease; Nucleosides; Nucleotidyltransferases; Nutritional Status; Obesity, Morbid; Ofloxacin; Oils, Volatile; Oligopeptides; Oncogene Protein v-akt; Optical Imaging; Organic Cation Transport Proteins; Organophosphonates; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Osteoblasts; Osteogenesis; Oxidation-Reduction; Oxidative Stress; Oxides; Oxygen Isotopes; Pancreas; Pancreaticoduodenectomy; Pandemics; Particle Size; Particulate Matter; Patient Acceptance of Health Care; Patient Compliance; PC-3 Cells; Peptide Fragments; Peptides; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Peroxides; Peru; Pest Control, Biological; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phylogeny; Pilot Projects; Piperidines; Plant Bark; Plant Extracts; Plant Leaves; Plasmids; Platelet Function Tests; Pneumonia, Viral; Podocytes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Polyethylene Terephthalates; Polymers; Polymorphism, Single Nucleotide; Porosity; Portugal; Positron-Emission Tomography; Postoperative Complications; Postural Balance; Potassium Channels, Inwardly Rectifying; Povidone; Powders; Precancerous Conditions; Precision Medicine; Predictive Value of Tests; Pregnancy; Prenatal Care; Prognosis; Promoter Regions, Genetic; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Proteasome Inhibitors; Protective Agents; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein Transport; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-akt; Psychiatric Nursing; PTEN Phosphohydrolase; Pulmonary Embolism; Pyrimethamine; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reactive Oxygen Species; Receptor, ErbB-2; Receptor, IGF Type 1; Receptors, Estrogen; Receptors, G-Protein-Coupled; Recombinational DNA Repair; Recovery of Function; Regional Blood Flow; Renal Dialysis; Renin; Renin-Angiotensin System; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Distress Syndrome; Retrospective Studies; Rhodamines; Risk Assessment; Risk Factors; RNA, Long Noncoding; RNA, Messenger; Running; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salinity; Salmeterol Xinafoate; Sarcoma; Seasons; Shoulder Injuries; Signal Transduction; Silicon Dioxide; Silver; Sirtuin 1; Sirtuins; Skull Fractures; Social Determinants of Health; Sodium; Sodium Fluoride; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Soil; Soil Pollutants; Spain; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Staphylococcal Protein A; Staphylococcus aureus; Stem Cells; Stereoisomerism; Stomach Neoplasms; Streptomyces; Strontium; Structure-Activity Relationship; Students, Nursing; Substance-Related Disorders; Succinic Acid; Sulfur; Surface Properties; Survival Rate; Survivin; Symporters; T-Lymphocytes; Temozolomide; Tensile Strength; Thiazoles; Thiobacillus; Thiohydantoins; Thiourea; Thrombectomy; Time Factors; Titanium; Tobacco Mosaic Virus; Tobacco Use Disorder; Toll-Like Receptor 4; Toluene; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Toxicity Tests, Acute; Toxicity Tests, Subacute; Transcriptional Activation; Treatment Outcome; Troponin I; Tumor Cells, Cultured; Tumor Escape; Tumor Hypoxia; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Tyrosine; Ubiquitin-Protein Ligases; Ubiquitination; Ultrasonic Waves; United Kingdom; United States; United States Department of Veterans Affairs; Up-Regulation; Urea; Uric Acid; Urinary Bladder Neoplasms; Urinary Bladder, Neurogenic; Urine; Urodynamics; User-Computer Interface; Vemurafenib; Verbenaceae; Veterans; Veterans Health; Viral Load; Virtual Reality; Vitiligo; Water Pollutants, Chemical; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Xylenes; Young Adult; Zinc; Zinc Oxide; Zinc Sulfate; Zoonoses | 2021 |
Potential of anthocyanin as an anti-inflammatory agent: a human clinical trial on type 2 diabetic, diabetic at-risk and healthy adults.
The present research aimed to investigate the anti-inflammatory potential of dietary anthocyanin (ACN) in type 2 diabetic (T2D), T2D-at-risk and healthy individuals. Furthermore, dietary inflammatory index (DII) was used to study the association of diet with biomarkers of inflammation.. An open-label clinical trial was conducted at Griffith University investigating the efficacy of 320 mg ACN supplementation per day over the course of 4 weeks. Diabetes-associated inflammatory biomarkers and relevant biochemical and physical parameters were tested pre-and post-intervention, and participants' dietary inflammatory potential was estimated.. A significant reduction in the pro-inflammatory biomarkers' interleukin-6, interleukin-18, and tumour necrosis factor-α was observed in the T2D group. In addition, some, but not all, biochemical parameters including fasting blood glucose, low-density lipoprotein cholesterol and uric acid were significantly improved in T2D-at-risk group. Moreover, a significant difference was detected between the DII scores of the healthy and T2D groups. DII score for the T2D group was consistent with an anti-inflammatory diet.. Anti-inflammatory potential of dietary ACN in T2D participants was evidenced in the present study. Although, anti-inflammatory dietary patterns of T2D participants may have accelerated the anti-inflammatory effect of the ACN capsules supplemented in this trial. Topics: Adult; Aged; Anthocyanins; Anti-Inflammatory Agents; Biomarkers; Blood Glucose; Cholesterol, LDL; Cytokines; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Inflammation; Leptin; Middle Aged; Uric Acid | 2021 |
Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis.
Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRG Topics: Adiponectin; Adult; Aged; Animals; Cell Line; Diet, High-Fat; Disease Models, Animal; Drug Therapy, Combination; Humans; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Middle Aged; Non-alcoholic Fatty Liver Disease; Polysaccharides; Xanthophylls; Young Adult | 2021 |
Secondary data analysis investigating effects of marine omega-3 fatty acids on circulating levels of leptin and adiponectin in older adults.
Higher leptin and lower adiponectin levels have been linked to progressing systemic inflammation and diseases of aging. Among older adults with obesity and an inflammatory conditions, we quantified effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on leptin, adiponectin, and the leptin-to-adiponectin ratio (LAR). We also examined associations among adipokine and cytokine levels.. Using a randomized, double-blind, placebo-controlled design, participants (mean age 61.3 ± 2.1) received 1.5 g EPA + 1.0 g DHA (n = 14) or mineral oil (n = 18) daily. Plasma adipokine and cytokine levels were quantified by electrochemiluminescence at all study intervals.. While no between-group differences were detected, there was a reduction in the LAR (by 23%, p=.065) between weeks 4 and 8 among the EPA+DHA group. Adiponectin levels were negatively associated with IL-1β levels at week 4 (p=.02) and TNF-α levels at week 8 (p=.03).. Potential benefits of EPA+DHA supplementation among aging populations warrant further study. Topics: Adiponectin; Aged; Aged, 80 and over; Cytokines; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Humans; Inflammation; Leptin; Male; Middle Aged | 2021 |
The effect of saffron supplementation on some inflammatory and oxidative markers, leptin, adiponectin, and body composition in patients with nonalcoholic fatty liver disease: A double-blind randomized clinical trial.
Nonalcoholic fatty liver disease (NAFLD) is characterized by oxidative stress and inflammation in the hepatocytes. Saffron and its constituents are reported to have several properties such as anti-inflammatory and anti-diabetic effects.. In a randomized double-blind placebo-controlled trial with two parallel groups including 76 eligible men and female patients with NAFLD aged 18-65, recruited from Hazrat Rasul Akram Hospital in Tehran, Iran. NAFLD was defined by a Gastroenterologist based on the American Gastrointestinal and Liver Association standards. Participants were randomly assigned to two groups receiving daily supplementation of either one tablet of 100 mg saffron (n = 38) or one placebo (n = 38) for 12 weeks. The primary outcome was high sensitive C-reactive protein (hs-CRP) and secondary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA), total anti-oxidant capacity (TAC), leptin, adiponectin, anthropometric, and body composition Both groups were assigned similar diet and physical activity.. In the treatment group, significant decreases in hs-CRP (-1.80 ng/ml, 95% CI = -2.97, -0.63, p = .032), leptin (-0.27 ng/ml, 95% CI = -0.65, -0.10, p = .040), MDA (-1.01 ng/ml, 95% CI = -1.89, -0.14, p = .023) and significant increase in TAC (0.34 μmol/L, 95% CI = 0.08, 0.61, p = .011) were observed compared to the placebo group. However, there were no significant changes in serum alanine aminotransferase, AST, TNF-α, body composition, and anthropometric indexes (p > .05).. In the present study, 12 weeks of 100 mg of saffron supplementation indicated beneficial effects on serum levels of some inflammatory, oxidative stress, and adipokines biomarkers but it had no significant effect on serum concentrations of liver enzymes, anthropometric, and body composition measurements. Topics: Adiponectin; Adolescent; Adult; Aged; Body Composition; Crocus; Double-Blind Method; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Young Adult | 2020 |
The Effect of Supplementation with Low Doses of a Cod Protein Hydrolysate on Satiety Hormones and Inflammatory Biomarkers in Adults with Metabolic Syndrome: A Randomized, Double-Blind Study.
Metabolic syndrome (MetS) is characterised by metabolic abnormalities that increase the risk of developing type 2 diabetes mellitus and cardiovascular disease. Altered levels of circulating ghrelin, several adipokines and inflammatory markers secreted from adipose tissue, such as leptin, adiponectin, tumor necrosis factor alpha, are observed in overweight and obese individuals. We assessed the effect of supplementation with low doses of a cod protein hydrolysate (CPH) on fasting and postprandial levels of acylated ghrelin, as well as fasting levels of adiponectin, leptin and inflammatory markers in subjects with MetS. A multicentre, double-blinded, randomized controlled trial with a parallel group design was conducted. Subjects received a daily supplement of CPH (4 g protein, Topics: Adiponectin; Adult; Biomarkers; Dietary Supplements; Female; Fish Proteins; Ghrelin; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Middle Aged; Protein Hydrolysates; Satiation | 2020 |
Association Between Insulin Resistance, Plasma Leptin, and Neurocognition in Vascular Cognitive Impairment.
Greater body weight has been associated impairments in neurocognition and greater dementia risk, although the mechanisms linking weight and neurocognition have yet to be adequately delineated.. To examine metabolic mechanisms underlying the association between obesity and neurocognition.. We conducted a secondary analysis of weight, neurocognition, and the potentially mediating role of metabolic and inflammatory biomarkers among 160 participants from the ENLIGHTEN trial of vascular cognitive impairment, no dementia (CIND). Neurocognition was assessed using a 45-minute assessment battery assessing Executive Function, Verbal and Visual Memory. We considered three metabolic biomarkers: insulin resistance (homeostatic model assessment [HOMA-IR]), plasma leptin, and insulin-like growth factor (IGF-1). Inflammation was assessed using C-reactive protein. Multiple regression analyses were used.. Participants included 160 sedentary older adults with CIND. Participants tended to be overweight or obese (mean BMI = 32.5 [SD = 4.8]). Women exhibited higher BMI (p = 0.043), CRP (p < 0.001), and leptin (p < 0.001) compared with men. Higher BMI levels were associated with worse performance on measures of Executive Function (β= -0.16, p = 0.024) and Verbal Memory (β= -0.16, p = 0.030), but not Visual Memory (β= 0.05, p = 0.500). Worse metabolic biomarker profiles also were associated with lower Executive Function (β= -0.12, p = 0.050). Mediation analyses suggested leptin was a plausible candidate as a mediator between BMI and Executive Function.. In overweight and obese adults with vascular CIND, the association between greater weight and poorer executive function may be mediated by higher leptin resistance. Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Cognition; Dementia, Vascular; Executive Function; Female; Humans; Inflammation; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Male; Memory; Middle Aged; Neuropsychological Tests; Obesity | 2019 |
Effects of β-glucan and Vitamin D Supplementation on Inflammatory Parameters in Patients with Diabetic Retinopathy.
The objective of this article is to evaluate the potential effects of beta-glucan and vitamin D supplementation in patients with diabetic retinopathy. We evaluated the levels of several parameters of inflammatory reactions (C-reactive protein [CRP], serum amyloid A [SAA], and interleukin- [IL-] 6), leptin, and vitamin D. Using a 3-month interval, we divided the patients into three groups: (1) supplemented with beta-glucan and vitamin D, (2) supplemented with vitamin D and placebo, and (3) supplemented with vitamin D alone. By this division, we aim not only to observe whether beta-glucan can increase the effects of vitamin D, but also to eliminate the potential effects of placebo. The doses of vitamin D corresponded to phototype, weight, age, and sex of the individual. Fifty-two diabetic retinopathy patients were selected for our study. We found significant vitamin D deficits in all cases, even after three months of supplementation with vitamin D. Significant changes in levels of CRP were observed in the beta-glucan-supplemented group; levels of SAA and IL-6 were not changed. Leptin levels were significantly lowered in the beta-glucan-supplemented group and increased in the other groups. More detailed studies and/or longer supplementation is necessary. Topics: Aged; Aged, 80 and over; beta-Glucans; Body Mass Index; C-Reactive Protein; Czech Republic; Diabetic Retinopathy; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Placebos; Serum Amyloid A Protein; Vitamin D; Vitamin D Deficiency | 2019 |
Total and differential white blood cell counts, inflammatory markers, adipokines, and incident metabolic syndrome in phase 1 of the clinical antipsychotic trials of intervention effectiveness study.
The metabolic syndrome is highly prevalent in patients with schizophrenia. We previously found that blood C-reactive protein (CRP), interleukin-6 (IL-6), and leptin levels were predictors of current metabolic syndrome in schizophrenia. In the present study, we investigated whether baseline levels of total and differential white blood cell (WBC) counts, inflammatory markers, and adipokines predicted incident metabolic syndrome in schizophrenia.. For subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial who did not have metabolic syndrome at baseline (n = 726), WBC counts, inflammatory markers, and adipokines were investigated as predictors of incident metabolic syndrome over 12 months of antipsychotic treatment. Cox proportional hazards regression models, controlling for multiple potential confounding factors, were used to investigate these associations.. 39% of subjects (n = 280) had incident metabolic syndrome over 12 months. After controlling for potential confounders, baseline blood IL-6 (HR = 1.12, 95% CI 1.01-1.24, p = 0.031) and leptin (HR = 1.12, 95% CI 1.01-1.24, p = 0.038) were significant predictors of incident metabolic syndrome, and there was a trend-level association with CRP (HR = 1.09, 95% CI 1.00-1.19, p = 0.059).. Our findings provide additional evidence that measurement of inflammatory markers and adipokines are germane to the clinical care of patients with schizophrenia. Specifically, these markers may identify-prior to treatment-patients with schizophrenia at heightened risk for incident adverse cardiometabolic effects of antipsychotics. Given the tremendous burden of cardiovascular disease morbidity and mortality in schizophrenia, vigilant screening for and treatment of metabolic risk factors in this patient population are warranted. Topics: Adipokines; Adult; Antipsychotic Agents; C-Reactive Protein; Female; Humans; Inflammation; Interleukin-6; Leptin; Leukocyte Count; Male; Metabolic Syndrome; Middle Aged; Schizophrenia | 2019 |
Combined aerobic and resistance training decreases inflammation markers in healthy men.
Our primary aim was to study the effects of 24 weeks of combined aerobic and resistance training performed on the same day or on different days on inflammation markers. Physically active, healthy young men were randomly divided into three groups that performed: aerobic and resistance training consecutively in the same training session (SS) 2-3 days wk Topics: Abdominal Fat; Adiponectin; Adult; Biomarkers; Body Composition; C-Reactive Protein; Chemokine CCL2; Exercise; Humans; Inflammation; Interleukin-6; Leptin; Male; Oxygen Consumption; Resistance Training; Resistin; Tumor Necrosis Factor-alpha | 2018 |
Effect of Low- Versus High-Intensity Exercise Training on Biomarkers of Inflammation and Endothelial Dysfunction in Adolescents With Obesity: A 6-Month Randomized Exercise Intervention Study.
To investigate the effects of a low- versus high-intensity aerobic training on biomarkers of inflammation and endothelial dysfunction in adolescents with obesity.. Sixty-two adolescents with obesity [age = 15 (14) y, body mass index = 34.87 (4.22) kg·m. HIT reduced neutrophils [from 4.4 (1.9) to 3.6 (1.3) µL. Both HIT and LIT improved the inflammatory profile. The study, however, indicated that the number of biomarkers and the magnitude of changes were higher in the HIT compared with LIT. Topics: Adolescent; Biomarkers; Body Mass Index; Cardiorespiratory Fitness; Exercise Therapy; Female; High-Intensity Interval Training; Humans; Inflammation; Insulin Resistance; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Male; Monocytes; Neutrophils; Oxygen Consumption; Pediatric Obesity; Peroxidase; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1 | 2018 |
Adipokines, Inflammation, and Adiposity in Hematopoietic Cell Transplantation Survivors.
Adult survivors of acute leukemia in childhood have a higher-than-expected frequency of obesity and are at increased risk for metabolic syndrome and early mortality from cardiovascular disease (CVD). Adipose tissue has been recognized as an endocrine and paracrine organ that secretes various adipokines involved in metabolic regulation and inflammatory processes. In this study, we examined inflammatory factors (IL-6 and TNF-α) and adipokines (adiponectin, leptin), in addition to body composition and adiposity, in cancer survivors who underwent hematopoietic cell transplantation (HCT) during childhood compared with sibling controls. Over 2-year survivors of HCT for hematologic malignancies during childhood were recruited from 2 institutions along with a control population of siblings. Participants underwent evaluation for body composition, anthropometric measurements, and assessment of CVD risk factors and adipokines. Cases were stratified by radiation exposure in the preparative regimen (total body irradiation [TBI] + central nervous system [CNS] irradiation, TBI only, chemotherapy only) and adjusted least squares means were estimated for each adipokine and adjusted by age, sex, race, Tanner stage, and percent fat mass (PFM) percentiles (0-24, 25-74, 75+). A total of 151 HCT survivors and 92 siblings underwent evaluation. Significant differences in mean adipokine levels were detected between survivors and siblings; leptin was significantly higher and adiponectin significantly lower in HCT survivors who received TBI with or without CNS irradiation compared with siblings. IL-6 was significantly higher in all groups of HCT survivors compared with siblings. Body mass index (BMI) was similar in survivors and controls, although PFM was significantly higher in all groups of HCT survivors and lean body mass (LBM) was lower in survivors who received TBI with or without CNS radiation compared with siblings. HCT survivors showed an unfavorable profile of inflammation, adipokines, and adiposity, despite similar BMI as controls. Higher PFM and lower LBM may contribute to these findings. TBI exposure is correlated with greater severity of these observations. Increasing LBM may represent a tangible target for mitigating the high cardiometabolic risks of HCT survivors. Topics: Adiponectin; Adiposity; Adolescent; Adult; Allografts; Body Mass Index; Cancer Survivors; Female; Hematopoietic Stem Cell Transplantation; Humans; Inflammation; Interleukin-6; Leptin; Male; Tumor Necrosis Factor-alpha | 2018 |
Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes.
Type 2 diabetes and obesity are pro-inflammatory states associated with increased risk of cardiovascular disease. Canagliflozin, an SGLT2 inhibitor, demonstrated superiority in lowering HbA1c versus glimepiride with less hypoglycemia and greater weight reduction via loss of fat mass in a 52-week trial of type 2 diabetes patients. This post hoc, exploratory analysis assessed the effects of canagliflozin versus glimepiride on select adipokines, inflammatory biomarkers, and chemokines.. Changes from baseline to Week 52 in serum leptin, adiponectin, IL-6, TNFα, CRP, PAI-1, VCAM-1, and MCP-1 were measured in a randomly selected subset of type 2 diabetes patients on metformin receiving canagliflozin 300 mg (n = 100) or glimepiride (n = 100) in the overall study. Correlations between change in biomarkers and change in select metabolic and anthropometric variables were assessed.. At Week 52, canagliflozin decreased median serum leptin by 25% (95% CI: -34%, -15%) and increased median serum adiponectin by 17% (95% CI: 11%, 23%) compared with glimepiride. There was a 22% reduction in median serum IL-6 (95% CI: -34%, -10%) and a 7% increase in median serum TNFα (95% CI: 1%, 12%) with canagliflozin versus glimepiride. No between-group differences were observed with the other biomarkers. The decrease in serum leptin with canagliflozin was correlated with change in weight (r ≥ 0.3) only; the increase in adiponectin and decrease in IL-6 with canagliflozin occurred independently of changes in HbA1c, weight, or lipids.. These results indicate that canagliflozin may improve adipose tissue function and induce changes in serum leptin, adiponectin, and IL-6 that favorably impact insulin sensitivity and cardiovascular disease risk. Topics: Adiponectin; Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Canagliflozin; Diabetes Mellitus, Type 2; Double-Blind Method; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Leptin; Male; Metformin; Middle Aged; Molybdoferredoxin; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds; Treatment Outcome; Tumor Necrosis Factor-alpha | 2018 |
The effects of adiposity and alcohol use disorder on adipokines and biomarkers of inflammation in depressed patients.
Patients with depression and alcohol use disorder frequently present with elevated markers of inflammation. Adipose tissue may function as a source for inflammation, yet the interplay between adiposity, alcohol use and depression has remained unknown. We examined 242 patients, referred to treatment for depressive symptoms, and followed for a period of 6 months. The assessments included screening for alcohol use and measurements of body mass index, serum adiponectin, leptin, resistin, progranulin, hs-CRP, IL-6 and MCP-1 at baseline and after 6 months of treatment. During follow-up, mean MADRS and AUDIT scores decreased significantly, whereas BMI increased. The changes in the levels of cytokines and adipokines were influenced by alcohol consumption and adiposity in a gender-dependent manner. The presence of AUD seemed to particularly influence the levels of cytokines. The levels of IL-6, hs-CRP, progranulin, and leptin differed between AUD and non-AUD groups at baseline, but no longer at 6 months. Baseline levels of leptin and resistin were higher in women and changes occurring in leptin, progranulin, and adiponectin were more notable in women. The data indicates significant gender-dependent interactions between depression, alcohol and mediators of inflammation, which should be considered in studies on the pathogenesis of depression and its comorbidities. Topics: Adipokines; Adiponectin; Adiposity; Adult; Alcohol Drinking; Alcoholism; Biomarkers; Body Mass Index; Cytokines; Depression; Female; Follow-Up Studies; Humans; Inflammation; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Resistin | 2018 |
The Effects of a 12-Week Combined Exercise Training Program on Arterial Stiffness, Vasoactive Substances, Inflammatory Markers, Metabolic Profile, and Body Composition in Obese Adolescent Girls.
Childhood and adolescent obesity is a major international public health crisis. It is crucial to prevent the negative effects of obesity at an early age by implementing appropriate lifestyle interventions, such as exercise training. We evaluated the effects of a combined resistance and aerobic exercise training (CET) regimen on arterial stiffness, vasoactive substances, inflammatory markers, metabolic profile, and body composition in obese adolescent girls.. A total of 30 obese adolescent girls were randomly assigned to a CET (n = 15) or a control group (n = 15). The CET group trained for 3 days per week. Plasma nitric oxide, endothelin-1, C-reactive protein, arterial stiffness, glucose, insulin, the adiponectin/leptin ratio, and body fat were measured before and after 12 weeks.. There were significant increases (P < .05) in nitric oxide (4.0 μM) and adiponectin/leptin ratio (0.33); and decreases (P < .05) in arterial stiffness (-1.0 m/s), C-reactive protein (-0.5 mg/L), glucose (-1.2 mmol/L), insulin (-17.1 μU/mL), and body fat (-3.6%) following CET compared with control. There were no significant changes in endothelin-1 after CET or control.. The findings of this study indicate that CET improves arterial stiffness, nitric oxide, and inflammatory and metabolic markers in obese adolescent girls. CET may have important health implications for the prevention of atherosclerosis at an early age. Topics: Adiponectin; Adolescent; Biomarkers; Blood Glucose; Body Composition; C-Reactive Protein; Endothelin-1; Exercise; Female; Humans; Inflammation; Insulin; Leptin; Metabolome; Nitric Oxide; Obesity; Resistance Training; Vascular Stiffness | 2018 |
Diurnal distribution of carbohydrates and fat affects substrate oxidation and adipokine secretion in humans.
A diet in which fat is mainly eaten in the morning and carbohydrates mainly in the evening (compared with the reverse order) was recently shown to worsen glycemic control in people with prediabetes.. We investigated the effects of these dietary patterns on energy metabolism, and on the daily profiles of circulating lipids, adipokines, and inflammatory markers.. In a randomized controlled crossover trial, 29 nonobese men (with normal glucose tolerance, n = 18; or impaired fasting glucose/glucose tolerance, n = 11) underwent 2 isocaloric 4-wk diets: 1) carbohydrate-rich meals until 1330 and fat-rich meals between 1630 and 2200 (HC/HF); or 2) the inverse sequence of meals (HF/HC). During a 12-h clinical investigation day after each intervention period, 2 meal tolerance tests were performed, at 0900 and 1540, respectively. Substrate oxidation and concentrations of circulating lipids, adipokines, and cytokines were assessed pre- and postprandially. The postprandial inflammatory response in leukocytes was analyzed ex vivo.. Fasting carbohydrate oxidation decreased (P = 0.004) and lipid oxidation increased (P = 0.012) after the HC/HF diet. Fasting concentrations of blood markers did not differ between diets. The diets modulated the daily profiles of carbohydrate oxidation, lipid oxidation, and β-hydroxybutyrate, although the average daily values of these parameters showed no difference between the diets, and no interaction between diet and glucose tolerance status. Diurnal patterns of triglycerides, low-density lipoprotein cholesterol, leptin, visfatin, and of LPS-induced cytokine secretion in blood leukocytes were also modulated by the diets. Average daily concentrations of leptin (P = 0.017) and visfatin (P = 0.041) were lower on the HF/HC diet than on the HC/HF diet.. Diurnal distribution of carbohydrates and fat affects the daily profiles of substrate oxidation, circulating lipids, and cytokine secretion, and alters the average daily concentrations of adipokine secretion in nonobese nondiabetic humans. The study was registered at clinicaltrials.gov as NCT02487576. Topics: Adipokines; Adult; Biomarkers; Body Mass Index; Circadian Rhythm; Cross-Over Studies; Cytokines; Dietary Carbohydrates; Dietary Fats; Energy Metabolism; Fasting; Glucose Intolerance; Humans; Inflammation; Leptin; Lipids; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Oxidation-Reduction; Postprandial Period | 2018 |
Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes.
Despite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in patients with type 2 diabetes (DM2) and established atherosclerosis.. To investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function, coagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients with atherosclerotic vascular disease and DM2 who receive optimal medical therapy.. We conducted a prospective, double-blind, placebo-controlled, randomized, double-center study, in which thrombin generation (plasma thrombogenic potential from automated thrombogram), fibrin clot properties (plasma fibrin clot permeability; lysis time), platelet aggregation (light transmission aggregometry with adenosine diphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid profiles, leptin and adiponectin levels, as well as markers of systemic inflammation (i.e., hsCRP, IL-6, TNF-α, ICAM-1, VCAM-1, and myeloperoxidase) were determined at baseline and at 3 months after treatment with 2 g/day of n-3 PUFAs (n = 36) or placebo (n = 38). Moreover, we assessed serum fatty acids of the phospholipid fraction by gas chromatography both at baseline and at the end of the study.. Majority of patients were treated with optimal medical therapy and achieved recommended treatment targets. Despite higher serum levels of eicosapentaenoic acid (EPA) (by 204%; p < 0.001) and docosahexaenoic acid (DHA) (by 62%; p < 0.0001) in n-3 PUFA group at the end of treatment no changes in platelet aggregation, thrombin generation, fibrin clot properties or markers of systemic inflammation were observed. No intergroup differences in the insulin, HbA1c and lipid levels were found at the end of the study. There was no change in adiponectin and leptin in interventional group, however leptin increased in control group (p = 0.01), therefore after study period leptin levels were lower in the interventional group (p = 0.01). Additionally, resolvin D1 did not differ between interventional and control group.. In conclusion, our study demonstrated that in patients with long-standing, well-controlled DM2 and atherosclerotic disease the treatment with a high dose of n-3 PUFAs (namely, 1 g/day of EPA and 1 g/day of DHA for 3 months) does not improve coagulation, metabolic, and inflammatory status when measured with the specified tests. The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014. Topics: Adiponectin; Aged; Atherosclerosis; Biomarkers; Blood Coagulation; Blood Platelets; Diabetes Mellitus, Type 2; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Glycated Hemoglobin; Humans; Inflammation; Inflammation Mediators; Insulin; Leptin; Lipids; Male; Middle Aged; Platelet Aggregation; Poland; Prospective Studies; Thrombin; Time Factors; Treatment Outcome | 2017 |
GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction.
Glucagon-like peptide-1 (GLP-1) analogues aid weight loss that improves obesity-associated adipose tissue (AT) dysfunction. GLP-1 treatment may however also directly influence AT that expresses the GLP-1 receptor (GLP-1R). The present study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT (SCAT) inflammatory and fibrotic responses, compared with weight loss by calorie reduction (control). Among the 39 participants with Type 2 diabetes recruited, 30 age-matched participants were randomized to 4 months treatment with Liraglutide ( Topics: Adiponectin; Adipose Tissue; Aged; Diabetes Mellitus, Type 2; Extracellular Matrix; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Inflammation; Leptin; Liraglutide; Male; Middle Aged; Obesity | 2017 |
Impact of lifestyle intervention for obese women during pregnancy on maternal metabolic and inflammatory markers.
Offspring of obese mothers have increased risk of developing obesity and related short- and long-term disease. The cause is multifactorial and may partly be explained by the unfavorable intrauterine environment. Intervention during pregnancy leading to a healthier lifestyle among obese may alter this.. To assess the effect of lifestyle intervention on markers of maternal metabolism and inflammation in 'the TOP (Treatment of Obese Pregnant Women) study', a randomized controlled trial.. In the TOP-study 425 participants with body mass index ⩾30 kg/m. Median levels of hsCRP in gestational week 28-30 were lower in each of the intervention groups (8.3 mg/l in PA+D group, P=0.03; and 8.8 mg/l in PA group, P=0.02) versus the control group (11.5 mg/l). Obtaining 11 000 steps per day as aimed for resulted in a 21% lower hsCRP compared to non-compliant women. Women reporting high carbohydrate intake had around 30% higher hsCRP concentrations in late gestation than women reporting the lowest intake. There were no differences in lipid profile or any of the metabolic markers in gestational week 28-30 when comparing the intervention and control groups.. Lifestyle intervention in obese women can reduce hsCRP representing a marker of inflammation during pregnancy. The effect may partly be mediated by more physical activity and partly by changes in intake of carbohydrates and the glycaemic load. Topics: Adult; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Energy Intake; Exercise; Female; Glucose Tolerance Test; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Netherlands; Obesity; Pregnancy; Pregnancy Complications; Risk Reduction Behavior; Weight Gain | 2017 |
Effect of Fat Intake on the Inflammatory Process and Cardiometabolic Risk in Obesity After Interdisciplinary Therapy.
Changes in diet and eating behavior along with excessive consumption of sugar or fat and a sedentary lifestyle are related to increased obesity and its associated comorbidities. The aim of this study was to investigate the role of the type of macronutrients on specific health benefits associated with the weight loss in treating obesity. A total of 30 obese women (34.89±3.04 kg/m(2) and 43.3±5.34 years) participated in an interdisciplinary therapy approach to lifestyle change, which consisted of nutritional counseling, exercise, and psychological therapy for over a period of 26 weeks. The profile was obtained by anthropometric measurements and body composition by bioelectrical impedance analysis (BIA). Usual food intake was assessed with 3-day food record diaries and blood tests were used to determine metabolic and adipokines parameters. After therapy, there was significant reduction in all anthropometric and body composition variables. Food consumption also decreased while still providing adequate nutrient intake. There was significant improvement in LDL-cholesterol, PAI-1, leptin, CRP, ICAM-1, and VCAM-1. Lower dietary carbohydrate and fat intake led to weight loss. The effect of lower carbohydrate intake on weight loss is related to changes in body composition and leptin levels. Weight loss by reducing fat intake modified the inflammatory process and cardiovascular risk, indicating dietary fat as an independent predictor factor of cell adhesion molecules. Therefore, decreasing dietary fat consumption had greater impact on the inflammatory process on obese individuals. Our results show that the type of macronutrient influences the health benefits associated with weight loss. Topics: Adult; C-Reactive Protein; Cholesterol, LDL; Dietary Fats; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Vascular Cell Adhesion Molecule-1 | 2016 |
Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes.
One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH.. A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks.. Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (-3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P < 0.01) compared with placebo. Visceral and hepatic fat did not change. The expression of insulin signaling genes (IR-β, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower in men with HH and was upregulated after testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1β, tumor necrosis factor-α, and leptin (P < 0.05 for all).. Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat. Topics: Adult; Body Composition; C-Reactive Protein; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Hormone Replacement Therapy; Humans; Hypogonadism; Inflammation; Insulin; Insulin Resistance; Interleukin-1beta; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Subcutaneous Fat; Testosterone; Tumor Necrosis Factor-alpha | 2016 |
Effects of 12 weeks of combined training without caloric restriction on inflammatory markers in overweight girls.
The objective of the present study was to investigate the effects of combined training without caloric restriction on inflammatory markers in overweight girls. Thirty-three girls (13-17 years) were assigned into overweight training (n = 17) or overweight control (n = 16) groups. Additionally, a normal-weight group (n = 15) was used as control for the baseline values. The combined training programme consisted of six resistance exercises (three sets of 6-10 repetitions at 60-70% 1 RM) followed by 30 min of aerobic exercise (walking/running) at 50-80% VO2peak, performed in the same 60 min session, 3 days/weeks, for 12 weeks. Body composition, dietary intake, aerobic fitness (VO2peak), muscular strength (1 RM), glycaemia, insulinemia, lipid profile and inflammatory markers (C-reactive protein, interleukin-6, tumour necrosis factor-alpha, interleukin-10, leptin, resistin and adiponectin) were measured before and after intervention. There was a significant decrease in body fat (P < 0.01) and increase in fat-free mass (P < 0.01), VO2peak (P < 0.01), 1 RM for leg press (P < 0.01) and bench press (P < 0.01) in the overweight training group. Concomitantly, this group presented significant decreases in serum concentrations of C-reactive protein (P < 0.05) and leptin (P < 0.05), as well as in insulin resistance (P < 0.05) after the experimental period. In conclusion, 12 weeks of combined training without caloric restriction reduced inflammatory markers associated with obesity in overweight girls. Topics: Adipokines; Adipose Tissue; Adolescent; Biomarkers; Body Composition; Body Fluid Compartments; C-Reactive Protein; Caloric Restriction; Cytokines; Exercise; Female; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Leptin; Muscle Strength; Obesity; Overweight; Oxygen Consumption; Resistance Training | 2016 |
Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans.
Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype. Topics: Adult; Biomarkers; Body Composition; C-Reactive Protein; Caloric Restriction; Diet; Energy Intake; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Lymphocyte Count; Male; Middle Aged; Treatment Outcome; Tumor Necrosis Factor-alpha | 2016 |
Weight loss induced by very low calorie diet is associated with a more beneficial systemic inflammatory profile than by Roux-en-Y gastric bypass.
Weight loss interventions such as Roux-en-Y gastric bypass (RYGB) and very low calorie diets (VLCD) lead to improvement of glucose metabolism in obese individuals with type-2 diabetes. Weight loss can also positively influence the unfavorable inflammatory profile associated with obesity. However, a direct comparison of the effect of VLCD and RYGB on systemic inflammation is lacking.. Systemic inflammation was investigated in age- and BMI-matched morbidly obese T2DM women by determining the number and activation- or memory status of peripheral blood leukocytes by flow cytometry, in addition to measuring circulating levels of cytokines and CRP. Systemic inflammation was assessed one month before and three months after RYGB (n=15) or VLCD (n=12). An age matched group of lean women (n=12) was studied as control group.. Three months after the intervention, CRP and leptin levels were reduced whereas adiponectin levels were increased both by RYGB and VLCD. TNF-α levels were increased by RYGB, but reduced by VLCD. IL-2 and IL-6 levels were reduced and IL-4 levels were increased by VLCD but not affected by RYGB. The number of activated peripheral cytotoxic T (CD8+CD25+) and B (CD19+CD38+) cells was significantly higher after RYGB than after VLCD.. In conclusion, RYGB and VLCD have differential effects on the activation status of peripheral leukocytes and levels of cytokines in obese women with T2DM, despite comparable weight loss three months after the intervention. VLCD seems to have more favorable effects on the inflammatory profile as compared to RYGB. Topics: Adiponectin; Adult; Blood Glucose; C-Reactive Protein; Caloric Restriction; Cytokines; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Humans; Inflammation; Insulin; Leptin; Lymphocyte Count; Middle Aged; Obesity, Morbid; Treatment Outcome; Weight Loss | 2016 |
Effects of a 12-month moderate weight loss intervention on insulin sensitivity and inflammation status in nondiabetic overweight and obese subjects.
Weight loss intervention is the principal non-pharmacological method for prevention and treatment of type 2 diabetes. However, little is known whether it influences insulin sensitivity directly or via its anti-inflammatory effect. The aim of this study was to assess the independent role of changes in inflammation status and weight loss on insulin sensitivity in this population.Overweight and obese nondiabetic participants without co-morbidities underwent a one-year weight loss intervention focused on caloric restriction and behavioral support. Markers of inflammation, body composition, anthropometric para-meters, and insulin sensitivity were recorded at baseline, 6, and 12 months. Insulin sensitivity was assessed with frequently sampled intravenous glucose tolerance test and Minimal Model. Twenty-eight participants (F: 15, M: 13, age 39±5 years, BMI 33.2±4.6 kg/m(2)) completed the study, achieving 9.4±6.9% weight loss, which was predominantly fat mass (7.7±5.6 kg, p<0.0001). Dietary intervention resulted in significant decrease in leptin, leptin-to-adiponectin ratio, hs-CRP, and IL-6 (all p<0.02), and improvement in HOMA-IR and Insulin Sensitivity Index (SI) (both p<0.001). In response to weight loss IL-1β, IL-2, leptin, and resistin were significantly associated with insulin, sensitivity, whereas sICAM-1 had only marginal additive effect. Moderate weight loss in otherwise healthy overweight and obese individuals resulted in an improvement in insulin sensitivity and in the overall inflammation state; the latter played only a minimal independent role in modulating insulin sensitivity. Topics: Adult; Blood Glucose; Body Composition; Body Mass Index; C-Reactive Protein; Caloric Restriction; Diet; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Lipids; Male; Middle Aged; National Institutes of Health (U.S.); Obesity; Overweight; Prospective Studies; United States; Weight Loss | 2015 |
Hesperidin supplementation modulates inflammatory responses following myocardial infarction.
A growing number of studies have suggested a crucial role for a variety of inflammatory mediators in myocardial infarction. Recently, several flavonoids have been shown to have cardioprotective and anti-inflammatory properties. Therefore, the aim of this study was to investigate the effect of hesperidin-a common constituent of citrus fruits-on the serum levels of inflammatory markers and adipocytocines in patients with myocardial infarction.. Seventy-five patients with myocardial infarction were participated in this randomized, double-blind controlled clinical trial and were assigned to 2 intervention and control groups. Subjects consumed 600 mg/d pure hesperidin supplement and placebo in the intervention and control groups, respectively, for 4 weeks. Serum concentrations of inflammatory markers and adipocytocines were measured at baseline and at the end of the intervention.. Consumption of 600 mg/day hesperidin significantly decreased the serum levels of E-selectin and increased adiponectin and high-density lipoprotein cholesterol (HDL-C) concentrations in patients with myocardial infarction. The improvement in other inflammatory markers, such as interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), leptin, and other lipid profile was also observed at the end of the intervention, compared to the baseline values, but the difference between the hesperidin and placebo groups was not statistically significant (p > 0.05).. Hesperidin supplementation could compensate for decreased levels of adiponectin and HDL-C and increased levels of E-selectin in patients with myocardial infarction. These results support the concept that certain flavonoids in the diet can be associated with significant health benefits, including heart health. Topics: Adipokines; Adiponectin; Adult; Biomarkers; C-Reactive Protein; Cholesterol, HDL; Dietary Supplements; Double-Blind Method; E-Selectin; Female; Hesperidin; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Myocardial Infarction; Placebos | 2015 |
Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial.
Observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels are associated with inflammatory markers. Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups. Thus, we aimed to determine the effect of supplementary vitamin D using secondary data from a population-based, randomised, placebo-controlled, double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84-year-old residents of one of the four eastern states of Australia. They were randomly selected from the electoral roll and were randomised to one of three trial arms: placebo (n 214), 750 μg (n 215) or 1500 μg (n 215) vitamin D3, each taken once per month for 12 months. Post-intervention blood samples for the analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels were available for 613 participants. Associations between intervention group and biomarker levels were evaluated using quantile regression. There were no statistically significant differences in distributions of CRP, leptin, adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group and either supplemented group. The 75th percentile IL-6 level was 2·8 pg/ml higher (95 % CI 0·4, 5·8 pg/ml) in the 1500 μg group than in the placebo group (75th percentiles:11·0 v. 8·2 pg/ml), with a somewhat smaller, non-significant difference in 75th percentiles between the 750 μg and placebo groups. Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation, we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels, with the possible exception of IL-6. Topics: Adipokines; Adiponectin; Aged; Biomarkers; C-Reactive Protein; Cholecalciferol; Cytokines; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Leptin; Male; Middle Aged; Vitamin D; Vitamin D Deficiency; Vitamins | 2015 |
Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM.
To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM).. A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day (n = 30) or insulin alone (n = 31) for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications.. Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 ± 3.06 to 4.99 ± 2.64, P = 0.006; leptin 25.8 ± 17.6 to 20.1 ± 12.55, P = 0.006; group 2: resistin 7.16 ± 2.30 to 5.57 ± 2.48, P = 0.031; leptin 16.72 ± 16.1 to 14.0 ± 13.4, P = 0.007) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 ± 1.98 to 13.16 ± 1.98, P = 0.015, and fibrinogen 4.00 ± 1.08 to 3.46 ± 0.90, P = 0.002). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower.. The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion. Topics: Adipokines; Adiponectin; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Fibrinogen; Humans; Hyperglycemia; Hypoglycemic Agents; Inflammation; Insulin; Insulin Secretion; Leptin; Male; Middle Aged; Prognosis; Prospective Studies; Resistin; Rosiglitazone; Thiazolidinediones; Young Adult | 2015 |
Effects of vaccination against respiratory pathogens on feed intake, metabolic, and inflammatory responses in beef heifers.
The objective of this study was to evaluate intake, metabolic, inflammatory, and acute-phase responses in beef heifers vaccinated against pathogens that cause bovine respiratory disease (BRD). Eighteen weaned Angus heifers (initial BW 257 ± 3 kg; initial age 245 ± 2 d) were ranked by BW and allocated to 2 groups, which were assigned to 2 experiments of 7 d and the following treatments on d 1 of each experiment: 1) revaccinated against infectious bovine rhinotracheitis virus, parainfluenza-3 virus, bovine respiratory syncytial virus, bovine viral diarrhea Types 1 and 2 viruses, and (VAC; 2 mL [s.c.]) and 2) receiving a 2-mL s.c. injection of 0.9% sterile saline (CON). The group receiving VAC in Exp. 1 was assigned to CON in Exp. 2 and vice versa. Heifers were weaned 21 d before Exp. 1, when they all received the first dose of the aforementioned vaccine. Heifers were maintained in individual pens and offered free-choice mixed alfalfa-grass hay and 3.5 kg/d (DM basis) of a corn-based supplement throughout the study. During Exp. 1, hay and concentrate intake were evaluated daily. During Exp. 2, blood samples were collected before (-2 and 0 h) and at 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 h after treatment administration. In Exp. 1, treatment × day interactions were detected ( < 0.01) for forage intake and total DMI; these parameters were reduced ( ≤ 0.05) in VAC heifers compared with CON heifers on d 1 and 2 by an average of 1.7 and 0.8 kg (DM basis), respectively. In Exp. 2, mean serum tumor necrosis factor α (TNFα) concentration was greater ( = 0.05) in VAC heifers compared with CON heifers and treatment × hour interactions were detected for all plasma variables ( ≤ 0.02), whereas a similar tendency was detected ( = 0.09) for blood α mRNA expression. Haptoglobin concentrations were greater ( ≤ 0.05) in VAC heifers compared with CON heifers from 16 to 120 h. Blood α mRNA expression was greater ( = 0.05) in VAC heifers compared with CON heifers at 12 h. Cortisol concentrations were greater ( ≤ 0.05) in VAC heifers compared with CON heifers from 2 to 16 h. Insulin concentration was greater ( = 0.02) in VAC heifers compared with CON heifers at 2 h. Leptin concentrations were greater ( ≤ 0.05) in VAC heifers compared with CON heifers from 6 to 16 h. In conclusion, vaccinating beef heifers against BRD pathogens decreased forage intake and total DMI during the 2 d following vaccination in Exp. 1, which can be associated with transient metabo Topics: Acute-Phase Proteins; Animal Feed; Animals; Cattle; Cattle Diseases; Eating; Energy Metabolism; Female; Gene Expression Regulation; Hydrocortisone; Inflammation; Insulin; Leptin; RNA, Messenger; Tumor Necrosis Factor-alpha; Vaccination; Vaccines | 2015 |
Sleep apnoea, sleepiness, inflammation and insulin resistance in middle-aged males and females.
In obese males obstructive sleep apnoea (OSA) is associated with inflammation and insulin resistance; however, findings are confounded by adipose tissue, a hormone- and cytokine-secreting organ. Our goal was to examine whether in a relatively nonobese population, OSA is associated with sleepiness and inflammation/insulin resistance, and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (CPAP) use. 77 subjects, 38 middle-aged males and post-menopausal females with OSA and 39 male and female controls, were studied in the sleep laboratory for 4 nights. Measures of sleepiness (objective and subjective), performance, serial 24-h blood samples for interleukin (IL)-6, tumour necrosis factor receptor (TNFR)-1, leptin and adiponectin, and single samples for high-sensitivity C-reactive protein (hsCRP), fasting glucose and insulin levels were obtained. Apnoeic males were significantly sleepier and had significantly higher hsCRP, IL-6, leptin and insulin resistance than controls. Apnoeic females had significantly higher hsCRP; however, objective sleepiness, IL-6, TNFR-1, insulin resistance (Homeostatic Model Assessment index), leptin and adiponectin were similar to controls. CPAP improved subjective sleepiness, but no changes were observed in any of the biomarkers. In conclusion, OSA is associated with sleepiness, inflammation and insulin resistance, even in nonobese males, and this association is stronger in males than in females. Short-term CPAP does not improve the inflammatory/metabolic aberrations in OSA. Topics: Adiponectin; Blood Glucose; Body Mass Index; C-Reactive Protein; Case-Control Studies; Continuous Positive Airway Pressure; Cross-Over Studies; Female; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Receptors, Tumor Necrosis Factor, Type I; Sex Factors; Sleep Apnea, Obstructive; Treatment Outcome | 2014 |
Low-grade systemic inflammation and leptin levels were improved by arm cranking exercise in adults with chronic spinal cord injury.
To ascertain the effect of arm cranking exercise on improving plasma levels of inflammatory cytokines and adipokines in untrained adults with chronic spinal cord injury (SCI).. Longitudinal study.. Community-based supervised intervention.. Men (N=17) with complete SCI at or below T5 volunteered for this study. Participants were randomly allocated to the intervention (n=9) or control group (n=8) using a concealed method.. A 12-week arm cranking exercise program of 3 sessions per week consisted of warm-up (10-15min), arm crank (20-30min; increasing 2min and 30s every 3wk) at a moderate work intensity of 50% to 65% of heart rate reserve (starting at 50% and increasing 5% every 3wk), and cool-down (5-10min).. Plasma levels of leptin, adiponectin, plasminogen activator inhibitor-1, tumor necrosis factor-alpha, and interleukin-6 were determined. Furthermore, physical fitness (maximum oxygen consumption [V˙O2max]) and body composition (anthropometric index, waist circumference, and body mass index) were also assessed.. Plasma levels of leptin, tumor necrosis factor-alpha, and interleukin-6 were significantly decreased after the completion of the training program. Similarly, the anthropometric index and waist circumference were diminished too. A moderate correlation was found between leptin and the anthropometric index. Finally, V˙O2max was significantly increased, suggesting an improvement of physical fitness in the intervention group. No changes were found in the control group.. Arm cranking exercise improved low-grade systemic inflammation by decreasing plasma levels of inflammatory cytokines. Furthermore, it also reduced plasma leptin levels. Long-term, well-conducted studies are still required to determine whether these changes may improve clinical outcomes of adults with chronic SCI. Topics: Adiponectin; Adult; Anthropometry; Arm; Exercise Therapy; Humans; Inflammation; Interleukin-6; Leptin; Longitudinal Studies; Male; Oxygen Consumption; Plasminogen Activator Inhibitor 1; Spinal Cord Injuries; Treatment Outcome; Tumor Necrosis Factor-alpha | 2014 |
Administration of IL-1ra improves adiponectin levels in chronic hemodialysis patients.
Adiponectin, an adipose tissue derived hormone, is known to have insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties in the general population. Adiponectin secretion is suppressed by systemic inflammation, a highly prevalent condition in maintenance hemodialysis (MHD) patients. We evaluated whether short-term administration of interleukin 1 receptor antagonist (IL-1ra) improves adiponectin levels and insulin sensitivity in MHD patients.. Ad hoc analysis was performed on a pilot randomized placebo-controlled trial of the administration of IL-1ra in chronically inflamed MHD patients. Twenty-two patients were randomly assigned to receive 100 mg of IL-1ra or placebo (1:1) for 4 weeks, and 14 completed the trial. ANCOVA was used to compare percent change from baseline to 4 weeks. The primary outcome was percent change in adiponectin and the secondary outcomes were changes in leptin, homeostatic model assessment of insulin resistance (HOMA-IR) and the leptin-to-adiponectin ratio (LAR).. Patients' mean age was 49 ± 13 years, and 71 % were males. At baseline, the median values for adiponectin, leptin, LAR and HOMA-IR were 11.5 μg/ml [interquartile range (IQR) 9, 28.5], 17.8 ng/ml (3.9, 50.0), 2.20 (0.13, 3.98), and 2.8 (2.0, 3.6), respectively. IL-1ra administration resulted in a mean percent increase in serum adiponectin of 22 % vs. 14 % decrease in the placebo arm (p = 0.003). Leptin, LAR or HOMA-IR levels did not change in either arm.. Short-term administration of IL-1ra significantly increased adiponectin levels among prevalent MHD patients. The intervention did not impact insulin sensitivity parameters. Studies of longer duration and larger sample size are needed to further evaluate the potential effect of anti-inflammatory interventions on metabolic markers and insulin sensitivity in MHD patients. Topics: Adiponectin; Adult; Aged; Anti-Inflammatory Agents; Biomarkers; Female; Humans; Inflammation; Insulin Resistance; Interleukin 1 Receptor Antagonist Protein; Leptin; Male; Middle Aged; Pilot Projects; Renal Dialysis; Renal Insufficiency, Chronic; Tennessee; Time Factors; Treatment Outcome; Up-Regulation | 2014 |
Aerobic plus resistance training was more effective in improving the visceral adiposity, metabolic profile and inflammatory markers than aerobic training in obese adolescents.
The purpose of this study was to determine whether aerobic plus resistance training (AT + RT) is more effective than aerobic training (AT) at reducing inflammatory markers and cardiovascular risk in obese adolescents. A total of 139 obese adolescents were enrolled, aged 15-19 years, body mass index (BMI) ≥ 95th percentile and participated in 1 year of interdisciplinary intervention. They were randomised into two groups: AT (n = 55), AT + RT (n = 61). Blood samples were collected to analyse glycaemia, insulin, the lipid profile, leptin and adiponectin concentrations. Insulin resistance was measured by homeostasis model assessment of insulin resistance index (HOMA-IR). The AT + RT group showed better results with regard to decreased body fat mass, low-density lipoprotein concentration (LDL-c) levels, subcutaneous and visceral fat and increased body lean mass. Indeed, a reduction of hyperleptinaemia and an increase in adiponectin concentrations, promoting an improvement in the leptin/adiponectin ratio, was observed. Important clinical parameters were improved in both types of exercise; however, AT + RT was more effective in improving the visceral adiposity, metabolic profile and inflammatory markers than AT alone, suggesting clinical applications for the control of intra-abdominal obesity and cardiovascular risk in the paediatric population. Topics: Abdominal Fat; Adiponectin; Adiposity; Adolescent; Biomarkers; Body Fluid Compartments; Body Mass Index; Cardiovascular Diseases; Cholesterol, LDL; Exercise; Humans; Inflammation; Intra-Abdominal Fat; Leptin; Obesity, Abdominal; Pediatric Obesity; Resistance Training; Subcutaneous Fat; Young Adult | 2014 |
Relationships between adipokines, biomarkers of endothelial function and inflammation and risk of type 2 diabetes.
Identification of novel biomarkers of diabetes risk help to understand mechanisms of pathogenesis and improve risk prediction. Our objectives were to examine the relationships between adipokines, biomarkers of inflammation and endothelial function and development of type 2 diabetes; and to assess the relevance of including these biomarkers in type 2 diabetes prediction risk models.. 1345 subjects from the SU.VI.MAX study, who were free of diabetes at baseline and who completed 13 years of follow-up were included in the present analyses. Odds ratios (OR) with 95% confidence intervals (95% CI) of incident type 2 diabetes associated with a 1-SD increase in adiponectin, leptin, C-reactive protein (CRP), soluble intracellular adhesion modecule-1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), E-selectin and monocyte chemoattractant protein-1 (MCP-1) were estimated. Predicitive performances of models including biomarkers were assessed with area under the receiver operating curves (AUC) and integrated discrimination improvement (IDI) statistics.. 82 subjects developed type 2 diabetes during follow-up. The risk of developing type 2 diabetes increased with increasing concentrations of leptin (2.04 (1.28;3.26)), sICAM-1 (1.39 (1.08;1.78)) and sVCAM-1 (1.29 (1.01;1.64)). Type 2 diabetes associations with leptin remained significant after adjusting for a combination of biomarkers. Models adjusted for novel biomarkers had improved performance compared to models adjusted for classical risk factors as assessed by IDI, but not by AUC.. Adipokines, biomarkers of inflammation and endothelial function were significantly associated to onset of type 2 diabetes. However their inclusion in predictive scores is not supported by the present study. Topics: Adipokines; Adiponectin; Adult; Biomarkers; C-Reactive Protein; Case-Control Studies; Chemokine CCL2; Diabetes Mellitus, Type 2; Double-Blind Method; E-Selectin; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Inflammation; Leptin; Male; Middle Aged; Odds Ratio; Risk Factors | 2014 |
Effects of probiotic yogurt on fat distribution and gene expression of proinflammatory factors in peripheral blood mononuclear cells in overweight and obese people with or without weight-loss diet.
The purpose of this study was to investigate whether probiotics had an effect on proinflammatory markers and cytokines in overweight and obese individuals and whether they could have synergistic effects with weight-loss diets.. A total of 75 healthy overweight and obese individuals completed this randomized doubled-blind controlled clinical trial. Participants were randomly assigned to groups consuming regular yogurt with a low-calorie diet (LCD, RLCD; n = 25) or receiving probiotic yogurt with LCD (PLCD; n = 25) or consuming probiotic yogurt without LCD (PWLCD; n = 25) for 8 weeks. The pribiotic regimen contained 200 g/day yogurt, enriched by Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 10(8) colony-forming units/g. Body fat percentage, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), leptin, and mRNA levels of inflammation-related genes (TNF-α and RAR-related orphan receptor gamma [ROR-γt]) in peripheral blood mononuclear cells (PBMCs) were measured.. A reduction in body mass index (BMI), fat percentage, and leptin level was observed that was more obvious in groups who received the weight-loss diet with probiotic yogurt. Reduction in the gene expression of ROR-γt was significant in the PLCD group (p < 0.001). The expression of TNF-α did not change among all groups after intervention. The mean concentration of leptin was significantly decreased in all groups after the dietary intervention, but the mean changes in leptin level in the PLCD group was more prominent compared to the other two groups (-2.38, p < 0.001 [PLCD] vs -1.75, p = 0.002 [RLCD] and -0.55 ng/mL, p = 0.12 [PWLCD]). The reduction in serum levels of hs-CRP was more evident in the PWLCD group compared to the PLCD and RLCD groups after the 8-week intervention (-3.4, p = 0.03 vs -1.76, p < 0.001 and -2.98 pg/mL, p < 0.001, respectively).. Our results suggested that the weight-loss diet and probiotic yogurt had synergistic effects on T-cells subset specific gene expression in PBMCs, fat percentage, and body weight among overweight and obese individuals. Topics: Adult; Biomarkers; Body Fat Distribution; Body Mass Index; C-Reactive Protein; Cytokines; Diet, Reducing; Double-Blind Method; Female; Gene Expression; Humans; Inflammation; Iran; Leptin; Leukocytes, Mononuclear; Male; Middle Aged; Nuclear Receptor Subfamily 1, Group F, Member 3; Obesity; Overweight; Probiotics; Tumor Necrosis Factor-alpha; Yogurt; Young Adult | 2014 |
Visceral fat resection in humans: effect on insulin sensitivity, beta-cell function, adipokines, and inflammatory markers.
The visceral fat is linked to insulin resistance, the metabolic syndrome, type 2 diabetes and an increased cardiovascular risk, but it is not clear whether it has a causative role.. Surgical resection of this fat depot is a research model to address this issue. Twenty premenopausal women with metabolic syndrome and grade III obesity were randomized to undergo Roux-en-Y gastric bypass (RYGBP) either alone or combined with omentectomy. Insulin sensitivity (IS; euglycemic-hyperinsulinemic clamp), acute insulin response to glucose (AIR; intravenous glucose tolerance test), disposition index (DI = AIR × IS measured by clamp), lipid profile, adipokine profile (leptin, adiponectin, resistin, visfatin, interleukin-6, TNF-α, MCP-1), ultra-sensitive C-reactive protein (CRP), body composition, and abdominal fat echography were assessed prior to surgery and 1, 6, and 12 months post-surgery.. Omentectomy was associated with greater weight loss at all time points. IS improved similarly in both groups. Omentectomy was associated to lower CRP after 12 months, but it did not influence adipokines and other metabolic parameters. Among non-diabetic subjects, omentectomy was associated with a preservation of baseline AIR after 12 months (as opposed to deterioration in the control group) and a greater DI after 6 and 12 months.. Although omentectomy did not enhance the effect of RYGBP on insulin sensitivity and adipokines, it was associated with a preservation of insulin secretion, a greater weight loss, and lower CRP. Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Chemokine CCL2; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucose Tolerance Test; Humans; Inflammation; Insulin Resistance; Insulin-Secreting Cells; Interleukin-6; Intra-Abdominal Fat; Leptin; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Obesity; Premenopause; Prospective Studies; Resistin; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss; Young Adult | 2013 |
Body composition, soluble markers of inflammation, and bone mineral density in antiretroviral therapy-naive HIV-1-infected individuals.
To determine the association among bone mineral density (BMD), inflammatory markers, and alterations in fat and lean mass in untreated HIV-infected individuals.. Cross-sectional analysis of antiretroviral therapy-naive persons enrolled into a randomized clinical trial.. Dual-energy x-ray absorptiometry for BMD and lean and fat mass and a laboratory assessment were performed. Soluble biomarkers included adipocytokines (leptin and adiponectin), inflammatory markers (high-sensitivity C-reactive protein and interleukin 6), and markers related to bone metabolism [osteoprotegerin (OPG)], receptor activator of nuclear factor κB ligand. BMD at the lumbar spine, total hip, and femoral neck was expressed as a Z score (number of standard deviations away from age-, race-, and sex-matched reference population).. Three hundred thirty-one subjects had a median (Q1, Q3) age of 36 (28, 45) years, were 89% men, and 44% white. The prevalence of low BMD (Z score ≤ -2 at any of the 3 sites) was 10%. No associations were detected between Z scores and high-sensitivity C-reactive protein, interleukin 6, or receptor activator of nuclear factor κB ligand (P ≥ 0.1). In a linear model adjusting for age, gender, race, and total fat mass, lower lumbar spine Z scores were associated with lower total lean mass, higher serum adiponectin, and lower OPG. Results at the total hip or femoral neck were similar.. Among antiretroviral therapy-naive HIV-infected individuals, lower BMD was associated with lower lean mass, higher adiponectin, and lower OPG, but not HIV disease variables or any of the inflammatory markers. These findings may have implications for bone metabolism in untreated HIV, in which hypoadiponectinemia and higher OPG may mitigate bone loss. Topics: Adiponectin; Adult; Body Composition; Body Mass Index; Bone Density; C-Reactive Protein; Cross-Sectional Studies; Female; HIV Infections; HIV-1; Humans; Inflammation; Interleukin-6; Leptin; Male; Metabolism, Inborn Errors; Middle Aged; Osteoprotegerin; RANK Ligand | 2013 |
Independent and combined effects of physical activity and weight loss on inflammatory biomarkers in overweight and obese older adults.
To determine the independent effect of long-term physical activity (PA) and the combined effects of long-term PA and weight loss (WL) on inflammation in overweight and obese older adults.. Eighteen-month randomized, controlled trial.. The community infrastructure of cooperative extension centers.. Overweight and obese (body mass index >28.0 kg/m(2) ) community-dwelling men and women aged 60 to 79 at risk for cardiovascular disease (CVD).. Physical activity + weight loss (PA + WL) (n = 98), PA only (n = 97), or successful aging (SA) health education (n = 93) intervention.. Biomarkers of inflammation (adiponectin, leptin, high-sensitivity interleukin (hsIL)-6, IL-6sR, IL-8, and soluble tumor necrosis factor receptor 1) were measured at baseline and 6 and 18 months.. After adjustment for baseline biomarker, wave, sex, and visit, leptin and hsIL-6 showed a significant intervention effect. Specifically, leptin was significantly lower in the PA + WL group (21.3 ng/mL, 95% confidence interval (CI) = 19.7-22.9 ng/mL) than in the PA (29.3 ng/mL, 95% CI = 26.9-31.8 ng/mL) or SA (30.3 ng/mL, 95% CI = 27.9-32.8 ng/mL) group (both P < .001), and hsIL-6 was significantly lower in the PA + WL group (2.1 pg/mL, 95% CI = 1.9-2.3 pg/mL) than in the PA (2.5 pg/mL, 95% CI = 2.3-2.7 pg/mL) or SA (2.4 pg/mL, 95% CI = 2.2-2.6 pg/mL) group (P = .02).. Addition of dietary-induced WL to PA reduced leptin and hsIL-6 more than PA alone and more than a SA intervention in older adults at risk for CVD. Results suggest that WL, rather than increased PA, is the lifestyle factor primarily responsible for improvement in the inflammatory profile. Topics: Adiponectin; Aged; Analysis of Variance; Biomarkers; Community Health Centers; Diet, Reducing; Exercise; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Leptin; Male; Middle Aged; North Carolina; Obesity; Overweight; Receptors, Tumor Necrosis Factor, Type I; Treatment Outcome; Weight Loss | 2013 |
Resistance circuit training reduced inflammatory cytokines in a cohort of male adults with Down syndrome.
It is widely accepted that muscle strength plays a key role on functional tasks of daily living and employability in individuals with Down syndrome (DS). Recent studies have also reported resistance training may improve chronic inflammation in other clinical situations. This is the first study conducted to determine the effect of resistance circuit training on low-grade systemic inflammation in adults with DS.. A total of 40 young male adults with DS were recruited for the trial through different community support groups for people with intellectual disabilities and their families. They had medical approval for physical activity participation. Twenty-four were randomly assigned to perform resistance circuit training with 6 stations, 3 days per week for 12 weeks. Exercise intensity was based on function of the 8RM assessments. The control group included 16 age-, sex-, and BMI-matched adults with Down syndrome. Plasma levels of leptin, adiponectin, and TNF-a were assessed by commercial ELISA kits. C-reactive protein (CRP) was assessed by nephelometry. Body composition was also determined, measuring fat-free mass percentage and waist circumference (WC). This protocol was approved by our Institutional Ethics Committee.. Plasma levels of leptin, TNF-a, and IL-6 were significantly decreased after the completion of the training program, as were fat-free mass and WC. No sports-related injuries or withdrawals from the program were reported during the entire study period. No changes were observed in the control group.. Resistance circuit training improved low-grade systemic inflammation in male sedentary adults with DS. Topics: Adiponectin; Adult; Body Composition; Down Syndrome; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation; Leptin; Male; Nephelometry and Turbidimetry; Resistance Training; Tumor Necrosis Factor-alpha | 2013 |
Resistin is associated with the inflammation process in patients with systemic autoimmune diseases undergoing glucocorticoid therapy: comparison with leptin and adiponectin.
We investigated the role of adipokines in patients with systemic autoimmune diseases who received glucocorticoid therapy.. Fifty-two patients with systemic autoimmune diseases who had started glucocorticoid therapy were prospectively enrolled. One hundred forty healthy persons were also studied as controls. Serum levels of 3 adipokines [resistin, leptin, and high molecular weight (HMW)-adiponectin] were measured with enzyme-linked immunosorbent assay kits before and at weekly intervals for 4 weeks during glucocorticoid therapy. The effects of lipopolysaccharide and dexamethasone on adipokine expression in human peripheral blood mononuclear cells (PBMCs) were also examined.. The serum resistin level was significantly higher in patients than in controls before glucocorticoid therapy, and it decreased after glucocorticoid therapy. Consistent with these results, dexamethasone inhibited lipopolysaccharide-induced upregulation of resistin expression in PBMCs in vitro. Serum leptin and HMW-adiponectin levels were lower in the patients than in the controls at baseline, and both adipokine levels were increased after glucocorticoid therapy. There was a significant correlation between serum resistin and high-sensitivity C-reactive protein. However, there was no association between serum adipokines and intima-media thickness.. Resistin may be associated with the inflammatory process but not atherosclerosis in patients with systemic autoimmune diseases. Topics: Adipokines; Adiponectin; Autoimmune Diseases; Biomarkers; Cells, Cultured; Dexamethasone; Drug Antagonism; Female; Glucocorticoids; Humans; Inflammation; Leptin; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Middle Aged; Molecular Weight; Prospective Studies; Resistin; Up-Regulation | 2013 |
Association between prediagnostic biomarkers of inflammation and endothelial function and cancer risk: a nested case-control study.
Experimental and prevalent case-control studies suggest an association between biomarkers of inflammation, endothelial function, and adiposity and cancer risk, but results from prospective studies have been limited. The authors' objective was to prospectively examine the relations between these biomarkers and cancer risk. A nested case-control study was designed within the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) Study, a nationwide French cohort study, to include all first primary incident cancers diagnosed between 1994 and 2007 (n = 512). Cases were matched with randomly selected controls (n = 1,024) on sex, age (in 2-year strata), body mass index (weight (kg)/height (m)(2); <25 vs. ≥25), and SU.VI.MAX intervention group. Conditional logistic regression was used to study the associations between prediagnostic levels of high-sensitivity C-reactive protein (hs-CRP), adiponectin, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1, soluble E-selectin, and monocyte chemoattractant protein 1 and cancer risk. All statistical tests were 2-sided. Plasma sICAM-1 level was positively associated with breast cancer risk (for quartile 4 vs. quartile 1, multivariate odds ratio (OR) = 1.86, 95% confidence interval (CI): 1.06, 3.26; P(trend) = 0.048). Plasma hs-CRP level was positively associated with prostate cancer risk (for quartile 4 vs. quartile 1, multivariate OR = 3.04, 95% CI: 1.28, 7.23; P(trend) = 0.03). These results suggest that prediagnostic hs-CRP and sICAM-1 levels are associated with increased prostate and breast cancer risk, respectively. Topics: Adiponectin; Adiposity; Adult; Biomarkers; Body Mass Index; Breast Neoplasms; C-Reactive Protein; Case-Control Studies; Cell Adhesion Molecules; Chemokine CCL2; Double-Blind Method; Endothelium; Female; Health Behavior; Humans; Inflammation; Leptin; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Factors | 2013 |
Prolonged fasting and the effects on biomarkers of inflammation and on adipokines in healthy lean men.
Obesity and insulin resistance are associated with low-grade systemic inflammation, which is related to increased concentrations of plasma FFAs, glucose, or insulin. Prolonged fasting induces insulin resistance due to elevated plasma FFAs, but is not accompanied by hyperinsulinemia or hyperglycemia. This makes it possible to study effects of physiologically increased FFA concentrations on inflammatory markers, when insulin and glucose concentrations are not increased. In random order, 10 healthy young lean men (mean BMI: 22.8 kg/m2) were fasted or fed in energy balance for 60 h with a 2-week wash-out period. Subjects stayed in a respiration chamber during the 60-h periods. Blood samples were taken after 12, 36, and 60 h. Then, a hyperinsulinemic-euglycemic clamp was performed.Fasting decreased insulin sensitivity by 45% and increased FFA concentrations 5-fold. Fasting did not change concentrations of the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-8, or of hs-CRP. Effects on vascular endothelial growth factor (VEGF)--which may positively relate to insulin resistance, and on chemerin and leptin--adipokines related to obesity, and obesity-related pathologies, were also studied. At t=60 h, VEGF concentrations were significantly increased during the fasted period (p<0.05). At the same time point, chemerin (p<0.01) and leptin (p<0.01) were significantly decreased after fasting. For leptin, this decrease was also significant after 36 h (p<0.01). Adiponectin levels remained unchanged. In healthy young lean men, fasting-induced increases in FFAs leading to insulin resistance do not cause changes in concentrations of the inflammatory cytokines. VEGF concentrations increased and those of chemerin decreased. Topics: Adipokines; Adiponectin; Biomarkers; Chemokines; Fasting; Health; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Male; Thinness; Vascular Endothelial Growth Factor A; Young Adult | 2013 |
Anti-inflammatory effect of exercise, via reduced leptin levels, in obese women with Down syndrome.
Recent studies have reported that obese young people with Down syndrome suffer from low-grade systemic inflammation. Whereas this condition may be improved in the general population by regular exercise, the problem has received no attention in the case of people with intellectual disability. Therefore, the authors' aim was to assess the influence of aerobic training on plasma adipokines in obese women with Down syndrome. Twenty obese young women with Down syndrome volunteered for this study, 11 of whom were randomly assigned to a 10-wk aerobic-training program. They attended 3 sessions/wk, which consisted of warm-up exercises followed by the main activity on a treadmill (30-40 min) at a work intensity of 55-65% of peak heart rate and ended with a cooling-down period. The control group included 9 women with Down syndrome matched for age, sex, and body-mass index. Fat-mass percentage and distribution were measured, and plasma adipokine levels (leptin and adiponectin) were assessed. In addition, each participant performed a maximal graded continuous treadmill exercise test. These parameters were assessed pre- and postintervention. Aerobic training produced a significant increase in participants' maximal oxygen uptake (20.2 ± 5.8 vs.23.7 ± 6.3 ml · kg-1 · min-1; p < .001), and plasma leptin levels were significantly reduced in the intervention group (54.2 ± 6.7 vs.45.7 ± 6.1 ng/ml; p = .026). Further significant correlations between plasma leptin and indices of obesity were found. In contrast, no significant changes were found in adiponectin levels (p > .05). None of the tested parameters changed in the control group. In conclusion, a 10-week training program reduced leptin levels in obese young women with Down syndrome. Topics: Adiponectin; Adolescent; Adult; Body Composition; Body Height; Body Mass Index; Body Weight; Down Syndrome; Exercise; Exercise Test; Female; Humans; Inflammation; Leptin; Obesity; Waist-Hip Ratio; Young Adult | 2013 |
Selective capacity of metreleptin administration to reconstitute CD4+ T-cell number in females with acquired hypoleptinemia.
Leptin is an adipocyte-derived hormone that controls food intake and reproductive and immune functions in rodents. In uncontrolled human studies, low leptin levels are associated with impaired immune responses and reduced T-cell counts; however, the effects of leptin replacement on the adaptive immune system have not yet been reported in the context of randomized, controlled studies and/or in conditions of chronic acquired leptin deficiency. To address these questions, we performed a randomized, double-blinded, placebo-controlled trial of recombinant methionyl-human leptin (metreleptin) administration in replacement doses in women experiencing the female triad (hypothalamic amenorrhea) with acquired chronic hypoleptinemia induced by negative energy balance. Metreleptin restored both CD4(+) T-cell counts and their in vitro proliferative responses in these women. These changes were accompanied by a transcriptional signature in which genes relevant to cell survival and hormonal response were up-regulated, and apoptosis genes were down-regulated in circulating immune cells. We also observed that signaling pathways involved in cell growth/survival/proliferation, such as the STAT3, AMPK, mTOR, ERK1/2, and Akt pathways, were activated directly by acute in vivo metreleptin administration in peripheral blood mononuclear cells and CD4(+) T-cells both from subjects with chronic hypoleptinemia and from normoleptinemic, lean female subjects. Our data show that metreleptin administration, in doses that normalize circulating leptin levels, induces transcriptional changes, activates intracellular signaling pathways, and restores CD4(+) T-cell counts. Thus, metreleptin may prove to be a safe and effective therapy for selective CD4(+) T-cell immune reconstitution in hypoleptinemic states such as tuberculosis and HIV infection in which CD4(+) T cells are reduced. Topics: Adolescent; Adult; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cell Proliferation; Cytokines; Down-Regulation; Female; Gene Expression Profiling; Hormones; Humans; Inflammation; Leptin; Metabolic Diseases; Phenotype; Signal Transduction; Transcription, Genetic; Treatment Outcome; Up-Regulation; Young Adult | 2013 |
Metformin decreases plasma resistin concentrations in pediatric patients with impaired glucose tolerance: a placebo-controlled randomized clinical trial.
The objective was to determine the effect of metformin on the concentrations of resistin and other markers of insulin resistance or inflammation (C-reactive protein, cytokines, body weight, HbA1c, among others) in minors with glucose intolerance. Patients aged 4 to 17 years with glucose intolerance were studied. They were randomized to receive 850 mg of either metformin or placebo twice daily for 12 weeks, during which all followed an iso-caloric diet and an exercise program. High sensitivity C-reactive protein, TNF-alpha, IL-6, IL1-beta, resistin, leptin, adiponectin, glucose, insulin, HbA1c, lipid profile and transaminases were measured at the beginning and at the end of the period. Fifty-two patients were included, 11.9±2.6 years old; 28 (12 males/16 females) received metformin and 24 placebo (11 males/13 females). Baseline characteristics were similar between groups (except for body mass index, which in the metformin group was slightly higher). Percentage weight loss was greater in the metformin group (-5.86% vs 2.75%, P<.05). At study end, there were statistically significant differences in resistin concentrations, even after adjusting for confounding variables (F=7.714; P<.006). Also, metformin was associated with a significant decrease in HOMA-IR index (P=.032) and HbA1c levels (P=.001), but no change was observed in the concentration of other markers of inflammation. Metformin resulted in significant reductions of plasma resistin levels in minors with glucose intolerance. This change is independent of its effects on body weight. In contrast, metformin did not alter the concentration of inflammatory markers. Topics: Adiponectin; Adolescent; Biomarkers; C-Reactive Protein; Child; Child, Preschool; Drug Administration Schedule; Energy Intake; Exercise; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Interleukin-1beta; Interleukin-6; Leptin; Male; Metformin; Resistin; Tumor Necrosis Factor-alpha; Weight Loss | 2012 |
Alterations of leptin in the course of inflammation and severe sepsis.
The adipokine leptin regulates energy expenditure, vascular function, bone and cartilage growth as well as the immune system and systemic inflammatory response. Several activating effects towards T cells, monocytes, endothelium cells and cytokine production have been reported suggesting a protective role of leptin in the setting of an acute systemic inflammation. However, the pathophysiological role of leptin during severe sepsis is currently not elucidated in detail. This study aims to investigate leptin expression in cultured human adipocytes within an inflammatory model and in patients suffering from severe sepsis and evaluates treatment effects of drotrecogin alpha (activated) (DAA), the recombinant form of human activated protein C.. In an in-vitro inflammatory model of adipocyte cell-culture the effect of DAA on leptin mRNA expression was evaluated. Synthesis of mRNA was measured by quantitative polymerase chain reaction (qPCR). Additionally, supernatants of these adipocytes as well as serum levels of adiponectin were measured in blood of 104 severe septic patients by ELISA-method. 26 patients were treated with DAA (DAA+), 78 patients were not treated with DAA (DAA-).. Stimulation of human adipocytes with TNF alpha over 6 and 24 hours resulted in a significant decrease by 46% and 59% of leptin mRNA transcripts compared to un-stimulated controls (p < 0.05). Leptin levels of supernatants of adipocyte culture decreased by 25% and 23% (p < 0.05) after incubation with TNF alpha after 6 and 24 hours. Incubation with DAA at 50 ng/ml DAA and 5 μg/ml doubled mRNA expression significantly at 24 hours (p < 0.05) but not at 6 hours. From day 1 to day 3 of sepsis, leptin levels increased in DAA+ compared to DAA- patients (p<0.10).. Leptin appears to be involved in the pathogenesis of a systemic inflammatory response during sepsis. Administration of DAA significantly increased leptin expression. The specific mechanism or even benefit of DAA towards leptin needs further ongoing research. Topics: Adipocytes; Adult; Aged; Aged, 80 and over; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Profiling; Humans; Inflammation; Leptin; Male; Middle Aged; Protein C; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Sepsis; Serum; Transcription, Genetic; Treatment Outcome | 2012 |
Effects of nebivolol in obese African Americans with hypertension (NOAAH): markers of inflammation and obesity in response to exercise-induced stress.
We sought to determine whether the antihypertensive drug nebivolol has beneficial effects on vascular markers of inflammation and oxidation in obese African-American patients with hypertension when exposed to exercise-induced stress. Forty-three obese, African-American subjects with hypertension were treated with nebivolol (5-10 mg/day) for 8 weeks. Before treatment the subjects underwent an exercise treadmill study to a level of eight metabolic equivalents. Circulating levels of soluble interleukin-6 (sIL-6), vascular cell adhesion molecule (VCAM-1), adiponectin and leptin were measured at pre-treadmill, and 1 min, 30 min, 60 min and 24 h after treadmill. After the 8-week treatment period, exercise treadmill study and the measurement of markers were repeated. Treatment with nebivolol reduced levels of sVCAM-1 at pre-exercise by 21% and at 1 and 30 min by 12.5 and 20%, respectively (P<0.005 from corresponding time point). In nebivolol-treated patients there was a reduction in sIL-6 levels by 20% and pre-exercise and at 1 and 60 min by 19.7 and 33.5%, respectively (P<0.005 from corresponding time point). Treatment with nebivolol increased levels of serum adiponectin by 28% (P=0.012) and decreased levels of leptin by 32% (P<0.005 from pre-treatment). Treatment with nebivolol improves markers of inflammation and obesity in a high-risk African-American population. Moreover, this effect is potentiated in response to exercise-induced stress. These results suggest that nebivolol differentially regulates markers of inflammation and obesity, thereby providing vascular protection. Topics: Adiponectin; Antihypertensive Agents; Benzopyrans; Biomarkers; Black or African American; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Ethanolamines; Exercise; Female; Humans; Hypertension; Inflammation; Interleukin-6; Leptin; Lipids; Male; Middle Aged; Nebivolol; Obesity; Stress, Physiological; Treatment Outcome; Vascular Cell Adhesion Molecule-1 | 2011 |
Effects of renal-specific oral supplementation in malnourished hemodialysis patients.
Protein-energy malnutrition is still a problem in patients with chronic renal failure, especially during replacement renal therapy. The chronic inflammatory status in these patients intensifies the malnutrition, as well as making treatment more complicated. The aim of the present study was to estimate the influence of oral supplementation on the nutritional status of malnourished hemodialysis (HD) patients depending on the existence of an inflammatory state.. To study the influence of oral supplementation on nutrition status, 30 HD patients with protein-energy malnutrition characteristics and 25 well-nourished HD patients were enrolled in the study. Malnourished HD patients were prescribed Renilon 7.5 at an oral intake dose of 125 mL twice a day for 3 months. The nutritional status was characterized based on body mass index, Subjective Global Assessment score, serum albumin and prealbumin concentrations. The intensity of the inflammatory state was determined by C-reactive protein and interleukin-6. Serum concentrations of leptin and adiponectin were also measured.. After 3 months of supplementation, malnourished patients had an increase in prealbumin, albumin, and leptin concentrations. No statistically significant differences were observed between patients lacking inflammation and those with inflammation.. The results indicate an improvement in the nutritional status of HD patients who were prescribed an oral supplementation. Furthermore, patients with inflammatory state characteristics also benefited from Renilon 7.5 treatment. Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Dietary Supplements; Female; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin | 2011 |
Variation of inflammatory parameters after sibutramine treatment compared to placebo in type 2 diabetic patients.
The efficacy of sibutramine has been demonstrated in randomized trials in obese/overweight patients including those with type 2 diabetes mellitus (T2DM). Our objective was to evaluate the effects of 1-year treatment with sibutramine compared to placebo on body weight, glycaemic control, lipid profile, and inflammatory parameters in type 2 diabetic patients.. Two hundred and forty-six patients with uncontrolled T2DM [glycated haemoglobin (HbA(1c) ) > 8·0%] in therapy with different oral hypoglycaemic agents or insulin were randomized to take 10 mg of sibutramine or placebo for 12 months. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c) , fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), leptin, tumour necrosis factor-α (TNF-α), adiponectin (ADN), vaspin, high sensitivity C-reactive protein (Hs-CRP).. We observed a decrease of body weight after 9 and 12 months in the group treated with sibutramine, but not in the control group. Regarding glycaemic and lipid profile, although there are differences seen over time within each of the groups, we did not obtain any significant differences between the two groups. Both placebo and sibutramine gave a similar improvement of HOMA-IR, leptin, TNF-α, ADN, and Hs-CRP. No vaspin variations were observed in either group.. Sibutramine resulted in a decrease in body weight at 9 months and at 12 months that was not observed with placebo. Although there were differences seen over time within each of the groups, there were no significant differences between groups for any other parameter that we measured. Topics: Adiponectin; Appetite Depressants; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Comorbidity; Cyclobutanes; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Leptin; Lipids; Male; Middle Aged; Obesity; Placebos; Randomized Controlled Trials as Topic; Thiazolidinediones; Time Factors | 2011 |
Comparison between orlistat plus l-carnitine and orlistat alone on inflammation parameters in obese diabetic patients.
To evaluate the effects of 1-year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and inflammatory parameters in obese type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated the following parameters at baseline and after 3, 6, 9, and 12 months: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c) ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), adiponectin (ADN), leptin, tumor necrosis factor-α (TNF-α), vaspin, and high-sensitivity C-reactive protein (Hs-CRP). We observed a better decrease in body weight, glycemic profile, HOMA-IR, LDL-C, and ADN and a faster improvement in FPI, TC, Tg, leptin, TNF-α, Hs-CRP with orlistat plus L-carnitine compared to orlistat alone. We also recorded an improvement in vaspin with orlistat plus l-carnitine not reached with orlistat alone. Orlistat plus L-carnitine gave a better improvement in body weight, glycemic and lipid profile compared to orlistat alone; furthermore, a faster and better improvement in inflammatory parameters was observed with orlistat plus L-carnitine compared to orlistat alone. Topics: Adiponectin; Anti-Inflammatory Agents; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Carnitine; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Lactones; Leptin; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Obesity; Orlistat; Thiazolidinediones; Time Factors | 2011 |
Acetate-free blood purification can impact improved nutritional status in hemodialysis patients.
Effects of online hemodiafiltration (HDF) using acetate-free bicarbonate dialysis (AFD) fluid on microinflammation, resulting in improved nutritional status in hemodialysis patients, were examined and compared with conventional acetate-containing bicarbonate dialysis (ACD) fluid. A total of 24 hemodialysis patients were registered for a cross-over design study for a 6-month period. These patients were subjected to ACD for the first 3 months followed by AFD fluid for the latter 3 months. Blood variables of C-reactive protein (CRP), interleukin-6 (IL-6), leptin, neuropeptide Y (NPY), protein catabolic rate (PCR) and %creatinine (Cr) index were determined after the first and last 3-month period. The filters and the conditions of HDF and drug regimens including erythropoiesis-stimulating agents were unchanged throughout the cross-over study. Predialysis blood pH and bicarbonate were significantly higher in the AFD phase than in the ACD phase. Blood CRP and IL-6 levels were significantly decreased in the AFD group compared to the ACD group. Concerning nutritional evaluation, leptin and NPY were significantly lower and higher, respectively, in the AFD phase than in the ACD phase. PCR tended to be higher in the AFD phase than in the ACD phase. A significantly higher %Cr index level was observed in the AFD phase than in the ACD phase. These results suggest that online HDF using AFD fluid contributes to alleviating bioincompatible events associated with microinflammation, leading to improvement in the nutritional status in hemodialysis patients. Topics: Acetates; Adult; Aged; C-Reactive Protein; Cross-Over Studies; Female; Hemodiafiltration; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Neuropeptide Y; Nutritional Status; Renal Dialysis; Renal Insufficiency; Treatment Outcome | 2011 |
Nutrition education guided by Dietary Guidelines for Chinese Residents on metabolic syndrome characteristics, adipokines and inflammatory markers.
The objective of this study was to test whether "Dietary Guidelines for Chinese Residents" have beneficial effects on anthropometric and metabolic variables, adipokines and inflammatory markers in metabolic syndrome patients.. A multi-stage sampling method was applied to select metabolic syndrome patients in two districts of Shanghai. Two hundred and seventy-two metabolic syndrome patients were divided into control and intervention groups according to their district. Nutrition education guided by "Dietary Guidelines for Chinese Residents" was performed in the intervention group for one year.. Nutrition-related knowledge, attitudes and behavior were improved in the intervention group. Potassium intake and food to total energy ratio for grain, vegetable and fruit increased while sodium intake as well as fat to total energy ratio decreased in the intervention group compared to the control group (p<0.05). Correspondently, the intervention group significantly improved its waist circumference, waist to hip ratio, high-density lipoprotein cholesterol, adiponectin, leptin and tumor necrosis factor-α compared to the control group (p<0.05). Waist circumference changes from baseline to end of the study in the intervention and the control groups were -3.9±0.3 and -2.3±0.4 cm respectively. There was a significant difference between the two groups (p=0.004). Means of waist circumference, waist to hip ratio, leptin and tumor necrosis factor-α were lower, and high density lipoprotein-cholesterol was higher in the intervention group than the control group (p<0.05).. This study confirmed "Dietary Guidelines for Chinese Residents" had beneficial effects on anthropometric, lipids, adipokines and inflammatory markers in metabolic syndrome patients. Topics: Adipokines; Adiponectin; Adult; Aged; Anthropometry; Biomarkers; Blood Pressure; China; Diet; Exercise; Female; Health Knowledge, Attitudes, Practice; Humans; Inflammation; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Nutrition Policy; Nutritional Physiological Phenomena; Patient Education as Topic; Tumor Necrosis Factor-alpha | 2011 |
Changes in the sex hormone profile of male patients with moderate-to-severe plaque-type psoriasis under systemic therapy: results of a prospective longitudinal pilot study.
Patients with moderate-to-severe plaque-type psoriasis exhibit increased cardiovascular mortality. Recent publications point towards psoriasis-induced insulin resistance as an important pathomechanism driving cardiovascular comorbidity in these patients. As the hormonal status in general and sex hormone-binding globulin (SHBG) in particular serve as sensitive indicators for insulin resistance, we analysed these parameters in the context of a set of multiple additional clinical and laboratory measurements in a cohort of male patients. Of 33 consecutively enrolled male patients receiving continuous systemic therapy for their moderate-to-severe plaque-type psoriasis, 23 male patients for whom all parameters could be collected over a 24-week treatment period were included in this analysis. At baseline, testosterone levels varied between 212 and 660 ng/ml (median: 377.0), and SHBG between 11.9 and 46.0 nmol/l (median: 29.2), thus documenting lack of hypogonadism among these patients. Clinically, 19/23 patients experienced at least a 50% reduction in their PASI under therapy. Using a multivariate regression model to further analyse the sub-group of patients responding to treatment, hs-CRP, PASI, leptin and resistin all improved under effective systemic anti-inflammatory therapy, thus losing their significant influence on SHBG. SHBG performed well as a sensitive biomarker for insulin resistance and systemic inflammation in these patients. Its improvement, as well as the reduction of resistin serum levels, most likely reflects a state of reduced cardiovascular risk in patients undergoing effective continuous systemic therapy. Long-term safety data, generated e.g. from psoriasis registries, are needed to assess whether this effect translates into reduced cardiovascular mortality. Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Disease Progression; Follow-Up Studies; Humans; Inflammation; Insulin Resistance; Leptin; Male; Middle Aged; Pilot Projects; Prospective Studies; Psoriasis; Resistin; Risk; Sex Hormone-Binding Globulin; Testosterone | 2011 |
The effect of quinapril treatment on insulin resistance, leptin and high sensitive C-reactive protein in hypertensive patients.
The aim of the study was to evaluate the effect of quinapril on HOMA-IR, high sensitive C-reactive protein and leptin. Total 54 hypertensive and 24 control subjects were included in this study. Blood pressure, leptin, high sensitive C-reactive protein, and HOMA-IR were determined at baseline and after 3 months quinapril treatment. After treatment with quinapril HOMA-IR (p = 0.04), high sensitive C-reactive protein (p = 0.027), and leptin (p = 0.046) were decreased in hypertensive patients. Quinapril may be used as a therapy for improving blood pressure as well as the insulin resistant, hyperleptinemic, and low-grade inflammatory state in hypertension. Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; C-Reactive Protein; Female; Homeostasis; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Male; Middle Aged; Quinapril; Tetrahydroisoquinolines; Treatment Outcome | 2011 |
Changes in circulating satiety hormones in obese children: a randomized controlled physical activity-based intervention study.
The aims of this study are to examine in children: (i) obesity-related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity-based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 +/- 0.6 for 15 obese and 56.2 +/- 1.1 for 6 lean). The obese subjects underwent a 3-month randomized controlled physical activity-based lifestyle intervention. Leptin, soluble leptin receptor (sOB-R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual-energy X-ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB-R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB-R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity-based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk. Topics: Adolescent; Biomarkers; Body Weight; Cardiovascular Diseases; Exercise; Female; Ghrelin; Humans; Inflammation; Insulin Resistance; Leptin; Life Style; Male; Motor Activity; Obesity; Receptors, Leptin; Satiation | 2010 |
Leptin and the post-operative inflammatory response. More insights into the correlation with the clinical course and glucocorticoid administration.
Cardiac surgery involving cardiopulmonary bypass (CPB) causes a systemic inflammatory process which can lead to multiple organ failure and postoperative morbidity. Recent animal and human studies suggested a possible involvement of leptin in the systemic inflammatory response.. To characterize the response of leptin to open heart surgery (OHS) and the relationship between the time course of leptin levels and the post-operative clinical course, and to examine the effect of exogenous glucocorticoids.. Forty-seven pediatric patients, undergoing OHS for congenital heart disease were studied. Thirty-four patients (Group 1) received methylprednisolone during CPB while 13 (group 2) did not. Serial blood samples were collected perioperatively and up to 24 h after surgery, and assayed for leptin and cortisol.. All patients' leptin levels decreased significantly during CPB (to 44-48% of baseline, p<0.001); they then increased, peaking at 12 h post-operatively. The levels of groups 1 and 2 were similar up to 8 h post-operatively; thereafter, those of group 1 were significantly higher. Recovery of leptin levels in patients with a more complicated post-operative course was comparatively slower. Cortisol levels of all patients increased significantly during CPB (p<0.001), gradually decreasing afterwards. Cortisol and leptin levels were inversely correlated in both patients' groups.. CPB is associated with acute changes in circulating leptin levels. A complicated postoperative course is associated with lower leptin levels which are inversely correlated with cortisol levels. Leptin may participate in post-CPB inflammatory and hemodynamic responses. Topics: Adolescent; Cardiopulmonary Bypass; Child; Child, Preschool; Female; Glucocorticoids; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Inflammation; Leptin; Male; Methylprednisolone; Postoperative Complications; Postoperative Period; Prognosis; Systemic Inflammatory Response Syndrome | 2010 |
Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study.
Men with the metabolic syndrome (MetS) have low plasma testosterone (T) levels. The aim of this study was to establish whether the normalization of plasma T improves the features of the MetS.. A randomized, placebo-controlled, double-blinded, phase III trial of 184 men suffering from both the MetS and hypogonadism.. One hundred and eighty-four men, aged 35-70, with the MetS and hypogonadism (baseline total T level <12·0 nm or calculated free T level <225 pm.), recruited in the outpatient andrology and urology clinic, Research Center for Endocrinology in Moscow, Russia.. Treatment for 30 weeks with either parenteral T undecanoate (n = 113; TU; 1000 mg IM) or placebo (n = 71), administered at baseline, and after 6 and 18 weeks. One hundred and five (92·9%) men receiving TU and 65 (91·5%) receiving placebo completed the trial.. Body weight, body mass index (BMI), waist circumference (WC), hip circumference, waist-to-hip ratio, insulin, leptin, glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, C-reactive protein (CRP), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor-alpha (TNF-α).. There were significant decreases in weight, BMI and WC in the TU vs placebo group. Levels of leptin and insulin also decreased, but there were no changes in serum glucose or lipid profile. Of the inflammatory markers, IL-1β, TNF-α and CRP decreased, while IL-6 and IL-10 did not change significantly.. Thirty weeks of T administration normalizing plasma T in hypogonadal men with the MetS improved some components of the MetS and a number of inflammatory markers. Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Humans; Hypogonadism; Inflammation; Insulin; Interleukin-10; Interleukin-6; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Testosterone; Tumor Necrosis Factor-alpha; Waist Circumference; Waist-Hip Ratio | 2010 |
Plasma adiponectin concentration has an inverse and a non linear association with estimated glomerular filtration rate in patients with K/DOQI 3 - 5 chronic kidney disease.
Chronic kidney disease (CKD) is associated with an increased incidence of cardiovascular disease (CVD). A few studies have demonstrated elevated plasma adiponectin and leptin levels in CKD. The aims of this study were to assess whether 1) estimated glomerular filtration rate (eGFR) is associated with plasma leptin and adiponectin; and 2) adiponectin and leptin (partly) explain associations of CKD with endothelial dysfunction, insulin resistance, and low-grade inflammation in patients with K/DOQI Stage 3 - 5 CKD.. Baseline data from 91 patients with Stage 3 - 4 CKD in the anti-oxidant therapy in chronic renal insufficiency study, a randomized, double-blind, placebo-controlled trial, in which the effects of oxidative stress-lowering treatment on vascular function and structure were studied, and from 50 dialysis naïve patients, who took part in an open-label, randomized study that compared two peritoneal dialysis regimens, used in the analysis. All subjects for both the studies were recruited in the same centres.. The association between eGFR and adiponectin was non-linear. In multivariate analysis, log-eGFR (unstandardized beta = 8.303 microg/ml, p < 0.0001) was the strongest determinant of adiponectin, and body mass index the strongest determinant of leptin (beta = 2.477 ng/ml, p < 0.0001). Plasma adiponectin and leptin did not modify the associations between eGFR and plasma von Willebrand factor or soluble vascular adhesion molecule-1. Plasma leptin had the strongest association with the homeostatic model assessment (HOMA-IR) index. Plasma C-reactive protein had no association with adiponectin or leptin.. In patients with K/DOQI Stage 3 - 5 CKD, renal function had a significant non-linear inverse association with and was the strongest predictor of adiponectin. BMI was the strongest predictor of plasma leptin. Plasma adiponectin and leptin did not explain, and thus presumably are not involved in, the association between eGFR and some markers of endothelial dysfunction. Topics: Adiponectin; Antioxidants; Body Mass Index; Cross-Sectional Studies; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Kidney Function Tests; Leptin; Male; Middle Aged; Multivariate Analysis; Peritoneal Dialysis; von Willebrand Factor | 2009 |
Serum leptin levels in patients with allergic rhinitis.
To investigate the serum leptin levels in patients with allergic rhinitis during the symptomatic period.. A randomized, prospective study was performed on 26 adult patients with allergic rhinitis and 20 control subjects with similar age, sex and body mass index in a tertiary otolaryngology center.. Leptin levels were 28.8 +/- 14.1 ng/mL in the patients with allergic rhinitis, and 20.8 +/- 13.5 ng/mL in the control group respectively. The difference between the groups was statistically significant (p = 0.04).. Serum leptin levels were found to be significantly higher in patients with allergic rhinitis in symptomatic period.. Apart from its primary role in the regulation of body weight and energy expenditure, leptin may have a role in the inflammatory process of the allergic rhinitis. Topics: Adult; Body Mass Index; Female; Humans; Inflammation; Leptin; Male; Prospective Studies; Rhinitis | 2006 |
Inflammatory markers in adults with Prader-Willi syndrome before and during 12 months growth hormone treatment.
In Prader-Willi syndrome (PWS) obesity and partial growth hormone (GH) deficiency are frequently observed. The risks of cardiovascular diseases and early death are increased. We examined inflammatory markers in adult PWS, before and during 12 months of GH treatment.. Twelve PWS adults, median age 23.5 years (17-37) and median BMI 33.8 kg/m2 (21.2-50.4), participated. Serum interleukin-6, tumour necrosis factor alpha, high sensitive protein C-reactive protein (HCRP), cholesterol, triglycerides, leptin, adiponectin, glucose, insulin, insulin-like growth factor I and body composition were measured at baseline and after 6 and 12 months of GH treatment.. Median and range at baseline for interleukin-6 was 9.87 ng/l (1.76-10.72), for tumour necrosis factor alpha 2.39 ng/l (1.00-3.26) and for HCRP 7.64 mg/l (0.41-41.1) (normal values < 5 ng/l, < 8 ng/l and<5 mg/l, respectively). At baseline correlations between inflammatory markers and age, anthropometry, body composition and the metabolic parameters were non-significant; only positive associations were found between tumour necrosis factor alpha and body weight (r = 0.617, p = 0.033) and between HCRP and BMI (r = 0.594, p = 0.041). GH treatment non-significantly decreased the levels of the inflammatory markers.. In this pilot study, levels of interleukin-6 and HCRP were increased, and GH intervention did not significantly reduce the levels. Chronic inflammation might contribute to the increased cardiovascular morbidity and mortality in PWS. Topics: Adiponectin; Adolescent; Adult; Anthropometry; Biomarkers; Blood Glucose; Body Composition; C-Reactive Protein; Cholesterol; Female; Human Growth Hormone; Humans; Inflammation; Insulin; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Male; Obesity; Prader-Willi Syndrome; Triglycerides; Tumor Necrosis Factor-alpha | 2006 |
Insulin resistance, inflammatory biomarkers, and adipokines in patients with chronic kidney disease: effects of angiotensin II blockade.
Patients with chronic kidney disease (CKD) present a high prevalence of insulin resistance (IR). Some studies suggest that angiotensin II may influence some cellular pathways that contribute to the pathogenesis of IR and stimulate the release of proinflammatory cytokines. Fifty-two patients who had stages 3 and 4 CKD and no diabetes were administered an angiotensin receptor blocker (ARB), olmesartan (40 mg), for 16 wk. Before and after ARB treatment, metabolic and inflammatory parameters and adipokines were measured. IR was calculated by Homeostasis Model Assessment (HOMA) index. Baseline data were compared with data that were obtained from 25 healthy control individuals of similar age and normal renal function. Compared with control subjects, patients with CKD presented significantly higher BP and waist circumference, higher triglycerides and lower HDL levels, higher insulin levels, and higher mean HOMA index (6.0 +/- 2.7 versus 2.9 +/- 2.2 muU/ml x mmol/L; P < 0.001). In addition, patients with CKD had increased levels of high-sensitivity C-reactive protein, TNF-alpha, and IL-6. In patients with CKD, leptin was positively correlated to abdominal obesity, insulin levels, and IL-6, and adiponectin was inversely correlated to abdominal obesity and insulin levels. Olmesartan treatment resulted in a significant decrease of BP, urinary protein excretion, plasma glucose (99 +/- 16 versus 92 +/- 14 mg/dl; P < 0.05), insulin (23.1 +/- 8.8 versus 19.9 +/- 9; P < 0.05), HOMA index (6.0 +/- 2.7 versus 4.7 +/- 2.8; P < 0.05), and glycated hemoglobin (5.33 +/- 0.58 versus 4.85 +/- 0.81%; P < 0.01). At the same time, there was a significant reduction of high-sensitivity C-reactive protein levels, from 4.45 mg/L (2.45 to 9.00) to 3.55 mg/L (1.80 to 5.40; P < 0.05) and fibrinogen (412 +/- 100 versus 370 +/- 105 mg/dl; P < 0.05). There were no significant differences in adipokine levels after olmesartan treatment. These data demonstrate that patients with CKD have a high prevalence of IR, metabolic syndrome, and chronic inflammation and that the administration of the ARB olmesartan improves IR and inflammation markers in these patients. Plasma adipokine levels that are related to several metabolic risk factors in patients with CKD were not modified by ARB therapy. Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; C-Reactive Protein; Chronic Disease; Female; Humans; Imidazoles; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Kidney Diseases; Leptin; Male; Metabolic Syndrome; Middle Aged; Olmesartan Medoxomil; Tetrazoles; Waist-Hip Ratio | 2006 |
Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis.
Leptin regulates food intake and modulates immunity and inflammation. A positive feedback mechanism has been described between tumour necrosis factor (TNF) and leptin, and it has been suggested that leptin potentiates inflammation in patients with rheumatoid arthritis (RA).. To assess whether inflammation correlates with leptin concentrations in patients with RA, and whether anti-TNF treatment modulates leptin concentrations in these patients.. Leptin, IL6 and CRP were measured (at baseline and after 2 weeks of treatment) in the blood of 31 patients with RA starting either anti-TNF treatment or placebo, and in 18 healthy controls.. In patients with RA, plasma leptin concentrations at baseline correlated inversely with the degree of inflammation as assessed by C reactive protein (CRP; r(s)(2) = 0.21, p<0.01) or interleukin (IL) 6 concentrations (r(s)(2) = 0.22, p<0.008). Mean (SD) leptin concentrations did not differ between patients with RA and controls (6.0 (4.6) v 4.2 (2.8) ng/ml in men; 15.1 (7.9) v 13.4 (5.2) ng/ml in women). Short course anti-TNF treatment for 2 weeks did not modify leptin concentrations, despite significant reduction of CRP and IL6.. A significant inverse correlation between inflammation and leptin concentrations was found in patients with active RA, although plasma leptin concentrations did not significantly differ from those in healthy controls. This suggests that active chronic inflammation may lower plasma leptin concentrations. Two weeks' treatment with anti-TNF did not change plasma leptin concentrations and longer treatment may be needed to see an effect on leptin. Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Double-Blind Method; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Male; Middle Aged; Tumor Necrosis Factor-alpha | 2005 |
Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients.
Malnutrition-inflammation complex syndrome and anorexia, common conditions in maintenance dialysis patients, are strongly associated with higher mortality and hospitalization and lower quality of life (QoL) in this population. Megestrol acetate, 800 mg/day, has been shown to increase appetite and food intake and to mitigate inflammation in cachectic AIDS and cancer patients, leading to weight gain, but it is also associated with side effects at this dose.. We evaluated the efficacy of the oral solution of megestrol acetate in half of its conventional dose in improving the nutritional state and inflammation in 10 hypoalbuminemic dialysis patients (albumin < 3.7 g/dL). Six women and 4 men, ages 60.2 years, took 400 mg of megestrol acetate solution daily for 16 weeks. Anthropometry, dual energy x-ray absorptiometry, 24-hour diet recalls, and biochemical measurements of nutrition and inflammation, including serum C-reactive protein and leptin, were performed.. At the end of the 16 weeks of intervention, weight and body mass index increased by 9%, body fat proportion by 31%, and triceps skinfold by 40% (P < .01). Serum albumin increased from 3.0 to 3.3 g/dL and continued to increase significantly to 3.6 g/dL after 3 months postintervention (P = .03). Serum leptin increased from 5.2 to 10.7 ng/mL (P = .09). Daily protein and energy intake increased progressively up to 27% to 42% by the end of the trial (P < or = .01). In 8 patients without acute infection, serum C-reactive protein declined from 1.24 to 0.78 mg/L (P = .06). QoL and appetite were reported to be improved. No major side effects were observed, and all 10 patients completed the 16 weeks of daily intake of megestrol acetate without interruption.. Megestrol acetate oral solution in half of its conventional dose is safe and improves the nutritional state, inflammation, and anorexia in maintenance dialysis patients. Larger-scale placebo-controlled randomized studies are needed to confirm the beneficial effects of 400 mg/day of megestrol acetate in dialysis patients. Topics: Adult; Aged; Aged, 80 and over; Anorexia; Anthropometry; Body Composition; Body Mass Index; Body Weight; C-Reactive Protein; Dietary Proteins; Energy Intake; Female; Humans; Hypoalbuminemia; Inflammation; Kidney Failure, Chronic; Leptin; Male; Megestrol Acetate; Middle Aged; Nutritional Status; Prospective Studies; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin; Syndrome; Treatment Outcome | 2005 |
Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation.
Leptin is a nutritionally regulated adipocyte-derived cytokine. Previous studies in obese patients have demonstrated increased inflammatory markers and increased platelet aggregation in association with leptin. However, the effects of leptin administration on markers of inflammation and platelet aggregation in a human model of undernutrition have not previously been studied.. The objective of the study was to investigate markers of inflammation, platelet activation, and platelet aggregation in a model of caloric deprivation and increased leptin sensitivity.. This study was a randomized, placebo-controlled study conducted between November 2002 and November 2003.. The study was conducted at an inpatient care setting at the General Clinical Research Center.. Twenty healthy, young (18-35 yr old), normal-weight (body mass index, 20-26 kg/m2) women were recruited from local advertisements. No subjects withdrew due to adverse effects.. The effects of physiological recombinant methionyl human leptin or identical placebo administration were investigated over a 4-d fast.. The primary outcome measures for this study were C-reactive protein (CRP) and indices of platelet activity.. Leptin administration prevented the fasting-induced decline in leptin (P < 0.05 vs. placebo at each time point). Leptin administration increased CRP (6.3 +/- 2.4 vs. 0.7 +/- 0.3 mg/liter; P = 0.04), circulating P-selectin (11.6 +/- 10.2 vs. -28.9 +/- 15.6 ng/ml; P = 0.04), and induction of platelet aggregation (5.8 +/- 2.6 vs. -2.7 +/- 2.9%, P = 0.04, percent maximum platelet aggregation) relative to placebo administration (change in leptin vs. change in placebo, respectively, for each variable). Leptin tended to increase serum amyloid A [0.1 +/- 0.2 vs. -0.3 +/- 0.1 log10 (ng/ml); P = 0.07], and the changes in serum amyloid A and CRP were highly correlated (r = 0.83; P < 0.0001). No changes in TNFalpha, IL-6, IL-10, plasminogen activator inhibitor-1, haptoglobin, intercellular adhesion molecule, or vascular cell adhesion molecule were seen between the groups.. Our data provide evidence that physiological leptin administration stimulates inflammatory and platelet responses in humans during caloric deprivation. Topics: Adult; Biomarkers; Blood Cell Count; Body Composition; Double-Blind Method; Endothelium, Vascular; Energy Intake; Fasting; Female; Food Deprivation; Hemodynamics; Humans; Inflammation; Leptin; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Count; Recombinant Proteins | 2005 |
Circulating leptin, zinc, and copper levels after extracorporeal circulation.
The role of leptin in the acute stress response to extracorporeal circulation has been well documented, however, the relationship between leptin and zinc has not been investigated previously. We aimed to research the circulating leptin, zinc, and copper levels before, during, and after the extracorporeal circulation, and effect of preoperative zinc administration to these.. Twenty patients who were taken to elective coronary artery bypass grafting operations using extracorporeal circulation were taken to this research and divided into two equal groups (n1, n2). In both groups blood samples were taken just before the operation (T0), at the end of operation (T1), and at the first postoperative day (T2). In the second group (n2) oral zinc (50 mg, once a day) was administered to patients for 5 days, preoperatively. The serum leptin, zinc, and copper levels were studied.. In group n1 circulating leptin levels were significantly increased at T2 when compared to T0 and T1 (p<0.05); zinc levels were decreased at T2 when compared to T0 and T1 (p<0.05); copper levels were decreased at T2 when compared to T0 (p<0.05), and decreased at T1 when compared to T0 (p<0.05). In group n2 circulating leptin levels were significantly increased at T2 when compared to T0 and T1 (p<0.05); zinc levels were decreased at T2 when compared to T0 and T1 (p<0.05); copper levels were increased at T2 when compared to T1 (p<0.05).. These results indicate that circulating leptin levels increase after the extracorporeal circulation as an acute response, while zinc and copper levels decrease at the same period. Preoperative zinc administration does not prevent the leptin response after extracorporeal circulation. Topics: Antioxidants; Copper; Coronary Artery Bypass; Extracorporeal Circulation; Humans; Inflammation; Leptin; Preoperative Care; Stress, Physiological; Zinc | 2005 |
Leptin and the proinflammatory state associated with human obesity.
It has been suggested that elevated leptin levels underlie the low grade proinflammatory state in human obesity. We reasoned that if elevated leptin levels are an important factor in the proinflammatory state in obesity, then exogenous leptin administration during weight loss should counteract the concurrent beneficial effects of weight loss on the proinflammatory state. We therefore determined whether long-acting pegylated recombinant leptin (PEG-OB) prevents the decrease in cellular and humoral inflammation parameters during a very low calorie diet in healthy overweight young men. Except for B cells, PEG-OB treatment did not influence the decline in total leukocyte count and mononuclear subfractions during the diet. Weight loss decreased the humoral inflammation parameters TNFalpha, tissue plasminogen activator, and von Willebrand factor (P < 0.05), but in combination with PEG-OB treatment, a significant decrease was shown for inflammation markers as a whole (P < 0.014) and that of the individual parameters tissue plasminogen activator, von Willebrand factor, plasminogen activator inhibitor type 1, and intercellular adhesion molecule-1 (P < 0.05). The increase in C-reactive protein levels (P < 0.05) was the sole indication for a humoral proinflammatory action of leptin. Although PEG-OB treatment significantly increased weight loss (P < 0.03), the data do not support a proinflammatory role of leptin in human obesity. Topics: Adult; Diet, Reducing; Humans; Inflammation; Injections, Subcutaneous; Intercellular Adhesion Molecule-1; Leptin; Leukocyte Count; Male; Monocytes; Obesity; Plasminogen Activator Inhibitor 1; Polyethylene Glycols; Recombinant Proteins; Tissue Plasminogen Activator; Tumor Necrosis Factor-alpha; von Willebrand Factor; Weight Loss | 2004 |
Pathways linking depression, adiposity, and inflammatory markers in healthy young adults.
Despite mounting evidence that depression increases risk for cardiovascular morbidity and mortality, little is known about the mechanisms responsible for this association. The current study examined the inter-relationships between depression, adiposity, and inflammatory molecules implicated in the pathogenesis of coronary heart disease. One hundred adults were enrolled. Half were clinically depressed; the others were matched controls with no history of psychiatric illness. All subjects were in excellent health, defined as having no acute infectious disease, chronic medical illness, or prescribed medication regimen. Structural equation modeling yielded support for a model in which depressive symptoms promote weight accumulation, which in turn activates an inflammatory response through two distinct pathways: expanded adipose tissue release of interleukin-6 and leptin-induced upregulation of interleukin-6 release by white blood cells (CFI =.99; NNFI =.99; RMSEA =.05). It did not support a sickness behavior model in which the inflammatory molecules arising from expanded adipose tissue promote depressive symptoms. Topics: Adaptation, Physiological; Adult; Biomarkers; Body Weight; C-Reactive Protein; Depression; Evaluation Studies as Topic; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Matched-Pair Analysis; Models, Biological; Models, Statistical; Obesity; Psychoneuroimmunology; Signal Transduction | 2003 |
Effects of human recombinant erythropoietin on inflammatory status in peritoneal dialysis patients.
Treatment with recombinant human erythropoietin (rHuEPO) in dialysis patients has been associated with improvement of nutritional and immune status through an increase of cytokine production [such as tumor necrosis factor alpha (TNF alpha)]. The high cytokine production can be a double-edged sword owing to the relationship of cytokines with the systemic inflammatory process, which has been associated with many complications of uremic status. Our aim was to analyze the medium-long term effects of rHuEPO treatment on uremic inflammatory markers. We studied 45 peritoneal dialysis (PD) patients divided in two groups: a rHuEPO group (40-70 subcutaneous units/kg weekly) and a control group (no rHuEPO). The treated group was analyzed in four periods. Period 1 (rHuEPO-1) included 24 patients who had been using rHuEPO at long-term. Period 2 (rHuEPO-2; n = 21) looked at the patients 2 months after rHuEPO withdrawal. Period 3 (rHuEPO-3; n = 19) looked at the patients after 2 months under rHuEPO therapy. Period 4 (rHuEPO-4; n = 17) looked at the patients after 4 months on rHuEPO treatment. With the reintroduction of rHuEPO, we observed a progressive, statistically significant (p < 0.05), and temporary increase in TNF alpha plasma levels, from 44 +/- 24 pg/mL (rHuEPO-2) to 76.8 +/- 25 pg/mL (rHuEPO-3), and then to 83 +/- 27 pg/mL (rHuEPO-4). But in the long term, TNF alpha decreased [33.5 +/- 10 pg/mL (rHuEPO-1)]. Similarly, albumin increased in the short term (3.73 +/- 0.5 g/dL to 4 +/- 0.5 g/dL, and then to 4 +/- 0.43 g/dL), and then decreased (3.8 +/- 0.44 g/dL). The normalized protein catabolic rate (nPCR) increased from 1 +/- 0.2 g/kg daily to 1.12 +/- 0.3 g/kg daily (rHuEPO-4). Long term, nPCR decreased to 1.06 +/- 0.3 g/kg daily. Leptin initially increased (60.1 +/- 48 ng/mL to 42.8 +/- 22 ng/mL, and then to 38 +/- 18.2 ng/mL); it also increased in the long term (62 +/- 50.9, p < 0.05). At baseline, we found a significant positive linear correlation (p < 0.05) between TNF alpha and leptin (r = 0.52), TNF alpha and C-reactive protein [(CRP) r = 0.4], CRP and leptin (r = 0.49), fibrinogen and CRP (r = 0.78, p < 0.01), fibrinogen and leptin (r = 0.37), and leptin and body mass index [(BMI) r = 0.67]. In conclusion, rHuEPO induces a temporary, non inflammatory immune hyperactivity mediated by TNF alpha, without the adverse effects associated with that cytokine. By decreasing leptin, rHuEPO could increase food intake and improve the nutritional status of PD patients Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; C-Reactive Protein; Erythropoietin; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Proteins; Recombinant Proteins; Serum Albumin; Tumor Necrosis Factor-alpha | 2002 |
Induction chemotherapy followed by concomitant chemoradiation therapy in advanced head and neck cancer: a phase II study for organ-sparing purposes evaluating feasibility, effectiveness and toxicity.
The purpose of the study was to assess response rate, clinical outcome, organ/function preservation and toxicity in head and neck cancer patients treated with induction chemotherapy followed by concomitant chemoradiotherapy and, when necessary, limited surgery. The study design was a phase II non-randomized trial in hospitalized patients setting. The treatment plan consisted of 3 cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), l-leucovorin and interferon alpha2b (PFL-IFN) followed by 7 cycles of 5-FU, hydroxyurea and concomitant radiation for 5 days (FHX) for a total radiation dose of 70 Gy. 13 Cis-retinoic acid was added to treatment regimen for chemoprevention and a systematic prophylaxis of mucositis was administered to all patients during FHX. Conservative surgical resection was reserved to patients with no optimal response (PR > or =70%), whereas radical surgery was performed as salvage treatment. Twenty-six patients were treated at one institution: more than 90% had stage IV disease and only 19.2% had laryngeal cancer. Eighty-one percent of patients had performance status 0 and 23.1% of patients had >5% weight loss at the start of treatment. Nineteen patients were analyzed for response to PFL-IFN: 3/19 (15.8%) patients achieved a CR and 7/19 (36.8%) achieved a PR for an ORR of 52.6%. FHX was administered on protocol to 12 patients: 6 patients (50%) had CR, 1 patient (8.3%) had PR for an ORR of 58.3%, 2 patients (16.7%) had SD and 3 patients (25%) had PD. At the completion of FHX, no patient underwent local therapy according to treatment plan. At a median follow-up time of 13.5 months (range 1-28+) at June 2001, among 26 patients enrolled 12 (46.1%) were still alive and 9 (75%) of them were progression-free. The median duration of response was 9 months (range 0-25+), the median progression-free survival was 10.5 months (range 0-28+), the median overall survival time was 9 months (range 1-22). The toxicity was significant and consisted mainly of mucositis and, to a lesser extent, neutropenia/thrombocytopenia. In the present study, the low serum levels of leptin and the high serum levels of proinflammatory cytokines in advanced stage cancer patients were confirmed. In conclusion, this sequential induction chemotherapy and chemoradiotherapy program has been found moderately active and significantly toxic; moreover, the long overall treatment duration must be taken into consideration. For these reasons, this regimen could not be rec Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cytokines; Dose-Response Relationship, Radiation; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Inflammation; Interferon-alpha; Leptin; Leucovorin; Male; Middle Aged; Quality of Life; Treatment Outcome | 2002 |
The effect of pegylated recombinant human leptin (PEG-OB) on weight loss and inflammatory status in obese subjects.
To investigate whether weekly subcutaneous administration of 60 mg of long-acting pegylated human leptin (PEG-OB) for 8 weeks was able to influence weight loss, metabolic profile and inflammatory status of obese subjects on a mildly hypoenergetic diet (deficit: 3.2 MJ/day).. A prospective, randomized, double-blind and placebo-controlled single-center trial.. Twenty-eight healthy, obese subjects (16 women, 12 men; age 22-65 y; body mass index 27.7-38.7 kg/m2).. Bodyweight, metabolic profile (including lipids), C-reactive protein (CRP) and soluble TNF alpha-receptor (sTNF-R) 55 and 75 levels.. At the end of the study no significant differences in the delta or percentage weight loss between the placebo (n = 14) and PEG-OB (n = 14) groups was observed. Also the changes in metabolic profile, CRP, sTNF-R55 and R75 concentrations between the two groups after 8 weeks of treatment did not differ.. Weekly injection of 60 mg PEG-OB did not lead to additional weight loss after 8 weeks of treatment. Furthermore, PEG-OB administration did not affect the changes in metabolic profile and the inflammatory status of obese subjects. Topics: Adolescent; Adult; Aged; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Double-Blind Method; Female; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Placebos; Prospective Studies; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Weight Loss | 2002 |
Effect of weight loss and the inflammatory response on leptin concentrations in gastrointestinal cancer patients.
Animal research suggests that leptin may have an important role in the regulation of energy balance. The role of leptin in the progressive involuntary weight loss associated with cancer in humans is of considerable interest. However, such studies are limited. In this study, we compared circulating leptin concentrations in gastrointestinal cancer patients and weight loss (n = 27) with those of healthy subjects (n = 27). The effect of the presence of an inflammatory response on leptin concentrations was also examined. There were significantly lower leptin concentrations in male (median, 2.4 microg/liter; range, <0.5-6.0 microg/liter) and female (median, 3.4 microg/liter; range, <0.5-9.8 microg/liter) cancer patients than there were in male (median, 6.5 microg/liter; range, 3.1-10.9 microg/liter) and female (median, 18.7 microg/liter; range, 8.0-31.5 mcirog/liter) healthy subjects (P < 0.001). However, the leptin concentrations in both patients and normal subjects were related to the predicted percentage of body fat (r = 0.731; P < 0.001). Circulating leptin concentrations in the cancer patients were not altered by the presence of an inflammatory response. These results suggest that cancer anorexia/cachexia is not due to a simple dysregulation of leptin production. Topics: Adult; Aged; Case-Control Studies; Energy Metabolism; Female; Gastrointestinal Neoplasms; Humans; Inflammation; Leptin; Male; Middle Aged; Proteins; Weight Loss | 1998 |
Relation of leptin and neuropeptide Y in human blood and cerebrospinal fluid.
Leptin and neuropeptide Y (NPY) are involved in the regulation of food intake and body weight. Both hormones act through specific receptors in the central nervous system. The objective of this study was to investigate the relation of leptin and NPY in human plasma and cerebrospinal fluid (CSF). Leptin and NPY in CSF and in serum/plasma were measured by radioimmunoassays in 35 patients. Leptin concentrations in serum were 100-200 fold higher than in CSF. There was a significant correlation between leptin levels in CSF and in serum (r=0.88, P<0.0001). Female patients had significantly higher leptin serum concentrations than males (16.6+/-10.9 microg/l vs. 6.5+/-7.3 microg/l, P=0.002). In contrast, NPY levels were only twofold higher in CSF than in plasma. There was no relation between leptin and NPY in CSF and serum/plasma, respectively. The ratio of CSF and peripheral leptin levels did not correlate with the respective albumin ratio, indicating that leptin did not merely leak into the CSF via a defective blood-CSF barrier. It is concluded that leptin uptake from the circulation into CSF is a regulated process. The NPY concentration in CSF is not directly related to leptin CSF levels. Topics: Female; Humans; Inflammation; Leptin; Male; Middle Aged; Neuropeptide Y; Proteins; Radioimmunoassay; Reference Values | 1997 |
772 other study(ies) available for leptin and Inflammation
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Regulation of cardiovascular health and disease by visceral adipose tissue-derived metabolic hormones.
Visceral adipose tissue (VAT) is a metabolic organ known to regulate fat mass, and glucose and nutrient homeostasis. VAT is an active endocrine gland that synthesizes and secretes numerous bioactive mediators called 'adipocytokines/adipokines' into systemic circulation. These adipocytokines act on organs of metabolic importance like the liver and skeletal muscle. Multiple preclinical and in vitro studies showed strong evidence of the roles of adipocytokines in the regulation of metabolic disorders like diabetes, obesity and insulin resistance. Adipocytokines, such as adiponectin and omentin, are anti-inflammatory and have been shown to prevent atherogenesis by increasing nitric oxide (NO) production by the endothelium, suppressing endothelium-derived inflammation and decreasing foam cell formation. By inhibiting differentiation of vascular smooth muscle cells (VSMC) into osteoblasts, adiponectin and omentin prevent vascular calcification. On the other hand, adipocytokines like leptin and resistin induce inflammation and endothelial dysfunction that leads to vasoconstriction. By promoting VSMC migration and proliferation, extracellular matrix degradation and inflammatory polarization of macrophages, leptin and resistin increase the risk of atherosclerotic plaque vulnerability and rupture. Additionally, the plasma concentrations of these adipocytokines alter in ageing, rendering older humans vulnerable to cardiovascular disease. The disturbances in the normal physiological concentrations of these adipocytokines secreted by VAT under pathological conditions impede the normal functions of various organs and affect cardiovascular health. These adipokines could be used for both diagnostic and therapeutic purposes in cardiovascular disease. Topics: Adipokines; Adiponectin; Adipose Tissue; Cardiovascular Diseases; Humans; Inflammation; Intra-Abdominal Fat; Leptin; Resistin | 2023 |
Longitudinal associations between cardiovascular biomarkers and metabolic syndrome during puberty: the PUBMEP study.
Puberty has been described as a life stage of considerable metabolic risk specially for those with obesity. The low-grade systemic inflammatory status associated with obesity could be one of the connections with metabolic syndrome (MetS). Thus, we aimed to assess the relationship between inflammatory and cardiovascular biomarkers and the development of MetS during puberty. Seventy-five children from the PUBMEP study (33 females), aged 4-18 years, were included. Cardiovascular and inflammatory biomarkers were measured in the prepubertal and pubertal stage, including high-sensitivity C-reactive protein (CRP), leptin, tumor necrosis factor-alpha (TNFα), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP-1), total plasminogen activator inhibitor-1 (tPAI), resistin, adiponectin, myeloperoxidase (MPO), and soluble intercellular adhesion molecule-1 (sICAM-1). MetS was diagnosed at each measurement point. Mixed-effects and logistic regressions were performed. Those children with MetS in puberty presented higher prepubertal values of several cardiometabolic biomarkers in comparison to those without MetS (z-score body mass index (zBMI), waist circumference, insulin, HOMA-IR, leptin, and tPAI (p < 0.05)). For prepubertal children with obesity, the odds of developing MetS in puberty were significantly higher in those having high zBMI (OR = 4.27; CI: 1.39-22.59) or high concentrations of tPAI (OR = 1.19; CI: 1.06-1.43).. Those with obesity with higher prepubertal tPAI plasma levels had 19% higher odds of having MetS at puberty highlighting the existence of association between MetS, obesity, and inflammation already in puberty. Thus, assessing cardiometabolic and inflammatory status in children with obesity already at prepuberty is key to avoiding future comorbidities.. • Inflammation, metabolic syndrome, and obesity may have their onset in childhood. • Puberty is a life stage characterized for an increased cardiovascular risk.. • Prepuberty state could be an early indicator of future cardiometabolic risk. • Children with obesity and high total plasminogen have higher odds of future metabolic syndrome. Topics: Adiponectin; Adolescent; Biomarkers; Body Mass Index; Cardiovascular Diseases; Child; Child, Preschool; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Puberty | 2023 |
Actin related protein 2/3 complex subunit 1 up-regulation in the hypothalamus prevents high-fat diet induced obesity.
Obesity is a major health crisis in the modern society. Studies have shown that the consumption of a high-fat diet (HFD) induces hypothalamic inflammation and leptin resistance, which consequently favours body mass gain. Actin related protein 2/3 complex subunit 1 (ARPC1B), an actin-binding protein, is highly expressed in immune cells. Recent studies have shown that ARPC1B has a certain anti-inflammatory effect. While ARPC1B expression is decreased in the hypothalamus of mice fed a HFD, the role of ARPC1B in HFD-induced obesity remains unclear. Thus, we investigated whether ARPC1B up-regulation in the hypothalamic arcuate nucleus (ARC) could inhibit the development of obesity. Herein, ARPC1B overexpression lentiviral particles were stereotaxically injected into the ARC of male C57BL/6J mice (7 weeks old) fed with HFD. Overexpression of ARPC1B in the hypothalamic ARC attenuated HFD-induced ARC inflammation, reduced body-weight gain and feed efficiency. Furthermore, up-regulation of ARC ARPC1B improved the glucose tolerance and reduced subcutaneous/epididymal fat mass accumulation, which decreased the serum total cholesterol, serum triglyceride and leptin levels. In addition, upon ARPC1B overexpression in the hypothalamic ARC, intraperitoneal injection of leptin increased the phosphorylation level of signal transducer and activator of transcription 3 (STAT3), an important transcription factor for leptin's action, in the ARC of obese mice. Accordingly, we suggest that up-regulation of ARPC1B in the hypothalamic ARC may improve the HFD-induced hypothalamic inflammation and leptin resistance. Our findings demonstrate that ARPC1B is a promising target for the treatment of diet-induced obesity. Topics: Actin-Related Protein 2; Actin-Related Protein 2-3 Complex; Actin-Related Protein 3; Animals; Arcuate Nucleus of Hypothalamus; Diet, High-Fat; Hypothalamus; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Up-Regulation | 2023 |
THE ROLE OF OBESITY AND PLASMA ADIPOCYTOKINES IN IMMUNE DYSREGULATION IN SEPSIS PATIENTS.
Introduction: The dysregulated immune response in sepsis is highly variable, ranging from hyperinflammation to immunoparalysis. Obesity is associated with the release of inflammatory mediators from adipose tissue, known as adipocytokines, causing a chronic inflammatory state. Perhaps counterintuitively, obesity is also associated with lower mortality in sepsis patients. We investigated the association between obesity, circulating adipocytokine concentrations, immune dysregulation, and outcome in sepsis patients. Methods In this secondary analysis of a prospective study, plasma concentrations of the adipocytokines leptin, adiponectin, and resistin were assessed in 167 patients at diagnosis of sepsis due to pneumonia, bacteremia, or acute cholangitis. Adipocytokines were compared between patients with normal weight (body mass index [BMI], 18.5-24.9 kg/m 2 ; n = 67), overweight (BMI, 25.0-29.9 kg/m 2 ; n = 56), and obesity (BMI ≥30 kg/m 2 ; n = 42), as well as between immunological endotypes: hyperinflammation (n = 40), immunoparalysis (n = 62), and unclassified (n = 55). Results: Higher circulating concentrations of leptin were observed in patients with obesity compared with patients with normal weight ( P = 0.008) and overweight ( P = 0.02), whereas adiponectin and resistin plasma concentrations were not different ( P = 0.08 and P = 0.85, respectively). Resistin concentrations were associated with immunological endotypes, with the highest levels found in hyperinflammatory patients ( P < 0.001). Furthermore, resistin concentrations were predictive for 28-day mortality (adjusted odds ratio, 1.03 per 10 ng/mL; P = 0.04). These associations were not found for leptin and adiponectin. Conclusion: Obesity and BMI-related adipocytokines are not related to the development of a hyperactive or suppressed immune response as defined by ferritin and mHLA-DR expression in sepsis patients. Although resistin is related to the immune response and an increased risk of adverse clinical outcomes, these associations are similar in patients with normal weight, overweight, and obesity. This implies that the relationship between resistin and clinical outcome is likely driven by the inflammatory response and not by obesity itself. Taken together, although there exists a strong association between inflammation and sepsis mortality, our results do not point toward a role for obesity and BMI-related adipocytokines in immune dysregulation in sepsis patients. Topics: Adipokines; Adiponectin; Humans; Inflammation; Leptin; Obesity; Overweight; Prospective Studies; Resistin; Sepsis | 2023 |
Circulating adipokine levels and COVID-19 severity in hospitalized patients.
Obesity is a risk factor for adverse outcomes in COVID-19, potentially driven by chronic inflammatory state due to dysregulated secretion of adipokines and cytokines. We investigated the association between plasma adipokines and COVID-19 severity, systemic inflammation, clinical parameters, and outcome of COVID-19 patients.. In this multi-centre prospective cross-sectional study, we collected blood samples and clinical data from COVID-19 patients. The severity of COVID-19 was classified as mild (no hospital admission), severe (ward admission), and critical (ICU admission). ICU non-COVID-19 patients were also included and plasma from healthy age, sex, and BMI-matched individuals obtained from Lifelines. Multi-analyte profiling of plasma adipokines (Leptin, Adiponectin, Resistin, Visfatin) and inflammatory markers (IL-6, TNFα, IL-10) were determined using Luminex multiplex assays.. Between March and December 2020, 260 SARS-CoV-2 infected individuals (age: 65 [56-74] BMI 27.0 [24.4-30.6]) were included: 30 mild, 159 severe, and 71 critical patients. Circulating leptin levels were reduced in critically ill patients with a high BMI yet this decrease was absent in patients that were administered dexamethasone. Visfatin levels were higher in critical COVID-19 patients compared to non-COVID-ICU, mild and severe patients (4.7 vs 3.4, 3.0, and 3.72 ng/mL respectively, p < 0.05). Lower Adiponectin levels, but higher Resistin levels were found in severe and critical patients, compared to those that did not require hospitalization (3.65, 2.7 vs 7.9 µg/mL, p < 0.001, and 18.2, 22.0 vs 11.0 ng/mL p < 0.001).. Circulating adipokine levels are associated with COVID-19 hospitalization, i.e., the need for oxygen support (general ward), or the need for mechanical ventilation and other organ support in the ICU, but not mortality. Topics: Adipokines; Adiponectin; Aged; COVID-19; Cross-Sectional Studies; Humans; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Prospective Studies; Resistin; SARS-CoV-2 | 2023 |
Exercise modulation in inflammation and metabolic hormonal disorders of COVID-19 to decrease risk factors in coronary heart disease.
Sedentary life style separated during COVID-19 pandemic. Patients with cardiovascular diseases (CVD) are vulnerable with sedentary life style. Therefore, the aim of this study was to investigate the effect of 8 weeks of combined and high intensity interval training (HIIT) on C Reactive protein, galectin-3, leptin, fibrinogen and insulin resistance index in coronary heart disease after COVID-19.. Thirty-six cardiovascular patients (55.14 ± 1.4 years, 78.6 ± 5.1 kg) were divided into three groups of combined exercise (n=13), HIIT (n=12) and control group (n=11). Combined exercise consisted of aerobic (4 weeks) and aerobic + HIIT exercise (4 weeks), three sessions per weeks. The protocol of the HIIT group included performing high intensity interval training, three sessions per weeks for 8 weeks. Blood samples were taken 24 h before the first training session and 48 h after the last training. C Reactive protein (CRP), galectin-3, leptin, fibrinogen measured with ELISA kit.. CRP, galectin-3 and fibrinogen decreased significantly after 8 weeks of combined training and HIIT (compare to pre-test). Also, insulin resistance index after 8 weeks of combined exercise showed a significant decrease compare to pre-test (p<0.05). After 8 weeks, CRP, galectin-3 and insulin resistance significantly decreased compare to control group (p<0.05).. In the patient with CVD, combined exercise training may be more effective than HIIT in reducing metabolic and heart risk factors after an epidemic such as COVID-19. However, change of leptin need to more studies. Topics: C-Reactive Protein; Cardiovascular Diseases; Coronary Disease; COVID-19; Exercise; Fibrinogen; Galectin 3; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Pandemics; Risk Factors | 2023 |
The inflammatory score and cardiovascular risk in young adults with overweight or obesity: The African-PREDICT study.
A complex relationship of adipokines and cytokines with cardiovascular risk motivates the use of an integrated approach to identify early signs of adiposity-related inflammation. We compared the inflammatory profiles, including an integrated inflammatory score, and cardiovascular profiles of young adults who are living with overweight and/or obesity (OW/OB).. This cross-sectional study included 1194 men and women with a median age of 24.5 ± 3.12 years from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT). Participants were divided into approximate quartiles based on adiposity measures (body mass index, waist circumference, and waist-to-height ratio). We compared an integrated inflammatory score (including leptin, adiponectin, interleukin-6, interleukin-8, interleukin-10, and tumour necrosis factor-α) as well as the individual inflammatory markers, between extreme quartiles. We also compared blood pressure measures, left ventricular mass index, carotid-femoral pulse wave velocity, and carotid intima-media thickness between these groups.. Individuals in the top quartile had worse inflammatory- and cardiovascular profiles as the integrated inflammatory score, leptin, interleukin-6, blood pressure measures, and left ventricular mass index were higher, while adiponectin was lower (all p ≤ 0.003). Unexpectedly, carotid-femoral pulse wave velocity was also lower (p < 0.001) in the top quartile. Exclusively in the top quartile, all adiposity measures related positively with the integrated inflammatory score and central systolic blood pressure (both r ≥ 0.24; p < 0.001), and negatively with interleukin-10 (all r ≤ -0.13; p < 0.03). Of these relationships, the correlations with the integrated inflammatory score were the strongest (p < 0.001). The percentage difference of being in the top quartile of all adiposity measures were higher for the inflammatory score (all ≥ 263 %), leptin (all ≥ 175 %), interleukin-6 (all ≥ 134 %), and tumour necrosis factor-α (all ≥ 26 %), and lower for adiponectin (all ≥ 57 %), interleukin-10 (all ≥ 9 %), and interleukin-8 (all ≥ 15 %) compared to being in the bottom quartile.. The inflammatory score, as a comprehensive marker of adiposity-related inflammation, is strongly related to adiposity and may be an indication of early cardiovascular risk in young adults; however, further work is required to establish the clinical use thereof. Topics: Adiponectin; Adiposity; Adult; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Female; Heart Disease Risk Factors; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Leptin; Male; Obesity; Overweight; Prospective Studies; Pulse Wave Analysis; Risk Factors; Tumor Necrosis Factor-alpha; Young Adult | 2023 |
Diet-induced obesity worsens allergen-induced type 2/type 17 inflammation in airways by enhancing DUOX1 activation.
More than 50% of people with asthma in the United States are obese, and obesity often worsens symptoms of allergic asthma and impairs response to treatment. Based on previously established roles of the epithelial NADPH oxidase DUOX1 in allergic airway inflammation, we addressed the potential involvement of DUOX1 in altered allergic inflammation in the context of obesity. Intranasal house dust mite (HDM) allergen challenge of subjects with allergic asthma induced rapid secretion of IL-33, then IL-13, into the nasal lumen, responses that were significantly enhanced in obese asthmatic subjects (BMI >30). Induction of diet-induced obesity (DIO) in mice by high-fat diet (HFD) feeding similarly enhanced acute airway responses to intranasal HDM challenge, particularly with respect to secretion of IL-33 and type 2/type 3 cytokines, and this was associated with enhanced epithelial DUOX1 expression and was avoided in DUOX1-deficient mice. DIO also enhanced DUOX1-dependent features of chronic HDM-induced allergic inflammation. Although DUOX1 did not affect overall weight gain by HFD feeding, it contributed to glucose intolerance, suggesting a role in glucose metabolism. However, glucose intolerance induced by short-term HFD feeding, in the absence of adiposity, was not sufficient to alter HDM-induced acute airway responses. DIO was associated with enhanced presence of the adipokine leptin in the airways, and leptin enhanced DUOX1-dependent IL-13 and mucin production in airway epithelial cells. In conclusion, augmented inflammatory airway responses to HDM in obesity are associated with increases in airway epithelial DUOX1, and by increased airway epithelial leptin signaling. Topics: Allergens; Animals; Asthma; Diet; Disease Models, Animal; Dual Oxidases; Glucose Intolerance; Inflammation; Interleukin-13; Interleukin-33; Leptin; Mice; Obesity; Pyroglyphidae | 2023 |
Obesity and metabolic dysfunction correlate with background parenchymal enhancement in premenopausal women.
This study tested the hypothesis that obesity and metabolic abnormalities correlate with background parenchymal enhancement (BPE), the volume and intensity of enhancing fibroglandular breast tissue on dynamic contrast-enhanced magnetic resonance imaging.. Participants included 59 premenopausal women at high risk of breast cancer. Obesity was defined as BMI ≥ 30 kg/m. BMI was positively correlated with BPE (r = 0.69; p < 0.001); participants with obesity had higher BPE than those without obesity (404.9 ± 189.6 vs. 261.8 ± 143.8 cm. In premenopausal women at high risk of breast cancer, increased BPE is associated with obesity, insulin resistance, leptin, and adiponectin. Topics: Adiponectin; Breast Neoplasms; Female; Humans; Inflammation; Insulin Resistance; Leptin; Lipids; Obesity | 2023 |
Cross-sectional associations between physical fitness and biomarkers of inflammation in children-The PANIC study.
Systemic low-grade inflammation has been proposed as an underlying pathophysiological mechanism for cardiometabolic diseases. We investigated the associations of physical fitness with a systemic low-grade inflammatory state in a population sample of children.. Altogether 391 children aged 6-9 years were examined. Cardiorespiratory fitness (maximal power output, W. Higher physical fitness is associated with a more favorable inflammatory biomarker profile in children. However, the associations were explained by BF%. Topics: Adiponectin; Biomarkers; C-Reactive Protein; Cardiorespiratory Fitness; Child; Cross-Sectional Studies; Exercise Test; Hand Strength; Humans; Inflammation; Interleukin-6; Leptin; Physical Fitness; Receptors, Leptin; Tumor Necrosis Factor-alpha | 2023 |
Dietary inflammatory index and its association with leptin and adiponectin in Uygur overweight/obese adults.
Introduction: chronic inflammation contributes to a wide range of metabolic disorders through the influence of diet. The dietary inflammatory index (DII) was developed to measure the inflammation potential of diet. Objectives: Uygur adults have a high prevalence of obesity, but the causes of this condition remain unclear. In this study we investigated the association between DII and adipocytokines among overweight and obese Uygur adults. Methods: a total of 283 obese and overweight Uygur adults were included. Sociodemographic characteristics, anthropometric measurements, dietary surveys and biochemical indicators were collected by standardized protocols. The DII score was calculated using a valid and reliable 93-item food frequency questionnaire (FFQ). Linear regression was used to estimate the relationship between DII and adipocytokines. Results: the DII score was 1.35 ± 1.08, ranging from -2.14 to +3.11. There was a significant inverse correlation between DII and high-density lipoprotein cholesterol (HDL-C) in the unadjusted model (β = -0.12, SE = 0.05, p = 0.02), and this remained after adjustment for age, gender, body mass index (BMI). DII was negatively associated with adiponectin (ADPN) ( = -203.15, p = 0.04) and positively associated with leptin (LEP) concentration ( = 1.64, p = 0.002) after adjustment for age, gender and BMI. Conclusion: a pro-inflammatory diet, as indicated by a higher DII score, is associated with adipose tissue inflammation in Uygur adults and supports the hypothesis that diet may play a role in the development of obesity through inflammatory modulation mechanisms. A healthy anti-inflammatory diet is feasible for obesity intervention in the future.. Introducción: la inflamación crónica causa múltiples trastornos metabólicos a través de la influencia de la dieta. El índice de inflamación dietética (DII) se estableció para medir el potencial inflamatorio de la dieta. Objetivo: los adultos uigur presentan una alta prevalencia de obesidad, pero las causas de esta condición aún no están claras. En el presente estudio se investigó la relación entre DII y adipocitocinas en adultos uigur con sobrepeso y obesidad. Métodos: se incluyeron 283 adultos uigur obesos y con sobrepeso. Las características sociodemográficas, antropométricas, dietéticas y bioquímicas se recogieron mediante un protocolo estandarizado. El índice DII se calculó utilizando un cuestionario de frecuencia alimentaria (FFQ) válido y fiable de 93 elementos. Se realizó una regresión lineal para estimar la relación entre DII y adipocitocinas. Resultados: la puntuación DII fue de 1,35 ± 1,08 y osciló entre -2,14 y +3,11. En el modelo no ajustado hubo una correlación negativa significativa entre DII y colesterol lipoproteínico de alta densidad (HDL-C) (β = -0,12, p = 0,02) que permaneció después de ajustar la edad, el sexo y el índice de masa corporal (IMC). Después de ajustar la edad, el sexo y el IMC, el DII se correlacionó negativamente con la concentración de adiponectina (β = - 203,15, p = 0,04) y positivamente con la concentración de leptina (β = 1,64, p = 0002). Conclusión: las puntuaciones más altas de DII sugieren que la dieta proinflamatoria está relacionada con la inflamación del tejido adiposo en los adultos uigur, y apoyan la hipótesis de que la dieta puede desempeñar un papel en el desarrollo de la obesidad a través del mecanismo de regulación de la inflamación. La dieta antiinflamatoria saludable es factible para futuras intervenciones de obesidad. Topics: Adiponectin; Adult; Diet; Humans; Inflammation; Leptin; Obesity; Overweight | 2023 |
SEX-DEPENDENT EFFECTS OF ADIPOCYTE STAT3 INHIBITION ON THE INFLAMMATORY RESPONSE DURING SEVERE SEPSIS.
Introduction: Sepsis is a dysregulated host response to infection that can lead to life-threatening organ dysfunction. Clinical and animal studies consistently demonstrate that female subjects are less susceptible to the adverse effects of sepsis, demonstrating the importance of understanding how sex influences sepsis outcomes. The signal transducer and activator of transcription 3 (STAT3) pathway are a major signaling pathway that facilitates inflammation during sepsis. STAT3 is abundantly expressed in white adipose tissue; however, little is known about the contribution of white adipose tissue STAT3 activation during sepsis. We hypothesize that adipocyte STAT3 inhibition during severe sepsis will exaggerate the inflammatory response and impact organ injury, in a sex-dependent manner. Methods: We generated STAT3 flox/flox (wild-type [WT]) and adipocyte STAT3 knock out (A-STAT3 KO) mice using Cre-lox technology. Studies were done in 12- to 16-week-old male and female mice. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Control nonseptic mice did not undergo CLP (0 h CLP). Tissues were harvested 18 h after CLP. Body composition was determined by echo magnetic resonance imaging. Energy metabolism was determined by indirect calorimetry. White adipose tissue morphology was determined by hematoxylin and eosin staining, while STAT3 activation in the white adipose tissue was determined by western blot analysis and immunohistochemistry staining of STAT3 activation/phosphorylation at tyrosine 705. Plasma cytokines (TNF-α, IL-6, and leptin) were determined by luminex assay. Neutrophil infiltration of the lung and liver was assessed by myeloperoxidase activity assay. Histological signs of organ injury on lung and liver tissue were assessed by hematoxylin and eosin staining. Liver injury was further assessed by measuring plasma alanine and aspartate aminotransferase. In a separate cohort of mice, sepsis was induced by CLP and mice were monitored every 6-12 h over a 7-day period to assess survival rate. Results: We demonstrate that neither body composition nor energy metabolism is altered with adipocyte STAT3 inhibition in male or female mice, under nonseptic conditions. Sepsis was associated with reduced adipocyte size in female WT and A-STAT3 KO mice, suggesting that this event is STAT3 independent. Sepsis did not alter adipocyte size in male WT and A-STAT3 KO mice, suggesting that this event is also sex dependent. Although STAT3 phosphorylat Topics: Adipocytes; Animals; Cytokines; Disease Models, Animal; Eosine Yellowish-(YS); Hematoxylin; Inflammation; Interleukin-6; Leptin; Lung Injury; Male; Mice; Mice, Inbred C57BL; Sepsis; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha | 2023 |
Linking Physical Activity to Breast Cancer Risk via Inflammation, Part 1: The Effect of Physical Activity on Inflammation.
The protective effect of physical activity on breast cancer incidence may partially be mediated by inflammation. Systematic searches of Medline, EMBASE, and SPORTDiscus were performed to identify intervention studies, Mendelian randomization studies, and prospective cohort studies that examined the effects of physical activity on circulating inflammatory biomarkers in adult women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the Grading of Recommendations Assessment, Development, and Evaluation system was used to determine the overall quality of the evidence. Thirty-five intervention studies and one observational study met the criteria for inclusion. Meta-analyses of randomized controlled trials (RCT) indicated that, compared with control groups, exercise interventions reduced levels of C-reactive protein (CRP) [standardized mean difference (SMD) = -0.27, 95% confidence interval (CI) = -0.62 to 0.08), tumor necrosis factor alpha (TNFα, SMD = -0.63, 95% CI = -1.04 to -0.22), interleukin-6 (IL6, SMD = -0.55, 95% CI = -0.97 to -0.13) and leptin (SMD = -0.50, 95% CI = -1.10 to 0.09). Owing to heterogeneity in effect estimates and imprecision, evidence strength was graded as low (CRP, leptin) or moderate (TNFα and IL6). High-quality evidence indicated that exercise did not change adiponectin levels (SMD = 0.01, 95% CI = -0.14 to 0.17). These findings provide support for the biological plausibility of the first part of the physical activity-inflammation-breast cancer pathway. Topics: Adult; Breast Neoplasms; C-Reactive Protein; Exercise; Female; Humans; Inflammation; Interleukin-6; Leptin; Quality of Life; Tumor Necrosis Factor-alpha | 2023 |
Treatment with bergamot (Citrus bergamia) leaves extract attenuates leptin resistance in obese rats.
Low-grade chronic inflammation in obesity is associated with leptin resistance. In order to alleviate this pathological condition, bioactive compounds capable of attenuating oxidative stress and inflammation have been researched, and bergamot (Citrus bergamia) presents these properties. The aim was to evaluate the effect of bergamot leaves extract on leptin resistance in obese rats. Animals were divided into 2 groups: control diet (C, n = 10) and high sugar-fat diet (HSF, n = 20) for 20 weeks. After detecting hyperleptinemia, animals were divided to begin the treatment with bergamot leaves extract (BLE) for 10 weeks: C + placebo (n = 7), HSF + placebo (n = 7), and HSF + BLE (n = 7) by gavage (50 mg/kg). Evaluations included nutritional, hormonal and metabolic parameters; adipose tissue dysfunction; inflammatory, oxidative markers and hypothalamic leptin pathway. HSF group presented obesity, metabolic syndrome, adipose tissue dysfunction, hyperleptinemia and leptin resistance compared to control group. However, the treated group showed a decrease in caloric consumption and attenuation of insulin resistance. Moreover, dyslipidemia, adipose tissue function, and leptin levels showed an improvement. At the level of the hypothalamus, the treated group showed a reduction of oxidative stress, inflammation and modulation of leptin signaling. In conclusion, BLE properties were able to improve leptin resistance through recovery of the hypothalamic pathway. Topics: Animals; Citrus; Diet, High-Fat; Inflammation; Leptin; Obesity; Plant Leaves; Rats | 2023 |
Changes in liver enzymes are associated with changes in insulin resistance, inflammatory biomarkers and leptin in prepubertal children with obesity.
Non-alcoholic fatty liver disease is associated with obesity. A subclinical inflammation state, endothelial dysfunction, and parameters related to metabolic syndrome (MetS), have been documented in children with obesity. We aimed to determine the changes that occur in liver enzymes levels in response to the standard treatment of childhood obesity, also assessing any associations with liver enzyme levels, leptin, and markers of insulin resistance (IR), inflammation, and parameters related to MetS in prepubertal children.. We carried out a longitudinal study in prepubertal children (aged 6-9 years) of both sexes with obesity; a total of 63 participants were recruited. Liver enzymes, C-reactive protein (CRP), interleukin-6, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), soluble intercellular adhesion molecule-1 (sICAM-1), leptin, homeostasis model assessment for IR (HOMA-IR), and parameters related to MetS were measured.. After standard treatment for 9 months, children who lowered their standardised body mass index (SDS-BMI) had significantly lower systolic blood pressure (p = 0.0242), diastolic blood pressure (p = 0.0002), HOMA-IR (p = 0.0061), and levels of alanine aminotransferase (ALT) (p = 0.0048), CRP (p = 0.0001), sICAM-1 (p = 0.0460), and IL-6 (p = 0.0438). There was a significant association between the changes that occur with treatment, in the ALT levels, and changes in leptin (p = 0.0096), inflammation biomarkers [CRP (p = 0.0061), IL-6 (p = 0.0337), NLR (p = 0.0458), PLR (p = 0.0134)], and HOMA-IR (p = 0.0322).. Our results showed that a decrease in ALT levels after the standard treatment for 9 months was associated with favourable changes in IR markers (HOMA-IR) and inflammation (IL-6, CRP, NLR, and PLR). Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Child; Female; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Liver; Longitudinal Studies; Male; Metabolic Syndrome; Pediatric Obesity | 2023 |
C-reactive protein partially mediates the inverse association between coffee consumption and risk of type 2 diabetes: The UK Biobank and the Rotterdam study cohorts.
Coffee is among the most consumed beverages worldwide. Coffee consumption has been associated with lower risk of type 2 diabetes mellitus (T2D), but underlying mechanisms are not well understood. We aimed to study the role of classic and novel-T2D biomarkers with anti- or pro-inflammatory activity in the association between habitual coffee intake and T2D risk. Furthermore, we studied differences by coffee types and smoking status in this association.. Using two large population-based cohorts, the UK-Biobank (UKB; n = 145,368) and the Rotterdam Study (RS; n = 7111), we investigated associations of habitual coffee consumption with incident T2D and repeated measures of insulin resistance (HOMA-IR), using Cox proportional hazards and mixed effect models, respectively. Additionally, we studied associations between coffee and subclinical inflammation biomarkers including C-reactive protein (CRP) and IL-13, and adipokines, such as adiponectin and leptin, using linear regression models. Next, we performed formal causal mediation analyses to investigate the role of coffee-associated biomarkers in the association of coffee with T2D. Finally, we evaluated effect modification by coffee type and smoking. All models were adjusted for sociodemographic, lifestyle and health-related factors.. During a median follow-up of 13.9 (RS) and 7.4 (UKB) years, 843 and 2290 incident T2D cases occurred, respectively. A 1 cup/day increase in coffee consumption was associated with 4% lower T2D risk (RS, HR = 0.96 [95%CI 0.92; 0.99], p = 0.045; UKB, HR = 0.96 [0.94; 0.98], p < 0.001), with lower HOMA-IR (RS, log-transformed β = -0.017 [-0.024;-0.010], p < 0.001), and with lower CRP (RS, log-transformed β = -0.014 [-0.022;-0.005], p = 0.002; UKB, β = -0.011 [-0.012;-0.009], p < 0.001). We also observed associations of higher coffee consumption with higher serum adiponectin and IL-13 concentrations, and with lower leptin concentrations. Coffee-related CRP levels partially mediated the inverse association of coffee intake with T2D incidence (average mediation effect RS β = 0.105 (0.014; 0.240), p = 0.016; UKB β = 6.484 (4.265; 9.339), p < 0.001), with a proportion mediated by CRP from 3.7% [-0.012%; 24.4%] (RS) to 9.8% [5,7%; 25.8%] (UKB). No mediation effect was observed for the other biomarkers. Coffee-T2D and coffee-CRP associations were generally stronger among consumers of ground (filtered or espresso) coffee and among never and former smokers.. Lower subclinical inflammation may partially mediate the beneficial association between coffee consumption and lower T2D risk. Consumers of ground coffee and non-smokers may benefit the most. KEYWORDS (MESH TERMS): coffee consumptions; diabetes mellitus, type 2; inflammation; adipokines; biomarkers; mediation analysis; follow-up studies. Topics: Adiponectin; Biological Specimen Banks; Biomarkers; C-Reactive Protein; Coffee; Diabetes Mellitus, Type 2; Humans; Inflammation; Interleukin-13; Leptin; Risk Factors; United Kingdom | 2023 |
Determinants of bone mass in older adults with normal- and overweight derived from the crosstalk with muscle and adipose tissue.
Lower bone mass in older adults may be mediated by the endocrine crosstalk between muscle, adipose tissue and bone. In 150 community-dwelling adults (59-86 years, BMI 17-37 kg/m Topics: Adiponectin; Adipose Tissue; Aged; Body Composition; Body Mass Index; Bone Density; Female; Humans; Inflammation; Leptin; Male; Muscles; Overweight | 2023 |
The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice.
db/db mice, which lack leptin receptors and exhibit hyperphagia, show disturbances in energy metabolism and are a model of obesity and type 2 diabetes. The geroneuroprotector drug candidate CMS121 has been shown to be effective in animal models of Alzheimer's disease and aging through the modulation of metabolism. Thus, the hypothesis was that CMS121 could protect db/db mice from metabolic defects and thereby reduce liver inflammation and kidney damage. The mice were treated with CMS121 in their diet for 6 months. No changes were observed in food and oxygen consumption, body mass, or locomotor activity compared to control db/db mice, but a 5% reduction in body weight was noted. Improved glucose tolerance and reduced HbA1c and insulin levels were also seen. Blood and liver triglycerides and free fatty acids decreased. Improved metabolism was supported by lower levels of fatty acid metabolites in the urine. Markers of liver inflammation, including NF-κB, IL-18, caspase 3, and C reactive protein, were lowered by the CMS121 treatment. Urine markers of kidney damage were improved, as evidenced by lower urinary levels of NGAL, clusterin, and albumin. Urine metabolomics studies provided further evidence for kidney protection. Mitochondrial protein markers were elevated in db/db mice, but CMS121 restored the renal levels of NDUFB8, UQCRC2, and VDAC. Overall, long-term CMS121 treatment alleviated metabolic imbalances, liver inflammation, and reduced markers of kidney damage. Thus, this study provides promising evidence for the potential therapeutic use of CMS121 in treating metabolic disorders. Topics: Animals; Diabetes Mellitus, Type 2; Hepatitis; Inflammation; Kidney; Leptin; Liver; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Receptors, Leptin | 2023 |
Excess weight and obesity are the fifth leading cause of death globally, and sustained efforts from health professionals and researchers are required to mitigate this pandemic-scale problem. Polyphenols and flavonoids found in Topics: Adipocytes; Adiponectin; Aspalathus; Cytokines; Humans; Inflammation; Leptin; Obesity; Plant Extracts; Tea | 2023 |
Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling.
Leptin inhibits food intake and reduces the size of body fat depots, changing adipocyte sensitivity to insulin to restrain lipid accrual. This adipokine may modulate the production of cytokines that could diminish insulin sensitivity, particularly in visceral adipose tissue. To explore this possibility, we examined the effects of chronic central administration of leptin on the expression of key markers of lipid metabolism and its possible relationship with changes in inflammatory- and insulin-signaling pathways in epididymal adipose tissue. Circulating non-esterified fatty acids and pro- and anti-inflammatory cytokines were also measured. Fifteen male rats were divided into control (C), leptin (L, icv, 12 μg/day for 14 days), and pair-fed (PF) groups. We found a decrease in the activity of glucose-6-phosphate dehydrogenase and malic enzyme in the L group, with no changes in the expression of lipogenic enzymes. A reduction in the expression of lipoprotein lipase and carnitine palmitoyl-transferase-1A, together with a decrease in the phosphorylation of insulin-signaling targets and a low-grade inflammatory pattern, were detected in the epididymal fat of L rats. In conclusion, the decrease in insulin sensitivity and increased pro-inflammatory environment could regulate lipid metabolism, reducing epididymal fat stores in response to central leptin infusion. Topics: Adipose Tissue; Animals; Cytokines; Inflammation; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Male; Rats | 2023 |
Associations of serum leptin levels with intra-articular inflammatory cytokine levels in acute arthritic and nonarthritic knees of mice.
The roles of serum leptin in knee joint inflammation are unclear. The objective of this study was to identify any associations of serum leptin level with intra-articular inflammatory cytokine levels in acute arthritic and nonarthritic knees of mice.. Acute arthritis was induced by intra-articular injection of 2% carrageenan. Three groups (leptin-deficient ob/ob, wild-type (WT) and high-fat diet (HFD)-fed WT) were made. Serum leptin and inflammatory cytokines in the infrapatellar fat pad and synovium were measured before and 24 hr after injection. Affected knee joints were excised for histology 24 hr after injection.. The HFD-WT group had significantly higher serum leptin than the ob/ob and WT groups before and after carrageenan injection. The HFD-WT group had significantly higher IL-1? and IL-6 in the infrapatellar fat pad and synovium than ob/ob and WT before injection but significantly lower IL-1?, IL-6 and TNF-? than the ob/ob group at 24 hr.. Hyperleptinemia induced by a HFD is involved in low-grade intra-articular inflammation in nonarthritic knee joints. In contrast, leptin deficiency causes excessive intra-articular inflammation in carrageenan-induced acute arthritis. Leptin alleviates acute arthritis, while chronic hyperleptinemia is involved in low-grade inflammation in normal knee joints. J. Med. Invest. 70 : 54-59, February, 2023. Topics: Animals; Arthritis; Carrageenan; Cytokines; Inflammation; Interleukin-1; Interleukin-6; Leptin; Mice; Mice, Inbred C57BL | 2023 |
Intermittent fasting combined with exercise training reduces body mass and alleviates hypothalamic disorders induced by high-fat diet intake.
High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF = HF diet mice submitted to IF; HF-T = HF diet mice submitted to ET; HF-IFT = HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei. Topics: Animals; Diet, High-Fat; Dietary Fats; Hypothalamus; Inflammation; Intermittent Fasting; Leptin; Male; Mice; Mice, Inbred C57BL | 2023 |
Association Between Adipokine Profile, Systemic Inflammation, Muscle and Protein Energy Wasting in Children With Chronic Kidney Disease.
This cross-sectional study explores the association of adipokines and interleukin-6 (IL-6) with muscle and protein energy wasting (PEW) in children with chronic kidney disease (CKD).. We measured serum adiponectin, leptin, resistin and IL-6 in 53 patients with CKD stage 3-5. Lean tissue (LTI) and fat tissue index (FTI) were estimated by bioimpedance analysis spectroscopy. PEW was defined as muscle wasting [LTI adjusted to height age (LTI HA) z-score < -1.65 SD) and at least 2 of the following: reduced body mass [body mass index adjusted to height age (BMI HA) z-score < -1.65 SD), poor growth [height z-score < -1.88 SD], questionnaire-based decreased appetite, and serum albumin ≤3.8 g/dL.. PEW, observed in 8 (15.1%) patients, was more prevalent in CKD stage 5 (P = .010). Among the adipokines, adiponectin, and resistin levels were significantly higher in CKD stage 5 (P < .001, P = .005). Adiponectin was correlated to LTI HA z-score (Rs = -0.417, P = .002), leptin to FTI z-score (Rs = 0.620, P < .001), while no correlation was observed between resistin and body composition parameters. Resistin was the only adipokine correlated to IL-6 (Rs = 0.513, P < .001). After adjustment for CKD stage and patient age, PEW was associated with adiponectin and IL-6 rise by 1 μg/mL and 10 pg/mL respectively (odds ratio (OR) 1.240, 95% confidence interval (CI) 1.040, 1.478 and OR 1.405, 95% CI 1.075-1.836) but not with leptin, while resistin association with PEW lost its significance.. In pediatric CKD, adiponectin is associated with muscle wasting, leptin with adiposity and resistin with systemic inflammation. Adiponectin and cytokine IL-6 may serve as PEW biomarkers. Topics: Adipokines; Adiponectin; Cachexia; Child; Cross-Sectional Studies; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Muscles; Renal Insufficiency, Chronic; Resistin | 2023 |
Maternal elevated inflammation impairs placental fatty acids β-oxidation in women with gestational diabetes mellitus.
An adverse proinflammatory milieu contributes to abnormal cellular energy metabolism response. Gestational diabetes mellitus (GDM) is closely related to an altered maternal inflammatory status. However, its role on lipid metabolism regulation in human placenta has not yet been assessed. The aim of this study was to examine the impact of maternal circulating inflammatory mediators ([TNF]-α, [IL]-6, and Leptin) on placental fatty acid metabolism in GDM pregnancies.. Fasting maternal blood and placental tissues were collected at term deliveries from 37 pregnant women (17 control and 20 GDM). Molecular approach techniques as radiolabeled lipid tracers, ELISAs, immunohistochemistry and multianalyte immunoassay quantitative analysis, were used to quantify serum inflammatory factors' levels, to measure lipid metabolic parameters in placental villous samples (mitochondrial fatty acid oxidation [FAO] rate and lipid content [Triglycerides]), and to analyze their possible relationships. The effect of potential candidate cytokines on fatty acid metabolism in. Enhanced maternal proinflammatory cytokines levels (essentially IL-6) is closely associated with an altered placental fatty acid metabolism in pregnancies with GDM, which may interfere with adequate delivery of maternal fat across the placenta to the fetus. Topics: Cytokines; Diabetes, Gestational; Fatty Acids; Female; Humans; Inflammation; Interleukin-6; Leptin; Placenta; Pregnancy; Triglycerides; Tumor Necrosis Factor-alpha | 2023 |
Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury.
Renal ischemia and reperfusion (IR) injury introduces cellular stress and is the main cause of acute kidney damage. Renal cells exposed to noxious stress induce the expression of the pleiotropic hormone leptin. As we have previously revealed a deleterious stress-related role for leptin expression, these results suggested that leptin is also involved in pathological renal remodeling. The systemic functions of leptin preclude the study of its local effects using conventional approaches. We have therefore designed a method to locally perturb leptin activity in specific tissues without affecting its systemic levels. This study explores whether local anti-leptin strategy is renoprotective in a post-IR porcine kidney model.. We induced renal IR injury in pigs by exposing kidneys to ischemia and revascularization. Upon reperfusion, kidneys instantly received an intra-arterial bolus of either a leptin antagonist (LepA) or saline solution. Peripheral blood was sampled to assess systemic leptin, IL-6, creatinine, and BUN levels, and postoperative tissue samples were analyzed by hematoxylin and eosin histochemistry and immunohistochemistry.. Histology of IR/saline kidneys exhibited extensive necrosis of proximal tubular epithelial cells, as well as elevated levels of apoptosis markers and inflammation. In contrast, IR/LepA kidneys showed no signs of necrosis or inflammation with normal IL-6 and tall-like receptor 4 levels. LepA treatment led to upregulation in mRNA levels of leptin, leptin receptor, ERK1/2, STAT3, and transport molecule Na/H exchanger-3.. Local, intrarenal postischemic LepA treatment at reperfusion prevented apoptosis and inflammation and was renoprotective. Selective intrarenal administration of LepA at reperfusion may provide a viable option for clinical implementation. Topics: Acute Kidney Injury; Animals; Inflammation; Interleukin-6; Ischemia; Kidney; Leptin; Necrosis; Reperfusion Injury; Swine | 2023 |
Leptin Concentrations Determine the Association between High-Sensitivity C-Reactive Protein Levels and Body Mass Index in Prepubertal Children.
Obesity is associated with the presence of low-grade inflammation even during childhood. The dysregulation in the secretion of adipokines, such as leptin, which occurs in obesity states, could be associated with an increase in inflammatory factors already at an early age. In this cross-sectional study, we aimed to investigate the role of leptin levels in the association between body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) in healthy schoolchildren. Leptin and hs-CRP levels were analyzed in two pediatric cohorts comprising 684 prepubertal children and 763 adolescents. hs-CRP concentrations correlated significantly with BMI and leptin levels in prepubertal males and females as well as in adolescents. However, after adjusting for leptin concentration, no significant correlation was observed between hs-CRP and BMI in prepubertal children, while the correlations remained significant in adolescents. The same differences were observed when analyzed BMI according to hs-CRP tertile after adjusting for leptin; mean BMI was not significantly different between hs-CRP tertile in prepubertal children but was significantly different in adolescents. In conclusion, the fact that leptin concentrations determine the association of BMI with hs-CRP levels in prepubertal children, but not in adolescents, suggests a role for leptin in low-grade inflammation at early ages, while other factors seem to contribute to hs-CRP levels later in life. Topics: Adolescent; Body Mass Index; C-Reactive Protein; Child; Cross-Sectional Studies; Female; Humans; Inflammation; Leptin; Male; Obesity | 2023 |
Associations between dietary inflammatory scores and biomarkers of inflammation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation.. We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DII. This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders.. Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DII. Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements. Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Diet; Humans; Inflammation; Leptin; Neoplasms; Prospective Studies; Tumor Necrosis Factor-alpha | 2023 |
Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats.
Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective β3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1β, and IL-6 gene expression and IL-1β and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area. Topics: Animals; Blood Glucose; Brain; Diabetes Mellitus, Type 2; Glucose; Hippocampus; Inflammation; Insulin; Leptin; Neuroinflammatory Diseases; Obesity; Rats; Rats, Wistar | 2023 |
Circulating MiRNAs Are Associated With Low-grade Systemic Inflammation and Leptin Levels in Older Adults.
Inflammaging refers to the low-grade systemic inflammation that occurs with aging present in chronic non-communicable diseases. MicroRNAs (miRNAs) are potential biomarkers for these diseases in older adults. This study aimed to assess the expression of 21 circulating miRNAs and their associations with inflammatory biomarkers in older adults. This cross-sectional study was performed with 200 individuals participating in ISA-Nutrition. The systemic low-grade inflammation score (SIS) was calculated from the plasma concentration of 10 inflammatory biomarkers. Circulating miRNA expression was assessed using the Fluidigm method. Wilcoxon-Mann-Whitney test was employed to determine differences in SIS among groups distributed according to sex and presence of MetS. Spearman's correlation was used to estimate correlations among SIS, leptin levels, miRNA expression, and variables of interest. Analyses were performed using software R version 4.2.3, with a significance level of 0.05. The final sample consisted of 193 individuals with a mean age of 69.1 (SE = 0.5) years, being 64.7% individuals with metabolic syndrome (MetS). Positive correlations were observed between leptin concentration and metabolic risk factors, and leptin concentration was higher in individuals with MetS compared to those without MetS. The expression of 15 circulating miRNAs was negatively correlated with leptin concentration. GLMs showed negative associations between miRNAs (miR-15a, miR-16, miR-223, miR-363, miR-532), leptin, and/or SIS values; and only miR-21 showed positive association with SIS values. The results suggest the presence of peripheral leptin resistance associated with low-grade inflammation and plasma expression of miRNAs in older adults. These findings suggest the potential role of miRNAs as biomarkers for cardiometabolic risk. Topics: Aged; Biomarkers; Cross-Sectional Studies; Humans; Inflammation; Leptin; Metabolic Syndrome; MicroRNAs | 2023 |
Leptin/obR signaling exacerbates obesity-related neutrophilic airway inflammation through inflammatory M1 macrophages.
Obesity-related asthma is a kind of nonallergic asthma with excessive neutrophil infiltration in the airways. However, the underlying mechanisms have been poorly elucidated. Among the adipokines related to obesity, leptin is related to the inflammatory response. However, little is understood about how leptin acts on the leptin receptor (obR) in neutrophilic airway inflammation in obesity-associated asthma. We explored the inflammatory effects of leptin/obR signaling in an obesity-related neutrophilic airway inflammation mouse model.. We established a neutrophilic airway inflammation mouse model using lipopolysaccharide (LPS)/ovalbumin (OVA) sensitization and OVA challenge (LPS + OVA/OVA) in lean, obese, or db/db (obR deficiency) female mice. Histopathological, bronchoalveolar lavage fluid (BALF) inflammatory cell, and lung inflammatory cytokine analyses were used to analyze airway inflammation severity. Western blotting, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the underlying mechanisms. In vitro bone marrow-derived macrophage (BMDM) and bone marrow-derived neutrophil experiments were performed.. We found that the serum leptin level was higher in obese than in lean female mice. Compared to LPS/OVA + OVA-treated lean female mice, LPS/OVA + OVA-treated obese female mice had higher peribronchial inflammation levels, neutrophil counts, Th1/Th17-related inflammatory cytokine levels, M1 macrophage polarization levels, and long isoform obR activation, which could be decreased by the obR blockade (Allo-Aca) or obR deficiency, suggesting a critical role of leptin/obR signaling in the pathogenesis of obesity-related neutrophilic airway inflammation in female mice. In in vitro experiments, leptin synergized with LPS/IFN-γ to promote the phosphorylation of the long isoform obR and JNK/STAT3/AKT signaling pathway members to increase M1 macrophage polarization, which was reversed by Allo-Aca. Moreover, leptin/obR-mediated M1 macrophage activity significantly elevated CXCL2 production and neutrophil recruitment by regulating the JNK/STAT3/AKT pathways. In clinical studies, obese patients with asthma had higher serum leptin levels and M1 macrophage polarization levels in induced sputum than non-obese patients with asthma. Serum leptin levels were positively correlated with M1 macrophage polarization levels in patients with asthma.. Our results demonstrate leptin/obR signaling plays an important role in the pathogenesis of obesity-related neutrophilic airway inflammation in females by promoting M1 macrophage polarization. Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Female; Inflammation; Leptin; Lipopolysaccharides; Lung; Macrophages; Mice; Mice, Inbred BALB C; Obesity; Ovalbumin; Proto-Oncogene Proteins c-akt; Receptors, Leptin; Signal Transduction | 2023 |
Epicardial Adipose Tissue-Derived Leptin Promotes Myocardial Injury in Metabolic Syndrome Rats Through PKC/NADPH Oxidase/ROS Pathway.
Topics: Adipose Tissue; Animals; Culture Media, Conditioned; Heart Injuries; Inflammation; Leptin; Metabolic Syndrome; NADP; NADPH Oxidases; Oxidative Stress; Oxidoreductases; Protein Kinase C; Rats; Rats, Wistar; Reactive Oxygen Species; Signal Transduction; Transcription Factor AP-1 | 2023 |
Characteristics of the obesogenic environment around schools are associated with body fat and low-grade inflammation in Brazilian children.
To assess the association of obesogenic environmental characteristics around schools with body adiposity and adipokine concentrations in Brazilian children.. Cross-sectional study. Body adiposity was assessed using the dual-energy X-ray absorptiometry. Concentrations of leptin, adiponectin, retinol-binding protein 4 (RBP4) and chemerin were measured. Predominantly ultra-processed food (UPF) stores, public physical activity (PA) facilities, green spaces, walkability, traffic accidents and crime were evaluated. The neighbourhood unit was the 400 m (0·25 miles) road network buffer around schools. The association of environmental characteristics with body adiposity and adipokine concentrations was assessed by linear regression models using generalised estimating equations.. Urban schools (. Children aged 8 and 9 years (. A higher density of predominantly UPF stores and a lower percentage of green space were associated with higher total (. Obesogenic environmental characteristics around schools were associated with total and android body fat, as well as with pro-inflammatory adipokine concentrations in Brazilian children from a medium-sized city. Topics: Adiponectin; Adipose Tissue; Adiposity; Brazil; Child; Cross-Sectional Studies; Humans; Inflammation; Leptin; Obesity; Retinol-Binding Proteins, Plasma; Schools | 2023 |
6-Gingerol Ameliorates Adiposity and Inflammation in Adipose Tissue in High Fat Diet-Induced Obese Mice: Association with Regulating of Adipokines.
We investigated the effects of 6-gingerol on adiposity and obesity-induced inflammation by focusing on the regulation of adipogenesis and adipokines in white adipose tissue (WAT) of diet-induced obese mice. C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% 6-gingerol for 8 weeks. 6-Gingerol supplementation significantly reduced body weight, WAT mass, serum triglyceride, leptin and insulin levels, and HOMA-IR in HFD-fed mice. Additionally, the size of adipocytes in epididymal fat pads was reduced in HFD-fed mice by 6-gingerol supplementation. 6-Gingerol reduced the mRNA and protein levels of adipogenesis-related transcription factors, such as SREBP-1, PPARγ, and C/EBPα in WAT. Furthermore, 6-gingerol suppressed the expression of lipogenesis-related genes, such as fatty acid synthase and CD36 in WAT. Adiponectin expression was significantly increased, whereas inflammatory adipokines (leptin, resistin, TNF-α, MCP-1, and PAI-1) and the macrophage marker F4/80 were significantly reduced in the WAT of HFD-fed mice by 6-gingerol supplementation. In conclusion, 6-gingerol effectively contributed to the alleviation of adiposity and inflammation in WAT, which is associated with the regulation of adipokines in diet-induced obese mice. Topics: Adipokines; Adipose Tissue; Adiposity; Animals; Diet, High-Fat; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity | 2023 |
Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice.
The prevalence of obesity and chronic kidney disease (CKD) is increasing simultaneously and rapidly worldwide. Our previous study showed that folate deficiency increased lipid accumulation and leptin production of adipocytes. Whether folate plays a role in CKD, particularly obesity-related nephropathy remains unclear. To investigate the effects of folate deficiency on CKD in diet-induced obese mice, four groups of male C57BL/6 mice were fed either a normal-fat diet (NF) with folate (NF+f); NF without folate (NF-f); high-fat high-fructose diet (HFF) with folate (HFF+f); or HFF without folate (HFF-f) for 12 months during the study. The results showed that HFF increased not only body weight, fasting blood glucose, total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and blood pressure, but also cytokines levels, such as interleukin (IL)-2, interferon (IFN)-γ, IL-17A/F, IL-6, monocyte chemoattractant protein (MCP)-1, and transforming growth factor (TGF)-β1. The indicators of kidney failure including urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), renal type I and IV collagen deposits and leptin content, and serum creatinine were also increased by HFF. Folate-deficient diets further elevated serum TC, LDL-cholesterol, IL-6, tumor necrosis factor (TNF)-α, MCP-1, TGF-β1, and leptin, but decreased IL-10 level, and thus exacerbated renal fibrosis. To investigate the possible mechanisms of folate deficiency on renal injury, phosphorylation of pro-fibrosis signaling molecules, including signal transducer and activator of transcription (STAT)3 and small mothers against decapentaplegic (Smad)2/3, were assayed. Both HFF and folate deficiency significantly increased the phosphorylation of STAT3 and Smad2/3, suggesting synergistic effects of HFF-f on chronic renal inflammation and fibrosis. In conclusion, the results demonstrated that folate deficiency might aggravate inflammatory status and enhance renal fibrosis. Topics: Animals; Folic Acid; Folic Acid Deficiency; Inflammation; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Renal Insufficiency, Chronic | 2023 |
Plant-based dietary indices and biomarkers of chronic low-grade inflammation: a cross-sectional analysis of adults in Ireland.
There is increasing interest in the health benefits of plant-based diets (PBDs). Evidence reports favourable associations with inflammatory profiles and reduced cardiovascular disease risk. However, limited studies have examined relationships between PBD indices (PDIs) and inflammatory biomarkers. We explored overall PDI, healthful PDI (hPDI) and unhealthful PDI (uPDI) associations with inflammatory biomarker profiles.. This cross-sectional analysis included 1986 middle- to older-aged adults from the Mitchelstown Cohort. PDI scores were calculated using validated food frequency questionnaires. PDI score associations with inflammatory biomarkers were assessed via linear regression analysis, with adjustment for potential confounders.. Comparison of quintiles (Q5 vs Q1) revealed lower concentrations of C-reactive protein (CRP), interleukin 6 (IL-6), white blood cells (WBCs), neutrophils and monocytes, and the leptin-to-adiponectin ratio (PDI and hPDI P < 0.05); lower leptin (PDI, P < 0.05), and complement component 3 (C3), tumour necrosis factor alpha (TNF-α), plasminogen activator inhibitor 1, lymphocytes and eosinophils (hPDI, P < 0.05); and higher concentrations of adiponectin (PDI and hPDI, P < 0.05). Conversely, higher concentrations of C3, CRP, IL-6, TNF-α, resistin, WBCs, neutrophils, lymphocytes, monocytes and eosinophils, and the neutrophil-to-lymphocyte ratio, and lower adiponectin concentrations were observed comparing uPDI quintiles (P < 0.05). In fully adjusted regression models, higher hPDI scores were associated with lower concentrations of C3, TNF-α, WBCs, neutrophils and monocytes (all P < 0.01). Higher uPDI scores were associated with higher C3 and TNF-α concentrations (all P < 0.01).. This study provides evidence that a more healthful PBD is associated with a more favourable inflammatory profile and that a more unhealthful PBD is associated with the reverse. Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Diet; Diet, Vegetarian; Humans; Inflammation; Interleukin-6; Ireland; Leptin; Middle Aged; Tumor Necrosis Factor-alpha | 2023 |
Leptin-mediated meta-inflammation may provide survival benefit in patients receiving maintenance immunotherapy for extensive-stage small cell lung cancer (ES-SCLC).
Only few ES-SCLC patients experience long-term survival benefit by maintenance IT. Adipokines-induced metabolic meta-inflammation has been related to enhanced responsiveness to IT in obese patients; however, their prognostic role in SCLC is currently controversial.. Pre-treatment CT scan was used for determining distribution of abdominal adiposity, and blood samples were collected at fasting for measuring glycemia, insulin, ghrelin, leptin and adipokines (TNF-α, IFN-γ, IL-6 and MCP-1). Patients with known history of DM type II or metabolic syndrome with HOMA index > 2.5 were considered insulin resistant (IR).. In ES-SCLC pts receiving maintenance IT, increased leptin concentration and higher leptin/visceral adipose tissue (VAT) ratio were significantly associated with prolonged PFS. By applying a hierarchical clustering algorithm, we identified a cluster of patients characterized by higher leptin values and lower pro-inflammatory cytokines (TNF-α, IFN-γ and IL-6) who experienced longer PFS (13.2 vs 8.05 months; HR: 0.42 [0.18-0.93] p = 0.02) and OS (18.04 vs 12.09 mo; HR: 0.53 [0.25-1.29] p = 0.07).. Adipokines can play a crucial role to determining effectiveness of anti-cancer immunotherapy. The role of metabolic immune dysfunctions needs further pre-clinical validation and is currently investigated in the larger prospective cohort. Topics: Adipokines; Humans; Immunotherapy; Inflammation; Insulins; Interleukin-6; Leptin; Lung Neoplasms; Prospective Studies; Small Cell Lung Carcinoma; Tumor Necrosis Factor-alpha | 2023 |
Oral probiotics increased the proportion of Treg, Tfr, and Breg cells to inhibit the inflammatory response and impede gestational diabetes mellitus.
Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention strategies that alter the gut microbiome may benefit the mother and kid long-term. This work uses metagenomic and transcriptome sequencing to investigate how probiotics affect gut microbiota dysbiosis and inflammation in GDM.. GDM and control metagenomic sequencing data were obtained from the SRA database. This metagenomic data helped us understand gut microbiota abundance and function. KEGG detected and extracted functional pathway genes. Transcriptome sequencing data evaluated GDM-related gene expression. Finally, GDM animal models were given probiotics orally to evaluate inflammatory response, regulatory immune cell fractions, and leptin protein levels.. GDM patients had more Fusobacteria and Firmicutes, while healthy people had more Bacteroidetes. Gut microbiota composition may affect GDM by altering the L-aspartate and L-asparagine super pathways. Mannan degradation and the super pathway of L-aspartate and L-asparagine synthesis enhanced in GDM mice with leptin protein overexpression. Oral probiotics prevent GDM by lowering leptin. Oral probiotics increased Treg, Tfr, and Breg cells, which decreased TNF-α and IL-6 and increased TGF-β and IL-10, preventing inflammation and preserving mouse pregnancy.. Dysbiosis of the gut microbiota may increase leptin expression and cause GDM. Oral probiotics enhance Treg, Tfr, and Breg cells, which limit the inflammatory response and assist mice in sustaining normal pregnancy. Thus, oral probiotics may prevent GDM, enabling targeted gut microbiota modulation and maternal and fetal health. Topics: Animals; Asparagine; Aspartic Acid; B-Lymphocytes, Regulatory; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dysbiosis; Female; Humans; Inflammation; Leptin; Mice; Pregnancy; T-Lymphocytes, Regulatory | 2023 |
Exploration of molecular signatures associated with different clinical features of Takayasu arteritis based on a prospective cohort study.
Takayasu arteritis (TAK) is complicated disorder without reliable biomarkers. Here, we aimed to explore TAK-associated factor panels and their changes after biologic treatment. Five factor panels were identified: 1. systemic inflammation: C3, ESR, CRP, PLT, IL-6, C4, and IgG; 2. vascular inflammation: YKL40, IL-16, PTX3, and CCL2; 3. immune regulation panel: IL-10, IFN-γ, CCL5, and MMP1; 4. angiogenesis and fibrosis: FGF, PDGFAB, and VEGF; and 5. vascular remodeling: CD19+ B cell ratio, MMP3, and leptin. Panel 1 parameters were closely related to disease activity, while Panel 5 parameters, particularly CD19+ B cell ratio and leptin, were significantly higher in ischemic patients. After treatment, tocilizumab had a stronger inhibitory effect on Panel 1 parameters, PTX3, and YKL-40, while adalimumab led to an increase in IL-16, CCL2, and leptin levels. Altogether, these data expanded our knowledge regarding molecular background in TAK development and shed light on precise treatment in future studies. Topics: Humans; Inflammation; Interleukin-16; Leptin; Prospective Studies; Takayasu Arteritis | 2023 |
Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study.
Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood.. Cross-sectional study.. We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH.. Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = -0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (-0.15 normalized protein expression [NPX], P = .0001, and -0.25 NPX, P = .0003, respectively).. We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small. Topics: Addison Disease; Biomarkers; Cardiovascular Diseases; Cosyntropin; Cross-Sectional Studies; Extracellular Matrix Proteins; Female; Glucocorticoids; Humans; Inflammation; Leptin; Male; Neoplasm Proteins; Quality of Life | 2023 |
Elevated plasma leptin levels are associated with vascular access dysfunction in patients on maintenance hemodialysis.
Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO).. A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin.. The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin.. In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO. Topics: Biomarkers; Body Mass Index; Female; Humans; Hypertension; Inflammation; Leptin; Renal Dialysis | 2023 |
Long-term high-fat diet disrupts lipid metabolism and causes inflammation in adult male rats: possible intervention of endoplasmic reticulum stress.
This study investigated the effect of long-term high-fat diet (HFD) on plasma lipid profile and probability of inflammation in adult rats. After weaning, male offspring were divided into six groups based on diet type and medication. After 20 weeks of dietary intake, 4-PBA (endoplasmic reticulum (ER) stress inhibitor) was injected for three days. Then, blood samples were taken to measure plasma concentrations of low-density lipoprotein (LDL), triglyceride (TG), high-density lipoprotein (HDL), cholesterol, leptin and interleukin 1-β (IL 1-β). The HFD increased body weight and food intake and intra-abdominal fat and thymus weights, which were associated with elevated plasma leptin level. Moreover, HFD increased plasma concentrations of TG, LDL, cholesterol and IL 1-β and decreased HDL level. Injection of 4-PBA reversed the plasma parameters changes caused by HFD. It seems that long-term HFD feeding through inducing the ER stress, disrupted the lipid metabolism and resulted in inflammation. Topics: Animals; Cholesterol; Diet, High-Fat; Endoplasmic Reticulum Stress; Inflammation; Interleukin-1; Leptin; Lipid Metabolism; Male; Rats; Triglycerides | 2023 |
Testing the Effects of Cinnamon Extract Supplementation on Inflammation and Oxidative Stress Induced by Acrylamide.
We investigated the effects of cinnamon water extract supplementation on inflammation and oxidative stress induced by acrylamide in rats. This revealed acrylamide-intoxicated control group had significant higher levels of malondialdehyde, tumor necrosis factor-alpha (TNF-α), high-sensitive C-reactive protein (hs-CRP), leptin and alanine transaminase, and lower levels of total antioxidant capacity compared to the negative control group. In contrast, cinnamon extract administration remedied the levels of total antioxidant capacity, malondialdehyde, TNF-α, hs-CRP, and leptin in the treatment groups. However, there was no significant effect on adiponectin or liver enzymes. This chapter presents a protocol involving production of the acrylamide-induced oxidative stress model, the aqueous extraction of cinnamon powder, and measurement of inflammatory and oxidative stress markers. Topics: Acrylamide; Animals; Antioxidants; C-Reactive Protein; Cinnamomum zeylanicum; Dietary Supplements; Inflammation; Leptin; Malondialdehyde; Oxidative Stress; Rats; Tumor Necrosis Factor-alpha | 2022 |
Exploring the endocannabinoidome in genetically obese (ob/ob) and diabetic (db/db) mice: Links with inflammation and gut microbiota.
Obesity and type 2 diabetes are two interrelated metabolic disorders characterized by insulin resistance and a mild chronic inflammatory state. We previously observed that leptin (ob/ob) and leptin receptor (db/db) knockout mice display a distinct inflammatory tone in the liver and adipose tissue. The present study aimed at investigating whether alterations in these tissues of the molecules belonging to the endocannabinoidome (eCBome), an extension of the endocannabinoid (eCB) signaling system, whose functions are important in the context of metabolic disorders and inflammation, could reflect their different inflammatory phenotypes.. The basal eCBome lipid and gene expression profiles, measured by targeted lipidomics and qPCR transcriptomics, respectively, in the liver and subcutaneous or visceral adipose tissues, highlighted a differentially altered eCBome tone, which may explain the impaired hepatic function and more pronounced liver inflammation remarked in the ob/ob mice, as well as the more pronounced inflammatory state observed in the subcutaneous adipose tissue of db/db mice. In particular, the levels of linoleic acid-derived endocannabinoid-like molecules, of one of their 12-lipoxygenase metabolites and of Trpv2 expression, were always altered in tissues exhibiting the highest inflammation. Correlation studies suggested the possible interactions with some gut microbiota bacterial taxa, whose respective absolute abundances were significantly different between ob/ob and the db/db mice.. The present findings emphasize the possibility that bioactive lipids and the respective receptors and enzymes belonging to the eCBome may sustain the tissue-dependent inflammatory state that characterizes obesity and diabetes, possibly in relation with gut microbiome alterations. Topics: Adipose Tissue; Animals; Arachidonate 12-Lipoxygenase; Calcium Channels; Diabetes Mellitus, Type 2; Disease Models, Animal; Endocannabinoids; Gastrointestinal Microbiome; Gene Expression Regulation; Humans; Inflammation; Leptin; Mice; Mice, Inbred NOD; Mice, Obese; Obesity; Receptors, Leptin; Transcriptome; TRPV Cation Channels | 2022 |
Obesity Is Associated with Sustained Symptomatology and Unique Inflammatory Features in Children with Asthma.
Obesity complicates the clinical manifestations of asthma in children. However, few studies have examined longitudinal outcomes or markers of systemic inflammation in obese asthmatic children.. We hypothesized that obese children with asthma would have: (1) poorer clinical outcomes over 12 months, (2) decreased responsiveness to systemic corticosteroid administration, (3) greater markers of systemic inflammation, and (4) unique amino acid metabolites associated with oxidative stress.. Children 6 to 17 years of age (lean, N = 257; overweight, N = 99; obese, N = 138) completed a baseline visit and follow-up visit at 12 months. Outcome measures included asthma control, quality of life, lung function, and exacerbations. A subset received intramuscular triamcinolone and were re-evaluated at 7(+7) days. Leptin, adiponectin, C-reactive protein, total cholesterol, interleukin (IL)-1β, IL-6, IL-17, interferon gamma, tumor necrosis factor alpha, monocyte-chemoattractant protein-1, and amino acid metabolites were also quantified in plasma as potential biomarkers of outcomes in obese children.. Obesity was associated with more symptoms, poorer quality life, and more exacerbations that persisted over 1 year despite greater medication requirements. Obese children also had minimal clinical improvement in asthma control and lung function after intramuscular triamcinolone. Leptin, C-reactive protein, and amino acid metabolites associated with glutathione synthesis and oxidative stress differed in obese children. Within the obese group, lower concentrations of arginine-related metabolites also distinguished uncontrolled from controlled asthma at 12 months.. Obesity is associated with poorer asthma outcomes and unique systemic inflammatory features that may not be adequately modified with conventional asthma therapies. Novel approaches may be needed given increased symptoms and unique inflammation and oxidative stress in obese children with asthma. Topics: Amino Acids; Asthma; Biomarkers; C-Reactive Protein; Child; Humans; Inflammation; Leptin; Pediatric Obesity; Quality of Life; Triamcinolone | 2022 |
Longitudinal changes in circulating concentrations of inflammatory markers throughout pregnancy: are there associations with diet and weight status?
The natural inflammation occurring during pregnancy can, under certain conditions, be associated with adverse pregnancy outcomes. This study aimed to (1) quantify changes in circulating concentrations of leptin, adiponectin, interleukin-6 (IL-6) and C-reactive protein (CRP) across trimesters of pregnancy, according to pre-pregnancy body mass index (ppBMI); and (2) examine the trimester-specific associations between the inflammatory markers' concentrations, a Mediterranean diet score (MDS) and the dietary inflammatory index (DII). We measured leptin, adiponectin and IL-6 by ELISA and CRP by high-sensitivity immunonephelometry, in blood samples from 79 pregnant women (age: 32.1 ± 3.7 years; ppBMI: 25.7 ± 5.8 kg/m Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Diet, Mediterranean; Female; Humans; Inflammation; Leptin; Pregnancy | 2022 |
Impact of Physical Activity Intensity Levels on the Cardiometabolic Risk Status of Children: The Genobox Study.
Childhood obesity has been related to metabolic syndrome and low-grade chronic inflammation. This study aimed to evaluate the impact of physical activity intensities and practice on inflammation, endothelial damage, and cardiometabolic risk factors in children. There were 513 participants, aged 6-14 years, recruited for the study. Physical activity was measured by accelerometry, and the children were classified into four groups according to quartiles of moderate to vigorous physical activity (MVPA) practice as very low active, low active, moderate active, and high active. Anthropometric measures, blood pressure, and plasma metabolic and proinflammatory parameters were analyzed. Very low active group presented a worse lipid profile and higher insulin, leptin, adiponectin, resistin, matrix metallopeptidase-9, and tissue plasminogen activator inhibitor-1, while lower levels of tumor necrosis factor-alpha, Type 1 macrophages, and interleukin 8 than high-active children. Regression analyses showed that a higher MVPA practice was associated with lower levels of triacylglycerols (β: -0.118; p = .008), resistin (β: -0.151; p = .005), tPAI (β: -0.105; p = .046), and P-selectin (β: -0.160; p = .006), independently of sex, age, and body mass index (BMI). In contrast, a higher BMI was associated with higher levels of insulin (β: 0.370; p < .001), Homeostasis Model Assessment (β: 0.352; p < .001), triacylglycerols (β: 0.209; p < .001), leptin (β: 0.654; p < .001), tumor necrosis factor-alpha (β: 0.182; p < .001), Type 1macrophages (β: 0.181; p < .001), and tissue plasminogen activator inhibitor (β: 0.240; p < .001), independently of sex, age, and MVPA. A better anthropometric, metabolic, and inflammatory profile was detected in the most active children; however, these differences were partly due to BMI. These results suggest that a higher MVPA practice and a lower BMI in children may lead to a better cardiometabolic status. Topics: Body Mass Index; Cardiovascular Diseases; Child; Exercise; Humans; Inflammation; Insulin; Leptin; Pediatric Obesity; Resistin; Risk Factors; Tissue Plasminogen Activator; Triglycerides; Tumor Necrosis Factor-alpha | 2022 |
Leptin Enhances Hepatic Fibrosis and Inflammation in a Mouse Model of Cholestasis.
Leptin is an adipokine with roles in food intake and energy metabolism through its actions on neurons in the hypothalamus. The role of leptin in obesity and cardiovascular disorders is well documented. However, its influence on liver conditions such as cholestasis is poorly understood. The effects of exogenous leptin and leptin-neutralizing antibody on biliary hyperplasia, hepatic fibrosis, and inflammation in the multidrug resistance protein 2 knockout (Mdr2KO) mouse model of cholestasis were assessed by quantifying markers specific for cholangiocytes, activated hepatic stellate cells (HSCs), and cytokines. Serum and hepatic leptin were increased in Mdr2KO mice compared with FVB/NJ (FVBN) controls, and exogenous leptin enhanced biliary hyperplasia and liver fibrosis in Mdr2KO and FVBN mice. Leptin administration increased hepatic expression of C-C motif chemokine ligand 2 and IL-6 in Mdr2KO mice. In contrast, leptin-neutralizing antibody reduced intrahepatic bile duct mass and decreased HSC activation in Mdr2KO mice compared with FVBN controls. Sex-related differences were noted, with female Mdr2KO mice having more leptin than males. In cholangiocytes and LX2 cells in vitro, leptin increased phosphorylated Akt and stimulated cell proliferation. Leptin receptor siRNA and inhibitors of Akt phosphorylation impaired leptin-induced cell proliferation and proinflammatory cytokines. The current data suggest that leptin is abnormally increased in cholestatic mice, and excess leptin increases ductular reaction, hepatic fibrosis, and inflammation via leptin receptor-mediated phosphorylation of Akt in cholangiocytes and HSCs. Topics: Animals; Antibodies, Neutralizing; Cholestasis; Cytokines; Disease Models, Animal; Female; Hepatic Stellate Cells; Hyperplasia; Inflammation; Leptin; Liver; Liver Cirrhosis; Male; Mice; Mice, Knockout; Proto-Oncogene Proteins c-akt; Receptors, Leptin | 2022 |
Intra-abdominal adipose depot variation in adipogenesis, lipogenesis, angiogenesis, and fibrosis gene expression and relationships with insulin resistance and inflammation in premenopausal women with severe obesity.
Although severe obesity is associated with insulin resistance (IR) and inflammation, secretory function of intra-abdominal adipose tissues and their relationships with IR and inflammation markers remain poorly understood. Aims were to measure gene expression of adipogenic (C/EBPα/β, PPARγ-1/2, SREBP-1c, LXRα), lipogenic (SCD1, DGAT-1/2), angiogenic (VEGFα, leptin), and fibrotic (LOX, COL6A3) factors in the round ligament (RL), omental (OM), and mesenteric (ME) fat depots and to evaluate their relationships with IR and inflammation markers in 48 women with severe obesity undergoing bariatric surgery. Gene expression was assessed by RT-qPCR, and plasma glucose and insulin (HOMA-IR calculated), PAI-1, IL-6, TNFα, adiponectin, and leptin levels were determined. C/EBPβ and PPARγ-1/2 mRNA levels were more expressed in the OM (0.001 Topics: Adipogenesis; Female; Fibrosis; Gene Expression; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Lipogenesis; Obesity, Morbid; Plasminogen Activator Inhibitor 1; PPAR gamma; Sterol Regulatory Element Binding Protein 1; Tumor Necrosis Factor-alpha | 2022 |
Adipokines: inflammation and the pleiotropic role of white adipose tissue.
I had been working on the endocrine and signalling role of white adipose tissue (WAT) since 1994 following the identification of the ob (Lep) gene(1), this after some 15 years investigating the physiological role of brown adipose tissue. The ob gene, a mutation in which it is responsible for the profound obesity of ob/ob (Lepob/Lepob) mice, is expressed primarily in white adipocytes and encodes the pleiotropic hormone leptin. The discovery of this adipocyte hormone had wide-ranging implications, including that white fat has multiple functions that far transcend the traditional picture of a simple lipid storage organ. Topics: Adipocytes; Adipokines; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Inflammation; Leptin; Mice | 2022 |
Gene expression of adipokines and inflammatory cytokines in peripheral blood mononuclear cells of obese dogs.
Peripheral blood mononuclear cells (PBMCs) have been identified as a possible marker of inflammation in obesity. Understanding the expression of pro- and anti-inflammatory cytokines in PBMCs in obese dogs will help control obesity-related inflammatory diseases.. The aim of this study was to evaluate the role of PBMCs in obesity-associated chronic inflammation by analyzing the expression of adipokines and inflammatory cytokines.. Blood samples were obtained from 25 subjects and real-time quantitative polymerase chain reaction determinations were performed to quantify the gene expression levels of adipokines and inflammatory cytokines, including TNF-α, IL-17, leptin, MCP-1, and adiponectin, in the PBMCs.. The results showed that the gene expression levels of TNF-α (p < 0.001), IL-17 (p < 0.0001), and leptin (p < 0.0001) were strongly upregulated in the PBMCs of obese dogs compared to that in non-obese dogs.. The changes in gene expression levels of inflammation-related adipokines and pro-inflammatory cytokines occur in PBMCs, which may contribute to the low-grade chronic inflammation that is present in obesity. Topics: Adipokines; Animals; Cytokines; Dog Diseases; Dogs; Gene Expression; Humans; Inflammation; Interleukin-17; Leptin; Leukocytes, Mononuclear; Obesity; Tumor Necrosis Factor-alpha | 2022 |
Laparoscopic sleeve gastrectomy for morbid obesity improves gut microbiota balance, increases colonic mucosal-associated invariant T cells and decreases circulating regulatory T cells.
Laparoscopic sleeve gastrectomy (LSG) for morbid obesity may improve gut microbiota balance and decrease chronic inflammation. This study examines the changes in gut microbiota and immune environment, including mucosal-associated invariant T cells (MAIT cells) and regulatory T cells (Treg cells) caused by LSG.. Ten morbidly obese patients underwent LSG at our institution between December 2018 and March 2020. Flow cytometry for Th1/Th2/Th17 cells, Treg cells and MAIT cells in peripheral blood and colonic mucosa and 16S rRNA analysis of gut microbiota were performed preoperatively and then 12 months postoperatively.. Twelve months after LSG, the median percent total weight loss was 30.3% and the median percent excess weight loss was 66.9%. According to laboratory data, adiponectin increased, leptin decreased, and chronic inflammation improved after LSG. In the gut microbiota, Bacteroidetes and Fusobacteria increased after LSG, and indices of alpha diversity increased after LSG. In colonic mucosa, the frequency of MAIT cells increased after LSG. In peripheral blood, the frequency of Th1 cells and effector Treg cells decreased after LSG.. After LSG for morbid obesity, improvement in chronic inflammation in obesity is suggested by change in the constituent bacterial species, increase in the diversity of gut microbiota, increase in MAIT cells in the colonic mucosa, and decrease in effector Treg cells in the peripheral blood. Topics: Adiponectin; Gastrectomy; Gastrointestinal Microbiome; Humans; Inflammation; Laparoscopy; Leptin; Mucosal-Associated Invariant T Cells; Obesity, Morbid; RNA, Ribosomal, 16S; T-Lymphocytes, Regulatory; Treatment Outcome; Weight Loss | 2022 |
Protective effect of nimbolide against streptozotocin induced gestational diabetes mellitus in rats via alteration of inflammatory reaction, oxidative stress, and gut microbiota.
Gestational diabetes mellitus (GDM) is a significant pregnancy-related condition, which showed effect on the development of fetal. Anti-inflammatory and antioxidant therapy commonly used for the treatment of GDM. Nimbolide already confirmed their anti-inflammatory and anti-oxidant effect against various animal disease model. Our objective in this research is to investigate the protective effect of nimbolide against STZ induced GDM and elucidate the mechanism.. In this experimental study, pregnant female Wistar rats were used and STZ (40 mg/kg) was used to induce the GDM. Blood glucose level (BGL), body weight and plasma insulin were assessed at regular time (gestational day 0, 9, and 18). Water intake, food intake, fecal and urine output were also estimated. In the female rats, hemoglobin (Hb), glycalated hemoglobin (HbA1c), hepatic glycogen, fructosamine, adiponectin, leptin, lipid, antioxidant and inflammatory cytokines parameters were estimated. In the fetuses, the fetues weight, implementation loss, and fetal weight were estimated. At the completion of the protocol, biochemical parameters were calculated. Gut microbiota was estimated in end of the study.. Nimbolide treatment significantly (p < .001) improved the fetuses level and suppressed the fetal weight and implantation loss. Nimbolide treatment significantly (p < .001) suppressed the BGL and enhanced the body weight, insulin level. Nimbolide treatment suppressed the water intake, food intake, urinary and fecal output. Nimbolide significantly (p < .001) suppressed the fructosamine, leptin and enhanced the adiponectin level. Nimbolide treatment significantly (p < .001) decreased the malonaldehyde (MDA) level and boosted the total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and catalase (CAT); suppressed the level of TNF-α, IL-1β, IL-6, and boosted the level of IL-10. Furthermore, nimbolide treatment reversed the gut microbiota alteration induced via STZ in female rats. At the phylum level, the Firmicutes and Bacteroidetes relative abundance was altered via nimbolide treatment. The ratio of F/B boosted in GDM group and nimbolide treatment significantly (p < .001) suppressed. Nimbolide considerably suppressed the firmicutes and enhanced the Bacteroidetes, CAG-352, Lacnospirace.. Based on the findings, we may conclude that nimbolide protects the pregnant rats from GDM via alteration of inflammation, oxidative stress, and gut microbiota. Topics: Adiponectin; Animals; Anti-Inflammatory Agents; Antioxidants; Blood Glucose; Diabetes, Gestational; Female; Fetal Weight; Fructosamine; Gastrointestinal Microbiome; Humans; Inflammation; Insulins; Leptin; Limonins; Oxidative Stress; Pregnancy; Rats; Rats, Wistar; Streptozocin; Water | 2022 |
Sulforaphane reduces obesity by reversing leptin resistance.
The ascending prevalence of obesity in recent decades is commonly associated with soaring morbidity and mortality rates, resulting in increased health-care costs and decreased quality of life. A systemic state of stress characterized by low-grade inflammation and pathological formation of reactive oxygen species (ROS) usually manifests in obesity. The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) is the master regulator of the redox homeostasis and plays a critical role in the resolution of inflammation. Here, we show that the natural isothiocyanate and potent NRF2 activator sulforaphane reverses diet-induced obesity through a predominantly, but not exclusively, NRF2-dependent mechanism that requires a functional leptin receptor signaling and hyperleptinemia. Sulforaphane does not reduce the body weight or food intake of lean mice but induces an anorectic response when coadministered with exogenous leptin. Leptin-deficient Topics: Animals; Inflammation; Isothiocyanates; Leptin; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Obesity; Quality of Life; Reactive Oxygen Species; Receptors, Leptin; Sulfoxides | 2022 |
Elevations in adipocytokines and mortality in rheumatoid arthritis.
This study assessed whether circulating levels of adiponectin and leptin are associated with higher mortality in patients with RA.. Participants were adults from the Veterans Affairs RA Registry. Adipokines and inflammatory cytokines were measured as part of a multi-analyte panel on banked serum at enrolment. Dates and causes of death were derived from the Corporate Data Warehouse and the National Death Index. Covariates were derived from medical record, biorepository and registry databases. Multivariable Cox proportional hazard models evaluated associations between biomarkers and all-cause and cause-specific mortality.. A total of 2583 participants were included. Higher adiponectin levels were associated with older age, male sex, white race, lower BMI, autoantibody seropositivity, radiographic damage, longer disease duration, prednisone use and osteoporosis. Higher adiponectin concentrations were also associated with higher levels of inflammatory cytokines but not higher disease activity at enrolment. Leptin was primarily associated with greater BMI and comorbidity. The highest quartile of adiponectin (vs lowest quartile) was associated with higher all-cause mortality [hazard ratio (HR): 1.46 (95% CI: 1.11, 1.93), P = 0.009] and higher cardiovascular mortality [HR: 1.85 (95% CI: 1.24, 2.75), P = 0.003], after accounting for covariates. Higher leptin levels were also associated with greater all-cause and cancer mortality.. Elevations in adipokines are associated with age, BMI, comorbidity and severe disease features in RA and independently predict early death. Associations between adiponectin and inflammatory cytokines support the hypothesis that chronic subclinical inflammation promotes metabolic changes that drive elevations in adipokines and yield adverse health outcomes. Topics: Adipokines; Adiponectin; Adult; Arthritis, Rheumatoid; Cytokines; Female; Humans; Inflammation; Leptin; Male | 2022 |
Telmisartan is the most effective ARB to increase adiponectin via PPARα in adipocytes.
Telmisartan and irbesartan are angiotensin II receptor blockers (ARBs) and reportedly stimulate adiponectin secretion from adipocytes via partial peroxisome proliferator-activated receptor γ (PPARγ) activation. However, quantitative evaluation among different ARBs has not been performed. Adiponectin exerts strong protection against a number of pathological events by suppressing cell death, inhibiting inflammation, and enhancing cell survival, while leptin promotes inflammation, oxidative stress, atherogenesis, and thrombosis. The aim of this study was to identify the most effective ARB enhancing adiponectin secretion without raising leptin secretion from human white adipocytes (HWAs). Among seven ARBs (azilsartan, candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan), telmisartan was the most effective ARB for the increase of adiponectin secretion and irbesartan was the second, whereas the other ARBs at 1 µM had no effect on adiponectin secretion. GW9662, a PPARγ antagonist, completely blocked pioglitazone (PPARγ agonist)-induced adiponectin secretion and mRNA expression, whereas it unexpectedly blocked neither telmisartan- nor irbesartan-induced adiponectin secretion and mRNA expression but rather increased them. GW6471, PPARα antagonist, and siRNA for PPARα suppressed telmisartan- and irbesartan-induced adiponectin secretion, suggesting that PPARα is the main target of these ARBs to increase adiponectin secretion in HWAs. Leptin secretion was not affected by any ARBs at 1 µM and GW9662 significantly decreased the basal secretion of leptin, suggesting that basal leptin secretion is regulated in a PPARγ-dependent manner. We conclude that telmisartan is the most effective ARB to increase adiponectin secretion via PPARα without raising leptin secretion from HWAs. Topics: Adipocytes; Adiponectin; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzoates; Humans; Inflammation; Irbesartan; Leptin; PPAR alpha; PPAR gamma; RNA, Messenger; Telmisartan | 2022 |
Leptin Signaling Suppression in Macrophages Improves Immunometabolic Outcomes in Obesity.
Obesity is a major concern for global health care systems. Systemic low-grade inflammation in obesity is a major risk factor for insulin resistance. Leptin is an adipokine secreted by the adipose tissue that functions by controlling food intake, leading to satiety. Leptin levels are increased in obesity. Here, we show that leptin enhances the effects of LPS in macrophages, intensifying the production of cytokines, glycolytic rates, and morphological and functional changes in the mitochondria through an mTORC2-dependent, mTORC1-independent mechanism. Leptin also boosts the effects of IL-4 in macrophages, leading to increased oxygen consumption, expression of macrophage markers associated with a tissue repair phenotype, and wound healing. In vivo, hyperleptinemia caused by diet-induced obesity increases the inflammatory response by macrophages. Deletion of leptin receptor and subsequently of leptin signaling in myeloid cells (ObR-/-) is sufficient to improve insulin resistance in obese mice and decrease systemic inflammation. Our results indicate that leptin acts as a systemic nutritional checkpoint to regulate macrophage fitness and contributes to obesity-induced inflammation and insulin resistance. Thus, specific interventions aimed at downstream modulators of leptin signaling may represent new therapeutic targets to treat obesity-induced systemic inflammation. Topics: Adipose Tissue; Animals; Inflammation; Insulin Resistance; Leptin; Macrophages; Mice; Mice, Inbred C57BL; Obesity | 2022 |
Effects of ivacaftor on systemic inflammation and the plasma proteome in people with CF and G551D.
Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator for people with CF and the G551D mutation. We aimed to investigate the biology of CFTR modulation and systemic effects of CFTR restoration by examining changes in circulating measurements of inflammation and growth and novel proteins with ivacaftor treatment.. Blood samples from 64 CF subjects with G551D-CFTR were analyzed for inflammatory and growth-related proteins at baseline, 1 and 6 months after ivacaftor initiation. In 30 subjects, plasma was assayed for 1,322 proteins using the SomaScan proteomic platform at baseline and 6 months post-ivacaftor. Correlations with clinical outcomes were assessed.. Significant reductions in high mobility group box-1 protein (HMGB-1), calprotectin, serum amyloid A, and granulocyte colony-stimulating factor (G-CSF), and an increase in insulin-like growth factor (IGF-1) occurred 1 month after ivacaftor. This treatment effect was sustained at 6 months for HMGB-1 and calprotectin. Correcting for multiple comparisons in the proteomic analysis, 9 proteins (albumin, afamin, leptin, trypsin, pancreatic stone protein [PSP], pituitary adenylate cyclase-activating polypeptide-38, repulsive guidance molecule A [RGMA], calreticulin, GTPase KRas) changed significantly with ivacaftor. Proteins changing with treatment are involved in lipid digestion and transport and extracellular matrix organization biological processes. Reductions in calprotectin and G-CSF and increases in calreticulin, and RGMA correlated with improved lung function, while increasing IGF-1, leptin and afamin and decreasing PSP correlated with increased weight.. Ivacaftor led to changes in inflammatory, lipid digestion, and extracellular matrix proteins, lending insights into the extrapulmonary effects of CFTR modulation. Topics: Aminophenols; Calreticulin; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Granulocyte Colony-Stimulating Factor; HMGB Proteins; Humans; Inflammation; Insulin-Like Growth Factor I; Leptin; Leukocyte L1 Antigen Complex; Lipids; Mutation; Proteome; Proteomics; Respiratory System Agents | 2022 |
Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation.
Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and Topics: Animals; Dermatitis; Dyslipidemias; Humans; Inflammation; Interleukin-17; Keratinocytes; Leptin; Mice; Obesity; Palmitic Acid; Psoriasis; Skin; Tumor Necrosis Factor-alpha | 2022 |
Quercetin ameliorates salivary gland apoptosis and inflammation in primary Sjögren's syndrome through regulation of the leptin/OB-R signaling.
Dry mouth is the main manifestation of Sjögren syndrome (SS). Quercetin has been reported to alleviate radiation-induced salivary gland damage, yet the effect of quercetin on SS-caused salivary gland damage remains unclear. This study aimed to investigate the effects of quercetin on SS-induced salivary gland damage and the mechanism underlying its therapeutic potential in SS. Here, NOD/Ltj mice were used to spontaneously mimic SS-induced salivary gland inflammation in vivo and salivary gland epithelial cells (SGECs) were stimulated by interferon-γ (IFN-γ) to mimic cell inflammation in vitro. Results showed that quercetin significantly reduced loss of saliva flow, salivary gland damage, cell apoptosis, and inflammatory response in NOD/Ltj mice. Quercetin treatment also significantly reduced the increased serum leptin (LP) levels in NOD/Ltj mice. Furthermore, quercetin blocked the increases in the expression of obesity receptor (OB-R) and its downstream Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling in the salivary glands. In vitro experiments confirmed that quercetin could protect SGECs from IFN-γ-induced cell apoptosis and inflammation through the LP/OB-R-activated JAK2/STAT3 signaling. Hence, quercetin might protect against SS-induced salivary gland damage by relieving cell apoptosis and inflammation by inhibiting the LP/OB-R signaling, providing a new perspective for treating SS-induced dry mouth. Topics: Animals; Apoptosis; Inflammation; Interferon-gamma; Leptin; Mice; Mice, Inbred NOD; Obesity; Quercetin; Salivary Glands; Sjogren's Syndrome | 2022 |
Inflammatory profile associated with insulin resistance in non-overweight versus overweight people living with HIV in Pune, Western India.
People living with HIV have greater diabetes (T2DM) than the general population despite lower prevalence of overweight/obesity. Both insulin resistance (IR), a T2DM precursor, and HIV are independently associated with chronic inflammation. Inflammation may be a pathophysiological link explaining IR in people living with HIV who are not overweight but is not well understood.. To study the association between inflammation and IR in non-overweight and overweight people living with HIV.. In a cohort of adult people living with HIV with undetectable viral load in Pune, India, we measured fasting insulin, glucose, and 9 inflammatory markers. IR was defined as HOMA-IR ≥2, and non-overweight as BMI ≤23 kg/m. Of 288 participants, 66% (n = 189) were non-overweight. Among non-overweight, prevalence of IR was 34% (n = 65). Each doubling of MCP-1 and leptin was associated with IR on univariate analysis (prevalence ratio (PR) 1.29, 95%CI 1.07-1.53, p < 0.01; PR 1.13 95%CI 1.01-1.26, p = 0.03). Leptin remained associated with IR after adjustment for age, MCP-1, gender, cholesterol, and waist circumference (adjusted PR 1.20 95%CI 1.06-1.36, p < 0.01). Among overweight, prevalence of IR was 69% and no markers were associated with IR.. One in 3 non-overweight people living with HIV in India with controlled viremia have IR. Leptin was associated with IR among non-overweight people living with HIV and may provide insight into the pathophysiology of metabolic disease in this population. Topics: Adult; Biomarkers; Body Mass Index; Diabetes Mellitus, Type 2; HIV Infections; Humans; India; Inflammation; Insulin; Insulin Resistance; Leptin; Overweight | 2022 |
Differential Immunometabolic Effects of High-Fat Diets Containing Coconut, Sunflower, and Extra Virgin Olive Oils in Female Mice.
To compare the effects of three high-fat diets (HFDs) based on coconut, sunflower, or extra virgin olive oils (EVOOs) on adipose tissue, metabolism, and inflammation.. Mice are fed for 16 weeks on their respective HFD. HFD based on coconut oil produces significantly lower body weight than EVOO- or sunflower oil-based HFDs. Furthermore, the coconut oil HFD leads to metabolic disturbances such as reduction of circulating leptin and adiponectin concentrations, hypertriglyceridemia, hepatomegaly, and liver triglyceride accumulation. Likewise, this diet produces an increase in serum pro-inflammatory cytokines (interleukin 6 [IL-6] and tumor necrosis factor-α [TNF-α]). In white (WAT) and brown (BAT) adipose tissue, the HFD based on coconut oil does not cause significant changes in the expression of studied proteins related to thermogenesis (uncoupling protein 1 [UCP-1]), mitochondrial biogenesis, and browning (peroxisome proliferator-activated receptor-γ coactivator 1α [PGC-1α] and nuclear factor E2-related factor 2 [Nrf2]). However, the HFD based on EVOO induces upregulation of UCP-1, PGC-1α, and Nrf2 expression in BAT, increases the expression of UCP-1 and PGC-1α in inguinal WAT, and enhances the expression of PGC-1α in epididymal WAT.. An HFD based on coconut oil could reduce circulating leptin and adiponectin concentrations, increase the liver fat content, raise serum triglycerides, and promote inflammation by increasing circulating pro-inflammatory cytokines, while an EVOO-based HFD could increase thermogenic activity. Topics: Adiponectin; Adipose Tissue; Animals; Coconut Oil; Diet, High-Fat; Female; Inflammation; Interleukin-6; Leptin; Mice; NF-E2-Related Factor 2; Olive Oil; Peroxisome Proliferator-Activated Receptors; Sunflower Oil; Triglycerides; Tumor Necrosis Factor-alpha; Uncoupling Protein 1 | 2022 |
Leptin receptor signaling sustains metabolic fitness of alveolar macrophages to attenuate pulmonary inflammation.
Alveolar macrophages (AMs) are critical mediators of pulmonary inflammation. Given the unique lung tissue environment, whether there exist AM-specific mechanisms that control inflammation is not known. Here, we found that among various tissue-resident macrophage populations, AMs specifically expressed Topics: Humans; Inflammation; Leptin; Lung; Macrophages, Alveolar; Pneumonia; Receptors, Leptin | 2022 |
Total and Plant Protein Consumption: The Role of Inflammation and Risk of Non-Communicable Disease.
Background: Inflammatory cytokine levels are associated with Non-Communicable Diseases (NCDs) and can be influenced by a person’s macronutrient profile. This work aims to evaluate the relationship between the compliance with the age-specific recommended protein intake and the levels of inflammatory markers related to the risk of NCDs. Methods: The study participants included 347 participants (119 men and 228 women), ages 18 to 86 years. Cardio-metabolic risk evaluations, including an assessment of the prevalence of Metabolic Syndrome, were performed. Leptin, IL-15, IL-6, and TNF-α levels were measured. Results: The adequacy of the total protein (TP) intake was lower in old people compared to individuals aged <60 years, and only few volunteers consumed the suggested 50% plant protein (PP) for a healthy and sustainable diet. A lower risk of NCDs with a PP consumption above at least 40% was observed only in old individuals. A differential effect on TNF-α and IL-6 was observed for both TP and PP intake by gender and age class, whereas for leptin and IL-15 only significant interactions among sex and the class of age were found. Conclusion: Although our data suggest that consuming more than 40% of PP can reduce the risk of NCDs, the effect of gender differences on cytokine levels should be considered in larger studies. Topics: Cross-Sectional Studies; Dietary Proteins; Female; Humans; Inflammation; Interleukin-15; Interleukin-6; Leptin; Male; Noncommunicable Diseases; Plant Proteins; Risk Factors; Tumor Necrosis Factor-alpha | 2022 |
Comparison of Pulmonary Function and Inflammation in Children/Adolescents with New-Onset Asthma with Different Adiposity Statuses.
(1) Background: The relationship between obesity and asthma is still uncertain. This study aimed to investigate the effect of overweight/obesity on the pulmonary function of patients with new-onset pediatric asthma and explore the possible causative factors related to concomitant obesity and asthma. (2) Methods: Patients aged 5 to 17 years old with newly diagnosed mild to moderate asthma were recruited from June 2018 to May 2019, from a respiratory clinic in Shanghai, China. Participants were categorized into three groups: normal weight, overweight, and obese asthma. A family history of atopy and patients' personal allergic diseases were recorded. Pulmonary function, fractional exhaled nitric oxide (FeNO), eosinophils, serum-specific immunoglobulins E (sIgE), serum total IgE (tIgE), and serum inflammatory biomarkers (adiponectin, leptin, Type 1 helper T, and Type 2 helper T cytokines) were tested in all participants. (3) Results: A total of 407 asthma patients (197 normal weight, 92 overweight, and 118 obese) were enrolled. There was a reduction in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC), FEV1/FVC%, and FEF25-75% in the overweight/obese groups. No difference was found between the study groups in the main allergy characteristics. Leptin levels were higher while adiponectin was lower in asthmatics with obesity. Higher levels of IL-16 were found in overweight/obese asthmatic individuals than in normal-weight individuals. (4) Conclusions: Obesity may have an effect on impaired pulmonary function. While atopic inflammation plays an important role in the onset of asthma, nonatopic inflammation (including leptin and adiponectin) increases the severity of asthma in overweight/obese patients. The significance of different levels of IL-16 between groups needs to be further studied. Topics: Adiponectin; Adiposity; Adolescent; Asthma; Biomarkers; Child; Child, Preschool; China; Forced Expiratory Volume; Humans; Hypersensitivity, Immediate; Inflammation; Interleukin-16; Leptin; Obesity; Overweight | 2022 |
The Effect of Leptin on the Blood Hormonal Profile (Cortisol, Insulin, Thyroid Hormones) of the Ewe in Acute Inflammation in Two Different Photoperiodical Conditions.
As a day animal with sensitivity to inflammation similar to that of humans, the sheep may highly outperform the rodent model in inflammation studies. Additionally, seasonality makes sheep an interesting model in endocrinology research. Although there are studies concerning inflammation's influence on leptin secretion and vice versa, a ewe model, with its possible 'long-day leptin resistance', is still not examined enough. The present study aimed to examine whether leptin may modulate an acute inflammation influence on plasma hormones in two photoperiodical conditions. The experiment was conducted on 48 ewes divided into four groups (control, lipopolysaccharide (LPS), leptin, LPS + leptin) during short and long days. Blood sampling started 1 hour before and continued 3 h after LPS/saline administration for further hormonal analysis. The results showed that the photoperiod is one of the main factors influencing the basal concentrations of several hormones with higher values of leptin, insulin and thyroid hormones during long days. Additionally, the acute inflammation effect on cortisol, insulin and thyroid hormones was photoperiod-dependent. The endotoxemia may also exert an influence on leptin concentration regardless of season. The effects of leptin alone on hormone blood concentrations are rather limited; however, leptin can modulate the LPS influence on insulin or thyroxine in a photoperiod-dependent way. Topics: Animals; Female; Hydrocortisone; Inflammation; Insulin; Leptin; Lipopolysaccharides; Photoperiod; Sheep; Thyroxine | 2022 |
Chitosan reduces inflammation and protects against oxidative stress in a hyperlipidemic rat model: relevance to nonalcoholic fatty liver disease.
An altered lipid profile may lead to the development of inflammation and NAFLD (Non-alcoholic fatty liver disease). Although statins have a positive effect on blood lipid levels their long-term use is known to cause adverse effects, in this backdrop there is an interest in natural compounds which may affect lipid metabolism and prevent NAFLD. We have examined the effect of Chitosan on rats subjected to a high-fat diet.. Male Wistar middle aged rats (12-16 months) were treated with high-fat diet orally for two months for creating a NAFLD model. Rats were also supplemented with Chitosan (2% chitosan daily) for 2 months. We assessed the activity of antioxidant enzymes, the histopathological profile of the liver. Inflammatory cytokines and adiponectin levels were also measured in serum. HFD induced significant changes in liver tissue and inflammatory markers (Il-6, TNF- alpha, NF-KB). Chitosan treatment protected rats from HFD induced alterations.. The findings suggest that Chitosan can effectively improve liver lipid metabolism by normalizing cholesterol, triglyceride, lowering NF-KB expression, and protecting the liver from oxidative stress by improving hepatic function. Chitosan also regulates genes related to lipidemic stress i,e leptin and adiponectin. Topics: Adiponectin; Animals; Antioxidants; Chitosan; Cholesterol; Cytokines; Diet, High-Fat; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Interleukin-6; Leptin; Lipid Metabolism; Lipids; Liver; Male; NF-kappa B; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Rats; Rats, Wistar; Triglycerides | 2022 |
Inflammatory biomarkers and risk of breast cancer among young women in Latin America: a case-control study.
Breast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer development, but data is limited in premenopausal women, especially in Latin America.. We investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors.. IL-6 (OR. The results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women. Topics: Biomarkers; Breast Neoplasms; Case-Control Studies; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Latin America; Leptin; Risk Factors; Tumor Necrosis Factor-alpha | 2022 |
Vitamin D insufficiency is associated with inflammation and deregulation of adipokines in patients with metabolic syndrome.
Previous studies have been reported that vitamin D deficiency increased the risk of metabolic syndrome (MetS). Nonetheless, the exact mechanisms underlying this association is unclear. Besides, inflammation and deregulation of adipokines secretion have been recognized as pivotal factors that contribute to the pathogenesis of these conditions. Therefore, we assessed whether serum vitamin D status is associated with serum levels of adipokines and inflammatory markers in these patients.. This case-control study was carried out among 65 patients with MetS who had vitamin D insufficiency (cases) and 130 MetS patients who had vitamin D sufficiency (controls). Cases and controls were recruited from among those referred to health centers in Zabol County, Iran. Vitamin D insufficiency was regarded as a serum 25-hydroxyvitamin D [25(OH)D] concentration below 30 ng/ml. Serum concentrations of leptin, adiponectin, visfatin, and resistin and also adiponectin/leptin ratio along with serum levels of interleukin 6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-α), were evaluated.. Serum levels of leptin, resistin, and TNF-α were significantly higher, whereas, serum adiponectin and adiponectin/leptin ratio were significantly lower in cases than the controls. There was no significant difference in serum visfatin, IL-6, and IL-10 between the groups. Serum levels of 25(OH)D were inversely correlated with leptin, resistin, and TNF-α in both unadjusted models and after adjustment for potential confounders.. Our findings indicated that vitamin D insufficiency in MetS patients is associated with increased inflammation and serum adipokine abnormalities which may be associated with developing metabolic complications in these patients. Topics: Adipokines; Adiponectin; Case-Control Studies; Humans; Inflammation; Interleukin-10; Interleukin-6; Leptin; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Resistin; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency; Vitamins | 2022 |
Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes.
To assess the potential direct effects of the integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human immunodeficiency virus (PLWH), on human adipose cells.. Drugs were added to the differentiation medium of human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells and morphological adipogenesis was monitored for 10 days. Also, adipocytes were exposed to drugs following differentiation (day 14). The gene expression levels of selected adipogenesis markers, adipocyte metabolism markers, adipokines, and cytokines were determined by quantitative-reverse transcription polymerase-chain reaction. The release of adiponectin and leptin into the culture medium was measured using specific enzyme-linked immunosorbent assay, and release of interleukin-6 and chemokine (CC motif) ligand-2 using Multiplex assays.. Overall morphological adipogenesis was unaltered by INsTIs. The expression of adipogenesis marker genes (peroxisome proliferator-activated receptor-Ɣ and lipoprotein lipase) was slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed gene expression and the release of pro-inflammatory cytokines in differentiating adipocytes. Dolutegravir and raltegravir increased interleukin-6 gene expression, but only dolutegravir increased interleukin-6 release. Dolutegravir repressed adiponectin expression and release in differentiating adipocytes and had a similar but milder effect on leptin. Drug treatment of mature adipocytes reduced adiponectin gene expression in response to dolutegravir.. The INsTIs studied do not have a significant effect on human adipose cell differentiation but exert distinct effects on gene expression and secretion of adipokines and cytokines. These findings will help understand and manage the effects of INsTI-containing treatments on body weight and metabolic dysregulation in PLWH. Topics: Adipocytes; Adipokines; Adiponectin; Amides; Cytokines; Heterocyclic Compounds, 3-Ring; Humans; Inflammation; Integrases; Interleukin-6; Leptin; Ligands; Lipoprotein Lipase; Oxazines; Peroxisome Proliferator-Activated Receptors; Piperazines; Pyridones; Raltegravir Potassium | 2022 |
Galactose in the Post-Weaning Diet Programs Improved Circulating Adiponectin Concentrations and Skeletal Muscle Insulin Signaling.
Short-term post-weaning nutrition can result in long-lasting effects in later life. Partial replacement of glucose by galactose in the post-weaning diet showed direct effects on liver inflammation. Here, we examined this program on body weight, body composition, and insulin sensitivity at the adult age. Three-week-old female C57BL/6JRccHsd mice were fed a diet with glucose plus galactose (GAL; 16 energy% (en%) each) or a control diet with glucose (GLU; 32 en%) for three weeks, and afterward, both groups were given the same high-fat diet (HFD). After five weeks on a HFD, an oral glucose tolerance test was performed. After nine weeks on a HFD, energy metabolism was assessed by indirect calorimetry, and fasted mice were sacrificed fifteen minutes after a glucose bolus, followed by serum and tissue analyses. Body weight and body composition were not different between the post-weaning dietary groups, during the post-weaning period, or the HFD period. Glucose tolerance and energy metabolism in adulthood were not affected by the post-weaning diet. Serum adiponectin concentrations were significantly higher ( Topics: Adiponectin; Animals; Body Weight; Diet, High-Fat; Female; Galactose; Glucose; Inflammation; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Mice; Mice, Inbred C57BL; Muscle, Skeletal; RNA, Messenger; Weaning | 2022 |
Postoperative Dynamic of Leptin and Fibroblast Growth Factor 21 in 123 Patients Recovering from Cardiac Surgery.
BACKGROUND Cardiac surgery triggers acute changes in serum leptin and fibroblast growth factor 21 (FGF-21). Considering their pleiotropic role in inflammation and abnormal glucose metabolism, perseverance of their abnormal serum level can have a long-term impact on recovery and end-organ failures. Long-term dynamics after cardiac surgery are unknown. MATERIAL AND METHODS Serum was collected from 123 patients before cardiac surgery (tbaseline) and 24 h (t24h), 7 days (t7d), and 3 months (t3m) later. Also, interleukin 6 (IL-6) and C-reactive protein (CRP) assessed nonspecific inflammatory responses. Neurodegeneration was gauged with serum amyloid ß1-40 and ß1-42. Demographic and clinical information, including disposition at 28 days and t3m from admission, were collected. RESULTS Serum leptin increased at t24h (leptinbaseline=613+747.9 vs leptin24h=768±718.1; P=0.0083) and decreased at t7d (leptin7d=499.5±540.2; P=0.043). FGF-21 levels increased at t24h and t7d. Cytokines normalized by t3m. Presurgical leptin levels were higher in Asians and were the primary determinant of postoperative leptin changes. Leptin levels were most elevated in patients undergoing aortic valve and arch surgery; the perioperative increase was significant only in patients with mitral valve surgery. Leptin and FGF-21 did not correlate with markers of general inflammation (CRP, IL-6), which partially resolved after t3m. Amyloid ß1-42 at t3m correlated with leptin peak at t24h. Low prehospital FGF-21 level correlated with the incidence of perioperative stroke; postoperative FGF-21 correlated with discharge to facility vs home. CONCLUSIONS Leptin and FGF-21 evolve independently from the inflammatory response in the aftermath of cardiac surgery and correlate with cardiac remodeling and neurodegeneration markers. Topics: Biomarkers; C-Reactive Protein; Cardiac Surgical Procedures; Cytokines; Fibroblast Growth Factors; Glucose; Humans; Inflammation; Interleukin-6; Leptin | 2022 |
Trimester-Specific Serum Fructosamine in Association with Abdominal Adiposity, Insulin Resistance, and Inflammation in Healthy Pregnant Individuals.
This study aimed to (1) characterize the variations in serum fructosamine across trimesters and according to pre-pregnancy BMI (ppBMI), and (2) examine associations between fructosamine and adiposity/metabolic markers (ppBMI, first-trimester adiposity, leptin, glucose homeostasis, and inflammation measurements) during pregnancy. Serum fructosamine, albumin, fasting glucose and insulin, leptin, adiponectin, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were measured at each trimester. In the first trimester, subcutaneous (SAT) and visceral (VAT) adipose tissue thicknesses were estimated by ultrasound. In the 101 healthy pregnant individuals included (age: 32.2 ± 3.5 y.o.; ppBMI: 25.5 ± 5.5 kg/m2), fructosamine concentrations decreased during pregnancy whereas albumin-corrected fructosamine concentrations increased (p < 0.0001 for both). Notably, fructosamine concentrations were inversely associated with ppBMI, first-trimester SAT, VAT, and leptin (r = −0.55, r = −0.61, r = −0.48, r = −0.47, respectively; p < 0.0001 for all), first-trimester fasting insulin and HOMA-IR (r = −0.46, r = −0.46; p < 0.0001 for both), and first-trimester IL-6 (r = −0.38, p < 0.01). However, once corrected for albumin, most of the correlations lost strength. Once adjusted for ppBMI, fructosamine concentrations were positively associated with third-trimester fasting glucose and CRP (r = 0.24, r = 0.27; p < 0.05 for both). In conclusion, serum fructosamine is inversely associated with adiposity before and during pregnancy, with markers of glucose homeostasis and inflammation, but the latter associations are partially influenced by albumin concentrations and ppBMI. Topics: Adiponectin; Adiposity; Adult; Blood Glucose; C-Reactive Protein; Female; Fructosamine; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Obesity; Obesity, Abdominal; Pregnancy | 2022 |
Docosahexaenoic Acid Counteracts the Hypoxic-Induced Inflammatory and Metabolic Alterations in 3T3-L1 Adipocytes.
Hypoxia is caused by the excessive expansion of the white adipose tissue (AT) and is associated with obesity-related conditions such as insulin resistance, inflammation, and oxidative stress. Docosahexaenoic acid (DHA) is an omega-3 fatty acid reported to have beneficial health effects. However, the effects of DHA in AT against hypoxia-induced immune-metabolic perturbations in adipocytes exposed to low O. The apoptosis and reactive oxygen species (ROS) rates were evaluated. Metabolic parameters such as lactate, FFA, glycerol release, glucose uptake, and ATP content were assessed by a fluorometer. The expression of HIF-1, GLUT1 and the secretion of adipocytokines such as leptin, adiponectin, and pro-inflammatory markers was evaluated.. DHA-treated hypoxic cells showed significantly decreased basal free fatty acid release, lactate production, and enhanced glucose consumption. In addition, DHA-treatment of hypoxic cells caused a significant reduction in the apoptosis rate and ROS production with decreased lipid peroxidation. Moreover, DHA-treatment of hypoxic cells caused a decreased secretion of pro-inflammatory markers (IL-6, MCP-1) and leptin and increased adiponectin secretion compared with hypoxic cells. Furthermore, DHA-treatment of hypoxic cells caused significant reductions in the expression of genes related to hypoxia (HIF-1, HIF-2), anaerobic metabolism (GLUT1 and Ldha), ATP production (ANT2), and fat metabolism (FASN and PPARY).. This study suggests that DHA can exert potential anti-obesity effects by reducing the secretion of inflammatory adipokines, oxidative stress, lipolysis, and apoptosis. Topics: 3T3-L1 Cells; Adenosine Triphosphate; Adipocytes; Adipokines; Adiponectin; Animals; Biomarkers; Docosahexaenoic Acids; Glucose Transporter Type 1; Hypoxia; Inflammation; Lactates; Leptin; Mice; Obesity; Reactive Oxygen Species | 2022 |
Synergism between Extracts of
This study aims to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating induced inflammation and impaired brain neurotransmitters commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into four experimental groups. Group I, control, obese, fed on a high-fat diet (HFD), and Group II-IV, fed on HFD then given mangosteen extract (400 mg/kg/day) and/or Curcuma (80 mg/kg/day), or a mixture of both for 6 weeks. Plasma pro-inflammatory cytokines, leptin, and brain serotonin, dopamine, and glutamate were measured in the five studied groups. G. mangostana and Curcuma longa extracts demonstrate antioxidant and DPPH radical scavenging activities. Both induced a significant reduction in the weight gained, concomitant with a non-significant decrease in the BMI (from 0.86 to 0.81 g/cm2). Curcuma either alone or in combination with MPE was more effective. Both extracts demonstrated anti-inflammatory effects and induced a significant reduction in levels of both IL-6 and IL-12. The lowest leptin level was achieved in the synergistically treated group, compared to independent treatments. Brain dopamine was the most affected variable, with significantly lower levels recorded in the Curcuma and synergistically treated groups than in the control group. Glutamate and serotonin levels were not affected significantly. The present study demonstrated that mangosteen pericarp extract (MPE) and Curcuma were independently and in combination effective in treating obesity-induced inflammation and demonstrating neuroprotective properties. Topics: Animals; Brain; Curcuma; Diet, High-Fat; Dopamine; Garcinia mangostana; Glutamates; Inflammation; Leptin; Male; Neurotransmitter Agents; Obesity; Plant Extracts; Rats; Rats, Wistar; Serotonin | 2022 |
Associations of leptin and corticostriatal connectivity in bipolar disorder.
Bipolar disorder (BD) and metabolic disturbance represent a chronic state of low-grade inflammation and corticostriatal circuitry alterations. Herein, we aimed to investigate whether plasma leptin, an adipokine that plays a key role in the interplay of metabolism and inflammation, is associated with corticostriatal connectivity in patients with BD. Twenty-eight BD I patients, 36 BD II patients and 66 healthy controls were enrolled and completed the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Recent Life Change Questionnaire. Fasting plasma leptin and C-reactive protein (CRP) levels were measured, and corticostriatal connectivity was examined using functional magnetic resonance imaging (fMRI). The relationships between leptin, CRP and body mass index (BMI) identified in the controls and BD II patients were absent in the BD I patients. We did not find a significant group difference in the leptin level; nevertheless, the negative correlation between leptin level and corticostriatal connectivity (ventrolateral prefrontal cortex and inferior temporal gyrus) observed in the healthy controls was absent in the BD patients. The disproportionate increase in leptin level with increasing BMI in BD indicated a potential inflammatory role of white adipose tissue in BD. Furthermore, higher CRP levels in BD I patients might induce leptin resistance. Collectively, our results implied vulnerability to inflammatory and metabolic diseases in patients with BD, especially BD I. Topics: Bipolar Disorder; Cerebral Cortex; Humans; Inflammation; Leptin; Magnetic Resonance Imaging; Temporal Lobe | 2022 |
Malnutrition and Erythropoietin Resistance among Patients with End-Stage Kidney Disease: Where Is the Perpetrator of Disaster?
Hemodialyzed patients with poor erythropoietin response tend to have low volume of visceral adipose tissue and score high on malnutrition-inflammation score. This study investigates in-depth the role of leptin and chosen cytokines in the development of malnutrition-inflammation syndrome (MIS) and erythropoietin resistance.. Eighty-one hemodialyzed patients with erythropoietin-treated anemia were enrolled in the study. Their body composition was measured. Erythropoietin resistance index was calculated. Blood samples for leptin, IL-6, IL-18, TNF-alpha, and IL-1-alpha serum levels were drawn.. Leptin showed negative correlation with erythropoietin resistance index (ERI), whilst IL-6 showed the opposite. IL-6 seemed to be linked more to HD parameters and vintage, while TNF-alpha and leptin were more dependent on body composition. IL-18 and IL-1-alpha did not affect nutritional parameters nor ERI.. Modulation of adipokine- and cytokine-related signaling is a promising target in tempering malnutrition in hemodialyzed, and thus achieving better outcomes in anemia treatment. Large clinical studies that target the inflammatory response in hemodialysis, especially regarding IL-6, TNF-alpha, and leptin, would be of great worth. Topics: Anemia; Erythropoietin; Humans; Inflammation; Interleukin-1; Interleukin-18; Interleukin-6; Kidney Failure, Chronic; Leptin; Malnutrition; Renal Dialysis; Tumor Necrosis Factor-alpha | 2022 |
Associations of physical activity, sedentary time, and diet quality with biomarkers of inflammation in children.
We investigated the associations of physical activity (PA), sedentary time (ST), and diet quality with biomarkers of inflammation in 390 children (192 girls, 198 boys) aged 6-8 years. PA energy expenditure (PAEE), light PA, moderate PA (MPA), vigorous PA (VPA), moderate-to-vigorous PA (MVPA), and ST were assessed by combined movement and heart rate sensor. Finnish Children Healthy Eating Index was calculated using data from 4 d food records. Body fat percentage (BF%) was measured by dual-energy X-ray absorptiometry. High-sensitivity C-reactive protein (Hs-CRP), leptin, interleukin-6 (IL-6), adiponectin, tumour necrosis factor-α, and glycoprotein acetyls were measured from fasting blood samples. PAEE, MPA, VPA, and MVPA were inversely associated with hs-CRP (β=-191 to -139, 95% CI=-0.294 to -0.024), leptin (β=-0.409 to -0.301, 95% CI=-0.499 to -0.107), IL-6 (β=-0.136 to -0.104, 95% CI=-0.240 to -0.001) and PAEE, MPA, and MVPA were inversely associated with glycoprotein acetyls (β=-0.117 to -0.103, 95% CI=-0.213 to -0.001). ST was directly associated with hs-CRP (β=0.170, 95% CI=0.070-0.269), leptin (β=0.355, 95% CI=0.265-0.445), and IL-6 (β=0.105, 95% CI=0.005-0.205). VPA was inversely associated with hs-CRP, leptin, and IL-6 in children with higher BF% (β=-0.344 to -0.181, 95% CI=-0.477 to -0.033) but not among children with lower BF% (β=-0.007-0.033, 95% CI=-0.183-0.184). In conclusion, PA was inversely and ST directly associated with circulating levels of biomarkers of inflammation among children. Furthermore, we observed that PA was inversely associated with these biomarkers for inflammation in children with a higher BF%. HighlightsSystemic inflammation, as indicated by increased circulating concentrations of biomarkers for inflammation, may be important in causal pathways leading to insulin resistance, sub-clinical atherosclerosis, and eventually clinical manifestations of cardiovascular diseases.Higher levels of physical activity and lower levels of sedentary time were associated with more favourable inflammatory profile.Body fat percentage modified these associations and especially vigorous intensity physical activity was inversely associated with biomarkers of inflammation on children with higher body fat percentage but not in children with lower body fat percentage. Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Child; Diet; Exercise; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Sedentary Behavior | 2022 |
Oxidative stress biomarkers in fetal growth restriction with and without preeclampsia.
Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be identified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications. We evaluate the performance of oxidative stress-associated potential biomarkers for FGR and PE, and their relationship with clinical characteristics.. A prospective clinical pilot study was performed in healthy controls and women with pregnancies complicated by severe FGR with or without PE. Blood samples were taken directly after inclusion and analyzed for FT; IMA; soluble FMS-like tyrosine kinase-1 (sFlt-1); placenta growth factor (PlGF); and biomarkers like leptin and soluble receptors for advanced glycation end products (sRAGE). Placentas were examined microscopically. Descriptive statistics and receiver operating characteristics statistics were performed.. Mothers with both severe FGR and PE had significantly reduced FT levels (p < 0.001) and PlGF levels (p < 0.001), and increased levels of plasma IMA (p < 0.05), sFlt (p < 0.001), leptin (p < 0.05) and sRAGE (p < 0.01) compared to women with FGR only. Systemic FT levels were significantly inversely associated with blood pressure (p < 0.01) and plasma IMA (p < 0.001), leptin (p = 0.01) and sRAGE (p < 0.001). Systemic FT and leptin showed significant discriminative ability to differentiate mothers with both FGR and PE from mothers with uncomplicated pregnancies or pregnancies complicated by FGR only.. There is a significant discriminative capacity of FT, IMA, leptin and sRAGE that harbor potential as biomarkers of pregnancies complicated by combined FGR and PE. Topics: Adult; Biomarkers; Female; Fetal Growth Retardation; Humans; Inflammation; Leptin; Oxidative Stress; Pilot Projects; Placenta; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Prospective Studies; Receptor for Advanced Glycation End Products; Serum Albumin, Human; Sulfhydryl Compounds; Vascular Endothelial Growth Factor Receptor-1 | 2021 |
Propensity to endoplasmic reticulum stress in deer mouse fibroblasts predicts skin inflammation and body weight gain.
The unfolded protein response (UPR) is involved in the pathogenesis of metabolic disorders, yet whether variations in the UPR among individuals influence the propensity for metabolic disease remains unexplored. Using outbred deer mice as a model, we show that the intensity of UPR in fibroblasts isolated early in life predicts the extent of body weight gain after high-fat diet (HFD) administration. Contrary to those with intense UPR, animals with moderate UPR in fibroblasts and therefore displaying compromised stress resolution did not gain body weight but developed inflammation, especially in the skin, after HFD administration. Fibroblasts emerged as potent modifiers of this differential responsiveness to HFD, as indicated by the comparison of the UPR profiles of fibroblasts responding to fatty acids in vitro, by correlation analyses between UPR and proinflammatory cytokine-associated transcriptomes, and by BiP (also known as HSPA5) immunolocalization in skin lesions from animals receiving HFD. These results suggest that the UPR operates as a modifier of an individual's propensity for body weight gain in a manner that, at least in part, involves the regulation of an inflammatory response by skin fibroblasts. This article has an associated First Person interview with the first author of the paper. Topics: Animals; Biomarkers; Cytokines; Diet, High-Fat; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Fatty Acids; Fibroblasts; Inflammation; Leptin; Models, Biological; Organ Size; Peromyscus; Skin; Transcriptome; Unfolded Protein Response; Weight Gain | 2021 |
Inflammatory arthritis increases the susceptibility to acute immune-mediated hepatitis in mice through enhancing leptin expression in T cells.
Liver function abnormalities are common in patients with inflammatory arthritis. However, the precise mechanism is still unclear. In this study, inflammatory arthritis was established in mice by subcutaneous injection of complete Freund's adjuvant, and the intravenous injection of concanavalin A (Con A) was employed to induce acute immune-mediated hepatitis in mice. The result showed that the arthritis mice were more susceptible to ConA-induced hepatitis than the control mice, as evidenced by increased hepatic necrosis, elevated serum alanine aminotransferase activity, and raised inflammatory cytokines. Besides, the in vitro assay demonstrated that the T cells from arthritis mice were more sensitive to the Con A stimulation than those from control mice. Moreover, we determined that the level of leptin, a kind of adipokine, was significantly increased in the serum and hepatic T cells of arthritis mice. Interestingly, the data indicated that the enhanced expression of leptin in hepatic T cells is responsible for the hypersensitivity of arthritis mice-derived T cells to Con A challenge. Collectively, our findings demonstrate an unexpected role of leptin in the connection between inflammatory arthritis and acute immune-mediated hepatitis, thus providing new insight into the clinical therapy of arthritis-related liver dysfunction. Topics: Acute Disease; Animals; Arthritis; Concanavalin A; Cytokines; Disease Susceptibility; Hepatitis; Hypersensitivity; Inflammation; Inflammation Mediators; Leptin; Liver; Lymphocyte Activation; Mice, Inbred C57BL; Signal Transduction; T-Lymphocytes | 2021 |
Physical Fitness Attenuates the Impact of Higher Body Mass and Adiposity on Inflammation in Women With Systemic Lupus Erythematosus.
Higher body mass and adiposity represent independent contributors to the systemic low-grade inflammatory state often observed in patients with systemic lupus erythematosus (SLE). This study assessed the role of physical fitness in the association of body mass and adiposity with inflammation in women with SLE.. A total of 77 women with SLE were included in this cross-sectional study. We obtained body mass index, waist-to-height ratio, and body fat percentage as indicators of body mass and adiposity. Inflammation was assessed through Serum levels of C-reactive protein, interleukin 6, and leptin. Cardiorespiratory fitness was assessed with the 6-minute walk test, range of motion with the back-scratch test, and muscular strength with handgrip dynamometry.. Cardiorespiratory fitness attenuated the association of both body mass index and body fat percentage with interleukin 6 (all, P<0.05). Range of motion attenuated the association of body mass index with interleukin 6 (P<0.05) and the association of body fat percentage with C-reactive protein (P<0.05). These interactions indicated that higher fitness was associated with a lower increase in inflammation per unit increase of body mass or adiposity. Muscular strength showed a non-significant trend to attenuate the association of body fat percentage with interleukin 6 (P=0.057) but potentiated the association of body fat percentage with leptin (P<0.05).. These findings suggest that higher levels of cardiorespiratory fitness and range of motion might attenuate the impact of higher body mass and adiposity on inflammation in women with SLE. The role of muscular strength requires further investigation. Topics: Adiposity; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiorespiratory Fitness; Cross-Sectional Studies; Exercise Tolerance; Female; Functional Status; Hand Strength; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Lupus Erythematosus, Systemic; Middle Aged; Range of Motion, Articular; Sex Factors | 2021 |
Resolvin D1 reduces inflammation in co-cultures of primary human macrophages and adipocytes by triggering macrophages.
Obesity leads to chronic inflammation of the adipose tissue which is tightly associated with the metabolic syndrome, type 2 diabetes and cardiovascular disease. Inflammation of the adipose tissue is mainly characterized by the presence of crown-like structures composed of inflammatory macrophages in the neighborhood of adipocytes. Resolvin D1 (RvD1), a potent anti-inflammatory and pro-resolving lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid, has been shown to reduce the inflammatory tone of adipose tissue in animal models but the underlying mechanism is not clear. We investigated the effect of RvD1 on the inflammatory state of a human co-culture system of adipocytes and macrophages. For this, human mesenchymal stem cells were differentiated into mature adipocytes and overlaid with human primary macrophages. In this co-culture, 10-500 nM RvD1 dose-dependently reduced the secretion of the pro-inflammatory cytokine IL-6 (-21%) and its soluble receptor IL-6Rα (-22%), of the chemokine MCP-1 (-13%), and of the adipokine leptin (-22%). Similarly, we observed a reduction in secretion of the soluble receptor IL-6Rα (-20%), and TNF-α (-11%) when macrophages alone were treated with RvD1, while no change of cytokine secretion was observed when adipocytes were treated with RvD1. We conclude that RvD1 polarizes macrophages to an anti-inflammatory phenotype, which in turn modulates inflammation in adipocytes. Topics: Adipocytes; Adipose Tissue; Anti-Inflammatory Agents; Cell Differentiation; Cell Polarity; Cells, Cultured; Coculture Techniques; Cytokines; Docosahexaenoic Acids; Humans; Inflammation; Inflammation Mediators; Leptin; Macrophages; Mesenchymal Stem Cells; Obesity; Phenotype; Signal Transduction | 2021 |
An Enriched Environment Alters DNA Repair and Inflammatory Responses After Radiation Exposure.
After the Fukushima Daiichi Nuclear Power Plant accident, there is growing concern about radiation-induced carcinogenesis. In addition, living in a long-term shelter or temporary housing due to disasters might cause unpleasant stress, which adversely affects physical and mental health. It's been experimentally demonstrated that "eustress", which is rich and comfortable, has beneficial effects for health using mouse models. In a previous study, mice raised in the enriched environment (EE) has shown effects such as suppression of tumor growth and enhancement of drug sensitivity during cancer treatment. However, it's not yet been evaluated whether EE affects radiation-induced carcinogenesis. Therefore, to evaluate whether EE suppresses a radiation-induced carcinogenesis after radiation exposure, in this study, we assessed the serum leptin levels, radiation-induced DNA damage response and inflammatory response using the mouse model. In brief, serum and tissues were collected and analyzed over time in irradiated mice after manipulating the raising environment during the juvenile or adult stage. To assess the radiation-induced DNA damage response, we performed immunostaining for phosphorylated H2AX which is a marker of DNA double-strand break. Focusing on the polarization of macrophages in the inflammatory reaction that has an important role in carcinogenesis, we performed analysis using tissue immunofluorescence staining and RT-qPCR. Our data confirmed that EE breeding before radiation exposure improved the responsiveness to radiation-induced DNA damage and basal immunity, further suppressing the chronic inflammatory response, and that might lead to a reduction of the risk of radiation-induced carcinogenesis. Topics: Animals; Arginase; DNA Damage; DNA Repair; Environment; Gene Expression Regulation; Inflammation; Leptin; Macrophages; Male; Mice; Radiation Injuries, Experimental; Tumor Necrosis Factor-alpha; X-Rays | 2021 |
Viral Infection Drives the Regulation of Feeding Behavior Related Genes in
Topics: Animals; Birnaviridae Infections; Cytokines; Feeding Behavior; Hypothalamus; Infectious pancreatic necrosis virus; Inflammation; Insulin; Leptin; Lipid Metabolism; Salmo salar; Signal Transduction | 2021 |
Dietary fibre intake and its association with inflammatory markers in adolescents.
A high dietary fibre intake has been associated with improvements in inflammatory conditions in adults. However, little is known on whether associations between dietary fibre and inflammation are evident during adolescence. We examined the relationship between dietary fibre intake measured by FFQ and the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin cross-sectionally in 17-year-olds participating in the Raine Study (n 621). In weighted analysis using tobit and linear regression, and after excluding participants with hs-CRP > 10 mg/l, higher total dietary fibre intake (per 5 g/d) was significantly associated with lower leptin (β = -0·13, 95 % CI -0·17, -0·09) and adiponectin (β = -0·28, 95 % CI -0·49, -0·07), but not hs-CRP, in unadjusted analyses. These associations were no longer significant after adjustment for sex, anthropometry and a number of lifestyle factors. However, higher cereal and grain fibre intake was significantly associated with lower leptin (β = -0·06, 95 % CI -0·10, -0·01) in fully adjusted analysis. Our findings suggest that a higher intake of cereal and grain fibre may contribute to lower leptin in adolescents. This may contribute to reductions in low-grade chronic inflammation and improved health outcomes. Topics: Adiponectin; Adolescent; Australia; Biomarkers; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Diet Surveys; Dietary Fiber; Energy Intake; Female; Humans; Inflammation; Leptin; Male | 2021 |
Effect of resveratrol on behavioral, biochemical, and immunological parameters of DBA/2J and tetrahybrid DBCB mice receiving diet with excess fat and fructose.
Polyphenolic biologically active substances (BAS) including resveratrol (R) can exert beneficial effects on fat accumulation, blood pressure, glycemia, insulin sensitivity, and plasma lipid profile in patients with obesity, and associated diseases. The study aimed to determine the effect of R at a dose of 25 mg/kg body weight on the DBA/2J and DBCB mice with diet-induced obesity followed by the consumption high-fat high-carbohydrate diet (HFCD). Behavioral reactions (elevated plus maze [EPM]) and muscle tone (the strength of the forepaw grip) were tested, and plasma biochemical and immunological parameters were assessed. In the repeated EPM test, anxiety increased only in DBCB mice during the second trial. In DBCB mice treated with HFCD, the muscle tone decreased with the second trial; however, this effect was not observed in the background of R consumption. R decreased the level of triglycerides, diminished the activities of alanine and asparagine aminotransferases, which were elevated upon HFCD consumption. Ghrelin level increased after R consumption in mice of both genotypes. The leptin to ghrelin ratio was reduced in DBCB mice receiving R. Consumption of R increased IL-3 and IL-10 levels in both DBA/2J and DBCB mice. IL-12p70 level increased in DBCB mice in response to R. R addition to HFCD reduced several symptoms of dyslipidemia in highly sensitive tetrahybrid mice. The results obtained indicate the importance of a personalized (depending on the genotype) approach when any R prescription, among other BAS and dietary factors, are used in diet therapy for patients with low, moderate and high-risk obesity. Topics: Animals; Antioxidants; Behavior, Animal; Diet, High-Fat; Dietary Carbohydrates; Dietary Fats; Elevated Plus Maze Test; Fructose; Ghrelin; Inflammation; Insulin Resistance; Interleukin-10; Interleukin-3; Leptin; Male; Mice; Mice, Inbred DBA; Obesity; Resveratrol; Triglycerides | 2021 |
Sex Differences in Macrophage Responses to Obesity-Mediated Changes Determine Migratory and Inflammatory Traits.
The mechanisms whereby obesity differentially affects males and females are unclear. Because macrophages are functionally the most important cells in obesity-induced inflammation, we sought to determine reasons for male-specific propensity in macrophage migration. We previously determined that male mice fed a high-fat diet exhibit macrophage infiltration into the hypothalamus, whereas females were protected irrespective of ovarian estrogen, in this study, we show that males accumulate more macrophages in adipose tissues that are also more inflammatory. Using bone marrow cells or macrophages differentiated in vitro from male and female mice fed control or high-fat diet, we demonstrated that macrophages derived from male mice are intrinsically more migratory. We determined that males have higher levels of leptin in serum and adipose tissue. Serum CCL2 levels, however, are the same in males and females, although they are increased in obese mice compared with lean mice of both sexes. Leptin receptor and free fatty acid (FFA) receptor, GPR120, are upregulated only in macrophages derived from male mice when cultured in the presence of FFA to mimic hyperlipidemia of obesity. Unless previously stimulated with LPS, CCL2 did not cause migration of macrophages. Leptin, however, elicited migration of macrophages from both sexes. Macrophages from male mice maintained migratory capacity when cultured with FFA, whereas female macrophages failed to migrate. Therefore, both hyperlipidemia and hyperleptinemia contribute to male macrophage-specific migration because increased FFA induce leptin receptors, whereas higher leptin causes migration. Our results may explain sex differences in obesity-mediated disorders caused by macrophage infiltration. Topics: Animals; Cell Movement; Chemokine CCL2; Fatty Acids, Nonesterified; Female; Hyperlipidemias; Inflammation; Leptin; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Multifactorial Inheritance; Obesity; Sex Characteristics; Sex Factors | 2021 |
Examining the obesity paradox: A moderating effect of fitness on adipose endocrine function in older adults.
Despite evidence linking obesity with increased mortality, older adults with excessive adiposity seem protected, resulting in a so-called obesity paradox. Obesity is characterized by leptin resistance, which contributes to increased risk of all-cause mortality. Therefore, lifestyle factors, such as physical fitness, that lower leptin independent of adiposity may be confounding the obesity paradox. To investigate this, we evaluated whether physical fitness moderated the relationship between leptin and adiposity. We found older adults with higher fitness had lower body mass (r(39) = -0.43, p < 0.01), leptin (r(39) = -0.29, p = 0.03) and inflammation (IL-1β: (r(39) = -0.69, p < 0.01); TNF-α: (r(39) = -0.30, p = 0.03)). Fitness moderated the relationship between leptin and adiposity (F(5, 37) = 3.73, p < 0.01, R Topics: Adipose Tissue; Adiposity; Aged; Aging; Biomarkers; Body Mass Index; Canada; Cardiometabolic Risk Factors; Cardiorespiratory Fitness; Cross-Sectional Studies; Effect Modifier, Epidemiologic; Female; Humans; Inflammation; Leptin; Male; Obesity; Physical Fitness; Protective Factors | 2021 |
Voluntary wheel running ameliorates select paclitaxel chemotherapy-induced sickness behaviors and associated melanocortin signaling.
While chemotherapy remains a common cancer treatment, it is associated with debilitating side effects (e.g., anorexia, weight loss, and fatigue) that adversely affect patient quality of life and increase mortality. However, the mechanisms underlying taxane chemotherapy-induced side effects, and effective treatments to ameliorate them, are not well-established. Here, we tested the longitudinal relationship between a clinically-relevant paclitaxel regimen, inflammation, and sickness behaviors (loss of body mass, anorexia, fever, and fatigue) in adult, female mice. Furthermore, we sought to identify the extent to which voluntary exercise (wheel running) attenuates paclitaxel-induced sickness behaviors and underlying central pathways. Body mass and food intake decreased following six doses of chemotherapy treatment relative to vehicle controls, lasting less than 5 days after the last dose. Paclitaxel treatment also transiently decreased locomotion (open field test), voluntary wheel running, home-cage locomotion, and core body temperature without affecting motor coordination (rotarod task). Circulating interleukin (IL)-6 and hypothalamic Il1b gene expression remained elevated in chemotherapy-treated mice at least 3 days after the last dose. Exercise intervention did not ameliorate fatigue or inflammation, but hastened recovery from paclitaxel-induced weight loss. Body mass recovery was associated with the wheel running-induced recovery of body composition, paclitaxel-induced alterations to hypothalamic melanocortin signaling, and associated peripheral circulating hormones (ghrelin and leptin). The present findings demonstrate the benefits of exercise on faster recovery from paclitaxel-induced body mass loss and deficits in melanocortin signaling and suggests the development of therapies targeting the melanocortin pathway to reduce paclitaxel-induced weight loss. Topics: Animals; Antineoplastic Agents; Behavior, Animal; Cachexia; Cytokines; Fatigue; Female; Fever; Ghrelin; Illness Behavior; Inflammation; Leptin; Melanocortins; Mice, Inbred C57BL; Motor Activity; Paclitaxel; Physical Conditioning, Animal; Signal Transduction | 2021 |
Characterizing disease progression of nonalcoholic steatohepatitis in
Nonalcoholic steatohepatitis (NASH) is an aggressive liver disease threatening human health, yet no medicine is developed to treat this disease. In this study, we first discovered that Topics: Animals; Disease Progression; Gene Expression Profiling; Gene Expression Regulation; Inflammation; Leptin; Liver; Mice; Non-alcoholic Fatty Liver Disease; Phenotype; Rats; Time Factors; Transcriptome | 2021 |
Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance.
Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis.. Four-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively.. Compared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT.. During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis. Topics: Animals; Energy Metabolism; Hypogonadism; Hypothalamus; Infertility, Male; Inflammation; Inflammation Mediators; Kisspeptins; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Reproduction; Signal Transduction | 2021 |
Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations.
Environmental factors such as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. Epigenetic mechanisms are a possible link between diet effect and neurodegeneration across generations. Here, we found a significant decrease in triglyceride levels in a high-fat diet with resveratrol (RSV) HFD + RSV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RSV groups and their offspring. Molecularly, a significant increase in DNA methylation (5-mC) levels, as well as increased gene expression of Topics: Adenosine; Animals; Body Weight; Brain; Cognition; Diet, High-Fat; Dietary Supplements; DNA Methylation; Epigenesis, Genetic; Epigenomics; Female; Inflammation; Leptin; Male; Maternal Exposure; Maze Learning; Methylation; Mice; Neurodegenerative Diseases; Neuronal Plasticity; Obesity; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Resveratrol; Triglycerides | 2021 |
The Impact of Diet and Fibre Fractions on Plasma Adipocytokine Levels in Prediabetic Adults.
The impact of diet and fibre fractions on adipocytokines in obese subjects with a risk of diabetes has not been investigated in detail yet. The purpose of the study is to evaluate the effects of a 12-month lifestyle intervention with different fibre profiles (resistant starch (RS)-rich fibre, or ordinary food fibre profiles) on adipocytokine levels. Fifty participants are divided into two groups (RS group and Fibre group). The groups differ only in the percentage of the recommended level of the RS consumed as a fraction of the same total fibre amount. The applied dietary intervention includes intake of 7531 KJ/daywith a total fibre portion of 25-35 g/dayfor both groups that includes 15 g/day of RS for the RS group only. The levels of leptin, adiponectin, apelin, resistin, tumor necrosis factor (TNF)-alpha and C-reactive protein (CRP) are measured, and their relationship to anthropometric and biochemical parameters is estimated. Along with significant body weight loss, only leptin is significantly reduced by 13% in the RS group while in the Fibre group, apelin levels are significant (-21%). Polynomial regression shows a negative correlation between RS intake and adiponectin (R2 = 0.145) and resistin level (R2 = 0.461) in the RS group. This study indicates the possibility that fibre fractions differently influence the outcome of lifestyle interventions, as well as their adipocytokine levels, in obese prediabetic adults. Topics: Adipokines; Adiponectin; Aged; Apelin; Biomarkers; Diet; Dietary Fiber; Exercise; Humans; Inflammation; Leptin; Life Style; Male; Middle Aged; Obesity; Prediabetic State; Resistant Starch; Resistin; Weight Loss | 2021 |
Sex differences in markers of metabolic syndrome and adipose tissue inflammation in obesity-prone, Osborne-Mendel and obesity-resistant, S5B/Pl rats.
The current study examined the role of sex differences in the development of risk factors associated with obesity and its comorbidities using models that differ in their susceptibility to develop obesity, obesity-resistant S5B/Pl (S5B) and obesity-prone Osborne-Mendel (OM) rats. Male and female rats were fed a low fat or high fat diet (HFD) and markers of metabolic syndrome (MetSyn) and expression of inflammatory cytokines/chemokines in visceral and subcutaneous adipose depots were measured. We hypothesized that male and female OM and S5B rats would exhibit differential responses to the consumption of HFD and that females, regardless of susceptibility to develop obesity, would display decreased obesity-related risk factors. Results suggested that consumption of HFD increased adiposity and fasting glucose levels in male OM and S5B rats, decreased circulating adiponectin levels in male S5B rats, and increased body weight and triglyceride levels in male OM rats. The consumption of HFD increased body weight and adiposity in female OM rats, not female S5B rats. Overall, female rats did not meet criteria for MetSyn, while male rats consuming HFD met criteria for MetSyn. Visceral and subcutaneous adipose tissue inflammation was higher in male rats. In visceral adipose tissue, HFD consumption differentially altered expression of cytokines in male and female S5B and OM rats. These findings suggest that resistance to obesity in males may be overridden by chronic consumption of HFD and lead to increased risk for development of obesity-related comorbidities, while female rats appear to be protected from the adverse effects of HFD consumption. Topics: Adipose Tissue; Animals; Biomarkers; Body Weight; Diet, High-Fat; Female; Inflammation; Leptin; Male; Metabolic Syndrome; Obesity; Rats; Sex Factors; Weight Gain | 2021 |
Adipocytokines in Untreated Newly Diagnosed Rheumatoid Arthritis: Association with Circulating Chemokines and Markers of Inflammation.
Adiponectin, leptin, and resistin are adipocytokines whose levels are elevated in blood and synovial fluid from patients with rheumatoid arthritis (RA). However, their role in RA pathogenesis is unclear. Here, we examined whether adipocytokines are associated with circulating chemokines, markers of inflammation and RA disease activity in patients with untreated newly diagnosed RA. Plasma levels of 15 chemokines, adiponectin, leptin, and resistin were measured using flow cytometry bead-based immunoassay or enzyme-linked immunosorbent assay (ELISA) in a cohort of 70 patients with untreated newly diagnosed RA. Markers of inflammation and disease activity were also assessed in all patients. Positive association was found between total adiponectin and CXCL10 (β = 0.344, Topics: Adipokines; Adiponectin; Adult; Arthritis, Rheumatoid; Chemokines; Cohort Studies; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Resistin; Tretinoin | 2021 |
Hepatoprotective Effects of Indole, a Gut Microbial Metabolite, in Leptin-Deficient Obese Mice.
The gut microbiota plays a role in the occurrence of nonalcoholic fatty liver disease (NAFLD), notably through the production of bioactive metabolites. Indole, a bacterial metabolite of tryptophan, has been proposed as a pivotal metabolite modulating inflammation, metabolism, and behavior.. The aim of our study was to mimic an upregulation of intestinal bacterial indole production and to evaluate its potential effect in vivo in 2 models of NAFLD.. Eight-week-old leptin-deficient male ob/ob compared with control ob/+ mice (experiment 1), and 4-5-wk-old C57BL/6JRj male mice fed a low-fat (LF, 10 kJ%) compared with a high-fat (HF, 60 kJ%) diet (experiment 2), were given plain water or water supplemented with a physiological dose of indole (0.5 mM, n ≥6/group) for 3 wk and 3 d, respectively. The effect of the treatments on the liver, intestine, adipose tissue, brain, and behavior was assessed.. Indole reduced hepatic expression of genes involved in inflammation [C-C motif chemokine ligand 2 (Ccl2), C-X-C motif chemokine ligand 2 (Cxcl2); 3.3- compared with 5.0-fold, and 2.4- compared with 3.3-fold of control ob/+ mice, respectively, P < 0.05], and in macrophage activation [Cd68, integrin subunit α X (Itgax); 2.1- compared with 2.5-fold, and 5.0- compared with 6.4-fold of control ob/+ mice, respectively, P < 0.01] as well as markers of hepatic damage (alaninine aminotransferase; -32%, P < 0.001) regardless of genotype in experiment 1. Indole had no effect on hepatic inflammation in mice fed the LF or HF diet in experiment 2. Indole did not change hepatic lipid content, anxiety-like behavior, or inflammation in the ileum, adipose tissue, and brain in experiment 1.. Our results support the efficacy of indole to reduce hepatic damage and associated inflammatory response and macrophage activation in ob/ob mice. These modifications appear to be attributable to direct effects of indole on the liver, rather than through effects on the adipose tissue or intestinal barrier. Topics: Animals; Chemokine CCL2; Chemokine CXCL2; Diet, High-Fat; Gastrointestinal Microbiome; Indoles; Inflammation; Leptin; Ligands; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Protective Agents | 2021 |
Circulating perilipin 2 levels are associated with fat mass, inflammatory and metabolic markers and are higher in women than men.
Perilipin 2 (PLIN2) is a protein involved in lipid storage and metabolism in non-adipose tissues. Detectable levels of circulating PLIN2 (cPLIN2) have been reported to be associated with some types of cancer, but no systematic analysis of age-related modifications in cPLIN2 levels has ever been performed. We measured serum cPLIN2 in a group of old people including centenarians in comparison with young subjects and tested possible correlations with parameters of body composition, fat and glucose metabolism, and inflammation. We found that: i. levels of cPLIN2 do not change with age, but women have higher levels of cPLIN2 with respect to men; ii. cPLIN2 levels strongly correlate to BMI, as well as fat and lean mass; iii. cPLIN2 levels strongly correlate with the proinflammatory adipokine leptin. Due to the adipogenic activity of leptin, it is hypothesized that cPLIN2 is affected and possibly regulated by this pleiotropic adipokine. Moreover, these results suggest that cPLIN2 (possibly together with leptin) could be assumed as a proxy for body adiposity. Topics: Adipose Tissue; Adult; Aged; Aged, 80 and over; Biomarkers; Body Composition; Body Mass Index; Female; Humans; Inflammation; Leptin; Lipids; Male; Middle Aged; Perilipin-2; Sex Characteristics; Waist Circumference; Young Adult | 2021 |
Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk.
Hypothalamic inflammation and endoplasmic reticulum (ER) stress are extensively linked to leptin resistance and overnutrition-related diseases. Surgical intervention remains the most efficient long-term weight-loss strategy for morbid obesity, but mechanisms underlying sustained feeding suppression remain largely elusive. This study investigated whether Roux-en-Y gastric bypass (RYGB) interacts with obesity-associated hypothalamic inflammation to restore central leptin signaling as a mechanistic account for post-operative appetite suppression.. RYGB or sham surgery was performed in high-fat diet-induced obese Wistar rats. Sham-operated rats were fed ad libitum or by weight matching to RYGB via calorie restriction (CR) before hypothalamic leptin signaling, microglia reactivity, and the inflammatory pathways were examined to be under the control of gut microbiota-derived circulating signaling.. RYGB, other than CR-induced adiposity reduction, ameliorates hypothalamic gliosis, inflammatory signaling, and ER stress, which are linked to enhanced hypothalamic leptin signaling and responsiveness. Mechanistically, we demonstrate that RYGB interferes with hypothalamic ER stress and toll-like receptor 4 (TLR4) signaling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the altered gut microbial environment upon RYGB surgery.. Our data demonstrate that RYGB interferes with hypothalamic TLR4 signaling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the post-surgical altered gut microbial environment. Topics: Animals; Caloric Restriction; Diet, High-Fat; Disease Models, Animal; Gastric Bypass; Gastrointestinal Microbiome; Hypothalamus; Inflammation; Leptin; Male; Microglia; Neurons; Obesity, Morbid; Rats; Rats, Wistar; Signal Transduction; Treatment Outcome; Weight Loss | 2021 |
Safflower seed oil improves steroidogenesis and spermatogenesis in rats with type II diabetes mellitus by modulating the genes expression involved in steroidogenesis, inflammation and oxidative stress.
Diabetes mellitus (DM), as a multiorgan syndrome, is an endocrine and metabolic disorder that is associated with male reproductive system dysfunction and infertility. Safflower (Carthamus tinctorius L.) as an herbal remedy improves DM and infertility-related disorders. The anti-hypercholesterolemic, anti-inflammatory, and antioxidative properties of this herb have been well documented, but its role in testosterone production, male reproductive system and zinc homeostasis has not been fully illustrated.. This study aimed to investigate the preventive and therapeutic properties of different doses of safflower seed oil against reproductive damage caused by type II DM by investigating zinc element homeostasis, inflammation and oxidative damage in testis tissue and their relationship with testosterone production and sperm parameters.. Eighty adult male Sprague-Dawley rats were randomly divided into eight groups and treated daily for 12 and 24 weeks in protective and therapeutic studies, respectively. Type II DM was induced by a High Fat Diet (HFD) in normoglycemic rats for three months. At the end of each study, serum level of glucose, testosterone, gonadotropins, TNF-α, insulin, and leptin were measured. Moreover, antioxidant enzymes activity, lipid peroxidation, zinc and testosterone along with the expression of Nrf-2, NF-κB, TNF-α, StAR, P450scc, and 17βHSD3 genes in the testis were detected.. After the intervention, the activity of antioxidant enzymes and the level of testosterone and gonadotropins significantly decreased in the rats with DM in comparison to the others. However, lipid peroxidation and serum level of insulin, leptin and TNF-α increased and the testicular level of zinc significantly changed in the rats with DM compared to the control groups (p < 0.05). The gene expression of NF-κB and TNF-α were also significantly increased and the gene expression of Nrf2, StAR, P450scc and 17βHSD3 were decreased in the testis of diabetic rats (p < 0.05). The results showed that pretreatment and treatment with safflower seed oil could improve these parameters in diabetic rats compared with untreated diabetic rats (p < 0.05).. HFD could impair the production of testosterone and sperm, and reduce gonadotropin by increasing the serum level of leptin and inducing insulin resistance, oxidative stress and inflammation. However, safflower oil in a dose-dependent manner could improve testosterone level and sperm parameters by improving the level of leptin, zinc and insulin resistance, and the genes expression involved in testosterone synthesis, inflammation and oxidative stress. Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Eating; Gene Expression Regulation; Gonadotropins; Inflammation; Insulin; Leptin; Lipid Peroxidation; Lipogenesis; Male; Oxidative Stress; Rats, Sprague-Dawley; Safflower Oil; Seeds; Spermatogenesis; Spermatozoa; Steroids; Testis; Testosterone; Tumor Necrosis Factor-alpha; Zinc | 2021 |
Leptin modulates gene expression in the heart, cardiomyocytes and the adipose tissue thus mitigating LPS-induced damage.
Leptin is an adipokine of pleiotropic effects linked to energy metabolism, satiety, the immune response, and cardioprotection. We have recently shown that leptin causally conferred resistance to myocardial infarction-induced damage in transgenic αMUPA mice overexpressing leptin compared to their wild type (WT) ancestral mice FVB/N. Prompted by these findings, we have investigated here if leptin can counteract the inflammatory response triggered after LPS administration in tissues in vivo and in cardiomyocytes in culture. The results have shown that LPS upregulated in vivo and in vitro all genes examined here, both pro-inflammatory and antioxidant, as well as the leptin gene. Pretreating mice with leptin neutralizing antibodies further upregulated the expression of TNFα and IL-1β in the adipose tissue of both mouse types, and in the αMUPA heart. The antibodies also increased the levels of serum markers for cell toxicity in both mouse types. These results indicate that under LPS, leptin actually reduced the levels of these inflammatory-related parameters. In addition, pretreatment with leptin antibodies reduced the levels of HIF-1α and VEGF mRNAs in the heart, indicating that under LPS leptin increased the levels of these mRNAs. In cardiomyocytes, pretreatment with exogenous leptin prior to LPS reduced the expression of both pro-inflammatory genes, enhanced the expression of the antioxidant genes HO-1, SOD2 and HIF-1α, and lowered ROS staining. In addition, results obtained with leptin antibodies and the SMLA leptin antagonist indicated that endogenous and exogenous leptin can inhibit leptin gene expression. Together, these findings have indicated that under LPS, leptin concomitantly downregulated pro-inflammatory genes, upregulated antioxidant genes, and lowered ROS levels. These results suggest that leptin can counteract inflammation in the heart and adipose tissue by modulating gene expression. Topics: Adipose Tissue; Animals; Energy Metabolism; Gene Expression; Inflammation; Leptin; Lipopolysaccharides; Mice, Transgenic; Myocytes, Cardiac | 2021 |
Lycopene Modulates Placental Health and Fetal Development Under High-Fat Diet During Pregnancy of Rats.
Lycopene plays an important role in improving immunity, promoting antioxidant capacity, and regulating fat metabolism. The placenta, an important organ for nutrients exchange between mother and child during pregnancy, directly affects fetal development. This study aims to characterize effects of lycopene on placental health and fetal development under a high-fat diet, and utilize RNA sequencing (RNA-seq) to investigate and integrate the differences of molecular pathways and biological processes in placenta. For placental health, high-fat diet during pregnancy increases placental oxidative stress, inflammation, and fat deposition. However, lycopene reduces the negative effects of high-fat diet on placenta to some extent, and further promotes fetal development. Under high-fat diet, lycopene reduces the levels of Interleukin 17 (IL-17), Interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) in placenta (p < 0.05) through the IL-17 pathway. Furthermore, lycopene supplementation in high-fat diet increases Glutaredoxin (Glrx) gene and protein expression in the placenta (p < 0.05), increases Glutathione peroxidase (GSH-Px) and Total antioxidant capacity (T-AOC) levels (p < 0.05), decreases reactive oxygen species (ROS) (p < 0.01) and Hydrogen peroxide (H Topics: Animals; Diet, High-Fat; Female; Fetal Development; Gene Expression; Gene Ontology; Glutaredoxins; Glutathione Peroxidase; Hydrogen Peroxide; Inflammation; Leptin; Lycopene; Maternal Nutritional Physiological Phenomena; Oxidative Stress; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; RNA-Seq | 2021 |
The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism.
Mice lacking a microbiota are protected from diet-induced obesity. Previous studies have shown that feeding a Western diet causes hypothalamic inflammation, which in turn can lead to leptin resistance and weight gain. Here, we show that wild-type (WT) mice with depleted gut microbiota, i.e., germ-free (GF) and antibiotic-treated mice, have elevated levels of glucagon-like peptide-1 (GLP-1), are protected against diet-induced hypothalamic inflammation, and have enhanced leptin sensitivity when fed a Western diet. Using GLP-1 receptor (GLP-1R)-deficient mice and pharmacological inhibition of the GLP-1R in WT mice, we demonstrate that intact GLP-1R signaling is required for preventing hypothalamic inflammation and enhancing leptin sensitivity. Furthermore, we show that astrocytes express the GLP-1R, and deletion of the receptor in glial fibrillary acidic protein (GFAP)-expressing cells diminished the antibiotic-induced protection against diet-induced hypothalamic inflammation. Collectively, our results suggest that depletion of the gut microbiota attenuates diet-induced hypothalamic inflammation and enhances leptin sensitivity via GLP-1R-dependent mechanisms. Topics: Animals; Diet, Western; Gastrointestinal Microbiome; Glucagon-Like Peptide-1 Receptor; Humans; Hypothalamus; Inflammation; Leptin; Male; Mice; Obesity | 2021 |
Changes in leptin, serotonin, and cortisol after eight weeks of aerobic exercise with probiotic intake in a cuprizone-induced demyelination mouse model of multiple sclerosis.
Multiple sclerosis (MS) is the most common non-traumatic neurological cause of disability in young adults. Physical activity, particularly exercise training, is an evidence-based approach to managing symptoms, restoring function, and improving overall wellness in people with MS. As well, the use of probiotics can be effective in reducing the damage from inflammation in MS patients.. The study aimed to address changes in leptin, serotonin, and cortisol following eight weeks of aerobic exercise along with probiotic intake in a cuprizone-induced demyelination mouse model of MS.. Mice were exposed to cuprizone for 12 weeks. After 5 weeks, beam and performance tests were performed on them. The mice (n = 5 per group) were randomly divided into five groups: control (C), MS, MS with exercise (MS + Exe), MS with probiotic (MS + Prob), and MS with probiotic and exercise (MS + Prob + Exe). Exercise groups performed aerobic exercises 5 days a week, 10 min in the first week, 20 min in the second week, and 30 min daily in the third week until the eighth week. In the probiotic groups, the mice received probiotic by gavage. They were sacrificed after 3 months. Biochemical and molecular biology analyses were performed.. The results showed that leptin gene expression values in the MS + Prob + Exe, MS + Prob, and MS + Exe groups showed a decrease compared to the MS group, but the reduction was not significant (p > 0.05). Also, the leptin Elisa test in these intervention groups showed a significant decrease (P < 0.05). The serotonin gene expression values in the MS + Prob + Exe, MS + Prob, and MS + Exe groups were increased compared to the MS group, but the increase was not significant (p > 0.05). Furthermore, the serotonin Elisa test in these intervention groups showed a significant increase (P < 0.05). The cortisol Elisa test values in the MS + Exe and MS + Prob groups exhibited a decrease compared to the MS group, but the reduction was not significant (p > 0.05).. Overall, these results suggest that lifestyle interventions can be effective in improving pathological factors in patients with MS. Topics: Animals; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Female; Hydrocortisone; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Physical Conditioning, Animal; Probiotics; Serotonin | 2021 |
Less airway inflammation and goblet cell metaplasia in an IL-33-induced asthma model of leptin-deficient obese mice.
Obesity-associated asthma is a phenotype of severe asthma. Late-onset, non-eosinophilic and female-dominant phenotype is highly symptomatic and difficult to treat. Leptin, an adipokine, exerts an immunomodulatory effect. IL-33 associated with innate immunity induces type 2 inflammation and is present in adipose tissue. The purpose of this study was to elucidate the pathogenesis of obesity-associated asthma by focusing on the interaction between leptin and IL-33.. In leptin-deficient obese (ob/ob) and wild-type mice, IL-33 was instilled intranasally on three consecutive days. In part of the mice, leptin was injected intraperitoneally prior to IL-33 treatment. The mice were challenged with methacholine, and airway hyperresponsiveness (AHR) was assessed by resistance (Rrs) and elastance (Ers) of the respiratory system using the forced oscillation technique. Cell differentiation, IL-5, IL-13, eotaxin, keratinocyte-derived chemokine (KC) in bronchoalveolar lavage fluid (BALF) and histology of the lung were analyzed. For the in vitro study, NCI-H292 cells were stimulated with IL-33 in the presence or absence of leptin. Mucin-5AC (MUC5AC) levels were measured using an enzyme-linked immunosorbent assay.. Ob/ob mice showed greater Rrs and Ers than wild-type mice. IL-33 with leptin, but not IL-33 alone, enhanced Ers rather than Rrs challenged with methacholine in ob/ob mice, whereas it enhanced Rrs alone in wild-type mice. IL-33-induced eosinophil numbers, cytokine levels in BALF, eosinophilic infiltration around the bronchi, and goblet cell metaplasia were less in ob/ob mice than in wild-type mice. However, leptin pretreatment attenuated these changes in ob/ob mice. MUC5AC levels were increased by co-stimulation with IL-33 and leptin in vitro.. Ob/ob mice show innate AHR. IL-33 with leptin, but not IL-33 alone, induces airway inflammation and goblet cell metaplasia and enhances AHR involving peripheral airway closure. This is presumably accelerated by mucus in ob/ob mice. These results may explain some aspects of the pathogenesis of obesity-associated asthma. Topics: Animals; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Goblet Cells; Inflammation; Interleukin-33; Leptin; Metaplasia; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity | 2021 |
Treadmill running induces remodeling of the infrapatellar fat pad in an intensity-dependent manner.
To investigate the response of the infrapatellar fat pad (IFP) to running at different intensities and further explore the underlying mechanisms of these responses under different running-induced loadings.. Animals were randomly assigned into the sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR) groups. The rats in the LIR, MIR, and HIR groups were subjected to an 8-week treadmill running protocol. In each group, the IFP was examined at the baseline and at the 8th week to perform histomorphology, immunohistochemistry, and mRNA expression analyses.. Compared with LIR and MIR, HIR for 8 weeks led to a substantial increase in the surface cellularity (1.67 ± 1.15), fibrosis (1.29 ± 0.36), and vascularity (33.31 ± 8.43) of the IFP but did not increase IFP inflammation or M1 macrophage polarization. Low-to-medium-intensity running resulted in unchanged or decreased fibrosis, vascularity, and surface cellularity in the IFP compared to those of the SED group. Furthermore, serum leptin and visfatin levels were significantly lower in the LIR and MIR groups than in the SED group or the HIR group (P < 0.05).. The effect of running on IFP remodeling was intensity dependent. In contrast to LIR and MIR, HIR increased the fibrosis and vascularity of the IFP. HIR-induced IFP fibrosis was probably due to mechanical stress, rather than pathological proinflammatory M1/M2 polarization. Topics: Adipose Tissue; Animals; Biomechanical Phenomena; Cartilage, Articular; Disease Models, Animal; Exercise Test; Fibrosis; Inflammation; Knee Joint; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Osteoarthritis, Knee; Patella; Rats, Sprague-Dawley; Running; Stress, Mechanical | 2021 |
Metabolic alterations and systemic inflammation in overweight/obese children with obstructive sleep apnea.
Systemic inflammation has been documented in obstructive sleep apnea (OSA). However studies on childhood OSA and systemic inflammation are limited. This study aimed to determine the relation between OSA in overweight/obese children and various inflammatory markers.. In this cross sectional study, we enrolled 247 overweight/ obese children from pediatric outpatient services. We evaluated demographic and clinical details, anthropometric parameters, body composition and estimation of inflammatory cytokines such as interleukin (IL) 6, IL-8, IL-10, IL-17, IL-18, IL-23, macrophage migration inhibitory factor (MIF), high sensitive C-reactive protein (Hs-CRP), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1) and leptin levels. Overnight polysomnography was performed.. A total of 247 children (190 with OSA and 57 without OSA) were enrolled. OSA was documented on polysomnography in 40% of patients. We observed significantly high values body mass index, waist circumference (WC), % body fat, fasting blood glucose (FBG), alanine transaminase (ALT), alkaline phosphate, fasting insulin and HOMA-IR in children with OSA. Inflammatory markers IL-6, IL-8, IL-17, IL-18, MIF, Hs CRP, TNF- α, PAI-1, and leptin levels were significantly higher in OSA patients (p<0.05). There was strong positive correlation of IL-6, IL-8, IL-17, IL-23, MIF, Hs CRP, TNF-A, PAI-1 and leptin with BMI, % body fat, AHI, fasting Insulin, triglyceride, FBG, WC, HOMA-IR, AST and ALT.. Children with OSA have increased obesity, insulin resistance and systemic inflammation. Further studies are require to confirm our findings and evaluate their utility in diagnosis of OSAs, assessing severity and possible interventions. Topics: Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Child; Cross-Sectional Studies; Cytokines; Female; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Overweight; Pediatric Obesity; Sleep Apnea, Obstructive | 2021 |
Resistin is Associated with Inflammation and Renal Function, but not with Insulin Resistance in Type 2 Diabetes.
The aim of the study was to investigate the association of adipokines (resistin, leptin and adiponectin) with obesity, insulin resistance (IR) and inflammation in type 2 diabetes mellitus (T2DM). A total of 284 patients with T2DM were included. Concentrations of resistin, leptin, adiponectin, and inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)] were measured and homeostatic model assessment for IR (HOMA-IR) index was calculated. Resistin correlated negatively with estimated glomerular filtration rate (eGFR) and positively with hsCRP, TNF-α, IL-6, and white blood cell count (WBC). Leptin correlated positively with HOMA-IR, whereas adiponectin correlated negatively. Leptin also correlated positively with body mass index (BMI), waist circumference, IL-6, WBC and negatively with eGFR. Adiponectin correlated negatively with waist circumference, WBC, and eGFR. Multivariate logistic regression indicated lower eGFR and higher WBC and IL-6 as independent predictive factors of resistin concentration above the upper quartile (CAQ3), whereas female sex and higher BMI and HOMA-IR of leptin CAQ3, and lower HOMA-IR and older age of adiponectin CAQ3. In conclusion, in contrast to leptin and adiponectin, in T2DM patients, resistin is not associated with BMI and IR, but with inflammation and worse kidney function. Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Inflammation; Insulin Resistance; Kidney Function Tests; Leptin; Male; Middle Aged; Prognosis; Prospective Studies; Resistin | 2021 |
Green banana flour supplementation improves obesity-associated systemic inflammation and regulates gut microbiota profile in mice fed high-fat diets.
This study evaluated the effect of green banana flour (GBF) consumption on obesity-related conditions in mice fed high-fat diets. GBF was prepared using stage 1 green banana pulp, which was dehydrated and milled. Mice were fed a control diet ( Topics: Adiposity; Animals; Diet, High-Fat; Disease Models, Animal; Food, Fortified; Gastrointestinal Microbiome; Inflammation; Interleukin-6; Leptin; Male; Mice, Inbred C57BL; Mice, Obese; Musa; Obesity; Tumor Necrosis Factor-alpha; Weight Gain | 2021 |
Modulation of Sirt1 and FoxO1 on Hypothalamic Leptin-Mediated Sympathetic Activation and Inflammation in Diet-Induced Obese Rats.
Background Hypothalamic leptin-mediated signaling contributes to the exaggerated sympatho-excitation and increased blood pressure in obesity-associated hypertension. The aim of the study was to investigate the roles of energy-sensing enzyme sirtuin1 (Sirt1) and forkhead box protein O1 (FoxO1) on the hypothalamic leptin-mediated high sympathetic nerve activity and inflammation in obesity. Methods and Results Sprague Dawley rats were fed with high-fat diet (HFD) for 12 weeks. In vivo, the potential of Srit1 and FoxO1 in the sympathetic effects of leptin was investigated via siRNA injection to knockdown Sirt1 or FoxO1 gene in the arcuate nucleus (ARCN) of hypothalamus in rats. In vitro, the effects of Sirt1 or FoxO1 on leptin-mediated inflammation were observed in proopiomelanocortin (POMC) and microglial cells. Knockdown Sirt1 by siRNA significantly reduced the renal sympathetic nerve activity (RSNA) and blood pressure responses to leptin injection in the ARCN in the HFD rats. Conversely, knockdown FoxO1 significantly enhanced the RSNA and blood pressure responses to leptin injection in the HFD rats. Knockdown Sirt1 reduced the levels of pro-inflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), C1q/TNF-related protein-1 (CTRP1), and immune cell infiltration in the ARCN in the HFD rats. Knockdown FoxO1 significantly increased the level of IL-6 in the ARCN of HFD rats. In cultured hypothalamic POMC and microglial cells, knockdown Sirt1 significantly reduced leptin-induced IL-6 expression, affected the levels of AMP-activated protein kinase (AMPK) and serine/threonine-specific protein kinase (Akt). Knockdown FoxO1 significantly increased leptin-induced IL-6 in both POMC cells and microglial cells. Conclusions These data suggest that both Sirt1 and FoxO1 are the key modulators of leptin signaling in the hypothalamus contributed to the over sympathetic activation and inflammation in obesity. Topics: Animals; Blotting, Western; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Energy Metabolism; Gene Expression Regulation; Gene Knockdown Techniques; Hypothalamus; Inflammation; Leptin; Male; Mice; Mice, Knockout; Obesity; Rats; Rats, Sprague-Dawley; RNA; Sirtuin 1 | 2021 |
C1q/TNF-related protein 4 restores leptin sensitivity by downregulating NF-κB signaling and microglial activation.
C1qTNF-related protein 4 (CTRP4) acts in the hypothalamus to modulate food intake in diet-induced obese mice and has been shown to exert an anti-inflammatory effect on macrophages. Since high-fat diet-induced microglial activation and hypothalamic inflammation impair leptin signaling and increase food intake, we aimed to explore the potential connection between the anorexigenic effect of CTRP4 and the suppression of hypothalamic inflammation in mice with DIO.. Using an adenovirus-mediated hypothalamic CTRP4 overexpression model, we investigated the impact of CTRP4 on food intake and the hypothalamic leptin signaling pathway in diet-induced obese mice. Furthermore, central and plasma proinflammatory cytokines, including TNF-α and IL-6, were measured by Western blotting and ELISA. Changes in the hypothalamic NF-κB signaling cascade and microglial activation were also examined in vivo. In addition, NF-κB signaling and proinflammatory factors were investigated in BV-2 cells after CTRP4 intervention.. We found that food intake was decreased, while leptin signaling was significantly improved in mice with DIO after CTRP4 overexpression. Central and peripheral TNF-α and IL-6 levels were reduced by central Ad-CTRP4 administration. Hypothalamic NF-κB signaling and microglial activation were also significantly suppressed in vivo. In addition, NF-κB signaling was inhibited in BV-2 cells following CTRP4 intervention, which was consistent with the decreased production of TNF-α and IL-6.. Our data indicate that CTRP4 reverses leptin resistance by inhibiting NF-κB-dependent microglial activation and hypothalamic inflammation. Topics: Adipokines; Animals; Cell Culture Techniques; Cytokines; Diet, High-Fat; Hypothalamus; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Microglia; NF-kappa B; Obesity; Signal Transduction | 2021 |
Fine particulate matter air pollution and aortic perivascular adipose tissue: Oxidative stress, leptin, and vascular dysfunction.
Exposure to fine particulate matter (PM Topics: Adipose Tissue; Air Pollution; Animals; Aortic Diseases; Atherosclerosis; Diet, High-Fat; Gene Expression Regulation; Inflammation; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Particulate Matter; Superoxide Dismutase | 2021 |
Association between inflammatory markers and serum paraoxonase and arylesterase activities in the general population: a cross-sectional study.
Recent studies focused on modulating factors of paraoxonase-1 (PON1) activity. In some studies the association between pro-inflammatory markers and PON1 activity was examined, but so far no population-based investigations on this issue have been conducted. The present study investigated the relationships between the pro-inflammatory markers tumor necrosis factor (TNF)-α, leptin, interleukin (IL)-6, and high-sensitive C-reactive protein (hs-CRP) and paraoxonase and arylesterase, two hydrolytic activities of PON1, in the population-based Bavarian Food Consumption Survey II.. Based on 504 participants (217 men, 287 women), the relationship between the pro-inflammatory markers and the outcomes paraoxonase and arylesterase activities were investigated using multivariable linear models.. Circulating plasma levels of leptin (P-value < 0.0001), hs-CRP (P-value = 0.031) and IL-6 (P-value = 0.045) were significantly non-linearly associated with arylesterase activity. Leptin levels were also significantly associated with paraoxonase activity (P-value = 0.024) independently from confounding factors, including high-density lipoprotein (HDL) cholesterol. With increasing levels of these inflammatory parameters, arylesterase and paraoxonase activities increased; however, at higher levels (> 75th percentile) the activities reached a plateau or even decreased somewhat. After Bonferroni-Holm correction, only leptin remained non-linearly but significantly associated with arylesterase activity (adjusted overall P-value < 0.0001). Neither age nor sex nor obesity modified the associations. No association was found between TNF-α and paraoxonase or arylesterase activity.. The present findings suggest that in persons with very high levels of inflammation, PON1 activity may be impaired, a fact that might subsequently be accompanied by a higher risk for cardiometabolic diseases. Whether or not the measurement of PON1 activity in combination with a lipid profile and certain inflammatory markers could improve the prediction of cardiometabolic diseases in middle-aged individuals from the general population should be evaluated in clinical studies. Topics: Adult; Aryldialkylphosphatase; C-Reactive Protein; Carboxylic Ester Hydrolases; Cross-Sectional Studies; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Regression Analysis; Tumor Necrosis Factor-alpha | 2021 |
Adiponectin to leptin ratio reflects inflammatory burden and survival in COVID-19.
Obesity is a risk factor for COVID-19, but the underlying mechanisms are unclear. We investigated the role of adiponectin (an anti-inflammatory adipokine), leptin (a pro-inflammatory adipokine) and their ratio (Adpn/Lep) in this context.. Single-centre, prospective observational study.. Adiponectin and leptin were measured in 60 COVID-19 patients with mild (not hospitalised, n=11), moderate (hospitalised but not requiring intensive care, n=25) and severe (admission to the intensive care unit [ICU] or death, n=24) disease.. Adiponectin and leptin levels were similar across severity groups, but patients with moderate severity had the highest Adpn/Lep ratio (1.2 [0.5; 2.0], 5.0 [1.6; 11.2], 2.1 [1.0; 3.6] in mild, moderate and severe disease; P = 0.019). Adpn/Lep, but not adiponectin or leptin alone, correlated with systemic inflammation (C reactive protein, CRP: Spearman's rho 0.293, P = 0.023). When dividing patients into Adpn/Lep tertiles, adiponectin was highest, whereas leptin was lowest in the third (highest) tertile. Patients in the highest Adpn/Lep tertile had numerically lower rates of obesity, diabetes and hypertension, and lower rates of death or admission to ICU versus other tertiles. At linear regression in the whole cohort, CRP significantly predicted Adpn/Lep (β 0.291, P = 0.022), while female gender (β -0.289, P = 0.016), diabetes (β -0.257, P = 0.028), and hypertension (β -239, P = 0.043) were negative predictors.. We speculate that the rise in Adpn/Lep, due to increased adiponectin and reduced leptin, is a compensatory response to systemic inflammation. In patients with worse cardiometabolic health (e.g. diabetes, hypertension) this mechanism might be blunted, possibly contributing to higher mortality. Topics: Adiponectin; COVID-19; Female; Humans; Inflammation; Leptin; Male; Prospective Studies; Survival Analysis | 2021 |
[Obesity, inflammation and COVID-19: preventive interest of ketogenic diet?]
Obesity is considered a pandemic responsible for millions of deaths worldwide for many years. At the end of 2019, the Coronavirus disease 2019 (COVID-19) appeared, causing the death of more than a million people in less than a year. Numerous studies suggest that obesity could be defined as key to the onset of severe forms of this emerging disease. Indeed, SARS-CoV2 infects the host by binding to ACE2 receptors present on the surface of the cells and causes excessive secretion of pro-inflammatory cytokines including IL-1, IL-6 and TNF-α, which lead to developing acute respiratory distress syndrome (ARDS). It therefore seems essential to make up effective preventive strategies to protect this part of the population from the risk of developing a severe form of COVID-19. The ketogenic diet, which is low in sugars and high in fat, has interesting properties, both in the fight against obesity but also against severe infections. This article focuses on the latest scientific advances that make it possible to consider the ketogenic diet as a preventive strategy that simultaneously reduces the development of obesity while strengthening the immune system, two key actions in the fight against SARS-CoV2 infections and severe forms of COVID-19.. Obésité, inflammation et COVID-19 : intérêt préventif de l’alimentation cétogène ?. L’obésité est considérée comme une pandémie responsable de plusieurs millions de morts dans le monde depuis de nombreuses années. Fin 2019 est apparue la maladie à Coronavirus 2019 (COVID-19) qui a provoqué la mort de plus d’un million de personnes en moins d’un an. De nombreuses études suggèrent que l’obésité pourrait être un paramètre clé dans l’apparition des formes graves de cette maladie émergente. En effet, le SARS-CoV2 infecte l’hôte en se fixant aux récepteurs ACE2 présents à la surface des cellules et entraîne une sécrétion excessive de cytokines pro-inflammatoires notamment l’IL-1, l’IL-6 et le TNF-α qui conduisent au développement d’un syndrome de détresse respiratoire aigu (SDRA). Il paraît essentiel d’élaborer des stratégies préventives efficaces pour protéger cette partie de la population du risque de développer une forme grave de COVID-19. L’alimentation cétogène, pauvre en sucres et riche en lipides, présente d’intéressantes propriétés, à la fois pour la lutte contre l’obésité mais également contre les infections sévères. Cet article fait le point sur les dernières avancées scientifiques qui permettent d’envisager l’alimentation cétogène comme une stratégie préventive visant à diminuer le développement de l’obésité et à renforcer le système immunitaire, deux actions clés dans la lutte contre l’infection au SARS-CoV2 et le développement de formes graves de COVID-19. Topics: Adipocytes; Animals; COVID-19; Cytokine Release Syndrome; Diet, Ketogenic; Disease Susceptibility; Humans; Inflammation; Leptin; Obesity; Pandemics; Respiratory Distress Syndrome; SARS-CoV-2 | 2021 |
Transgenic mice expressing human IL-32 develop adipokine profiles resembling those of obesity-induced metabolic changes.
Low-grade inflammation is associated with the development of insulin resistance in obese individuals. The present study aims to provide additional evidence strengthening the role of interleukin (IL)-32 in this key process. Using an IL-32 transgenic (IL-32tg) mouse model, we observed that IL-32tg fed a normal diet had greater body weight, due to greater accumulation of white adipose tissue (WAT) along with larger sized adipocytes. This led to metabolic consequences, with significant higher leptin levels and a trend towards hyperinsulinemia, indicating a phenotype resembling the metabolic syndrome. Adipocytes of IL-32tg mice were more prone to induce a pro-inflammatory response locally, which would be expected when predisposed to insulin resistance and type2 diabetes mellitus (T2D). In conclusion, our study provides novel evidence of a direct contribution of IL-32 to pathophysiological perturbations within the adipose tissue, possibly contributing to the metabolic syndrome that precedes frank insulin resistance and T2D. Future research should focus on the role of IL-32 in the obesity epidemic. Topics: Adipocytes; Adipokines; Adipose Tissue, White; Animals; Body Weight; Cytokines; Hyperinsulinism; Inflammation; Interleukins; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity | 2020 |
The effects of Vitis vinifera L. phenolic compounds on a blood-brain barrier culture model: Expression of leptin receptors and protection against cytokine-induced damage.
The medicinal properties of grapes (Vitis vinifera L.) are well known since ancient times. Ethnobotanical grape preparations, like the Ayurvedic Darakchasava are used as cardiotonic and for the treatment of cardiovascular diseases. Dried grape products are also applied in Iranian traditional medicine for memory problems, which are linked to the pathology of brain microvessels, a special part of the cardiovascular system. The anti-inflammatory and protective effects of these traditional preparations on the cardiovascular system are related to their bioactive phenolic compounds.. The blood-brain barrier (BBB), formed by brain capillaries, is not only involved in inflammatory and other diseases of the central nervous system, but also in many systemic diseases with an inflammatory component. Dietary obesity is a systemic chronic inflammatory condition in which the peripheral and central vascular system is affected. Among the cerebrovascular changes in obesity defective leptin transport across the BBB related to central leptin resistance is observed. Our aim was to study the protective effects of grape phenolic compounds epicatechin (EC), gallic acid (GA) and resveratrol (RSV) and grape-seed proanthocyanidin-rich extract (GSPE) on a cytokine-induced vascular endothelial inflammation model. Using a culture model of the BBB we investigated cytokine-induced endothelial damage and changes in the expression of leptin receptors and leptin transfer.. For the BBB model, primary cultures of rat brain endothelial cells, glial cells and pericytes were used in co-culture. Cells were treated by tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) (10 ng/ml each) to induce damage. Cell toxicity was evaluated by the measurement of impedance. The expression of leptin receptors was assessed by RT-qPCR and western blot. The production of reactive oxygen species (ROS) and nitric oxide (NO) were detected by fluorescent probes.. GSPE (10 μg/ml), EC (10 μM), GA (1 μM) or RSV (10 μM) did not change the viability of brain endothelial cells. The gene expression of the short leptin receptor isoform, Ob-Ra, was up-regulated by GSPE, EC and RSV, while the mRNA levels of Lrp2 and clusterin, clu/ApoJ were not affected. The tested compounds did not change the expression of the long leptin receptor isoform, Ob-Rb. RSV protected against the cytokine-induced increase in albumin permeability of the BBB model. GSPE and EC exerted an antioxidant effect and GSPE increased NO both alone and in the presence of cytokines. The cytokine-induced nuclear translocation of transcription factor NF-κB was blocked by GSPE, GA and RSV. Cytokines increased the mRNA expression of Lrp2 which was inhibited by EC. RSV increased Ob-Ra and Clu in the presence of cytokines. Cytokines elevated leptin transfer across the BBB model, which was not modified by GSPE or RSV.. Our results obtained on cell culture models confirm that natural grape compounds protect vascular endothelial cells against inflammatory damage in accordance with the ethnopharmacological use of grape preparations in cardiovascular diseases. Furthermore, grape compounds and GSPE, by exerting a beneficial effect on the BBB, may also be considered in the treatment of obesity after validation in clinical trials. Topics: Animals; Animals, Newborn; Astrocytes; Blood-Brain Barrier; Catechin; Cells, Cultured; Cytokines; Drug Evaluation, Preclinical; Endothelial Cells; Endothelium, Vascular; Ethnopharmacology; Gallic Acid; Grape Seed Extract; Humans; Inflammation; Leptin; Medicine, Ayurvedic; Primary Cell Culture; Proanthocyanidins; Rats; Reactive Oxygen Species; Receptors, Leptin; Resveratrol; Vitis | 2020 |
Neuroinflammation induced by lipopolysaccharide leads to memory impairment and alterations in hippocampal leptin signaling.
Peripheral inflammation promotes immune-to-brain communication, mediated by cytokines that affect brain activity. Lipopolysaccharide (LPS) has been widely used to mimic systemic inflammation, and the adipokine leptin, released in this condition, modulates hypothalamic leptin receptors (ObR), contributing to sickness behavior. In this study, we used the intracerebroventricular (ICV) route for LPS administration in an attempt to evaluate an acute and direct of this pathogen-associated molecular pattern on leptin-mediated signaling in the hippocampus, where ObR has been implicated in modulating cognitive response. We used bilateral ICV injection of LPS (25 μg/ventricle) in 60-day-old male Wistar rats and the analysis were performed 48 h after surgery. Neuroinflammation was characterized in the LPS group by an increase in concentration of IL-1β, COX-2 and TLR4 in the hippocampus as well as glial fibrillary acidic protein (GFAP), indicating an astrocyte commitment. Cognitive damage was observed in the animals of the LPS group by an inability to increase the recognition index during the object recognition test. We observed an increase in the concentration of leptin receptors in the hippocampus, which was unaccompanied by changes in the proteins involved in leptin intracellular signaling (p-STAT3 and SOCS3). Moreover, we found a decrease in leptin concentration in the serum of the animals in the LPS group accompanied by an increase in TNF-α levels. Our results showed that neuroinflammation, even in an acute state, can lead to cognitive impairment and may be associated with leptin signaling disturbances in the hippocampus. Topics: Animals; Cognitive Dysfunction; Hippocampus; Inflammation; Leptin; Lipopolysaccharides; Male; Memory Disorders; Rats; Rats, Wistar; Receptors, Leptin; Signal Transduction | 2020 |
The adipokines and inflammatory status in the era of pediatric obesity.
Obesity is associated with a chronic inflammation due to the deficiency in immune activity related to adipose tissue. A wide-spectrum of pro-inflammatory cytokines secreted by adipocytes play an important role in the assessment of obesity-associated inflammatory status. The aim of this study was to assess the relationship between IL and 1β, IL-6, TNF α, leptin, and inflammatory status in children with overweight/obesity.. We performed a cross-sectional study on 193 children, admitted to a Pediatric Tertiary Hospital in Romania. The children were divided according to BMI into: the study group-91 children with overweight/obesity, and the control group-102 children with normal BMI. Demographic, anthropometric, and laboratory parameters including the serum levels of several adipokines (leptin, IL-1β, IL-6, and TNF α) were assessed in both groups.. Our findings revealed significantly higher values of leukocytes, lymphocytes, platelets, AST, and ALT, as well as for the lipid metabolism parameters including cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and CRP, in children with overweight/obesity. We found significantly higher levels of adipokines in the serum of children with overweight and obesity assessed for leptin, IL6, and TNF α (p = 0.0145/p < 0.0001/p = 0.004/), except for IL-1β serum levels.. Childhood overweight and/or obesity is associated with a systemic inflammatory status demonstrated by increased levels of CBC parameters. Pro-inflammatory adipokines are also an essential factor in obesity-related inflammatory status according to our findings that underlined the importance of increased serum levels of IL-6, TNF α, and leptin in pediatric patients with overweight/obesity. Clinically, CBC parameters along with adipokines might represent useful diagnostic tools for low-grade systemic inflammation in children with overweight or obesity. Topics: Adipokines; Adipose Tissue; Adolescent; Body Mass Index; C-Reactive Protein; Child; Child, Preschool; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Cytokines; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Leptin; Lipid Metabolism; Male; Pediatric Obesity; Romania; Triglycerides; Tumor Necrosis Factor-alpha | 2020 |
Exercise lowers leptin and leukocytosis.
Topics: Exercise; Hematopoietic Stem Cells; Humans; Inflammation; Leptin; Leukocytosis | 2020 |
Analysis of inflammatory markers and hormones in old cancer patients: A descriptive study.
Advanced cancers are associated with a chronic inflammation, especially high interleukin-6 (IL-6) and with various levels of adipokines (leptin and adiponectin), while ghrelin counteracts the anorexigenic effect of leptin in cancer-induced anorexia-cachexia syndrome. We aimed to understand how IL-6, adipokines and ghrelin plasma levels could be influenced by cancer on the one hand, and by age, frailty, and nutritional status in old cancer patients on the other hand. Ninety-nine patients aged 79[76-83] years old were included. Sixty-six percent had advanced stages of cancer, and 34% had cachexia. Fifty percent were at risk of malnutrition, and 10% had overt malnutrition. None of the variables studied was significantly correlated with the advanced stage, or cachexia. In multiple regression, the only parameter significantly and positively associated with age was adiponectin (p = 0.008). Despite a high prevalence of frailty in our study, we did not find any independent association of frailty (assessed by G8) with IL-6, leptin, adiponectin, or ghrelin in multivariate analysis. We observed that a low albumin level was independently associated with a higher level of IL-6 (p < 0.0001), but not with the MNA score. However, leptin showed a positive correlation with BMI (p < 0.0001), confirming the persistence of a relationship between leptin and adiposity, even in older cancer patients. Finally, high IL-6 level was associated with a higher mortality rate (p = 0.027). In conclusion, IL-6, leptin, adiponectin, and ghrelin are not associated with advanced stages of cancer or cancer-induced cachexia in older subjects with cancer, but they are significantly correlated with anthropometric factors and body composition. Topics: Adipokines; Adiponectin; Adiposity; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cachexia; Female; Frailty; Ghrelin; Humans; Inflammation; Interleukin-6; Leptin; Male; Malnutrition; Neoplasms; Nutritional Status; Tumor Necrosis Factor-alpha | 2020 |
Low serum leptin levels are associated with malnutrition status according to malnutrition-inflammation score in patients undergoing chronic hemodialysis.
Leptin is an adipokine secreted from adipocytes that mediate lipid metabolism and inflammation. This cross-sectional study investigated the relationship between serum leptin level and nutrition status evaluated by malnutrition-inflammation score (MIS) among patients undergoing hemodialysis (HD).. This study included 100 patients on HD. Nutritional status was based on MIS (malnutrition ≥7 points). Body composition, biochemistry data, and serum leptin level were evaluated.. Of 100 subjects, 33 (33.0%) were categorized as having malnutrition. Compared with subjects in the well-nourished group, those in the malnutrition group had on average an older age, longer HD duration, and lower height, weight, body mass index, waist circumference, body fat mass, serum triglyceride level, and creatinine level. Serum leptin levels were also significantly lower in the malnutrition group (P < 0.001), whereas C-reactive protein (CRP) levels were higher (P = 0.002). Multivariable linear regression analysis revealed that HD duration (β = 2.06, P = 0.009), serum leptin level (β = -5.16, P < 0.001), CRP level (β = 3.33, P < 0.001), and albumin level (β = -1.95, P = 0.008) were factors independently associated with MIS. The discriminative power of serum leptin level to predict malnutrition was 0.834 (95% confidence interval: 0.747-0.901, P < 0.001).. Low serum leptin level was associated with malnutrition, and serum leptin level may be a valuable marker for nutrition assessment in patients undergoing HD. Topics: Aged; Cross-Sectional Studies; Female; Humans; Inflammation; Leptin; Male; Malnutrition; Middle Aged; Renal Dialysis | 2020 |
A high-sucrose diet aggravates Alzheimer's disease pathology, attenuates hypothalamic leptin signaling, and impairs food-anticipatory activity in APPswe/PS1dE9 mice.
High-fat and high-sugar diets contribute to the prevalence of type 2 diabetes and Alzheimer's disease (AD). Although the impact of high-fat diets on AD pathogenesis has been established, the effect of high-sucrose diets (HSDs) on AD pathogenesis remains unclear. This study sought to determine the impact of HSDs on AD-related pathologies. Male APPswe/PS1dE9 (APP/PS1) transgenic and wild-type mice were provided with HSD and their cognitive and hypothalamus-related noncognitive parameters, including feeding behaviors and glycemic regulation, were compared. HSD-fed APP/PS1 mice showed increased neuroinflammation, as well as increased cortical and serum levels of amyloid-β. HSD-fed APP/PS1 mice showed aggravated obesity, hyperinsulinemia, insulin resistance, and leptin resistance, but there was no induction of hyperphagia or hyperleptinemia. Leptin-induced phosphorylation of signal transducer and activator of transcription 3 in the dorsomedial and ventromedial hypothalamus was reduced in HSD-fed APP/PS1 mice, which might be associated with attenuated food-anticipatory activity, glycemic dysregulation, and AD-related noncognitive symptoms. Our study demonstrates that HSD aggravates metabolic stresses, increases AD-related pathologies, and attenuates hypothalamic leptin signaling in APP/PS1 mice. Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anticipation, Psychological; Diet, Carbohydrate Loading; Eating; Hypothalamus; Inflammation; Leptin; Mice, Transgenic; Signal Transduction; STAT3 Transcription Factor; Sucrose | 2020 |
Hesperidin improves insulin resistance via down-regulation of inflammatory responses: Biochemical analysis and in silico validation.
Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Diet, High-Fat; Disease Models, Animal; Drug Therapy, Combination; Hesperidin; Hyperlipidemias; Inflammation; Insulin Resistance; Leptin; Molecular Docking Simulation; Molecular Dynamics Simulation; Obesity; Orlistat; Rats, Wistar | 2020 |
Impact of Weight Loss on Inflammation State and Endothelial Markers Among Individuals with Extreme Obesity After Gastric Bypass Surgery: a 2-Year Follow-up Study.
The medium-term impact of gastric bypass (GB) surgery on the inflammatory state and endothelial function of patients has yet to be confirmed.. This study aims to elucidate the inflammatory profile and endothelial dysfunction response of adults with obesity 6 and 24 months after undergoing GB surgery.. The anthropometric and biochemical markers of 32 adults with obesity (two men and 30 females) were collected preoperatively, and 6 and 24 months postoperatively.. Our results demonstrated that after GB there was an improvement in the inflammatory profile, identified by a reduction in pro-inflammatory markers (CRP, IL-6, leptin) and an increase in anti-inflammatory markers (adiponectin, IL-10). The decrease in PAI-1 and ICAM-1 levels may suggest improvement in endothelial function. These findings provide clear evidence of the medium-term impact of GB on inflammation state and a number of endothelial markers, and a consequent reduction in the risk of cardiovascular diseases. Topics: Adiponectin; Adult; Biomarkers; Female; Follow-Up Studies; Gastric Bypass; Humans; Inflammation; Leptin; Male; Obesity; Obesity, Morbid; Weight Loss | 2020 |
Effects of a four-week very low-carbohydrate high-fat diet on biomarkers of inflammation: Non-randomised parallel-group study.
It is commonly assumed that increased dietary fat and/or caloric excess induces chronic inflammatory processes, since the association between obesity and chronic adipose tissue with systemic inflammation has been shown previously. As far as we know, the reported health benefits of a VLCHF or ketogenic diet have not adequately involved an evaluation of biomarkers of inflammation.. This study investigated the effects of a four-week very low-carbohydrate high-fat (VLCHF) diet in healthy young individuals on biomarkers of inflammation.. Eighteen moderately trained males (age 23.8 ± 2.1 years) were assigned to two groups. One group switched to a non-standardised VLCHF diet for four weeks, while the second group remained consuming their normal habitual diet (HD). Biomarkers of inflammation (adiponectin, leptin, resistin and interleukin-6) and substrate metabolism (fasting glucose and triacylglyceride concentrations) were analysed from blood at baseline and after four weeks.. There was moderate evidence for substantial changes in leptin serum concentrations in the VLCHF group, with small to large decreases compared to the HD group after four weeks (effect size = 0.78, 95% CI 0.42, 0.93,. A four-week period of consuming a VLCHF diet in healthy young men was not associated with any considerable changes in markers of inflammation but showed evidence for lowered serum leptin concentrations relative to the HD group. Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Diet, Carbohydrate-Restricted; Diet, High-Fat; Diet, Ketogenic; Dietary Fats; Humans; Inflammation; Interleukin-6; Leptin; Male; Resistin; Triglycerides; Young Adult | 2020 |
High-refined carbohydrate diet consumption induces neuroinflammation and anxiety-like behavior in mice.
Consumption of poor nutrients diets is associated with fat tissue expansion and with a central and peripheral low-grade inflammation. In this sense, the microglial cells in the central nervous system are activated and release pro-inflammatory cytokines that up-regulate the inducible nitric oxide synthase (iNOS), promoting Nitric Oxide (NO) production. The excess of NO has been proposed to facilitate anxious states in humans and rodents. We evaluated whether consumption of a high-refined carbohydrate-containing diet (HC) in mice induced anxiety-like behavior in the Novelty Suppressed Feeding Test (NFST) trough facilitation of NO, in the prefrontal cortex (PFC) and hippocampus (HIP). We also verified if HC diet induces activation of microglial cells, alterations in cytokine and leptin levels in such regions. Male BALB/c mice received a standard diet or a HC diet for 3 days or 12 weeks. The chronic consumption of HC diet, but not acute, induced an anxiogenic-like effect in the NSF test and an increase in the nitrite levels in the PFC and HIP. The preferential iNOS inhibitor, aminoguanidine (50 mg/kg, i.p.), attenuated such effects. Moreover, microglial cells in the HIP and PFC were activated after chronic consumption of HC diet. Finally, the expression of iNOS in the PFC and TNF, IL6 and leptin levels in HIP were higher in chronically HC fed mice. Taken together, our data reinforce the notion that diets containing high-refined carbohydrate facilitate anxiety-like behavior, mainly after a long period of consumption. The mechanisms involve, at least in part, the augmentation of neuroinflammatory processes in brain areas responsible for anxiety control. Topics: Adipose Tissue; Animals; Anxiety; Behavior, Animal; Dietary Carbohydrates; Disease Models, Animal; Guanidines; Hippocampus; Inflammation; Leptin; Male; Mice; Mice, Inbred BALB C; Nitric Oxide Synthase Type II; Nitrites; Prefrontal Cortex | 2020 |
Maize extract rich in ferulic acid and anthocyanins prevents high-fat-induced obesity in mice by modulating SIRT1, AMPK and IL-6 associated metabolic and inflammatory pathways.
The aim was to compare the antiobesity efficacy of different concentrations of a phenolic-rich water extract from purple maize pericarp (PPE) in a murine model of obesity for 12 weeks. Forty C57BL/6 mice (n=10/group) were randomized: standard diet (SD), high-fat diet (HFD), HFD+200 mg PPE/kg (200 PPE) and HFD+500 mg PPE/kg (500 PPE). PPE contained mainly ferulic acid, anthocyanins and other phenolics (total phenolics: 448.5 μg/mg dry weight, DW). Body weight (-27.9%), blood glucose (-26.5%) and blood triglycerides (-22.1%) were most attenuated (P<.05) in 500 PPE group compared to HFD group. Also, 500 PPE group had reduced (P<.05) plasma levels of TNF-α, MCP-1, resistin and leptin compared to HFD group. Fatty liver disease scores were highest for HFD (8.4), followed by 200 PPE (6.1), 500 PPE (2.7) and SD (0.4) groups. Relative adipose tissue was lower (P<.05) in 200 PPE (7.6%), 500 PPE (8.0%) and SD (0.8%) compared to HFD (12.1%) group. In 500 PPE group, compared to HFD group, important genes were modulated related to adipogenesis (Mmp3, fold-change [FC]=7.4), inflammation (Nfkb1, FC=-1.8) and glucose metabolism (Slc2a4, FC=23.6) in adipose tissue. In liver, 500 PPE group showed modulation of genes related to gluconeogenesis (Pck1, FC=-2.9), lipogenesis (Fasn, FC=-2.4) and β-oxidation (Cpt1b, FC=3.1). Maize rich in ferulic acid and anthocyanins prevented obesity through the modulation of TLR and AMPK signaling pathways reducing adipogenesis and adipose inflammation, and promoting energy expenditure. Topics: Adipogenesis; Adipose Tissue; AMP-Activated Protein Kinases; Animals; Anthocyanins; Anti-Obesity Agents; Coumaric Acids; Diet, High-Fat; Inflammation; Interleukin-6; Leptin; Lipogenesis; Male; Mice; Mice, Inbred C57BL; Obesity; Sirtuin 1; Zea mays | 2020 |
Increase in Leptin and PPAR-γ Gene Expression in Lipedema Adipocytes Differentiated in vitro from Adipose-Derived Stem Cells.
Lipedema is a painful loose connective tissue disorder characterized by a bilaterally symmetrical fat deposition in the lower extremities. The goal of this study was to characterize the adipose-derived stem cells (ASCs) of healthy and lipedema patients by the expression of stemness markers and the adipogenic and osteogenic differentiation potential. Forty patients, 20 healthy and 20 with lipedema, participated in this study. The stromal vascular fraction (SVF) was obtained from subcutaneous thigh (SVF-T) and abdomen (SVF-A) fat and plated for ASCs characterization. The data show a similar expression of mesenchymal markers, a significant increase in colonies ( Topics: Adipocytes; Adipogenesis; Adipose Tissue; Adult; Biomarkers; Cell Differentiation; Cell Proliferation; Colony-Forming Units Assay; Female; Gene Expression Regulation; Humans; Inflammation; Leptin; Lipedema; Male; Middle Aged; Osteogenesis; PPAR gamma; Stem Cells | 2020 |
Comparison of plasma adipocytokines & C-reactive protein levels in healthy schoolgoing adolescents from private & government-funded schools of Delhi, India.
Obesity-mediated chronic inflammatory state is primarily governed by lifestyle and food habits in adolescents and marked by alterations in the level of various inflammatory markers. This cross-sectional study was aimed to compare the inflammatory status of healthy Indian adolescents vis-à-vis their obesity profile. The inflammatory state of urban adolescents attending private and government-funded schools, and the relationship between inflammatory marker levels and anthropometric indices in the study participants from both groups were examined.. A total of 4438 study participants (10-17 yr) were chosen from various schools of Delhi, India, and their anthropometric parameters were measured. Plasma adipocytokines (adiponectin, leptin and resistin) of the study participants were measured by enzyme-linked immunosorbent assay, and plasma C-reactive protein (CRP) levels were assayed by a biochemical analyzer. Metabolic syndrome-related risk factors such as waist circumference, hip circumference (HC), fasting glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and triglycerides of normal-weight adolescents were also evaluated.. The level of leptin and CRP increased with increasing adiposity, whereas adiponectin levels were found to be negatively related to obesity. All plasma cytokine levels (adiponectin, leptin and resistin) were significantly elevated in female than male adolescents. Age-based classification revealed a distinct trend of variability in the levels of all the inflammatory markers among adolescents of varying age groups. Significant differences were observed between private and government schoolgoing adolescents in terms of anthropometric and inflammatory parameters, with higher adiposity indices in the former group. The relationship of plasma adipokine and CRP levels with various adiposity indices was found to be distinctly different between private and government schoolgoing students.. Inflammatory markers were significantly elevated in overweight/obese adolescents. The socio-economic condition of urban Indian schoolgoing adolescents reflecting lifestyle transition has profound effects on their adiposity indices and inflammatory states. Longitudinal studies in different regions of the country need to be done to further confirm the findings. Topics: Adiponectin; Adolescent; Biomarkers; C-Reactive Protein; Child; Feeding Behavior; Female; Humans; India; Inflammation; Leptin; Life Style; Male; Obesity; Pediatric Obesity; Resistin; Risk Factors | 2020 |
Relationship among the leptin-to-adiponectin ratio, systemic inflammation, and anisocytosis in well-controlled type 2 diabetic patients with atherosclerotic cardiovascular disease.
Previous studies have shown that red blood cell distribution width (RDW) is an independent predictor of poor prognosis in type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). The mechanisms underlying increased anisocytosis in patients with T2D and confirmed ASCVD remain poorly understood.. We sought to evaluate the relationship among the leptin-to-adiponectin ratio, systemic low -grade inflammation, and RDW in optimally treated patients with T2D and established ASCVD.. A total of 68 patients, aged 47 to 85 years (mean [SD], 65.3 [6.8] years) and including 21 women (30.9%), were enrolled and grouped according to median RDW into those with RDW <13.5% (n = 33) and those with RDW ≥13.5% (n = 35).. Patients with RDW ≥13.5% had a significantly higher median (interquartile range [IQR]) serum leptin-to-adiponectin ratio (1.7 [0.49-2.3] ng/μg vs 0.66 [0.31-1.25] ng/μg; P = 0.04) and median (IQR) tumor necrosis factor α levels (1.58 [1.42-1.97] pg/ml vs 1.39 [1.18-1.57] pg/ml; P = 0.02). There were no significant differences in the concentrations of other inflammatory markers. The leptin-to-adiponectin ratio (r = 0.25; P = 0.04) and levels of tumor necrosis factor α (r = 0.32; P = 0.01) and soluble intercellular adhesion molecule 1 (r = 0.31; P = 0.01) were positively correlated with RDW, which was confirmed by univariate linear regression analysis. A multivariable regression model, which included demographic, clinical, and laboratory data, showed that white blood cell count (β = 0.25; 95% CI, 0.05-0.45; P = 0.01), soluble intercellular adhesion molecule 1 levels (β = 0.21; 95% CI, 0.02-0.41; P = 0.03), and mean corpuscular hemoglobin concentration (MCHC), (β = -0.48; 95% CI, 0.67 to -0.28; P < 0.001) were independent predictors of RDW in our patients.. In well-controlled patients with T2D and ASCVD, the RDW values are associated with leptin-to-adiponectin imbalance and selected inflammatory markers. Topics: Adiponectin; Aged; Aged, 80 and over; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Erythrocyte Indices; Female; Humans; Inflammation; Leptin; Male; Middle Aged | 2020 |
Energy Metabolism and Nutritional Status in Hospitalized Patients with Chronic Heart Failure.
Malnutrition is a factor that defines vital prognosis in chronic heart failure.. This study investigated nutritional and metabolic disorders in patients with heart failure by examining the association of severity of heart failure with inflammatory cytokines, appetite-regulating hormones, and energy metabolism.. Subjects were 50 patients with heart failure. On admission, nutritional status was assessed, and biochemical blood tests were performed, including for serum tumor necrosis factor-α, interleukin-6, ghrelin, and leptin levels. Resting energy expenditure (REE) was also measured by indirect calorimetry to examine its association with severity of heart failure and levels of inflammatory cytokines and appetite-regulating hormones.. There were significant associations between serum brain natriuretic peptide (BNP) level and nutrition indices, indicating that nutritional status was worse when heart failure was more severe. Inflammatory cytokine levels showed significant positive correlations with BNP level. Measured REE/bodyweight was not associated with severity of heart failure, but was negatively correlated with body fat percentage and leptin levels.. Energy metabolism was not associated with serum BNP level among patients with heart failure with New York Heart Association functional class up to III. Body fat percentage and leptin levels may be a good predictor of energy metabolism in patients with heart failure. Topics: Aged; Aged, 80 and over; Body Composition; Body Mass Index; Cytokines; Energy Metabolism; Female; Heart Failure; Hospitalization; Humans; Inflammation; Leptin; Male; Middle Aged; Natriuretic Peptide, Brain; Nutritional Status; Prognosis | 2020 |
Leptin induces interleukin-6 production in keratinocytes via decreased expression of caveolin-1: a possible link between obesity and psoriatic inflammation.
Topics: Caveolin 1; Cells, Cultured; Humans; Inflammation; Interleukin-6; Interleukin-8; Keratinocytes; Leptin; Obesity; Psoriasis | 2020 |
Caloric restriction reverses left ventricular hypertrophy through the regulation of cardiac iron homeostasis in impaired leptin signaling mice.
Leptin-deficient and leptin-resistant mice manifest obesity, insulin resistance, and left ventricular hypertrophy (LVH); however, LVH's mechanisms are not fully understood. Cardiac iron dysregulation has been recently implicated in cardiomyopathy. Here we investigated the protective effects of caloric restriction on cardiac remodeling in impaired leptin signaling obese mice. RNA-seq analysis was performed to assess the differential gene expressions in the heart of wild-type and ob/ob mice. In particular, to investigate the roles of caloric restriction on iron homeostasis-related gene expressions, 10-week-old ob/ob and db/db mice were assigned to ad libitum or calorie-restricted diets for 12 weeks. Male ob/ob mice exhibited LVH, cardiac inflammation, and oxidative stress. Using RNA-seq analysis, we identified that an iron uptake-associated gene, transferrin receptor, was upregulated in obese ob/ob mice with LVH. Caloric restriction attenuated myocyte hypertrophy, cardiac inflammation, fibrosis, and oxidative stress in ob/ob and db/db mice. Furthermore, we found that caloric restriction reversed iron homeostasis-related lipocalin 2, divalent metal transporter 1, transferrin receptor, ferritin, ferroportin, and hepcidin expressions in the heart of ob/ob and db/db mice. These findings demonstrate that the cardioprotective effects of caloric restriction result from the cellular regulation of iron homeostasis, thereby decreasing oxidative stress, inflammation, and cardiac remodeling. We suggest that decreasing iron-mediated oxidative stress and inflammation offers new therapeutic approaches for obesity-induced cardiomyopathy. Topics: Animals; Caloric Restriction; Hypertrophy, Left Ventricular; Inflammation; Iron; Leptin; Male; Mice; Mice, Obese; Oxidative Stress; Signal Transduction | 2020 |
Leptin Resistance in the Ovary of Obese Mice is Associated with Profound Changes in the Transcriptome of Cumulus Cells.
Obesity is associated with infertility, decreased ovarian performance and lipotoxicity. However, little is known about the aetiology of these reproductive impairments. Here, we hypothesise that the majority of changes in ovarian physiology in diet-induced obesity (DIO) are a consequence of transcriptional changes downstream of altered leptin signalling. Therefore, we investigated the extent to which leptin signalling is altered in the ovary upon obesity with particular emphasis on effects on cumulus cells (CCs), the intimate functional companions of the oocyte. Furthermore, we used the pharmacological hyperleptinemic (LEPT) mouse model to compare transcriptional profiles to DIO.. Mice were subjected to DIO for 4 and 16 weeks (wk) and leptin treatment for 16 days, to study effects in the ovary in components of leptin signalling at the transcript and protein levels, using Western blot, Real-time PCR and immunostaining. Furthermore, we used low-cell RNA sequencing to characterise changes in the transcriptome of CCs in these models.. In the DIO model, obesity led to establishment of ovarian leptin resistance after 16 wk high fat diet (HFD), as evidenced by increases in the feedback regulator suppressor of cytokine signalling 3 (SOCS3) and decreases in the positive effectors phosphorylation of tyrosine 985 of leptin receptor (ObRb-pTyr985) and Janus kinase 2 (pJAK2). Transcriptome analysis of the CCs revealed a complex response to DIO, with large numbers and distinct sets of genes deregulated at early and late stages of obesity; in addition, there was a striking correlation between body weight and global transcriptome profile of CCs. Further analysis indicated that the transcriptome profile in 4 wk HFD CCs resembled that of LEPT CCs, in the upregulation of cellular trafficking and impairment in cytoskeleton organisation. Conversely, after 16 wk HFD CCs showed expression changes indicative of augmented inflammatory responses, cell morphogenesis, and decreased metabolism and transport, mainly as a consequence of the physiological changes of obesity.. Obesity leads to ovarian leptin resistance and major time-dependent changes in gene expression in CCs, which in early obesity may be caused by increased leptin signalling in the ovary, whereas in late obesity are likely to be a consequence of metabolic changes taking place in the obese mother. Topics: Animals; Cumulus Cells; Disease Models, Animal; Female; Gene Expression Regulation; Inflammation; Janus Kinase 2; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oocytes; Ovary; Phosphorylation; Receptors, Leptin; RNA-Seq; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein | 2020 |
Correlation between leptin and IFN-γ involved in granulosa cell apoptosis in PCOS.
Our study aimed to explore the relationship between leptin and IFN-γ in PCOS patients, and confirmed the effect of leptin-induced IFN-γ on granulosa cells furtherly.. 29 patients with PCOS and 36 healthy controls were enrolled. Leptin level and the proportion of Th1 cells were detected and association between them were analyzed. Meanwhile, peripheral blood mononuclear cells (PBMCs) isolated from PCOS patients were treated with leptin and then the proportion of Th1 was analyzed. Besides that, the apoptotic level of KGN cells was monitored after IFN-γ treatment.. In the circulation of PCOS patients, leptin level dramatically increased compared with controls. And, this was associated with upregulated Th1 cells proportion and IFN-γ level.. Our results indicated that leptin takes part in process of PCOS Topics: Adult; Apoptosis; Case-Control Studies; Cell Line, Tumor; Female; Follicle Stimulating Hormone; Granulosa Cells; Humans; In Vitro Techniques; Inflammation; Interferon-gamma; Leptin; Leukocytes, Mononuclear; Luteinizing Hormone; Polycystic Ovary Syndrome; Prolactin; Receptors, Leptin; Testosterone; Th1 Cells | 2020 |
Combined effects of moderate exercise and short-term fasting on markers of immune function in healthy human subjects.
This study aimed to investigate the effects of a short-term (36 h) fasting period combined with an acute bout of exercise on markers of immune function and inflammation in healthy human subjects. Fourteen moderately trained male subjects (aged 19-39 yr) participated in a 36-h fasting trial (FA-T), followed by an acute bout of moderate exercise (60% V̇o Topics: Adult; Apoptosis; Biomarkers; Chemokine CCL2; Exercise; Fasting; Healthy Volunteers; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Male; Oxidative Stress; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha; Young Adult | 2020 |
PPARγ-mediated microglial activation phenotype is involved in depressive-like behaviors and neuroinflammation in stressed C57BL/6J and ob/ob mice.
There is an increased risk for obese patients with chronic low-grade inflammation to develop depression. Stress induces microglial activation and neuroinflammation that play crucial roles in the pathogenesis of depression. Peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear transcription factor, regulates microglial polarization and neuroinflammation. Our study aimed to investigate the role of PPARγ in the development of depressive symptoms and neuroinflammation induced by chronic unpredictable mild stress (CUMS) in wild-type/C57BL/6J (wt) and leptin-deficient (ob/ob) mice.. CUMS was used to build a depression model with wt and ob/ob mice. Depressive-like behaviors were evaluated by sucrose preference test, open field test, tail suspension test, and Morris water maze test. Cytokines, the activated microglial state, and nuclear factor-κB (NF-κB) and PPARγ expression in the prefrontal cortex (PFC) and hippocampus (HIP) were examined by enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and western blotting. Additionally, pioglitazone, an agonist of PPARγ, was used as a treatment intervention.. After CUMS, ob/ob mice exhibited severe behavioral disorders and spatial memory impairment, and higher levels of pro-inflammatory cytokines, M1/M2 ratios, and NF-κB activation, as well as lower levels of anti-inflammatory cytokines and PPARγ expression in the PFC and HIP compared to wt mice. Administration of pioglitazone relieved these alterations in wt and ob/ob mice.. CUMS was able to induce severe depressive-like behaviors, neuroinflammation, and reduced expression of PPARγ in ob/ob mice as compared to wt mice. This suggests that PPARγ mediates the microglial activation phenotype, which might be related to the susceptibility of stressed ob/ob mice to develop depressive disorder. Topics: Animals; Behavior, Animal; Cognitive Dysfunction; Cytokines; Depression; Disease Models, Animal; Hippocampus; Hypoglycemic Agents; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Microglia; Obesity; Phenotype; Pioglitazone; PPAR gamma; Prefrontal Cortex; Stress, Psychological | 2020 |
Relationship among the leptin-to-adiponectin ratio, systemic inflammation, and anisocytosis: a plausible pathophysiological mechanism of a novel cardiovascular risk marker.
Topics: Adiponectin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Inflammation; Leptin; Risk Factors | 2020 |
Biological senescence risk score. A practical tool to predict biological senescence status.
Ageing and biological senescence, both related to cardiovascular disease, are mediated by oxidative stress and inflammation. We aim to develop a predictive tool to evaluate the degree of biological senescence in coronary patients.. Relative telomere length (RTL) of 1002 coronary patients from the CORDIOPREV study (NCT00924937) was determined at baseline in addition to markers of inflammatory response (hs-C-Reactive Protein, monocyte chemoattractant protein-1, IL-6, IL-1β, TNF-α, adiponectin, resistin and leptin) and oxidative stress (nitric oxide, lipid peroxidation products, carbonylated proteins, catalase, total glutathione, reduced glutathione, oxidized glutathione, superoxide dismutase and peroxidated glutathione). Biological senescence was defined using the cut-off value defined by the lower quintile of relative telomere length in our population (RTL = 0.7629). We generated and tested different predictive models based on logistic regression analysis to identify biological senescence. Three models were designed to be used with different sets of information.. We selected those patients with all the variables proposed to develop the predictive models (n = 353). Statistically significant differences between both groups (Biological senescence vs. Nonbiological senescence) were found for total cholesterol, catalase, superoxide dismutase, IL-1β, resistin and leptin. The area under the curve of receiver-operating characteristic to predict biological senescence for our models was 0.65, 0.75 and 0.72.. These predictive models allow us to calculate the degree of biological senescence in coronary patients, identifying a subgroup of patients at higher risk and who may require more intensive treatment. Topics: Aged; Aging; C-Reactive Protein; Catalase; Cholesterol; Coronary Disease; Female; Humans; Inflammation; Interleukin-1beta; Leptin; Male; Middle Aged; Oxidative Stress; Randomized Controlled Trials as Topic; Resistin; Risk Assessment; Secondary Prevention; Superoxide Dismutase; Telomere | 2020 |
Leptin improves intestinal flora dysfunction in mice with high-fat diet-induced obesity.
This study investigated the effects of leptin on intestinal flora and inflammation in mice with high-fat diet (HFD)-induced obesity.. Mice were fed an HFD for 8 weeks; some were concurrently administered oral leptin for 4 weeks. Pathological changes in adipose tissue were detected using hematoxylin-eosin staining; endotoxin content in adipose tissue was measured by enzyme-linked immunosorbent assay. Intestinal flora were characterized by 16S bacterial rDNA sequencing. Levels of Toll-like receptor 4 (TLR4), nuclear factor-κB inhibitor α (IκB-α), and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by western blotting.. Mice in the HFD group exhibited weight gain, elevated endotoxin content, and adipocyte hypertrophy, compared with the non-obese control group. Moreover, abundance of bacteria in the. Leptin administration improved intestinal flora dysfunction and inflammation in mice with HFD-induced obesity. Topics: Adipose Tissue; Administration, Oral; Animals; Diet, High-Fat; Disease Models, Animal; Endotoxins; Gastrointestinal Microbiome; Humans; Inflammation; Leptin; Male; Mice; Obesity | 2020 |
Short-term exposure to air pollution (PM
A previous study demonstrated that a high-fat diet (HFD), administered for one-three-days, induces hypothalamic inflammation before obesity's established, and the long term affects leptin signaling/action due to inflammation. We investigate whether exposure to particulate matter of a diameter of ≤2.5 μm (PM Topics: Adipocytes, Brown; Air Pollution; Animals; Energy Metabolism; Gene Expression; Hyperphagia; Hypothalamus; I-kappa B Kinase; Inflammation; Leptin; Mice, Transgenic; Microglia; Obesity; Particulate Matter; Signal Transduction; Time Factors; Toll-Like Receptor 4; Uncoupling Protein 1 | 2020 |
Interleukin-4 Improves Metabolic Abnormalities in Leptin-Deficient and High-Fat Diet Mice.
Obesity is a metabolic disorder that results from complex interactions between genetic predisposition and dietary factors. Interleukin-4 (IL-4), besides its role in immunity, has metabolic effects on insulin efficacy. We studied the effects of IL-4 on metabolic abnormalities in a mice model of obesity involving leptin deficiency and leptin resistance. Leptin-deficient 145E and leptin-resistant high-fat diet (HFD) mice showed lower levels of circulating IL-4. 145E and HFD mice showed a number of abnormalities: Obesity, hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia, liver injury, and adiposity with concurrent inflammation, decreases in Akt, signal transducer and activator of transcription 3 (STAT3), and STAT6 phosphorylation in the hypothalamus, liver, and epididymal fat. Independent of leptin-deficient obesity and dietary obesity, a course of 8-week IL-4 supplementation improved obesity and impairment in Akt, STAT3, and STAT6 signaling. Amelioration of cytokine expression, despite variable extents, was closely linked with the actions of IL-4. Additionally, the browning of white adipocytes by IL-4 was found in epididymal white adipose tissues and 3T3-L1 preadipocytes. Chronic exercise, weight management, and probiotics are recommended to overweight patients and IL-4 signaling is associated with clinical improvement. Thus, IL-4 could be a metabolic regulator and antiobesity candidate for the treatment of obesity and its complications. Topics: Adjuvants, Immunologic; Animals; Diet, High-Fat; Inflammation; Insulin Resistance; Interleukin-4; Leptin; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Obesity | 2020 |
Leptin mediates improvements in cognitive function following treatment with infliximab in adults with bipolar depression.
A potential role for leptin in the pathophysiology of bipolar disorder (BD) has been proposed. We recently investigated the effects of the tumor necrosis factor-alpha (TNF-α) antagonist infliximab in individuals with bipolar depression. Leptin is known to interact with the TNF-α system. Herein, we aimed to explore infliximab's effects on leptin and its relationship with brain structure and function. Sixty adults with bipolar depression were enrolled in this randomized, double-blind, 12-week clinical trial of adjunctive infliximab (n = 29) and saline control (n = 31), which were administered intravenously at weeks 0, 2, and 6. Plasma concentrations of leptin, TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. We observed a significant decrease in leptin levels in infliximab-treated patients, relative to placebo. Infliximab treatment also significantly reduced TNF-α and sTNFR2, but not sTNFR1 levels. Changes in sTNR2 levels at week 6 significantly determined changes in leptin at week 12 in infliximab-, but not placebo-treated participants. Improvements in verbal memory and increases in global cortical volume were associated with reduction in leptin levels in the treatment group. Mediation analysis indicated that cognitive improvement in infliximab-treated patients was mediated by reductions in leptin levels, which in its turn were determined by decreases in sTNR2 levels. In conclusion, infliximab treatment reduced plasma leptin levels in individuals with BD, through modulation of sTNFR2. Decreases in leptin signaling were associated with an increase in global cortical volume and better performance in a verbal memory task. Topics: Adult; Bipolar Disorder; Cognition; Double-Blind Method; Female; Humans; Inflammation; Infliximab; Leptin; Male; Middle Aged; Random Allocation; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha | 2020 |
DHA reduces hypothalamic inflammation and improves central leptin signaling in mice.
Anti-obesity effects and improved leptin sensitivity from n-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported in diet-induced obese animals. This study sought to determine the beneficial central effects and mechanism of docosahexaenoic acid (DHA, 22:6 n-3) in high-fat (HF) diet fed mice.. Male C57BL/6J mice were given HF diet with or without intracerebroventricular (icv) injection of docosahexaenoic acid (DHA, 22:6 n-3) for two days. Central leptin sensitivity, hypothalamic inflammation, leptin signaling molecules and tyrosine hydroxylase (TH) were examined by central leptin sensitivity test and Western blot. Furthermore, the expression of hepatic genes involved in lipid metabolism was examined by RT-PCR.. We found that icv administration of DHA not only reduced energy intake and body weight gain but also corrected the HF diet-induced hypothalamic inflammation. DHA decreased leptin signaling inhibitor SOCS3 and improved the leptin JAK2-Akt signaling pathways in the hypothalamus. Furthermore, icv administration of DHA improved the effects of leptin in the regulation of mRNA expression of enzymes related to lipogenesis, fatty acid β-oxidation, and cholesterol synthesis in the liver. DHA increased leptin-induced activation of TH in the hypothalamus.. Therefore, increasing central DHA concentration may prevent the deficit of hypothalamic regulation, which is associated with disorders of energy homeostasis in the liver as a result of a high-fat diet. Topics: Animals; Body Weight; Diet, High-Fat; Docosahexaenoic Acids; Energy Intake; Energy Metabolism; Hypothalamus; Inflammation; Leptin; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Signal Transduction | 2020 |
Body Mass Index (BMI) and Its Influence on the Cardiovascular and Operative Risk Profile in Coronary Artery Bypass Grafting Patients: Impact of Inflammation and Leptin.
Obesity is related to coronary artery disease (CAD) and worse outcomes in coronary artery bypass graft (CABG) patients. Adipose tissue itself is an endocrine organ that secretes many humoral mediators, such as adipokines, which can induce or reduce inflammation and oxidative stress.. We investigate the relationship between the body mass index (BMI), inflammation, and oxidative stress by measuring serum levels of leptin, interleukin-6, and 3-nitrotyrosine in CABG patients and correlate their levels to the cardiovascular and operative risk profiles.. 45 men (<75 years) with a median BMI of 29 (21-51) kg/m. There seems to be a correlation between inflammatory processes and cardiovascular morbidity in our cohort. Further, the incidence of deep sternal wound infections is related to a higher BMI and leptin serum level. Topics: Aged; Body Mass Index; Coronary Artery Bypass; Coronary Artery Disease; Humans; Inflammation; Leptin; Male; Middle Aged | 2020 |
Fas mutation reduces obesity by increasing IL-4 and IL-10 expression and promoting white adipose tissue browning.
Brown adipose tissue generates heat via the mitochondrial uncoupling protein UCP1 to protect against obesity and hypothermia. Fas mutant MRL/lpr mice exhibit a significantly leaner phenotype compared to wild type MRL/MpJ mice. In this study, we evaluated the inflammatory cell population in the adipose tissue of MRL/lpr mice, which could potentially influence their lean phenotype. Furthermore, we compared beige fat activity between the MRL/MpJ and MRL/lpr mice. Fas mutation resulted in high body temperature, improved glucose tolerance, and decreased fat mass and adipocyte size. Fas mutation prevented high-fat diet-induced obesity and decreased the white adipose tissue M1:M2 ratio. When mice were fed a high-fat diet, UCP1, IL-4, IL-10, and tyrosine hydroxylase genes had significantly higher expression in Fas-mutant mice than in wild type mice. After a cold challenge, UCP1 expression and browning were also significantly higher in the Fas-mutant mice. In summary, Fas-mutant mice are resistant to high-fat diet-induced obesity due to increased IL-4 and IL-10 levels and the promotion of thermogenic protein activity and browning in their adipose tissues. STAT6 activation might contribute to M2 polarisation by increasing IL-4 and IL-10 levels while increases in M2 and tyrosine hydroxylase levels promote browning in response to Fas mutation. Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Cholesterol; Diet, High-Fat; Energy Metabolism; Epididymis; fas Receptor; Glucose Tolerance Test; Glycerol; Inflammation; Insulin; Interleukin-10; Interleukin-4; Leptin; Male; Mice; Mutation; Obesity; Phenotype; RNA, Messenger; Thermogenesis | 2020 |
Evaluation of Fat Accumulation and Adipokine Production during the Long-Term Adipogenic Differentiation of Porcine Intramuscular Preadipocytes and Study of the Influence of Immunobiotics.
The degree of fat accumulation and adipokine production are two major indicators of obesity that are correlated with increased adipose tissue mass and chronic inflammatory responses. Adipocytes have been considered effector cells for the inflammatory responses due to their capacity to express Toll-like receptors (TLRs). In this study, we evaluated the degree of fat accumulation and adipokine production in porcine intramuscular preadipocyte (PIP) cells maintained for in vitro differentiation over a long period without or with stimulation of either TNF-α or TLR2-, TLR3-, or TLR4-ligands. The cytosolic fat accumulation was measured by liquid chromatography and the expression of adipokines (CCL2, IL-6, IL-8 and IL-10) were quantified by RT-qPCR and ELISA at several time points (0 to 20 days) of PIP cells differentiation. Long-term adipogenic differentiation (LTAD) induced a progressive fat accumulation in the adipocytes over time. Activation of TLR3 and TLR4 resulted in an increased rate of fat accumulation into the adipocytes over the LTAD. The production of CCL2, IL-8 and IL-6 were significantly increased in unstimulated adipocytes during the LTAD, while IL-10 expression remained stable over the studied period. An increasing trend of adiponectin and leptin production was also observed during the LTAD. On the other hand, the stimulation of adipocytes with TLRs agonists or TNF-α resulted in an increasing trend of CCL2, IL-6 and IL-8 production while IL-10 remained stable in all four treatments during the LTAD. We also examined the influences of several immunoregulatory probiotic strains (immunobiotics) on the modulation of the fat accumulation and adipokine production using supernatants of immunobiotic-treated intestinal immune cells and the LTAD of PIP cells. Immunobiotics have shown a strain-specific ability to modulate the fat accumulation and adipokine production, and differentiation of adipocytes. Here, we expanded the utility and potential application of our in vitro PIP cells model by evaluating an LTAD period (20 days) in order to elucidate further insights of chronic inflammatory pathobiology of adipocytes associated with obesity as well as to explore the prospects of immunomodulatory intervention for obesity such as immunobiotics. Topics: Adipocytes; Adipogenesis; Adiponectin; Adiposity; Animals; Cell Count; Cell Line; Cell Proliferation; Cell Size; Fatty Acids; Inflammation; Leptin; Ligands; Muscles; Swine; Toll-Like Receptors; Tumor Necrosis Factor-alpha | 2020 |
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Obesity has been recognized as a low-grade, chronic inflammatory disease that leads to an increase in obesity-associated disorders, including type 2 diabetes (T2D), fatty liver diseases and cancer. Glucagon-like peptide-1 (GLP-1) is an effective drug for T2D, and it not only has glucose-regulating effects but also has anti-inflammatory effects in obesity. In our previous study, we designed a novel GLP-1 analogue, (E Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Cytokines; Diabetes Mellitus, Type 2; Diet, High-Fat; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Inflammation; Leptin; Macrophage Activation; Macrophages; Male; Mice, Inbred C57BL; Mice, Obese; NF-kappa B; Obesity; Signal Transduction | 2020 |
Inflammatory mediators in the adipo-renal axis: leptin, adiponectin, and soluble ICAM-1.
A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney's capacity for net acid excretion (NAE). There is increasing evidence, not only for patients with type 2 diabetes but also for healthy individuals, that higher body fatness or waist circumference (WC) has a negative impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules might mediate this relation between adiposity and renal acid excretion function. Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18-25 yr old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny's (B&K's) steps to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24-h pH relationship after strictly controlling for laboratory-measured NAE. In B&K's mediation analysis, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), and adiponectin significantly associated with the outcome 24-h pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the "natural indirect effects" of WC on 24-h pH via leptin ( Topics: Adiponectin; Adipose Tissue; Adolescent; Adult; Biomarkers; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Leptin; Male; Urinalysis; Young Adult | 2020 |
Deletion of liver kinase B1 in POMC neurons predisposes to diet-induced obesity.
Liver kinase B1 (LKB1) is a serine/threonine kinase. Although many biological functions of LKB1 have been identified, the role of hypothalamic LKB1 in the regulation of central energy metabolism and susceptibility to obesity is unknown. Therefore, we constructed POMC neuron-specific LKB1 knockout mice (PomcLkb1 KO) and studied it at the physiological, morphological, and molecular biology levels.. Eight-week-old male PomcLkb1 KO mice and their littermates were fed a standard chow fat diet (CFD) or a high-fat diet (HFD) for 3 months. Body weight and food intake were monitored. Dual-energy X-ray absorptiometry was used to measure the fat mass and lean mass. Glucose and insulin tolerance tests and serum biochemical markers were evaluated in the experimental mice. In addition, the levels of peripheral lipogenesis genes and central energy metabolism were measured.. PomcLkb1 KO mice did not exhibit impairments under normal physiological conditions. After HFD intervention, the metabolic phenotype of the PomcLkb1 KO mice changed, manifesting as increased food intake and an enhanced obesity phenotype. More seriously, PomcLkb1 KO mice showed increased leptin resistance, worsened hypothalamic inflammation and reduced POMC neuronal expression.. We provide evidence that LKB1 in POMC neurons plays a significant role in regulating energy homeostasis. LKB1 in POMC neurons emerges as a target for therapeutic intervention against HFD-induced obesity and metabolic diseases. Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Diet, High-Fat; Epididymis; Feeding Behavior; Gene Deletion; Gene Expression Regulation; Glucose; Hypothalamus; Inflammation; Leptin; Liver; Male; Mice, Inbred C57BL; Mice, Knockout; Neurons; NF-kappa B; Obesity; Pro-Opiomelanocortin; Protein Serine-Threonine Kinases; Weight Gain | 2020 |
Maternal biomarker patterns for metabolism and inflammation in pregnancy are influenced by multiple micronutrient supplementation and associated with child biomarker patterns and nutritional status at 9-12 years of age.
Maternal nutritional status influences fetal development and long-term risk for adult non-communicable diseases. However, the underlying mechanisms remain poorly understood. We examined whether biomarkers for metabolism and inflammation during pregnancy were associated with maternal health and with child biomarkers and health at 9-12 years of age in 44 maternal-child dyads from the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT, ISRCTN34151616) in Lombok, Indonesia. Archived blood for each dyad from maternal enrollment, later in pregnancy, postpartum, and from children at 9-12 years comprised 132 specimens. Multiplex microbead immunoassays were used to quantify vitamin D-binding protein (D), adiponectin (A), retinol-binding protein 4 (R), C-reactive protein (C), and leptin (L). Principal component analysis (PCA) revealed distinct variance patterns, i.e. principal components (PC), for baseline pregnancy, bp.pc1.D↓A↓R↓ and bp.pc2.C↓L↑; combined follow-up during pregnancy and postpartum, dp-pp.pc1.D↑↓A↑R↑↓L↓ and dp-pp.pc2.A↑C↑L↑; and children, ch.pc1.D↑R↑C↑ and ch.pc2.D↓A↑L↑. Maternal multiple micronutrient (MMN) supplementation led to an association of baseline maternal bp.pc2.C↓L↑ with decreased post-supplementation maternal dp-pp.pc2.A↑C↑L↑ (p = 0.022), which was in turn associated with both increased child ch.pc1.D↑R↑C↑ (p = 0.036) and decreased child BMI z-score (BMIZ) (p = 0.022). Further analyses revealed an association between maternal dp-pp.pc1.D↑↓A↑R↑↓L↓ and increased child BMIZ (p = 0.036). Child ch.pc1.D↑R↑C↑ was associated with decreased birth weight (p = 0.036) and increased child BMIZ (p = 0.002). Child ch.pc2.D↓A↑L↑ was associated with increased child BMIZ (p = 0.005), decreased maternal height (p = 0.030) and girls (p = 0.002). A pattern of elevated maternal adiponectin and leptin in pregnancy was associated with increased C-reactive protein, vitamin A, and D binding proteins pattern in children, suggesting biomarkers acting in concert may have qualitative as well as quantitative influence beyond single biomarker effects. Patterns in pregnancy proximal to birth were more associated with child status. In addition, child patterns were more associated with child status, particularly child BMI. MMN supplementation affects maternal biomarker patterns of metabolism and inflammation in pregnancy, and potentially in the child. However, child nutrition conditions after birth may have a greater impact on metabolism and inflamm Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Child; Dietary Supplements; Family; Female; Folic Acid; Humans; Indonesia; Infant, Newborn; Inflammation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Micronutrients; Nutrition Therapy; Nutritional Status; Pregnancy; Retinol-Binding Proteins, Plasma; Vitamin A; Vitamin D-Binding Protein | 2020 |
Allergic Inflammation Alters microRNA Expression Profile in Adipose Tissue in the Rat.
Adipose tissue is a major source of circulating exosomal microRNAs (miRNAs) that are modulators of the immune response in various types of tissues and organs, including airways. Still, no evidence exists if allergic airway inflammation may affect fat tissue inflammation via alterations in the miRNA expression profile. Therefore, we investigated the miRNA expression profile in the adipose tissue upon induced allergic inflammation in the airways in the rat. Brown Norway rats were chronically sensitized to house dust mite extract for seven weeks. Body composition was performed using MiniSpec Plus. The eosinophil count and the total IgE level were determined to confirm the induction of allergic inflammation. MiRNA expression profiling was done using the next-generation sequencing with validation by qPCR. We found that allergic airway inflammation significantly increased fat in adipose tissue, glucose concentration, and the gene expression of adipose tissue-derived proinflammatory peptides (leptin, TNFα). In miRNA-seq analysis, we showed significant differences in the expression of 36 mature miRNAs, three precursors, and two miRNA families in adipose tissue of allergic rats. Two miRNAs-miRNA-151-5p and miRNA-423-3p-showed significantly increased expression in qPCR in adipose tissue and lungs of sensitized animals. Allergic airway inflammation affects fat tissue and alters miRNA expression profile in adipose tissue in the rat. Topics: Adipose Tissue; Animals; Gene Expression; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Hypersensitivity; Immunoglobulin E; Inflammation; Leptin; Lung; Male; MicroRNAs; Rats; Rats, Inbred BN; Transcriptome | 2020 |
Hepatic Lipidomics and Molecular Imaging in a Murine Non-Alcoholic Fatty Liver Disease Model: Insights into Molecular Mechanisms.
An imbalance between hepatic fatty acid uptake and removal results in ectopic fat accumulation, which leads to non-alcoholic fatty liver disease (NAFLD). The amount and type of accumulated triglycerides seem to play roles in NAFLD progression; however, a complete understanding of how triglycerides contribute to NAFLD evolution is lacking. Our aim was to evaluate triglyceride accumulation in NAFLD in a murine model and its associations with molecular mechanisms involved in liver damage and adipose tissue-liver cross talk by employing lipidomic and molecular imaging techniques. C57BL/6J mice fed a high-fat diet (HFD) for 12 weeks were used as a NAFLD model. Standard-diet (STD)-fed animals were used as controls. Standard liver pathology was assessed using conventional techniques. The liver lipidome was analyzed by liquid chromatography-mass spectrometry (LC-MS) and laser desorption/ionization-mass spectrometry (LDI-MS) tissue imaging. Liver triglycerides were identified by MS/MS. The transcriptome of genes involved in intracellular lipid metabolism and inflammation was assessed by RT-PCR. Plasma leptin, resistin, adiponectin, and FABP4 levels were determined using commercial kits. HFD-fed mice displayed increased liver lipid content. LC-MS analyses identified 14 triglyceride types that were upregulated in livers from HFD-fed animals. Among these 14 types, 10 were identified in liver cross sections by LDI-MS tissue imaging. The accumulation of these triglycerides was associated with the upregulation of lipogenesis and inflammatory genes and the downregulation of β-oxidation genes. Interestingly, the levels of plasma FABP4, but not of other adipokines, were positively associated with 8 of these triglycerides in HFD-fed mice but not in STD-fed mice. Our findings suggest a putative role of FABP4 in the liver-adipose tissue cross talk in NAFLD. Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Chromatography, Liquid; Diet, High-Fat; Disease Models, Animal; Fatty Acid-Binding Proteins; Fatty Acids; Inflammation; Leptin; Lipid Metabolism; Lipidomics; Liver; Male; Mice, Inbred C57BL; Molecular Imaging; Non-alcoholic Fatty Liver Disease; Resistin; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry; Triglycerides | 2020 |
HIV Protease Inhibitor Ritonavir Impairs Endothelial Function Via Reduction in Adipose Mass and Endothelial Leptin Receptor-Dependent Increases in NADPH Oxidase 1 (Nox1), C-C Chemokine Receptor Type 5 (CCR5), and Inflammation.
Topics: Adipose Tissue; Animals; Body Weight; Cardiovascular Diseases; Endothelial Cells; HIV Protease Inhibitors; Inflammation; Leptin; Mice; NADPH Oxidase 1; Oxidative Stress; Receptors, CCR5; Receptors, Leptin; Ritonavir; Signal Transduction | 2020 |
The Associations between Dairy Product Consumption and Biomarkers of Inflammation, Adipocytokines, and Oxidative Stress in Children: A Cross-Sectional Study.
The association between dairy product consumption and biomarkers of inflammation, adipocytokines, and oxidative stress is poorly studied in children. Therefore, these associations were examined in a representative subsample of 1338 schoolchildren with a mean age of 11.5 (±0.7) years in the Healthy Growth Study. Information on dairy product consumption was collected by dietary recalls. Total dairy consumption was calculated by summing the intake of milk, yogurt, and cheese. Inflammatory markers, i.e., high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and adipocytokines, i.e., leptin, adiponectin, and the antioxidant enzyme glutathione peroxidase (GPx) were analysed. Due to the skewed distribution hs-CRP, IL-6, and leptin were log transformed. Multivariable regression analyses adjusted for age, sex, energy intake, physical activity, parental education, Tanner stage, and fat mass were used to assess the associations between consumption of total dairy, milk, yogurt, cheese, and markers of inflammation, adipocytokines, oxidative stress, and adiponectin-leptin ratio. Our results showed that milk consumption was inversely associated with leptin (β: -0.101; 95% CI: -0.177, -0.025, Topics: Adipokines; Adiponectin; Adolescent; Antioxidants; Biomarkers; Child; Child Nutritional Physiological Phenomena; Cross-Sectional Studies; Dairy Products; Eating; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Oxidative Stress | 2020 |
Hypothermic Effect of Acute Citral Treatment during LPS-induced Systemic Inflammation in Obese Mice: Reduction of Serum TNF-α and Leptin Levels.
Topics: Acyclic Monoterpenes; Animals; Anti-Inflammatory Agents; Cytokines; Diet, High-Fat; Humans; Inflammation; Interleukin-6; Leptin; Lipopolysaccharides; Mice; Mice, Obese; Oils, Volatile; Tumor Necrosis Factor-alpha; Zingiber officinale | 2020 |
Stratified layer analysis reveals intrinsic leptin stimulates cryptal mesenchymal cells for controlling mucosal inflammation.
Mesenchymal cells in the crypt play indispensable roles in the maintenance of intestinal epithelial homeostasis through their contribution to the preservation of stem cells. However, the acquisition properties of the production of stem cell niche factors by the mesenchymal cells have not been well elucidated, due to technical limitations regarding the isolation and subsequent molecular and cellular analyses of cryptal mesenchymal cells. To evaluate the function of mesenchymal cells located at the large intestinal crypt, we established a novel method through which cells are harvested according to the histologic layers of mouse colon, and we compared cellular properties between microenvironmental niches, the luminal mucosa and crypts. The gene expression pattern in the cryptal mesenchymal cells showed that receptors of the hormone/cytokine leptin were highly expressed, and we found a decrease in Wnt2b expression under conditions of leptin receptor deficiency, which also induced a delay in cryptal epithelial proliferation. Our novel stratified layer isolation strategies thus revealed new microenvironmental characteristics of colonic mesenchymal cells, including the intrinsic involvement of leptin in the control of mucosal homeostasis. Topics: Animals; Cellular Microenvironment; Colon; Homeostasis; Inflammation; Intestinal Mucosa; Leptin; Male; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Receptors, Leptin; Transcriptome; Wnt Proteins | 2020 |
Effects of High and Low Protein Diets on Inflammatory Profiles in People with Morbid Obesity: A 3-Week Intervention Study.
Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Chemokine CCL2; Chemokines; Cytokines; Diet, High-Protein; Diet, Protein-Restricted; Dietary Proteins; Female; GPI-Linked Proteins; Humans; Inflammation; Interleukin-10; Interleukin-6; Lectins; Leptin; Male; Middle Aged; Obesity, Morbid; Tumor Necrosis Factor-alpha | 2020 |
Biomarkers of cardiometabolic complications in survivors of childhood acute lymphoblastic leukemia.
Survivors of childhood acute lymphoblastic leukemia (cALL) are at higher risk of developing cardiometabolic complications. We aimed at exploring the associations between biomarkers of inflammation, oxidative stress, endothelial function, endotoxemia and cardiometabolic risk factors. We conducted a cross-sectional analysis in 246 cALL survivors (mean age, 22.1 ± 6.3 years; mean time since diagnosis, 15.5 ± 5.2 years) and evaluated the associations using a series of logistic regressions. Using structural equation models, we also tested if the relationship between endotoxemia and cardiometabolic complications was mediated by the latent (unobserved) variable inflammation inferred from the observed biomarkers CRP, TNF-α and IL-6. High leptin-adiponectin ratio was associated with obesity [adjusted OR = 15.7; 95% CI (6.2-39.7)], insulin resistance [20.6 (5.2-82.1)] and the metabolic syndrome [11.2 (2.6-48.7)]. Higher levels of plasminogen activator inhibitor-1 and tumor necrosis factor-α were associated with obesity [3.37 (1.6-7.1) and 2.34 (1.3-4.2), respectively] whereas high C-reactive protein levels were associated with insulin resistance [3.3 (1.6-6.8)], dyslipidemia [2.6 (1.4-4.9)] and MetS [6.5 (2.4-17.9)]. Our analyses provided evidence for a directional relationship between lipopolysaccharide binding protein, related to metabolic endotoxemia, inflammation and cardiometabolic outcomes. Identification of biomarkers and biological mechanisms could open new avenues for prevention strategies to minimize the long-term sequelae, improve follow-up and optimize the quality of life of this high-risk population. Topics: Adiponectin; Adolescent; Adult; Biomarkers; Cancer Survivors; Cardiovascular Diseases; Cross-Sectional Studies; Dyslipidemias; Female; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Obesity; Oxidative Stress; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Quality of Life; Risk Factors; Young Adult | 2020 |
Obesity induced by high-fat diet is associated with critical changes in biological and molecular functions of mesenchymal stromal cells present in visceral adipose tissue.
The mesenchymal stromal cells (MSCs) residing within the stromal component of visceral adipose tissue appear to be greatly affected by obesity, with impairment of their functions and presence of senescence. To gain further insight into these phenomena, we analyzed the changes in total proteome content and secretome of mouse MSCs after a high-fat diet (HFD) treatment compared to a normal diet (ND). In healthy conditions, MSCs are endowed with functions mainly devoted to vesicle trafficking. These cells have an immunoregulatory role, affecting leukocyte activation and migration, acute inflammation phase response, chemokine signaling, and platelet activities. They also present a robust response to stress. We identified four signaling pathways (TGF-β, VEGFR2, HMGB1, and Leptin) that appear to govern the cells' functions. In the obese mice, MSCs showed a change in their functions. The immunoregulation shifted toward pro-inflammatory tasks with the activation of interleukin-1 pathway and of Granzyme A signaling. Moreover, the methionine degradation pathway and the processing of capped intronless pre-mRNAs may be related to the inflammation process. The signaling pathways we identified in ND MSCs were replaced by MET, WNT, and FGFR2 signal transduction, which may play a role in promoting inflammation, cancer, and aging. Topics: Aging; Animals; Diet, High-Fat; Granzymes; HMGB1 Protein; Inflammation; Interleukin-1; Intra-Abdominal Fat; Leptin; Mesenchymal Stem Cells; Methionine; Mice; Obesity; Proteome; Proto-Oncogene Proteins c-met; Receptor, Fibroblast Growth Factor, Type 2; RNA Precursors; RNA Processing, Post-Transcriptional; Secretory Vesicles; Signal Transduction; Transforming Growth Factor beta; Vascular Endothelial Growth Factor Receptor-2; Wnt Signaling Pathway | 2020 |
Micronutrients and Markers of Oxidative Stress and Inflammation Related to Cardiometabolic Health: Results from the EHES-LUX Study.
Metabolic syndrome (MetS) characteristics include chronic inflammation and elevated oxidative stress. This study assessed associations between circulating concentrations of micronutrients/phytochemicals and inflammatory/oxidative stress markers with MetS and MetS components. Adults (N = 606) from the European Health Examination Survey in Luxembourg (2013-2015) were randomly selected. We performed a multivariable logistic regression model using the least absolute shrinkage and selection operator to identify MetS-associated variables. Participants with MetS had higher concentrations of C-reactive protein (CRP), 8-iso-prostaglandin F2α, leptin, insulin, and vitamins E/A, but lower concentrations of adiponectin, beta-carotene, and oxidized low-density lipoprotein. A one-unit increase in log-CRP was associated with 51% greater odds of MetS (OR = 1.51 (95% CI: 1.16, 1.98)). Adults with a one-unit increase in log-leptin were 3.1 times more likely to have MetS (3.10 (2.10, 4.72)). Women with a one-unit increase in vitamin A were associated with 3% increased odds of MetS (1.03 (1.01, 1.05)), while those with a one-unit increase in log-adiponectin were associated with 82% decreased odds (0.18 (0.07, 0.46)). Chronic inflammation best characterized adults with MetS, as CRP, adiponectin, and leptin were selected as the main MetS determinants. Micronutrients did not seem to affect MetS, except for vitamin A in women. Topics: Adipokines; Adiponectin; Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Insulin; Leptin; Logistic Models; Luxembourg; Male; Metabolic Syndrome; Micronutrients; Middle Aged; Oxidative Stress; Prostaglandins; Surveys and Questionnaires | 2020 |
Leptin Receptor Deficiency Protects Mice against Chronic Cerebral Hypoperfusion-Induced Neuroinflammation and White Matter Lesions.
Topics: Animals; Behavior, Animal; Brain Ischemia; Carotid Artery, Common; Cerebrovascular Circulation; Cognition Disorders; Corpus Callosum; Cytokines; Hypoxia; Inflammation; Leptin; Male; Memory, Short-Term; Mice; Mice, Inbred C57BL; Microglia; Neuroglia; Perfusion; Phenotype; Receptors, Leptin; White Matter | 2020 |
Appetite changes reveal depression subgroups with distinct endocrine, metabolic, and immune states.
There exists little human neuroscience research to explain why some individuals lose their appetite when they become depressed, while others eat more. Answering this question may reveal much about the various pathophysiologies underlying depression. The present study combined neuroimaging, salivary cortisol, and blood markers of inflammation and metabolism collected prior to scanning. We compared the relationships between peripheral endocrine, metabolic, and immune signaling and brain activity to food cues between depressed participants experiencing increased (N = 23) or decreased (N = 31) appetite and weight in their current depressive episode and healthy control participants (N = 42). The two depression subgroups were unmedicated and did not differ in depression severity, anxiety, anhedonia, or body mass index. Depressed participants experiencing decreased appetite had higher cortisol levels than subjects in the other two groups, and their cortisol values correlated inversely with the ventral striatal response to food cues. In contrast, depressed participants experiencing increased appetite exhibited marked immunometabolic dysregulation, with higher insulin, insulin resistance, leptin, CRP, IL-1RA, and IL-6, and lower ghrelin than subjects in other groups, and the magnitude of their insulin resistance correlated positively with the insula response to food cues. These findings provide novel evidence linking aberrations in homeostatic signaling pathways within depression subtypes to the activity of neural systems that respond to food cues and select when, what, and how much to eat. In conjunction with prior work, the present findings strongly support the existence of pathophysiologically distinct depression subtypes for which the direction of appetite change may be an easily measured behavioral marker. Topics: Adolescent; Adult; Appetite; C-Reactive Protein; Depression; Female; Ghrelin; Humans; Hydrocortisone; Inflammation; Insulin; Insulin Resistance; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Leptin; Male; Middle Aged; Saliva; Young Adult | 2020 |
Physical Activity and HIV: Effects on Fitness Status, Metabolism, Inflammation and Immune-Activation.
Several studies evidenced that a sedentary lifestyle is related with higher levels of systemic inflammation and highlighted that physical activity can trigger anti-inflammatory effects. To evaluate the impact of self-prescribed physical activity on fitness status, metabolism, inflammation and immune-activation in people living with HIV, an interim analysis of the results of the clinical trial PRIMO (NCT03392805) was performed. Patients enrolled were divided in 2 groups on the basis of self-prescribed physical activity: a physically active group (self-prescribed physical activity) and a sedentary group. Physical fitness was evaluated by sport medicine specialists and related to nutritional status, anthropometric variables, adipokines levels (adiponectin, leptin, resistin), peripheral immune-activation (CD38, HLA-DR on CD4 and CD8), and plasma inflammatory markers (IL-6 and TNF-α). The physically active group had a better profile in anthropometric measures and aerobic fitness but did not show lower levels of immune-activation compared to sedentary group. Also serum IL-6, TNF-α, and adipokines levels showed no statistical differences. On the basis of these data, a regular self-organized physical activity seems useful to improve cardio-respiratory fitness, but unable to control HIV-related immune-activation. Topics: Adipokines; Adiponectin; Adult; Anthropometry; Biomarkers; Exercise; Female; HIV Infections; HIV-1; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Nutritional Status; Physical Fitness; Resistin; Sedentary Behavior; Tumor Necrosis Factor-alpha | 2020 |
Adipokines and the control of mast cell functions: from obesity to inflammation?
Adipokines are peptide mediators produced by fat cells in adipose tissue that exert a powerful influence on many body systems, including the immune system. Leptin and adiponectin are among the best known of these molecules and have been shown to affect the functions of, for instance, dendritic cells, neutrophils, and innate lymphoid cells. Here we present the results of a new study that describes the effects of leptin and adiponectin on mast cells, a cell type which plays an important role in controlling inflammatory responses. This provides an improved understanding of how obesity may contribute to chronic inflammation, and lead to a wide range of inflammatory pathologies. Topics: Adipokines; Adiponectin; Adipose Tissue; Humans; Immunity, Innate; Inflammation; Leptin; Lymphocytes; Mast Cells; Obesity | 2019 |
Supplementation of the Flavonoid Myricitrin Attenuates the Adverse Metabolic Effects of Long-Term Consumption of a High-Fat Diet in Mice.
The flavonoid myricitrin exhibits various pharmacological and physiological effects. However, studies on the effects of myricitrin on obesity are limited. We hypothesized that dietary myricitrin would attenuate the adiposity and metabolic dysfunction that occur in obesity. To test this hypothesis, mice were randomly fed a high-fat diet (HFD) or HFD supplemented with myricitrin for 16 weeks. Myricitrin significantly reduced white adipose tissue (WAT) mass, adipocyte size, and plasma leptin levels, and also attenuated dyslipidemia. These changes appeared to result from increased energy expenditure and activation of the carnitine acyltransferase (CPT) and Topics: Adipose Tissue, White; Adiposity; Animals; Diet, High-Fat; Dietary Supplements; Dyslipidemias; Fatty Liver; Flavonoids; Inflammation; Insulin Resistance; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Obesity | 2019 |
Differences in neurocognitive performance and metabolic and inflammatory indices in male adults with obesity as a function of regular exercise.
What is the central question of this study? Does regular exercise have benefits with regard to the neurocognitive problems related to obesity and are regular-exercise-induced neurocognitive changes associated with changes in the levels of metabolic/inflammatory biomarkers? What is the main finding and its importance? Although obese individuals with regular exercise showed higher C-reactive protein levels as compared to the healthy-weight individuals, only the obese individuals with a sedentary lifestyle showed deviant neurocognitive performance and higher metabolic and tumour necrosis factor-α levels. The P3 amplitude was correlated with the levels of leptin in the obese individuals with regular activity, implicating that the potential mechanism of neurocognitive facilitation as a result of regular exercise could be reduced serum leptin levels.. Obesity has been shown to be highly associated with deterioration in executive functions, elevated energy metabolic indices and low-grade systemic inflammation. Exercise has the capacity to reduce these negative phenomena. This work examined the effect of regular exercise on neurocognitive deficits and metabolic/inflammatory markers in obesity. Fifty-four participants were divided into three groups: healthy-weight (HW), obesity with regular exercise (ORE) and obesity with sedentary lifestyle (OSL), according to their BMI and frequency of exercise. Dual-energy X-ray absorptiometry was applied to assess the whole-body composition of the participants. The assessment included neurocognitive measures during the Posner paradigm test and fasting blood measurements. Relative to the HW group, only the OSL group showed significantly longer reaction times and smaller P3 amplitudes, even when controlling for the cardiorespiratory fitness co-variable. Although the OSL group exhibited a greater N2 amplitude than the HW group, when controlling for cardiorespiratory fitness the difference between the two groups disappeared. The OSL group showed greater levels of metabolic indices (i.e. leptin, insulin and glucose) than the HW group. The three groups had comparable interleukin (IL)-1β and IL-6 levels. However, the ORE and OSL groups showed higher levels of C-reactive protein than the HW group. The OSL group exhibited higher tumour necrosis factor-α levels than the HW and ORE groups. P3 amplitude was negatively correlated with the levels of leptin in the ORE group. Individuals with obesity can still obtain advantages with regard to neurocognitive and metabolic/inflammatory indices through engaging in regular exercise, possibly due to reduced serum leptin levels. Topics: Absorptiometry, Photon; Adult; Body Composition; Body Mass Index; Body Weight; C-Reactive Protein; Cardiorespiratory Fitness; Exercise; Humans; Inflammation; Leptin; Male; Mental Status and Dementia Tests; Obesity; Sedentary Behavior; Tumor Necrosis Factor-alpha; Young Adult | 2019 |
Differential metabolic and inflammatory responses to intermittent hypoxia in substrains of lean and obese C57BL/6 mice.
This study was to investigate the degree of susceptibility to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), between the two mice inbred lines C57BL/6N (6N) and C57BL/6J (6J).. Four-week old male mice of 6N and 6J substrains (n = 8) were randomized to standard diet (SD) group or high fat (HF) diet group. At the age of 13-week, all two groups of mice were subjected to either air or IH (IH30; thirty hypoxic events per hour) for one week.. All mice fed with HF diet exhibited obesity with more body weight and fat mass (percentage to body weight) gain. IH reduced serum LDL, HDL and total cholesterol levels in lean 6J mice. In obese mice, IH lowered obesity-induced serum total cholesterol level in 6J substrain but raised further in 6N substrain. Furthermore, IH caused elevation of serum FFA and MDA levels, and pro-inflammatory cytokines MCP-1 and IL-6 levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of lean 6J but not lean 6N mice. There was reduced number of adipocytes and elevation of macrophages in SAT and VAT of HF-induced obese mice of both substrains. IH led to increased number of adipocytes and macrophages in SAT of lean 6J mice.. The genetic difference between 6N and 6J mice may have direct impact on metabolic and inflammatory responses after IH. Therefore, attention must be given for the selection of C57BL mice substrains in the experimental IH-exposed mouse model. Topics: Adiponectin; Animals; Biomarkers; Blood Glucose; Diet, High-Fat; Disease Models, Animal; Hypoxia; Inflammation; Inflammation Mediators; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Thinness; Weight Gain | 2019 |
Altered temporal sensitivity in obesity is linked to pro-inflammatory state.
Temporal sensitivity to multisensory stimuli has been shown to be reduced in obesity. We sought to investigate the possible role of the pro-inflammatory state on such alteration, considering the effect of the expression of markers, such as leptin and IL6, which are notably high in obesity. The performance of 15 male individuals affected by obesity and 15 normal-weight males was compared using two audiovisual temporal tasks, namely simultaneity judgment and temporal order judgment. Analyses of serum levels of inflammatory markers of leptin and IL6, and of neurotrophic factors of BDNF and S100SB were quantified. At the behavioral level we confirmed previous evidence showing poorer temporal sensitivity in obesity compared to normal-weight participants. Furthermore, leptin, that is a cytokine overexpressed in obesity, represented the best predictor of behavioral differences between groups in both tasks. The hypothesis we put forward is that the immune system, rather than overall cerebral dysfunction, might contribute to explain the altered temporal sensitivity in obesity. The present finding is discussed within the context of the role of cytokines on the brain mechanisms supporting temporal sensitivity. Topics: Adult; Body Weight; Brain-Derived Neurotrophic Factor; Case-Control Studies; Humans; Hydrocortisone; Inflammation; Interleukin-6; Leptin; Male; Obesity; S100 Calcium Binding Protein beta Subunit; Task Performance and Analysis | 2019 |
Elevated expression of the leptin receptor ob‑R may contribute to inflammation in patients with ulcerative colitis.
The effect of leptin on ulcerative colitis (UC) has been controversial. The present study aimed to investigate the role of leptin and its receptor ob‑R in UC and the underlying mechanism of this role. The level of serum leptin and the protein expression of the leptin receptor ob‑R in the colonic mucosa were determined in patients with UC. Experimental colitis was induced through intrarectal administration of 2,4,6‑trinitrobenzene sulfonic acid (TNBS) in leptin receptor‑deficient Zucker rats (LR‑D). The body weight, disease activity index, colon length, and macroscopic and histopathological appearance were evaluated. Furthermore, the myeloperoxidase (MPO) enzyme activity and cytokine levels in colon tissues were also determined. The expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p‑STAT3), nuclear factor (NF)‑κB‑p65, and Ras homolog gene family member A (RhoA) proteins in colon tissues was assessed. The results revealed that the expression of the leptin receptor ob‑R was increased in the colonic mucosa but the serum leptin level was not altered in patients with UC compared with healthy volunteers. The severity of experimental colitis, represented by body weight loss, disease activity index, colon length, and macroscopic and histological changes, was ameliorated in LR‑D rats compared with the wild‑type (WT) rats. Moreover, the MPO activity; levels of cytokines including interleukin (IL)‑1β, IL‑6, and tumor necrosis factor‑α; and expression of p‑STAT3, NF‑κB, and RhoA proteins were reduced in colon tissues of LR‑D rats compared with WT rats. In conclusion, activation of the leptin receptor ob‑R is an important pathogenic mechanism of UC, and leptin receptor deficiency may provide resistance against TNBS‑induced colitis by inhibiting the NF‑κB and RhoA signaling pathways. Topics: Adult; Aged; Aged, 80 and over; Animals; Colitis, Ulcerative; Colon; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Rats; Rats, Zucker; Receptors, Leptin; Signal Transduction; Trinitrobenzenes | 2019 |
Attenuation of Inflammation and Leptin Resistance by Pyrogallol-Phloroglucinol-6,6-Bieckol on in the Brain of Obese Animal Models.
Topics: Adipose Tissue; Animals; Brain; Diet; Disease Models, Animal; Eating; Endoplasmic Reticulum Stress; Inflammation; Leptin; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Obese; NF-kappa B; Obesity; Phaeophyceae; Phloroglucinol; Pyrogallol; RAW 264.7 Cells; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Toll-Like Receptor 4; Weight Gain | 2019 |
Circulating CRP Levels Are Associated with Epicardial and Visceral Fat Depots in Women with Metabolic Syndrome Criteria.
Topics: Adipose Tissue; C-Reactive Protein; Female; Humans; Inflammation; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Pericardium; Risk Factors; Sex Characteristics | 2019 |
Effects of Medium-chain Triglycerides Administration in Chemically-induced Carcinogenesis in Mice.
The aim of this study was to investigate the effects of medium-chain triglycerides (MCTs) on chemically-induced hepatic carcinogenesis (HCC) in mice.. In a first set of experiments, mice were treated with diethylnitrosoamine intraperitoneally at two weeks of age. They were fed chow containing MCT or a normal chow diet and sacrificed after 28 weeks. Incidence of hepatic tumor was compared between the two groups. Expression of oxidative stress, and inflammatory cytokines and chemokines in liver tissues were examined. In a second set of experiments, the histopathological findings of the intraperitoneal adipose tissue were assessed, and expression of adipocytokines in the fat tissue was measured. In a third set of experiments, plasma β-hydroxybutyrate (HB) concentration was measured in both animals fed chow containing MCT and a normal chow diet. Mouse HCC cells were co-cultured with β-HB, and the numbers of tumor cells were counted at days 3 and 7.. In the first set of experiments, the tumor count observed in the control group was significantly blunted in the MCT group. Maximum tumor diameter also decreased in the MCT group compared to the control group. The expression of inflammatory cytokines and chemokines was significantly decreased by MCT. Furthermore, expression of 4-hydroxynonenal was lower in the MCT group compared to the control group. In the second set of experiments, hypertrophy of the adipocytes was suppressed, and the concentration of adiponectin and leptin in the adipose tissue decreased by MCT. In the third set of experiments, plasma β-HB concentration increased in the MCT group as expected. β-HB significantly inhibited the proliferation of HCC cells.. MCT administration markedly suppresses the incidence of chemically-induced HCC by inhibition of inflammation and increase of ketone bodies. Topics: 3-Hydroxybutyric Acid; Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Aldehydes; Animal Feed; Animals; Carcinogens; Carcinoma, Hepatocellular; Cell Count; Cell Proliferation; Chemokines; Cytokines; Diethylnitrosamine; Hypertrophy; Inflammation; Leptin; Liver; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred C3H; Oxidative Stress; Triglycerides | 2019 |
Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn's disease.
Leptin has been shown to modulate intestinal inflammation in mice. However, clinical evidence regarding its immune-stimulatory potential in human Crohn's disease remains sparse. We here describe a patient with the unique combination of acquired generalized lipodystrophy and Crohn's disease (AGLCD) featuring a lack of adipose tissue, leptin deficiency and intestinal inflammation. Using mass and flow cytometry, immunohistochemistry and functional metabolic analyses, the AGLCD patient was compared to healthy individuals and Crohn's disease patients regarding immune cell composition, function and metabolism and the effects of recombinant N-methionylleptin (rLeptin) were evaluated. We provide evidence that rLeptin exerts diverse pro-inflammatory effects on immune cell differentiation and function, including the metabolic reprogramming of immune cells and the induction of TNFα, ultimately aggravating Crohn's disease in the AGLCD patient, which can be reversed by anti-TNFα therapy. Our results indicate that leptin is required for human immune homeostasis and contributes to autoimmunity in a TNFα-dependent manner. Topics: Cell Line; Crohn Disease; Humans; Inflammation; Killer Cells, Natural; Leptin; Lipodystrophy, Congenital Generalized; Male; Phenotype; T-Lymphocytes; Tumor Necrosis Factor-alpha; Wound Healing | 2019 |
Reduced central and peripheral inflammatory responses and increased mitochondrial activity contribute to diet-induced obesity resistance in WSB/EiJ mice.
Energy imbalance due to excess of calories is considered to be a major player in the current worldwide obesity pandemic and could be accompanied by systemic and central inflammation and mitochondrial dysfunctions. This hypothesis was tested by comparing the wild-derived diet-induced obesity- (DIO-) resistant mouse strain WSB/EiJ to the obesity-prone C57BL/6J strain. We analysed circulating and hypothalamic markers of inflammatory status and hypothalamic mitochondrial activity in both strains exposed to high-fat diet (HFD). We further analysed the regulations of hypothalamic genes involved in inflammation and mitochondrial pathways by high throughput microfluidic qPCR on RNA extracted from laser micro-dissected arcuate (ARC) and paraventricular (PVN) hypothalamic nuclei. HFD induced increased body weight gain, circulating levels of leptin, cholesterol, HDL and LDL in C57BL/6J whereas WSB/EiJ mice displayed a lower inflammatory status, both peripherally (lower levels of circulating cytokines) and centrally (less activated microglia in the hypothalamus) as well as more reactive mitochondria in the hypothalamus. The gene expression data analysis allowed identifying strain-specific hypothalamic metabolic pathways involved in the respective responses to HFD. Our results point to the involvement of hypothalamic inflammatory and mitochondrial pathways as key factors in the control of energy homeostasis and the resistance to DIO. Topics: Animals; Cytokines; Diet, High-Fat; Disease Models, Animal; Energy Metabolism; Hypothalamus; Inflammation; Inflammation Mediators; Leptin; Lipid Metabolism; Male; Metabolic Networks and Pathways; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondrial Dynamics; Obesity; Paraventricular Hypothalamic Nucleus; Species Specificity; Transcriptome | 2019 |
Serum biomarkers of inflammation and adiposity in the LABS cohort: associations with metabolic disease and surgical outcomes.
The utility of serum biomarkers related to inflammation and adiposity as predictors of metabolic disease prevalence and outcomes after bariatric surgery are not well-defined.. Associations between pre- and post-operative serum levels of four biomarkers (C-reactive protein (CRP), cystatin C (CC), leptin, and ghrelin) with baseline measures of adiposity and metabolic disease prevalence (asthma, diabetes, sleep apnea), and weight loss and metabolic disease remission after bariatric surgery were studied in the Longitudinal Assessment of Bariatric Surgery (LABS) cohort.. Baseline CRP levels were positively associated with the odds of asthma but not diabetes or sleep apnea; baseline CC levels were positively associated with asthma, diabetes, and sleep apnea; baseline leptin levels were positively associated with asthma and negatively associated with diabetes and sleep apnea; baseline ghrelin levels were negatively associated with diabetes and sleep apnea. Increased weight loss was associated with increased baseline levels of leptin and CRP and decreased baseline levels of CC. Remission of diabetes and asthma was not associated with baseline levels of any biomarker. A higher likelihood of asthma remission was associated with a greater decrease in leptin levels, and a higher likelihood of diabetes remission was predicted by a lesser decrease in CC. Bariatric surgery was associated with decreased post-operative CC, CRP, and leptin levels, and increased post-operative ghrelin levels.. This is the largest study to date of serum biomarkers of inflammation and adiposity in a bariatric surgery cohort. Biomarker levels correlate with metabolic disease prevalence prior to bariatric surgery, and with weight loss but not metabolic disease remission after surgery. Bariatric surgery regulates serum biomarker levels in a manner consistent with anti-inflammatory and compensatory orexigenic effects. These data contribute to our understanding of the mechanisms underlying the biologic effects of bariatric surgery. Topics: Adiposity; Adult; Bariatric Surgery; Biomarkers; C-Reactive Protein; Female; Ghrelin; Humans; Inflammation; Leptin; Longitudinal Studies; Male; Metabolic Diseases; Middle Aged; Obesity; Treatment Outcome | 2019 |
Altered expression of inflammation-associated genes in the hypothalamus of obesity mouse models.
Metabolic inflammation is a distinct feature of obesity. Increased inflammation in the adipose tissue and the liver has been so far implicated to affect metabolic homeostasis, mainly insulin resistance. In addition to the peripherals, the inflammation in the hypothalamus which governs systemic metabolism by linking neuronal and endocrine signals has been suggested to be linked to the metabolic disease. However, the underlying molecular mechanisms are poorly understood. We hypothesized that a high-fat diet (HFD) led to central metabolic inflammation via transcriptional changes in the hypothalamus. To address the hypothesis, we characterized obesity-related hypothalamic, transcriptional alterations, and their effects on functional networks. Male C57BL/6J mice were fed with either a control diet (CD) or an HFD for 20 weeks. Microarray and gene ontology analyses of the hypothalamus demonstrated that immune-related pathways, including inflammatory and cytokine signaling, were overrepresented in the hypothalamus of HFD-fed mice compared to that of CD mice. In addition, through secondary analysis of leptin-deficient obese (ob/ob) mouse hypothalamus, we found that enriched gene sets for tumor necrosis factor-α signaling pathways and cancer pathways were common in both the obese mouse models. The results suggest that inflammatory pathway is transcriptionally enriched in the hypothalamus in obesity models and is related with hyperadiposity rather than the primary causes of obesity including the dietary fat and the genetic mutation. Topics: Adipose Tissue; Adiposity; Animals; Diet, High-Fat; Dietary Fats; Disease Models, Animal; Hypothalamus; Inflammation; Insulin Resistance; Leptin; Liver; Male; Metabolic Diseases; Mice, Inbred C57BL; Mice, Obese; Neoplasms; Obesity; Transcription, Genetic; Tumor Necrosis Factor-alpha | 2019 |
Abdominal obesity in normal weight versus overweight and obese hemodialysis patients: Associations with nutrition, inflammation, muscle strength, and quality of life.
The biological basis of abdominal obesity leading to more severe outcomes in patients with normal body mass index (BMI) on maintenance hemodialysis (MHD) is unclear. The aim of this study was to compare the properties of abdominal obesity in different BMI categories of patients on MHD.. We performed a cross-sectional study of 188 MHD patients (52.7% women; mean age, 69.4 ± 11.5 y) with abdominal obesity in different BMI groups using criteria from the World Health Organization. Appetite and dietary intake, body composition, handgrip strength, malnutrition inflammation score (MIS), inflammatory biomarkers, adipokines, and health-related quality-of-life (QoL) questionnaires were studied.. According to multivariable analyses, abdominally obese patients with normal BMIs consumed less protein per day (P = 0.04); had lower measurements of surrogates of lean (P < 0.001) and fat mass (P < 0.001); and had higher total cholesterol, tumor necrosis factor-α (P < 0.05), and ratios of adiponectin to leptin (P = 0.003) than overweight and obese patients with abdominal obesity. Multivariable analyses showed no differences in handgrip strength among the study groups.The abdominally obese study participants with normal weight had significantly lower scores in role physical (P = 0.003) and pain (P = 0.04) scales after multivariable adjustments.. Normal-weight MHD patients with abdominal obesity exhibited a more proatherogenic profile in terms of inflammatory markers and adipokine expression, lower body composition reserves, and lower physical ability than patients with abdominal obesity with overweight and obesity. This at least partially explains the abdominal obesity paradox in the MHD population in which worse clinical outcomes are seen in abdominally obese patients with normal BMIs, as opposed to overweight and obese patients who are also abdominally obese. Topics: Adiponectin; Aged; Biomarkers; Body Composition; Body Mass Index; Cholesterol; Cross-Sectional Studies; Dietary Proteins; Female; Hand Strength; Humans; Ideal Body Weight; Inflammation; Inflammation Mediators; Leptin; Male; Middle Aged; Muscle Strength; Nutritional Status; Obesity; Obesity, Abdominal; Overweight; Quality of Life; Renal Dialysis; Treatment Outcome; Tumor Necrosis Factor-alpha | 2019 |
Metabolic endotoxemia promotes adipose dysfunction and inflammation in human obesity.
Impaired adipose tissue (AT) lipid handling and inflammation is associated with obesity-related metabolic diseases. Circulating lipopolysaccharides (LPSs) from gut microbiota (metabolic endotoxemia), proposed as a triggering factor for the low-grade inflammation in obesity, might also be responsible for AT dysfunction. Nevertheless, this hypothesis has not been explored in human obesity. To analyze the relationship between metabolic endotoxemia and AT markers for lipogenesis, lipid handling, and inflammation in human obesity, 33 patients with obesity scheduled for surgery were recruited and classified according to their LPS levels. Visceral and subcutaneous AT gene and protein expression were analyzed and adipocyte and AT in vitro assays performed. Subjects with obesity with a high degree of metabolic endotoxemia had lower expression of key genes for AT function and lipogenesis ( SREBP1, FABP4, FASN, and LEP) but higher expression of inflammatory genes in visceral and subcutaneous AT than subjects with low LPS levels. In vitro experiments corroborated that LPS are responsible for adipocyte and AT inflammation and downregulation of PPARG, SCD, FABP4, and LEP expression and LEP secretion. Thus, metabolic endotoxemia influences AT physiology in human obesity by decreasing the expression of factors involved in AT lipid handling and function as well as by increasing inflammation. Topics: Adipocytes; Adipose Tissue; Adult; Endotoxemia; Fatty Acid Synthase, Type I; Fatty Acid-Binding Proteins; Female; Gastrointestinal Microbiome; Gene Expression; Humans; Inflammation; Intra-Abdominal Fat; Leptin; Lipogenesis; Lipopolysaccharides; Male; Middle Aged; Obesity; PPAR gamma; Stearoyl-CoA Desaturase; Sterol Regulatory Element Binding Protein 1; Subcutaneous Fat | 2019 |
The effect of di-2-ethylhexyl phthalate on inflammation and lipid metabolic disorder in rats.
Plasticizer di-2-ethylhexyl phthalate (DEHP) can induce lipid metabolic disorder. There was a chronic low level inflammatory response in adipose tissue of patients with lipid metabolic disorder. But the effect of inflammation on lipid metabolic disorder induced by DEHP is unclear. The present study was undertaken to explore the effect of di-2-ethylhexyl phthalate on inflammation and lipid metabolic disorder in rats.. Eighty healthy 21-day-old Wistar rats were randomly divided into 4 groups and administered DEHP by gavage at 0, 5, 50, and 500 mg/kg/ d for 8 weeks. Morphological changes of adipose tissue, the levels of IL-1β, TNF-α, LEP, and ADP in rat serum and adipose tissue, the serum TC, TG, HDL-C and LDL-C, the mRNA and protein expression levels of lipid metabolism-related gene CEBP/β and inflammation-related gene CD68 were measured.. After exposure to DEHP, the weight of rats in the high dose group was significantly higher than that in the control group (p < 0.05). And the number of adipose tissue cells in the medium-dose and high-dose DEHP groups increased, with much more macrophage infiltrated. The levels of LDL-C, HDL-C, TC in serum and LEP in adipose tissue of rats exposed to 500 mg/kg DEHP were significantly higher than those in the control group (p < 0.05); while the level of ADP in adipose tissue in rats exposed to DEHP was significantly lower (p < 0.05). The levels of IL-1β and TNF-α in surum and adipose tissue of rats exposed to DEHP were significantly higher than those in the control group (p < 0.05). The mRNA and protein expression levels of CEBP/β and CD68 in adipose tissue of rats exposed to DEHP were significantly higher than those in the control group. The TC, LEP and ADP Levels of rats were significantly different among different subgroup of IL-1β and TNF-α, and in high level subgroup, the TC, LEP and ADP Levels were increased. The levels of TC and LEP was increased in high level subgroup of CD68.. DEHP induced more macrophage infiltrated in adipose tissue of rats, promoted the secretion of IL-1β, TNF-α and the formation of inflammation, and disturbed the normal lipid metabolism and lead to lipid metabolic disorders. What is more, the levels of inflammation were associated with the lipid levels. Topics: Adipocytes; Adiponectin; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Body Weight; CCAAT-Enhancer-Binding Protein-beta; Cholesterol; Diethylhexyl Phthalate; Disease Models, Animal; Female; Inflammation; Interleukin-1beta; Leptin; Lipid Metabolism; Male; Metabolic Diseases; Rats; Rats, Wistar; Triglycerides; Tumor Necrosis Factor-alpha | 2019 |
Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting.
The Sarcolab pilot study of 2 crewmembers, investigated before and after a 6-mo International Space Station mission, has demonstrated the substantial muscle wasting and weakness, along with disruption of muscle's oxidative metabolism. The present work aimed at evaluating the pro/anti-inflammatory status in the same 2 crewmembers (A, B). Blood circulating (c-)microRNAs (miRs), c-proteasome, c-mitochondrial DNA, and cytokines were assessed by real-time quantitative PCR or ELISA tests. Time series analysis was performed ( i.e., before flight and after landing) at 1 and 15 d of recovery (R+1 and R+15, respectively). C-biomarkers were compared with an age-matched control population and with 2-dimensional proteomic analysis of the 2 crewmembers' muscle biopsies. Striking differences were observed between the 2 crewmembers at R+1, in terms of inflamma-miRs (c-miRs-21-5p, -126-3p, and -146a-5p), muscle specific (myo)-miR-206, c-proteasome, and IL-6/leptin, thus making the 2 astronauts dissimilar to each other. Final recovery levels of c-proteasome, c-inflamma-miRs, and c-myo-miR-206 were not reverted to the baseline values in crewmember A. In both crewmembers, myo-miR-206 changed significantly after recovery. Muscle biopsy of astronaut A showed an impressive 80% increase of α-1-antitrypsin, a target of miR-126-3p. These results point to a strong stress response induced by spaceflight involving muscle tissue and the proinflammatory setting, where inflamma-miRs and myo-miR-206 mediate the systemic recovery phase after landing.-Capri, M., Morsiani, C., Santoro, A., Moriggi, M., Conte, M., Martucci, M., Bellavista, E., Fabbri, C., Giampieri, E., Albracht, K., Flück, M., Ruoss, S., Brocca, L., Canepari, M., Longa, E., Di Giulio, I., Bottinelli, R., Cerretelli, P., Salvioli, S., Gelfi, C., Franceschi, C., Narici, M., Rittweger, J. Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting. Topics: Astronauts; Biomarkers; Cytokines; DNA, Mitochondrial; Humans; Inflammation; Leptin; MicroRNAs; Muscle Proteins; Muscle, Skeletal; Pilot Projects; Proteasome Endopeptidase Complex; Proteomics; Space Flight | 2019 |
Increased mast cell abundance in adipose tissue of metabolic syndrome: relevance to the proinflammatory state and increased adipose tissue fibrosis.
Metabolic Syndrome (MetS) affects 35% of American adults > 40 yr and portends an increased risk for both atherosclerotic cardiovascular disease (ASCVD) and diabetes. The role of mast cells in the proinflammatory state of MetS is not well elucidated. We propose that mast cells in subcutaneous adipose tissue (SAT) of MetS patients without diabetes or clinical ASCVD contribute to insulin resistance and inflammation. Matched controls ( n = 15) and MetS ( n = 19) subjects were recruited from Sacramento, CA, and selected based on Adult Treatment Panel III criteria. SAT biopsy was performed on all subjects and processed for immunohistochemistry. The SAT sections were stained using Astra Blue stain and tryptase stain for mast cells. Fasting blood was obtained for chemistries and biomarkers. Abundance of mast cells (Astra Blue stain) in SAT of MetS subjects compared with controls was increased 2.5-fold ( P < 0.0001). Mast cells correlated positively and significantly with waist circumference, glucose, triglycerides, homeostatic model of assessment-insulin resistance (HOMA-IR), AT insulin resistance, leptin, interleukin (IL)-1β, IL-6, chemerin, p38 MAPK activity, and nuclear factor κB activity in circulating monocytes. Mast cells also correlated significantly with markers of fibrosis and angiogenesis. Tryptase staining of mast cells in AT revealed a significant increase ( P = 0.008) with similar correlations. We make the novel observation that there are increased mast cells in SAT of MetS, and these mast cells correlate with insulin resistance (hepatic and adipose tissue), inflammation, and AT fibrosis. Hence, these immune cells appear to occupy a pivotal role in the pathogenesis of MetS. Topics: Adipose Tissue; Adult; Aged; Blood Glucose; Case-Control Studies; Chemokines; Female; Fibrosis; Humans; Inflammation; Insulin Resistance; Interleukin-1beta; Interleukin-6; Leptin; Male; Mast Cells; Metabolic Syndrome; Middle Aged; Monocytes; Neovascularization, Pathologic; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Subcutaneous Fat; Triglycerides; Waist Circumference; Young Adult | 2019 |
Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?
Colorectal cancer affects the large intestine, leading to loss of white adipose tissue (WAT) and alterations in adipokine secretion. Lower incidence of colorectal cancer is associated with increased fibre intake. Fructooligosaccharides (FOS) are fibres that increase production of butyrate by the intestinal microbiota. Tributyrin, a prodrug of butyric acid, exerts beneficial anti-inflammatory effects on colorectal cancer. Our aim was to characterise the effects of diets rich in FOS and tributyrin within the context of a colon carcinogenesis model, and characterise possible support of tumorigenesis by WAT. C57/BL6 male mice were divided into four groups: a control group (CT) fed with chow diet and three colon carcinogenesis-induced groups fed either with chow diet (CA), tributyrin-supplemented diet (BUT), or with FOS-supplemented diet. Colon carcinogenesis decreased adipose mass in subcutaneous, epididymal, and retroperitoneal tissues, while also reducing serum glucose and leptin concentrations. However, it did not alter the concentrations of adiponectin, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF)-α in WAT. Additionally, the supplements did not revert the colon cancer affected parameters. The BUT group exhibited even higher glucose tolerance and levels of IL-6, VEGF, and TNF-α in WAT. To conclude our study, FOS and butyrate supplements were not beneficial. In addition, butyrate worsened adipose tissue inflammation. Topics: Adiponectin; Adipose Tissue, White; Animals; Blood Glucose; Butyrates; Colon; Colorectal Neoplasms; Dietary Supplements; Inflammation; Interleukin-6; Leptin; Male; Mice, Inbred C57BL; Oligosaccharides; Triglycerides; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A | 2019 |
Dietary Inflammatory Index Score and Its Association with Body Weight, Blood Pressure, Lipid Profile, and Leptin in Indonesian Adults.
It was previously reported that dietary intake is an important trigger for systemic inflammation and one of the lifestyle factors for the development of cardiovascular diseases. The aim of this study was to evaluate the association between Dietary Inflammatory Index (DII) score and body weight, blood pressure, lipid profile and leptin in an Indonesian population. This was a cross-sectional study conducted in 503 Indonesian adults. The DII score was calculated based on data of 30 nutrients and food components. Anthropometric profile, blood pressure, lipid profile, and leptin were measured. The association of these variables with the DII score was analyzed. The DII score was not associated with body weight, body mass index (BMI), body fat, waist circumference, hip circumference, systolic and diastolic blood pressure, triglycerides, and high-density lipoprotein (HDL) (both unadjusted and after adjustment for covariates). However, plasma leptin concentration was significantly associated with the DII score (B = 0.096, Topics: Adult; Biomarkers; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Cross-Sectional Studies; Diet; Exercise; Female; Humans; Indonesia; Inflammation; Leptin; Life Style; Male; Middle Aged; Triglycerides; Waist Circumference | 2019 |
Obesity programmed by prenatal dexamethasone and postnatal high-fat diet leads to distinct alterations in nutrition sensory signals and circadian-clock genes in visceral adipose tissue.
Prenatal dexamethasone treatment has been shown to enhance the susceptibility of offspring to postnatal high-fat (HF) diet-induced programmed obesity. We investigated the metabolic phenotypes, nutrient-sensing signal and circadian-clock genes in adipose tissue that are programmed by prenatal dexamethasone exposure and postnatal HF diet.. Male offspring of Sprague-Dawley rats were divided into four experimental groups: normal diet, prenatal dexamethasone exposure, postnatal HF diet, and prenatal dexamethasone plus postnatal HF diet. Postnatal HF diet was prescribed from weaning to 6 months of age.. Prenatal dexamethasone and postnatal HF diet exerted synergistic effects on body weight and visceral adiposity, whereas prenatal dexamethasone and postnatal HF diet altered the metabolic profile and caused leptin dysregulation. Prenatal dexamethasone and postnatal HF diet distinctly influenced nutrient-sensing molecules and circadian-clock genes in adipose tissue. The mRNA expression of mTOR, AMPK-α2, PPAR-α, and PPAR-γ was suppressed by prenatal dexamethasone but enhanced by postnatal HF diet.. Prenatal dexamethasone and postnatal HF treatment cause dysregulation of nutrient-sensing molecules and circadian-clock genes in visceral adipose tissue. Characterizing altered nutrient-sensing molecules and circadian-clock genes has potential therapeutic relevance with respect to the pathogenesis and treatment of prenatal stress and postnatal HF diet-related metabolic disorders. Topics: Animal Nutritional Physiological Phenomena; Animals; Biomarkers; Blood Glucose; Body Weight; Circadian Clocks; Dexamethasone; Diet, High-Fat; Female; Inflammation; Intra-Abdominal Fat; Leptin; Obesity; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Sirtuin 1 | 2019 |
Epigenetic Age Acceleration in Adolescence Associates With BMI, Inflammation, and Risk Score for Middle Age Cardiovascular Disease.
"Accelerated aging," assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age.. DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA; preserved across cell types) and extrinsic (EEAA; dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors [lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers] were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development.. In 995 participants (49.6% female; age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ-inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors.. Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction. Topics: Absorptiometry, Photon; Adiponectin; Adolescent; Aging; Aging, Premature; Algorithms; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Chemokine CXCL10; Cholesterol, HDL; Cholesterol, LDL; DNA Methylation; Epigenesis, Genetic; Female; Humans; Inflammation; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-18; Leptin; Male; Middle Aged; Receptors, Tumor Necrosis Factor, Type II; Risk Assessment; Risk Factors; Western Australia; Young Adult | 2019 |
Maternal resistin predisposes offspring to hypothalamic inflammation and body weight gain.
Resistin promotes hypothalamic neuroinflammation and insulin resistance through Toll like receptor 4 (TLR4), this hormone is thought to be a link between obesity and insulin-resistance. Indeed, resistin plasma levels are higher in obese and insulin resistant subjects. However, the impact of maternal resistin on the predisposition of offspring to hypothalamic neuroinflammation is unknown. Here, female mice were treated with resistin during gestation/lactation periods, then hypothalamic neuroinflammation was investigated in male offspring at p28 and p90. At p28, resistin increased the expression of inflammation markers (IL6, TNFα and NFκB) and TLR4 in the hypothalamus and decreased both hypothalamic insulin and leptin receptors' expression. The hypothalamic up-regulation IL6, TNFα and TLR4 was sustained until p90 promoting most likely hypothalamic inflammation. Maternal resistin also increased IL6 and TNFα in the adipose tissue of offspring at p90 associated with a higher body weight gain. In contrast, liver and muscle were not affected. These findings reveal that the augmentation of maternal resistin during gestation and lactation promotes hypothalamic and adipose tissue inflammation of offspring as evidenced by sustained increase of inflammation markers from weaning to adulthood. Thus, maternal resistin programs offspring hypothalamic and adipose tissue inflammation predisposing then offspring to body weight gain. Topics: Animals; Animals, Newborn; Body Weight; Female; Glucose Intolerance; Hypothalamus; Inflammation; Inflammation Mediators; Insulin Resistance; Insulinoma; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Mice; Pregnancy; Resistin; Weaning; Weight Gain | 2019 |
Leptin Promotes Monosodium Urate Crystal-Induced Inflammation in Human and Murine Models of Gout.
Gouty arthritis is an inflammatory disease that is triggered by abnormal uric acid metabolism, which is usually attributed to obesity, a risk factor of hyperuricemia and gout attack. A high level of leptin in plasma is a marker of individuals with obesity. Population studies show that leptin promotes obesity-related arthritis, such as osteoarthritis, but it is unknown whether leptin contributes to gouty arthritis, another form of obesity-related arthritis. Our present study showed that the levels of leptin and leptin receptor in patients with active gouty arthritis were elevated. Leptin facilitates the stimulation of human synoviocytes, mouse peritoneal macrophages, and HL-60 cells induced by monosodium urate, leading to higher levels of acute gout-related proinflammatory factors. Leptin obviously exacerbates the inflammation of monosodium urate-induced acute gouty arthritis in wild-type mice, whereas that in leptin-deficient C57BL6/J Topics: Animals; Arthritis, Gouty; Disease Models, Animal; Female; HL-60 Cells; Humans; Inflammation; Leptin; Macrophages, Peritoneal; Male; Mechanistic Target of Rapamycin Complex 1; Mice; Signal Transduction; Synoviocytes; Uric Acid | 2019 |
Effects of rilpivirine, 17β-estradiol and β-naphthoflavone on the inflammatory status of release of adipocytokines in 3T3-L1 adipocytes in vitro.
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor, recently developed as a drug of choice for initial anti-retroviral (ARV) treatment of HIV-1 infection, whereas estradiol is a major component of hormonal contraceptives. Both drugs have effects on lipid metabolism, impairment of adipocyte differentiation and alteration of adipose tissue distribution and function.This study investigated the effects of different concentrations of either rilpivirine or estradiol either alone or in combination on adipocyte differentiation and adipocytokines status in vitro in the absence and presence of β-naphthoflavone, (BNF),a potent agonist of the aryl hydrocarbon receptor. 3T3-L1 human pre-adipocytes were cultured and differentiated with different concentrations of treatment drugs. After 10 days of differentiation procedure, cells were examined for their morphology and viability. Glycerol,adiponectin, leptin, resistin and interleukin-8 (IL-8) were quantified using commercially available kits. The results show that either rilpivirine or estradiol individually or during their combination can evoke significant increases in glycerol release and a concomitant significant decrease of adiponectin from adipocytes. These effects were dose-dependent. The effects of combined treatments were much larger than individual concentration for each drug. Both drugs had little of no effect on leptin levels, except for a small decrease with 10 µM rilpivirine alone or when combined with estradiol. In addition, both drugs evoked small increases in the release of resistin and interleukin-8 with significant values at higher doses compared to untreated adipocytes.When adipocytes were pretreated with BNF, either rilpivirine or, estradiol or when combined evoked a much larger release in glycerol and a much larger decrease in adiponectin compared to the absence of BNF. In contrast, BNF pretreatment had little of no effect on either leptin, resistin or IL-8 metabolism compared to the results obtained in the presence of either rilpivirine or estradiol alone or in combination.These results show that rilpivirine and estradiol either alone or when combined or pretreated with BNF can evoke marked effects on glycerol and cytokines levels from adipocytes. However, their mechanism (s) in inducing adipogenesis warrants further investigation of different transcription factors at gene expression levels. Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipokines; Animals; beta-Naphthoflavone; Cell Differentiation; Cytokines; Estradiol; Gene Expression; Humans; Inflammation; Leptin; Lipid Metabolism; Mesenchymal Stem Cells; Mice; Rilpivirine | 2019 |
An act of balance: Interaction of central and peripheral chemosensitivity with inflammatory and anti-inflammatory factors in obstructive sleep apnoea.
Central and peripheral chemosensitivity i.e. ventilatory response to CO. Ventilatory response to hypercapnic-hyperoxic and hypercapnic-hypoxic gas mixtures in patients with OSA (n = 46) and healthy individuals (n = 45) was measured. C-reactive protein (CRP), leptin, adiponectin, and endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) were measured in blood samples.. Mediation analysis revealed that association of chemoresponse to CO. Inflammatory and anti-inflammatory factors could explain differential alterations in peripheral and central ventilatory chemoresponse in patients with OSA. Topics: Adiponectin; Adult; C-Reactive Protein; Cannabinoid Receptor Agonists; Endocannabinoids; Humans; Inflammation; Leptin; Middle Aged; Obesity; Oxygen; Pulmonary Ventilation; Sleep Apnea, Obstructive | 2019 |
Obesity as an Inflammatory Agent Can Cause Cellular Changes in Human Milk due to the Actions of the Adipokines Leptin and Adiponectin.
Adiponectin and leptin play roles in the hunger response, and they can induce the inflammatory process as the initial mechanism of the innate immune response. It is possible for alterations in the levels of these adipokines to compromise the functional activity of human colostrum phagocytes. Therefore, the objective of this study is to analyze the effects of adiponectin and leptin on colostrum mononuclear (MN) cells. Colostrum was collected from 80 healthy donors, who were divided into two groups: the control group and the high body mass index (BMI) group. MN cells were used to analyze phagocytosis by flow cytometry, and reactive oxygen species (ROS), intracellular calcium, and apoptosis were assessed by fluorimetry using a microplate reader. Adipokines restored the levels of phagocytosis to the high BMI group ( Topics: Adiponectin; Adult; Apoptosis; Body Mass Index; Calcium; Colostrum; Female; Humans; Inflammation; Leptin; Milk, Human; Obesity; Phagocytosis; Pregnancy; Respiratory Burst | 2019 |
Pro-inflammatory adipokine profile in psoriatic arthritis: results from a cross-sectional study comparing PsA subset with evident cutaneous involvement and subset "sine psoriasis".
Adipokines have been considered in the pathogenesis of the inflammatory processes of psoriatic arthritis (PsA). The main aim of the current study is to investigate possible differences and correlations between adipokines and clinical expression in PsA patients with and without clinical evident psoriasis.. Serum levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin were measured in 80 consecutive PsA patients, 42 PsA patients with clinically evident psoriasis (group 1) and 38 PsA patients sine psoriasis (group 2), fulfilling the CASPAR criteria.. Patients of the two groups were not significantly different for levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin. In the entire cohort, a positive association has been shown between leptin levels and female gender (β = 0.3, p = 0.001), BMI (β = 0.8, p < 0.0001), tender joint count (β = 0.23, p = 0.05), and patient pain-VAS score (β = 0.4, p = 0.049). In group 1, serum concentration of leptin was associated with female gender (β = 0.41, p < 0.0001) and BMI (β = 0.6, p = 0.012), whereas in group 2, a positive association was shown between leptin levels and BMI (β = 0.7, p = 0.003) and CRP (β = 0.35, p = 0.012). With regard to resistin, in the multivariate model, only the association between resistin and IL-6 was found (β = 0.33, p = 0.002). The association between resistin and IL-6 was confirmed in group 1 (β = 0.46, p = 0.004) but not in group 2.. Until today, the present study represents the first investigating difference in the adipokine pattern between PsA patients with psoriasis and sine psoriasis. We report a strict interplay between leptin, female gender, BMI, and inflammatory activity in overall PsA patients. In PsA patients with clinical evident psoriasis, leptin was associated with female gender and BMI, and a close association between resistin and IL-6 was found. Further, a positive association between leptin levels and BMI and CRP was found in PsA sine psoriasis patients. Further studies are also advocated for clarifying the possible role of these adipokines as laboratory findings or as disease mediators in addressing the different phenotypes of the disease. Key Points •Levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin did not differ between PsA patients with clinical evident psoriasis and PsA sine psoriasis. •There is a strict interplay between leptin, female gender, BMI, and inflammatory activity in PsA. •There is a close association between resistin and IL-6 in PsA patients with clinical evident psoriasis. Topics: Adipokines; Adult; Arthritis, Psoriatic; Cross-Sectional Studies; Female; Ghrelin; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Psoriasis; Resistin; Sex Factors; Tumor Necrosis Factor-alpha | 2019 |
Fat-Produced Adipsin Regulates Inflammatory Arthritis.
We explored the relationship of obesity and inflammatory arthritis (IA) by selectively expressing diphtheria toxin in adipose tissue yielding "fat-free" (FF) mice completely lacking white and brown fat. FF mice exhibit systemic neutrophilia and elevated serum acute phase proteins suggesting a predisposition to severe IA. Surprisingly, FF mice are resistant to K/BxN serum-induced IA and attendant bone destruction. Despite robust systemic basal neutrophilia, neutrophil infiltration into joints of FF mice does not occur when challenged with K/BxN serum. Absence of adiponectin, leptin, or both has no effect on joint disease, but deletion of the adipokine adipsin (complement factor D) completely prevents serum-induced IA. Confirming that fat-expressed adipsin modulates the disorder, transplantation of wild-type (WT) adipose tissue into FF mice restores susceptibility to IA, whereas recipients of adipsin-deficient fat remain resistant. Thus, adipose tissue regulates development of IA through a pathway in which adipocytes modify neutrophil responses in distant tissues by producing adipsin. Topics: Adipocytes; Adipose Tissue; Animals; Arthritis; Complement Factor D; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Neutrophil Infiltration; Neutrophils | 2019 |
Increased eosinophils in adipose tissue of metabolic syndrome.
Metabolic Syndrome (MetS) is a common global disorder that predisposes to both Type 2 diabetes mellitus (T2DM) and cardiovascular disease (ASCVD). Adipose tissue (AT) contributes significantly to increased inflammation and insulin resistance (IR) in MetS which appear to be the crucial underpinnings of MetS. Compared to macrophages and lymphocytes in human subcutaneous AT (SAT), there is sparse data on the role of other immune cells, especially eosinophils (EOS). In this study, we investigated the abundance of EOS in the SAT of 19 patients with MetS without diabetes, ASCVD, smoking or any inflammatory condition, and matched controls.. SAT EOS were quantified by immunohistochemistry.. Both circulating and SAT EOS were significantly increased 2-fold in MetS and correlated with each other. Circulating EOS correlated significantly with triglycerides (TG), high-sensitivity CRP, leptin, and IL-6. SAT EOS correlated significantly with plasma glucose, TG, FFA, adipose-IR, leptin, IL-6, endotoxin, chemerin and inversely with adiponectin. They also correlated with SAT markers of fibrosis: collagen and Sirius red staining of SAT.. We make the novel and seminal observation that eosinophils are increased in SAT of MetS patients, and are associated with the pro-inflammatory state. Hence, in humans, they appear to contribute to the dysregulation of SAT biology in MetS. Topics: Adipose Tissue; Adult; Biomarkers; C-Reactive Protein; Eosinophils; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Subcutaneous Fat; Triglycerides | 2019 |
A multidimensional analysis of the longitudinal effects of roux en y gastric bypass on fatigue: An association with visceral obesity.
Severe obesity is associated with fatigue, however, the effects of weight loss after bariatric surgery on particular dimensions of fatigue are unknown. In a secondary analysis of a prospective cohort study of women undergoing roux-en-y gastric bypass (RYGB) we explored relationships among multiple dimensions of fatigue and improving adiposity, insulin resistance and inflammation.. Before, and 1 and 6 months after RYBG, dimensions of fatigue were assessed using the validated, self-report, Multidimensional Fatigue Inventory. Total, abdominal visceral (VAT) and subcutaneous (SAT) adiposity, insulin sensitivity (Si and HOMA) and plasma concentrations of leptin, C-reactive protein (CRP) and interleukin-6 (Il-6) were measured using air displacement plethysmography, computed tomography, glucose tolerance testing and enzyme-linked immunoassay. Associations were assessed using Spearman correlations and linear regression.. At baseline, the majority of our female participants (N = 19, body mass index, 46.5 kg/m. In the 6 months after RYGB, fatigue improved, especially physical fatigue. Decreases in mental fatigue were strongly associated with decreases in visceral adiposity. Nevertheless, the biologic mechanisms underlying changes in these specific fatigue dimensions remain undetermined. Topics: Adiposity; Adult; Anastomosis, Roux-en-Y; Body Mass Index; C-Reactive Protein; Fatigue; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Mental Fatigue; Middle Aged; Motivation; Obesity, Abdominal; Obesity, Morbid; Prospective Studies; Self Report; Treatment Outcome | 2019 |
Leptin signaling impairs macrophage defenses against
Topics: Adult; Animals; Female; Humans; Inflammation; Leptin; Lysosomes; Macrophages; Mechanistic Target of Rapamycin Complex 2; Mice; Mice, Inbred C57BL; Models, Biological; Phagosomes; Phosphoprotein Phosphatases; Phosphorylation; Proto-Oncogene Proteins c-akt; RAW 264.7 Cells; Receptors, Leptin; Salmonella Infections, Animal; Salmonella typhimurium; Signal Transduction; Young Adult | 2019 |
Overpressure blast injury-induced oxidative stress and neuroinflammation response in rat frontal cortex and cerebellum.
Overpressure blast-wave induced brain injury (OBI) and its long-term neurological outcome pose significant concerns for military personnel. Our aim is to investigate the mechanism of injury due to OBI.. Rats were divided into 3 groups: (1) Control, (2) OBI (exposed 30psi peak pressure, 2-2.5ms), (3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and brain (cortex and cerebellum) tissues were collected at 24h post injury.. The neurological examination score was worse in OBI and r-OBI (4.2±0.6 and 3.7±0.5, respectively) versus controls (0.7±0.2). A significant positive correlation between lung and brain edema was found. Malondialdehyde (index for lipid peroxidation), significantly increased in OBI and r-OBI groups in cortex (p<0.05) and cerebellum (p<0.01-0.001). The glutathione (endogenous antioxidant) level decreased in cortex (p<0.01) and cerebellum (p<0.05) of r-OBI group when compared with the controls. Myeloperoxidase activity indicating neutrophil infiltration, was significantly (p<0.01-0.05) elevated in r-OBI. Additionally, tissue thromboplastin activity, a coagulation marker, was elevated, indicating a tendency to bleed. NGF and NF-κB proteins along with Iba-1 and GFAP immunoreactivity significantly augmented in the frontal cortex demonstrating microglial activation. Serum biomarkers of injury, NSE, TNF-alpha and leptin, were also elevated.. OBI triggers both inflammation and oxidative injury in the brain. This data in conjunction with our previous observations suggests that OBI triggers a cascade of events beginning with impaired cerebral vascular function leading to ischemia and chronic neurological consequences. Topics: Animals; Blast Injuries; Blood-Brain Barrier; Brain Edema; Cerebellum; Disease Models, Animal; Frontal Lobe; Gliosis; Glutathione; Inflammation; Leptin; Lung; Male; Malondialdehyde; Microglia; Oxidative Stress; Peroxidase; Rats, Sprague-Dawley; Thromboplastin | 2018 |
Functional correlates of detailed body composition in healthy elderly subjects.
Methods of body composition analysis are now widely used to characterize health status, i.e., nutritional status, metabolic rates, and cardiometabolic risk factors. However, the functional correlates of individual body components have not been systematically analyzed. In this study, we have used a two-compartment model, which was assessed by air displacement plethysmography. Detailed body composition was measured by whole body magnetic resonance imaging in a healthy population of 40 Caucasians, aged 65-81 yr (20 men; body mass index range: 18.6-37.2 kg/m Topics: Aged; Aged, 80 and over; Body Composition; Energy Metabolism; Female; Geriatric Assessment; Hand Strength; Humans; Inflammation; Insulin Resistance; Leptin; Magnetic Resonance Imaging; Male; Whole Body Imaging | 2018 |
Foxc2 coordinates inflammation and browning of white adipose by leptin-STAT3-PRDM16 signal in mice.
The objective of this study is to characterize the relationship between forkhead box C2 protein (Foxc2) and leptin under adipose inflammatory response.. Lipopolysaccharide (LPS)-induced inflammatory model was conducted. Data from wild-type and ob/ob mice were used to compare the alternative role of leptin on Foxc2-mediated inflammation and browning. Transcriptional regulation and protein-protein interaction were analyzed by bioinformatics and proved by chromatin immunoprecipitation and co-immunoprecipitation experiment.. Foxc2 and leptin correlated with inflammation and browning of white adipose tissue (WAT) in LPS-treated mice. Moreover, Foxc2-mediated inhibition of inflammation involved downstream activation of leptin signal and promoted WAT browning. We then determined CREB, the potential transcriptional factor of leptin, was required for Foxc2-mediated inflammation in the regulation of WAT browning. Foxc2 alleviated adipocyte inflammation by reducing leptin-mediated Janus-activated kinase 2/signal transducer and activator of transcription 3 (STAT3) pathway. Importantly, STAT3 physically interacted with PRDM16 and formed a complex to promote WAT browning. Exogenous Foxc2 overexpression also ameliorated inflammation and promoted adipose browning in high fat diet (HFD)-induced obese mice.. Our results indicated that Foxc2 inhibited inflammation and promoted browning of WAT through positive regulation of leptin signal and the STAT3-PRDM16 complex. These findings identify a new potential means to prevent and treat obese caused metabolic syndrome of mammals. Topics: Adipose Tissue, Brown; Adipose Tissue, White; Adiposity; Animals; Disease Models, Animal; DNA-Binding Proteins; Forkhead Transcription Factors; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Signal Transduction; STAT3 Transcription Factor; Transcription Factors | 2018 |
The effects of overnight nutrient intake on hypothalamic inflammation in a free-choice diet-induced obesity rat model.
Consumption of fat and sugar induces hyperphagia and increases the prevalence of obesity and diabetes type 2. Low-grade inflammation in the hypothalamus, a key brain area involved in the regulation of energy homeostasis is shown to blunt signals of satiety after long term high fat diet. The fact that this mechanism can be activated after a few days of hyperphagia before apparent obesity is present led to our hypothesis that hypothalamic inflammation is induced with fat and sugar consumption. Here, we used a free-choice high-fat high-sugar (fcHFHS) diet-induced obesity model and tested the effects of differential overnight nutrient intake during the final experimental night on markers of hypothalamic inflammation. Male Wistar rats were fed a control diet or fcHFHS diet for one week, and assigned to three different feeding conditions during the final experimental night: 1) fcHFHS-fed, 2) fed a controlled amount of chow diet, or 3) fasted. RT-qPCR and Western blot were utilized to measure hypothalamic gene and protein expression, of cytokines and intermediates of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Lastly, we investigated the effects of acute fat intake on markers of hypothalamic inflammation in fat-naïve rats. fcHFHS-fed rats consumed more calories, increased adipose tissue, and showed elevated expression of hypothalamic inflammation markers (increased phosphorylation of NF-κB protein, Nfkbia and Il6 gene expression) compared to chow-fed rats. These effects were evident in rats consuming relative high amounts of fat. Removal of the fat and sugar, or fasting, during the final experimental night ameliorated hypothalamic inflammation. Finally, a positive correlation was observed between overnight acute fat consumption and hypothalamic NF-κB phosphorylation in fat-naïve rats. Our data indicate that one week of fcHFHS diet, and especially the fat component, promotes hypothalamic inflammation, and removal of the fat and sugar component reverses these detrimental effects. Topics: Adiposity; Animals; Cytokines; Diet, High-Fat; Dietary Fats; Dietary Sugars; Disease Models, Animal; Eating; Food Deprivation; Hyperphagia; Hypothalamus; Inflammation; Leptin; Male; NF-kappa B; Obesity; Phosphorylation; Rats; Rats, Wistar | 2018 |
Actein ameliorates hepatic steatosis and fibrosis in high fat diet-induced NAFLD by regulation of insulin and leptin resistant.
Insulin and leptin resistance are highly involved in metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Presently, no approved treatment is available. Actein is isolated from the rthizomes of Cimicifuga foetida, a triterpene glycoside, exhibiting important biological properties, such as anti-inflammatory, anti-cancer, and anti-oxidant activity. However, its effects on metabolic syndrome are poorly understood. The aims of the study were mainly to investigate the molecular mechanisms regulating insulin and leptin resistance, and lipogenic action of actein in high fat diet-fed mice. Our data indicated that actein-treated mice displayed lower body weight, epididymal and subcutaneous fat mass, as well as serum lipid levels. Also, improved insulin and leptin resistance were observed in actein-treated groups. Liver inflammation and fibrosis triggered by high fat diet were decreased for actein administration. Moreover, hepatic lipid accumulation was also reduced by actein along with reductions of hepatic de novo lipogenesis-linked signals in actein-treated rodents with high fat diet. High fat diet-induced activation of insulin receptor substrate 1/Forkhead box protein O1 (IRS1/FOXO1), Janus kinase 2 gene/signal transducer and activator of transcription (JAK2/STAT3) and Protein Kinase B/Glycogen synthase kinase 3 beta (AKT/GSK3β) pathways in liver was inhibited by actein, a potential mechanism by which hyperinsulinemia, hyperleptindemia and dyslipidemia were attenuated. Thus, the findings above might be of nutritional and therapeutic importance for the treatment of NAFLD. Topics: Animals; Cell Line; Diet, High-Fat; Dyslipidemias; Fatty Liver; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Saponins; Triterpenes | 2018 |
Reallocating sitting time to standing or stepping through isotemporal analysis: associations with markers of chronic low-grade inflammation.
Although high levels of sitting time are adversely related to health, it is unclear whether moving from sitting to standing provides a sufficient stimulus to elicit benefits upon markers of chronic low-grade inflammation in a population at high risk of type 2 diabetes (T2DM). Three hundred and seventy two participants (age = 66.8 ± 7.5years; body mass index (BMI) = 31.7 ± 5.5kg/m Topics: Actigraphy; Adult; Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Diabetes Mellitus, Type 2; Exercise; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Posture; Risk Factors; Sedentary Behavior; Sex Factors | 2018 |
The effect of weight change over a 2-year period on inflammatory status in postmenopausal women.
Body fat distribution has been shown to be a predictor of adhesion molecule and inflammatory marker expression albeit the effect of modest weight change on concentrations of adhesion molecules and inflammatory markers in postmenopausal women are not fully understood. The primary aim was to investigate the effects of weight change on adhesion molecules and inflammatory markers over 24 months in postmenopausal women.. Body composition was assessed in 254 healthy postmenopausal women using dual-energy X-ray absorptiometry (DXA). Adhesion molecules and inflammatory markers were analysed by multiplex ELISA. Participants weight gain/loss at 24 months was defined as any value that was either above/below the weight value recorded at baseline.. Postmenopausal women with an average weight loss of 3% had significantly decreased leptin concentrations by 18% at 24 months (P < 0.01). A 4% increase in body weight or a 9% increase in FMI significantly increased intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor-α (TNF-α) and leptin concentrations in postmenopausal women at 24 months (P < 0.01).. Modest weight loss in postmenopausal women has a lowering effect on leptin concentrations over 24 months which may improve inflammatory status whilst modest weight gain increases ICAM-1, leptin and TNF-α, markers which are associated with a pro-inflammatory state and vascular complications. Topics: Aged; Biomarkers; Body Weight; Cohort Studies; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Middle Aged; Postmenopause; Tumor Necrosis Factor-alpha; Weight Gain; Weight Loss | 2018 |
Ability of Nontraditional Risk Factors and Inflammatory Biomarkers for Cardiovascular Disease to Identify High Cardiometabolic Risk in Adolescents: Results From the LabMed Physical Activity Study.
Then objective of this study was to evaluate the ability of several nontraditional cardiometabolic and inflammatory biomarkers in identifying high cardiometabolic risk in adolescents.. A cross-sectional study was conducted with 529 Portuguese adolescents (267 girls) aged 14.3 ± 1.7 years. A clustered cardiometabolic risk score (body fat percentage, systolic blood pressure, ratio of total cholesterol to high-density lipoprotein cholesterol, triglycerides, homeostatic model assessment of insulin resistance, and negative values of cardiorespiratory fitness) was computed. The nontraditional cardiometabolic biomarkers assessed were complement factors (C3 and C4), C-reactive protein (CRP), fibrinogen, leptin, white blood cells (WBCs), albumin, interleukin-6, and a clustered score of inflammatory biomarkers (InflaScore) (C3, C4, CRP, fibrinogen, and leptin).. Receiver operating characteristic curves analyses showed that C3, C4, CRP, fibrinogen, leptin, and the InflaScore were able to present discriminatory ability in identifying an unfavorable cardiometabolic profile in both girls and boys (p <.01 for all). Logistic regression analyses showed that C3, C4, CRP, fibrinogen, leptin, the InflaScore (in both sexes), and WBC (boys) were associated with high cardiometabolic risk, independent of age, pubertal stage, socioeconomic status, or adherence to a Mediterranean diet (p <.05 for all).. C3, C4, CRP, fibrinogen, and leptin were associated with high cardiometabolic risk in both sexes and WBC in boys. In addition, the clustered inflammatory biomarkers seem to have a better diagnostic accuracy in identifying an unfavorable cardiometabolic profile than single biomarkers. Such biomarkers may have utility in motivating health professionals, public health workers, and adolescents' families toward lifestyle changes, improving prevention efforts early in life. Topics: Adolescent; Biomarkers; C-Reactive Protein; Cardiorespiratory Fitness; Cardiovascular Diseases; Cross-Sectional Studies; Exercise; Female; Fibrinogen; Humans; Inflammation; Leptin; Male; Portugal; Risk Factors | 2018 |
Insulin resistance in 3T3-L1 adipocytes by TNF-α is improved by punicic acid through upregulation of insulin signalling pathway and endocrine function, and downregulation of proinflammatory cytokines.
Insulin resistance (IR) has become a major threat to public health due to its role in metabolic syndrome. Inflammation associated with IR is an interesting area of biomedical research in recent years and is expected to affect insulin signalling pathway via downregulating glucose transporters. In the present study, we evaluate the potential of punicic acid (PA), a nutraceutical found in pomegranate seed oil, against TNF-α induced alteration in 3T3-L1 adipocytes on glucose metabolism, endocrine function and inflammation. IR was induced in 3T3-L1 adipocytes by treating with TNF-α (10 ng/mL) and various concentrations of PA (5, 10, 30 μM) were incubated simultaneously. After 24 h, we found that TNF-α treatment increased mRNA expression of SOCS3, PTP1B and a decrease in IRS1 causing diminished glucose uptake. Further, it showed significantly increased transcriptional activity of NFκB and leptin secretion while PA maintained leptin levels normal. Additionally, PA prevented the over-expression of phosphorylated JNK in a dose dependent manner during IR. PA also ameliorated significantly the upregulation of proinflammatory cytokines. From the results, we conclude that PA is effective to ameliorate TNF-α induced IR and also we recommend the intake of PA for control and management of IR and its associated complications. Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Animals; Biological Transport; Cytokines; Drug Synergism; Glucose; Glucose Transporter Type 4; Inflammation; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Leptin; Linolenic Acids; Mice; Phosphorylation; PPAR gamma; Protein Tyrosine Phosphatase, Non-Receptor Type 1; RNA, Messenger; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Up-Regulation | 2018 |
Peripheral Leptin Signaling Mediates Formalin-Induced Nociception.
Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high-fat diet, we found that: (1) the acute thermal pain sensory threshold did not change in obese mice; (2) the model obese mice had fewer nociceptive responses in formalin-induced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation; (3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice, indicating the dysmodulation of topical leptin-leptin receptor signaling in these mice; and (4) leptin-leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin-leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wild-type mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin-leptin receptor pathway could be a peripheral target against acute inflammatory pain. Topics: Animals; Diet, High-Fat; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Nociception; Nociceptive Pain; Obesity; Pain Measurement; Pain Threshold; Receptors, Leptin; Signal Transduction | 2018 |
Systemic inflammation mediates the detrimental effects of obesity on asthma control.
Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood.. To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control.. The subjects with stable asthma (n = 108) underwent assessment of clinical characteristics, which included using The Asthma Control Questionnaire (ACQ)-6. Obesity was defined as a body mass index (BMI) of ≥30 kg/m2, overweight was defined as BMI between 25 to 29.9 kg/m2, and lean weight was defined as BMI < 25 kg/m2. Body composition, including fat mass (FM), visceral fat area (VFA), and percentage body fat (PBF) was analyzed by bioimpedance. Serum interleukin (IL) 4, IL-5, IL-8, IL-13, IL-17, chemokine (C-C motif) ligand (CCL) 17, CCL22, leptin, adiponectin, C-reactive protein (CRP), and interferon (IFN) gamma were measured by using ELISA. Linear regression models were fitted according to the Baron and Kenny procedures for mediation analysis.. FM (12.73 ± 3.95 versus 18.59 ± 2.95 versus 27.82 ± 5.17 kg; p < 0.0001), VFA (65.99 ± 23.17 versus 93.96 ± 10.28 versus 123.10 ± 18.34 cm2; p < 0.0001), PBF (23.86 ± 7.46 versus 30.74 ± 5.08 versus 36.21 ± 6.28 %; p = 0.0003) and ACQ-6 values (0.83 [0, 1.17]) versus 1.15 [0.50, 1.75] versus 1.33 [0.83, 1.83] score; p = 0.002) were different among lean (n = 52), overweight (n = 37), and obese (n = 19) subjects. Serum levels of leptin, IL-5, IL-13, IL-17, CCL17, CRP, and IFN-gamma in the obese group were significantly elevated compared with the subjects who were lean or overweight (all p < 0.05). The mediation analyses found that the effect of obesity, assessed by BMI, on ACQ-6 was significantly mediated through IL-13 and CCL17. Furthermore, IL-13 and CCL17 mediated the effects of body composition (FM, VFA and PBF) on ACQ-6. The effects of obesity assessed by body composition, but not by using BMI, on ACQ-6 were mediated by leptin.. Our mediation analysis confirmed that systemic inflammation biomarkers, such as leptin, CCL17, IL-4, and IL-13, mediated the effects of obesity on asthma control. This warrants prospective exploration in this distinct asthma phenotype in the future. Topics: Asthma; Biomarkers; Body Composition; Body Mass Index; Chemokine CCL17; Humans; Inflammation; Interleukin-13; Interleukin-4; Leptin; Obesity | 2018 |
Frontline Science: High fat diet and leptin promote tumor progression by inducing myeloid-derived suppressor cells.
Obesity is a risk factor for cancer incidence and cancer mortality. The association of obesity and cancer is attributed to multiple factors, but the tightest linkage is with the chronic, low-grade inflammation that accompanies obesity. Myeloid-derived suppressor cells (MDSC) are known facilitators of cancer progression that act by suppressing the activation and function of tumor-reactive T cells. Because MDSC quantity and function are driven by chronic inflammation, we hypothesized that MDSC may accumulate in obese individuals and facilitate tumor growth by suppressing antitumor immunity. To test this hypothesis, tumor-bearing mice on a high fat or low fat diet (HFD or LFD) were assessed for tumor progression and the metabolic dysfunction associated with obesity. HFD enhanced the accumulation of MDSC, and the resulting MDSC had both beneficial and detrimental effects. HFD-induced MDSC protected mice against diet-induced metabolic dysfunction and reduced HFD-associated inflammation, but also increased the accumulation of fat, enhanced tumor progression, and spontaneous metastasis and reduced survival time. HFD-induced MDSC facilitated tumor growth by limiting the activation of tumor-reactive CD8 Topics: Animals; Breast Neoplasms; Diet, High-Fat; Female; Inflammation; Leptin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Myeloid-Derived Suppressor Cells; Obesity; Tumor Cells, Cultured; Xenograft Model Antitumor Assays | 2018 |
Intestinal parasites: Associations with intestinal and systemic inflammation.
The aim of the present study was to evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. Plasma concentrations of C-Reactive Protein (CRP), leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and count of stool leukocytes as marker of intestinal inflammation in 291 children (6-10 years). Intestinal parasitic infection was measured by stool examination. Logistic regression analyses were performed to determine the odds of having high inflammatory markers for each parasite or group of parasites as compared to parasite-free children while adjusting for sex, age, mother's educational level and percentage of body fat. The prevalence of soil-transmitted helminths and intestinal protozoa infections was 12% and 36%, respectively. Parasitic infection was not associated with CRP, IL-6, IL-10 or TNF-α. Children infected with Ascaris lumbricoides (aOR: 5.91, 95% CI: 1.97-17.70) and Entamoeba coli (aOR: 8.46, 95% CI: 2.85-25.14) were more likely to have higher stool leucocytes than parasite-free children. Children with multiple infections (aOR: 10.60, 95% CI: 2.85-25.14) were more likely to have higher leptin concentrations than parasite-free children. Intestinal parasitic infection was not associated with systemic inflammation, but was associated with intestinal inflammation. Having multiple infections were associated with higher leptin concentrations. Topics: Animals; Ascaris lumbricoides; C-Reactive Protein; Child; Cross-Sectional Studies; Entamoeba histolytica; Feces; Female; Helminthiasis; Humans; Inflammation; Interleukin-10; Interleukin-6; Intestinal Diseases, Parasitic; Intestines; Leptin; Male; Obesity; Prevalence; Surveys and Questionnaires; Tumor Necrosis Factor-alpha | 2018 |
Maternal obesity increases insulin resistance, low-grade inflammation and osteochondrosis lesions in foals and yearlings until 18 months of age.
Obesity is a growing concern in horses. The effects of maternal obesity on maternal metabolism and low-grade inflammation during pregnancy, as well as offspring growth, metabolism, low-grade inflammation, testicular maturation and osteochondrotic lesions until 18 months of age were investigated.. Twenty-four mares were used and separated into two groups at insemination according to body condition score (BCS): Normal (N, n = 10, BCS ≤4) and Obese (O, n = 14, BCS ≥4.25). BCS and plasma glucose, insulin, triglyceride, urea, non-esterified fatty acid, serum amyloid A (SAA), leptin and adiponectin concentrations were monitored throughout gestation. At 300 days of gestation, a Frequently Sampled Intravenous Glucose Tolerance Test (FSIGT) was performed. After parturition, foals' weight and size were monitored until 18 months of age with plasma SAA, leptin, adiponectin, triiodothyronine (T3), thyroxine (T4) and cortisol concentrations measured at regular intervals. At 6, 12 and 18 months of age, FSIGT and osteoarticular examinations were performed. Males were gelded at one year and expression of genes involved in testicular maturation analysed by RT-qPCR.. Throughout the experiment, maternal BCS was higher in O versus N mares. During gestation, plasma urea and adiponectin were decreased and SAA and leptin increased in O versus N mares. O mares were also more insulin resistant than N mares with a higher glucose effectiveness. Postnatally, there was no difference in offspring growth between groups. Nevertheless, plasma SAA concentrations were increased in O versus N foals until 6 months, with O foals being consistently more insulin resistant with a higher glucose effectiveness. At 12 months of age, O foals were significantly more affected by osteochondrosis than N foals. All other parameters were not different between groups.. In conclusion, maternal obesity altered metabolism and increased low-grade inflammation in both dams and foals. The risk of developing osteochondrosis at 12 months of age was also higher in foals born to obese dams. Topics: Adiponectin; Animals; Animals, Newborn; Blood Glucose; Female; Glucose Tolerance Test; Horse Diseases; Horses; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Maternal-Fetal Exchange; Obesity; Osteochondrosis; Pregnancy; Pregnancy Complications | 2018 |
Soda Intake Is Directly Associated with Serum C-Reactive Protein Concentration in Mexican Women.
Soda intake is associated with an increased risk of cardiovascular disease. Consumption of diet sodas, often considered healthy alternatives to sodas, could also increase the likelihood of cardiovascular outcomes.. This study aims to evaluate the relation between soda and diet soda and biomarkers of cardiovascular risk.. We conducted a cross-sectional analysis among 825 Mexican women free of diabetes, cardiovascular disease, and cancer, and for whom serum concentrations of C-reactive protein (CRP), C-peptide, adiponectin, and leptin were available. Mean ± SD age was 45.9 ± 6.6 y, the majority of women were premenopausal (60.4%), and the prevalence of obesity was 35%. We estimated the adjusted percentage differences in biomarkers and 95% CIs by performing multiple linear regression models comparing categories of consumption for soda and diet soda adjusting for age, family history of heart disease, menopause, menopausal hormone therapy, socioeconomic status, region, smoking, physical activity, alcohol intake, and dietary patterns.. In the entire study sample we observed a 50% higher serum CRP concentration in women in the highest soda intake quartile (median intake: 202.9 mL/d, IQR: 101.4, 304.3 mL/d) compared to those in the lowest (median intake: 11.8 mL/d, IQR: 0.0, 152.1 mL/d). After stratification by menopausal status, results remained significant only for premenopausal women. Premenopausal women in the highest quartile of soda intake had 56% higher CRP concentration relative to women in the lowest quartile. We observed no significant association with the other biomarkers. After further adjustment for body mass index, a potential mediator, results remained significant only for CRP. Diet soda consumption was not associated with any of the biomarkers.. Consumption of soda was associated with adverse levels in a biomarker of inflammation and cardiovascular risk, serum CRP, in Mexican women. These results add to the accumulating evidence on soda and cardiovascular risk. More research is necessary to understand the potential impact of artificially sweetened sodas. Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Peptide; C-Reactive Protein; Carbonated Beverages; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Exercise; Female; Humans; Inflammation; Leptin; Mexico; Middle Aged; Nutritive Sweeteners; Obesity; Risk Factors; Socioeconomic Factors | 2018 |
Increased Serum Leptin Levels in New-Onset, Untreated Female Patients with Coronary Artery Disease and Positively Associated with Inflammatory Markers.
Previous studies have suggested that leptin was associated with atherosclerosis and involved in inflammation. Gender differences between leptin and inflammatory markers have been evaluated less in untreated patients with stable coronary artery disease (CAD).. In this study, a total of 394 consecutive Chinese patients who received coronary artery angiography were enrolled, including 243 patients with CAD and 151 non-CAD controls. The baseline clinical characteristics were collected and serum leptin levels were determined using ELISA.. The relation of serum leptin levels to inflammatory markers was found only in female patients. Leptin and white blood cell count (WBCC) as well as its subsets were significantly higher in female patients than female controls. In female patients, leptin was positively associated with C-reactive protein (CRP; r = 0.28, p = 0.016), WBCC (r = 0.261, p = 0.02), neutrophil, r = 0.268, p = 0.018, and monocyte, r = 0.228, p = 0.044. Multivariable regression analysis revealed that leptin was significantly and independently associated with CRP (β = 0.317, p = 0.004), WBCC (β = 0.278, p = 0.020), neutrophil (β = 0.262, p = 0.032), and monocyte (β = 0.245, p = 0.032).. The serum leptin levels were higher in female patients and independently associated with CRP, WBCC, and its subsets, suggesting a potential interaction between leptin and inflammation in female CAD patients. Topics: Adult; Aged; Asian People; Biomarkers; C-Reactive Protein; Case-Control Studies; China; Coronary Angiography; Coronary Artery Disease; Female; Humans; Inflammation; Leptin; Leukocyte Count; Male; Middle Aged | 2018 |
Inflammation and coronary artery calcification in South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study.
Inflammatory biomarkers and adipocytokines (IBA) may contribute to atherosclerosis by promoting vascular inflammation. The association between IBA and coronary artery calcium (CAC), a marker of subclinical atherosclerosis, is not well defined in South Asians (SA). We hypothesized that IBA (high sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TNF-α], adiponectin, and leptin) were independently associated with and improved discrimination of CAC among SA.. We analyzed IBA and CAC among participants in the prospective Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. We used logistic regression models to examine cross-sectional associations of IBA with CAC presence (CAC >0) and severity (CAC >100), and C-statistics to assess the incremental contribution of each IBA to traditional risk factors (TRF) from the AHA/ACC Pooled Cohort Equations (PCE) for discrimination of CAC.. Among 906 participants in the MASALA study, women (n = 420) had significantly higher levels of hsCRP, adiponectin, and leptin but lower levels of TNF-α than men (p < .01 for all). There was no significant association between any of the four IBA and either CAC category in multivariable-adjusted models, respectively. Lastly, none of the four IBA improved discrimination of CAC presence or severity when added to elements of the PCE.. IBA were not associated with CAC presence or severity in the MASALA population. IBA did not help identify SA at risk of subclinical atherosclerosis, although associations with ASCVD events remain unclear. In SA, CAC may have a distinct pathophysiology independent of inflammation as measured by IBA. Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Asian People; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Middle Aged; Prevalence; Prospective Studies; Risk Factors; Severity of Illness Index; Tumor Necrosis Factor-alpha; United States; Vascular Calcification | 2018 |
Obesity and High-Fat Diet Induce Distinct Changes in Placental Gene Expression and Pregnancy Outcome.
Obese women are at high risk of pregnancy complications, including preeclampsia, miscarriage, preterm birth, stillbirth, and neonatal death. In the current study, we aimed to determine the effects of obesity on pregnancy outcome and placental gene expression in preclinical mouse models of genetic and nutritional obesity. The leptin receptor (LepR) null-reactivatable (LepRloxTB), LepR-deficient (Leprdb/+), and high-fat diet (HFD)-fed mice were assessed for fertility, pregnancy outcome, placental morphology, and placental transcriptome using standard quantitative polymerase chain reaction (qPCR) and qPCR arrays. The restoration of fertility of LepRloxTB was performed by stereotaxic delivery of adeno-associated virus-Cre into the hypothalamic ventral premammillary nucleus. Fertile LepRloxTB females were morbidly obese, whereas the wild-type mice-fed HFD showed only a mild increase in body weight. Approximately 80% of the LepRloxTB females had embryo resorptions (∼40% of the embryos). In HFD mice, the number of resorptions was not different from controls fed a regular diet. Placentas of resorbed embryos from obese mice displayed necrosis and inflammatory infiltrate in the labyrinth and changes in the expression of genes associated with angiogenesis and inflammation (e.g., Vegfa, Hif1a, Nfkbia, Tlr3, Tlr4). In contrast, placentas from embryos of females on HFD showed changes in a different set of genes, mostly associated with cellular growth and response to stress (e.g., Plg, Ang, Igf1, Igfbp1, Fgf2, Tgfb2, Serpinf1). Sexual dimorphism in gene expression was only apparent in placentas from obese LepRloxTB mice. Our findings indicate that an obese environment and HFD have distinct effects on pregnancy outcome and the placental transcriptome. Topics: Animals; Diet, High-Fat; Female; Gene Expression Regulation; Hypothalamus; Inflammation; Leptin; Mice; Mice, Transgenic; Neovascularization, Pathologic; Obesity; Placenta; Pregnancy; Pregnancy Outcome; Receptors, Leptin | 2018 |
Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C.
Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice.. The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg. Leptin deficiency increased inflammation and fibrosis in AT. As expected, leptin treatment improved the obesity phenotype. iNOS deficiency in ob/ob mice improved insulin sensitivity, AT inflammation, and ECM remodeling, as evidenced by lower AT macrophage infiltration and collagen deposition, a downregulation of proinflammatory and profibrogenic genes Tnf, Emr1, Hif1a, Col6a1, Col6a3, and Tnc, as well as lower circulating TNC levels. Interestingly, leptin upregulated TNC expression and release in 3T3-L1 adipocytes, and iNOS knockdown in 3T3-L1 fat cells produced a significant decrease in basal and leptin-induced Tnc expression.. Ablation of iNOS in leptin-deficient mice improved AT inflammation and ECM remodeling-related genes, attenuating fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in adipocytes, suggesting an important role of this alarmin in the development of AT inflammation and fibrosis. Topics: 3T3-L1 Cells; Adipose Tissue; Animals; Fibrosis; Gene Silencing; Inflammation; Leptin; Mice; Mice, Knockout; Mice, Obese; Nitric Oxide Synthase Type II; Obesity; Tenascin | 2018 |
Hypothalamic ER-associated degradation regulates POMC maturation, feeding, and age-associated obesity.
Pro-opiomelanocortin (POMC) neurons function as key regulators of metabolism and physiology by releasing prohormone-derived neuropeptides with distinct biological activities. However, our understanding of early events in prohormone maturation in the ER remains incomplete. Highlighting the significance of this gap in knowledge, a single POMC cysteine-to-phenylalanine mutation at position 28 (POMC-C28F) is defective for ER processing and causes early onset obesity in a dominant-negative manner in humans through an unclear mechanism. Here, we report a pathologically important role of Sel1L-Hrd1, the protein complex of ER-associated degradation (ERAD), within POMC neurons. Mice with POMC neuron-specific Sel1L deficiency developed age-associated obesity due, at least in part, to the ER retention of POMC that led to hyperphagia. The Sel1L-Hrd1 complex targets a fraction of nascent POMC molecules for ubiquitination and proteasomal degradation, preventing accumulation of misfolded and aggregated POMC, thereby ensuring that another fraction of POMC can undergo normal posttranslational processing and trafficking for secretion. Moreover, we found that the disease-associated POMC-C28F mutant evades ERAD and becomes aggregated due to the presence of a highly reactive unpaired cysteine thiol at position 50. Thus, this study not only identifies ERAD as an important mechanism regulating POMC maturation within the ER, but also provides insights into the pathogenesis of monogenic obesity associated with defective prohormone folding. Topics: Animals; Axons; Cysteine; Endoplasmic Reticulum; Endoplasmic Reticulum-Associated Degradation; Feeding Behavior; Female; Green Fluorescent Proteins; Humans; Hypothalamus; Inflammation; Intracellular Signaling Peptides and Proteins; Leptin; Male; Mice; Mice, Inbred C57BL; Mutation; Neurons; Obesity; Phenylalanine; Pro-Opiomelanocortin; Proteins; Sulfhydryl Compounds; Ubiquitin; Ubiquitin-Protein Ligases; Ubiquitination | 2018 |
Inflammatory biomarkers responses after acute whole body vibration in fibromyalgia.
The aims of this study were 1) to characterize the intensity of the vibration stimulation in women diagnosed with fibromyalgia (FM) compared to a control group of healthy women (HW) matched by age and anthropometric parameters, and 2) to investigate the effect of a single session of whole body vibration (WBV) on inflammatory responses. Levels of adipokines, soluble tumor necrosis factor receptors (sTNFr1, sTNFr2), and brain-derived neurotrophic factor (BDNF) were determined by enzyme-linked immunosorbent assay. Oxygen consumption (VO2) was estimated by a portable gas analysis system, heart rate (HR) was measured using a HR monitor, and perceived exertion (RPE) was evaluated using the Borg scale of perceived exertion. Acutely mild WBV increased VO2 and HR similarly in both groups. There was an interaction (disease vs vibration) in RPE (P=0.0078), showing a higher RPE in FM compared to HW at rest, which further increased in FM after acute WBV, whereas it remained unchanged in HW. In addition, there was an interaction (disease vs vibration) in plasma levels of adiponectin (P=0.0001), sTNFR1 (P=0.000001), sTNFR2 (P=0.0052), leptin (P=0.0007), resistin (P=0.0166), and BDNF (P=0.0179). In conclusion, a single acute session of mild and short WBV can improve the inflammatory status in patients with FM, reaching values close to those of matched HW at their basal status. The neuroendocrine mechanism seems to be an exercise-induced modulation towards greater adaptation to stress response in these patients. Topics: Adipokines; Biomarkers; Brain-Derived Neurotrophic Factor; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Exercise; Female; Fibromyalgia; Heart Rate; Humans; Inflammation; Inflammation Mediators; Interleukin-8; Leptin; Middle Aged; Oxygen Consumption; Receptors, Tumor Necrosis Factor; Resistin; Vibration | 2018 |
In Vitro Cocktail Effects of PCB-DL (PCB118) and Bulky PCB (PCB153) with BaP on Adipogenesis and on Expression of Genes Involved in the Establishment of a Pro-Inflammatory State.
(1) Objective: Highlight the in vitro effects of 3T3-L1 cell exposure to polychlorinated biphenyls (PCB118 and 153) or benzo(a)pyrene (BaP) alone or as a cocktail on adipogenesis (ADG) by focusing on changes in lipid metabolism and inflammatory-related genes expression (INFG) and ADG-related genes expression (ADGG); (2) Results: Treatment from the early stage of cell differentiation by BaP alone or in combination with PCBs decreased the expression of some of the ADGG ( Topics: 3T3 Cells; Adipogenesis; Animals; Benzo(a)pyrene; Cytokines; Down-Regulation; Drug Antagonism; Drug Synergism; Environmental Pollutants; Glucose Transporter Type 4; Inflammation; Leptin; Mice; Polychlorinated Biphenyls; PPAR gamma; Response Elements | 2018 |
E74-Like Factor (ELF3) and Leptin, a Novel Loop Between Obesity and Inflammation Perpetuating a Pro-Catabolic State in Cartilage.
The E74-like factor 3 (ELF3) is an inflammatory mediator that participates in cartilage destruction in osteoarthritis. Leptin and other adipokines negatively impact articular cartilage, triggering catabolic and inflammatory responses in chondrocytes. Here, we investigated whether leptin induces ELF3 expression in chondrocytes and the signaling pathway involved in this process.. We determined mRNA and protein levels of ELF3 by RT-qPCR and Western blotting using cultured human primary chondrocytes and the human T/C-28a2 chondrocyte cell line. Further, we measured luciferase activities of different reporter constructs, and we assessed the contribution of leptin to the induction of ELF3 mRNA by knocking down hLEPR gene expression using siRNA technology.. Leptin synergizes with IL-1β in inducing ELF3 expression in chondrocytes. We also found that PI3K, p38, and JAK2 signaling pathways are at play in the leptin-driven induction of ELF3. Moreover, we confirm the participation of NFΚB in the leptin/IL-1β synergistic induction of ELF3.. Here we show, for the first time, the regulation of ELF3 expression by leptin, suggesting that this transcription factor likely mediates the inflammatory responses triggered by leptin in articular chondrocytes. Topics: Cartilage; Cell Line; Cells, Cultured; Chondrocytes; DNA-Binding Proteins; Gene Expression Regulation; Humans; Inflammation; Interleukin-1beta; Leptin; Obesity; Promoter Regions, Genetic; Proto-Oncogene Proteins c-ets; Receptors, Leptin; RNA Interference; RNA, Messenger; RNA, Small Interfering; Transcription Factors; Transcriptional Activation | 2018 |
Astragaloside IV Prevents Obesity-Associated Hypertension by Improving Pro-Inflammatory Reaction and Leptin Resistance.
Topics: Animals; Hypertension; Inflammation; Leptin; Male; Obesity; Rats; Rats, Wistar; Saponins; Triterpenes | 2018 |
Role of dysfunctional adipocytes in cholesterol-induced nonobese metabolic syndrome.
Many studies have reported the causes of obese metabolic syndrome (MS); however, the causes of nonobese MS (NMS) remain unknown. In this study, we demonstrated that inflamed dysfunctional adipose tissue plays a crucial role in cholesterol-induced NMS. Control (C), high cholesterol (HC) and HC with 10% fructose in drinking water (HCF) diets were fed to Sprague-Dawley rats for 12 weeks. After 12 weeks, the body weights of the C- and HC-fed rats were comparable, but the weights of the HCF-fed rats were relatively low. Cholesterol caused metabolic problems such as high blood pressure, hypercholesterolemia and hypoinsulinemia. The HCF-fed rats exhibited whole-body insulin resistance with low circulating high-density lipoprotein levels. Increases in the tumor necrosis factor α level in the plasma, the number of CD68+ macrophages and the free nuclear factor-κB level in gonadal white adipose tissue (gWAT) resulted in local inflammation, which appeared as inflamed dysfunctional gWAT. Reduced superoxide dismutases (SODs) deteriorate natural antioxidant defense systems and induce reactive oxygen species in gWAT. Dysregulation of plasma levels of catecholamine, adipokines (leptin and adiponectin), hormone-sensitive lipase and perilipin in cholesterol-induced inflamed adipose tissue contributed to increased lipolysis and increased circulating nonesterified fatty acids. Cholesterol activated inflammation, lipolysis and cell death in 3T3-L1 adipocytes. Moreover, Chol-3T3-CM reduced the population of M2-type Raw264.7 macrophages, indicating that the macrophage polarization is mediated by cholesterol. Together, our findings indicate that inflamed dysfunctional adipocytes are critical in NMS, supporting the development of anti-inflammatory agents as potential therapeutic drugs for treating NMS. Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Adipose Tissue, White; Animals; Cell Death; Cholesterol; Energy Metabolism; Epinephrine; Fatty Acids; Feeding Behavior; Fructose; Inflammation; Insulin; Insulin Resistance; Leptin; Lipolysis; Macrophages; Male; Metabolic Syndrome; Mice; Norepinephrine; Obesity; Phosphorylation; Rats, Sprague-Dawley; RAW 264.7 Cells | 2018 |
Salivary biomarkers of inflammation in systemic lupus erythematosus.
Saliva is currently used as a reliable diagnostic fluid in a wide range of local and systemic diseases. However, the link between salivary diagnosis and the inflammatory process in autoimmune diseases has not yet been explored. The aim of our study is to assess possible correlations between salivary inflammatory markers and systemic lupus erythematosus (SLE). Patients fulfilling the Systemic Lupus International Collaborating Clinics (SLICC) diagnosis criteria were included. Salivary and serum levels of interleukin-6 (IL-6), leptin, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) were determined using stochastic sensors. Serum leptin and IL-6 had significantly higher levels in SLE patients compared to non-SLE. Also, salivary IL-6 levels highly correlated with the serum IL-6 levels. A positive correlation was found between salivary and serum levels of IL-6, signaling salivary IL-6 as a reliable marker for assessing the inflammation process in SLE. Topics: Adult; Biomarkers; Case-Control Studies; Chemokine CCL2; Female; Humans; Inflammation; Interleukin-6; Leptin; Lupus Erythematosus, Systemic; Middle Aged; Plasminogen Activator Inhibitor 1; Pregnancy; Pregnancy Complications; Saliva; Serum | 2018 |
Early warning biomarkers in major depressive disorder: a strategic approach to a testing question.
Identification of biomarkers in major depressive disorder (MDD) has proceeded in an extemporised manner. No single biomarker has been identified with utility in screening, diagnosis, prognosis, or monitoring, and screening tests have different characteristics than the other functions. Using chaos, bifurcation, and perturbation (CBP) theories, the aim is to identify biomarkers to aid clinicians in screening for MDD.. MDD is a complex disorder; consequently, a reductionist approach to characterize the complex system changes found in MDD will be inchoate and unreliable. A holistic approach is used to identify biomarkers reflecting the tipping points seen before the catastrophic bifurcation that results in MDD.. Applying CBP theories revealed skew, resistance to change, flickering, increased variance and autocorrelation as patterns of biomarkers. Integrals and differentials of extracellular and intracellular biomarkers were identified, specifically focussed on hypothalamo-pituitary axis (HPA) dysfunction, metabolic dysfunction, inflammation and mitochondrial oxidative stress, and tryptophan metabolism.. Applying CBP theories to the dysfunctional complex biological systems in MDD led to development of integrals and differentials of biomarkers that can be used in screening for MDD and planning future biomarker research, targeting intracellular and extracellular inflammation, HPA axis dysfunction, and tryptophan metabolism. Topics: Biomarkers; Blood Glucose; C-Reactive Protein; Depressive Disorder, Major; Early Diagnosis; Ghrelin; Glycated Hemoglobin; Humans; Hypothalamo-Hypophyseal System; Inflammation; Interleukin-6; Leptin; Oxidative Stress; Tumor Necrosis Factor-alpha | 2018 |
Bone and Inflammatory Responses to Training in Female Rowers over an Olympic Year.
To examine whether fluctuations in training load during an Olympic year lead to changes in bone mineral densities and factors that regulate bone (sclerostin, osteoprotegerin and receptor activator of nuclear factor kappa-B ligand), energy metabolism (insulin-like growth factor-1 and leptin), and inflammation (tumor necrosis factor-α and interleukin 6) in elite heavyweight female rowers.. Blood samples were drawn from 15 female heavyweight rowers (27.0 ± 0.8 yr, 80.9 ± 1.3 kg, 179.4 ± 1.4 cm) at baseline (T1-45 wk before Olympic Games) and after 7, 9, 20, 25, and 42 wk (T1-6, respectively). Ongoing nutritional counseling was provided. Total weekly training load was recorded over the week before each time point. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry at T1 and T6.. Total BMD increased significantly before to after training (+0.02 g·cm), but was below the least significant change (±0.04 g·cm). Osteoprotegerin, insulin-like growth factor-1, and leptin remained stable across all time points. Fluctuations in training load (high vs low) were accompanied by parallel changes in tumor necrosis factor-α (2.1 ± 0.2 vs 1.5 ± 0.2 pg·mL), interleukin 6 (1.2 ± 0.08 vs 0.8 ± 0.09 pg·mL), and sclerostin (high: 993 ± 109 vs low: 741 ± 104 pg·mL).. In this population of young female athletes with suitable energy availability, sclerostin and inflammation markers responded to fluctuations in training load, whereas BMD and bone mineral content were stable during the season, suggesting that training load periodization is not harmful for the bone health in athletes. Topics: Adaptor Proteins, Signal Transducing; Adult; Biomarkers; Bone and Bones; Bone Density; Bone Morphogenetic Proteins; Energy Metabolism; Female; Genetic Markers; Humans; Inflammation; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Osteoprotegerin; Physical Conditioning, Human; Tumor Necrosis Factor-alpha; Water Sports | 2018 |
High circulatory leptin mediated NOX-2-peroxynitrite-miR21 axis activate mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty liver disease.
High circulatory insulin and leptin followed by underlying inflammation are often ascribed to the ectopic manifestations in non-alcoholic fatty liver disease (NAFLD) but the exact molecular pathways remain unclear. We have shown previously that CYP2E1-mediated oxidative stress and circulating leptin in NAFLD is associated with renal disease severity. Extending the studies, we hypothesized that high circulatory leptin in NAFLD causes renal mesangial cell activation and tubular inflammation via a NOX2 dependent pathway that upregulates proinflammatory miR21. High-fat diet (60% kcal) was used to induce fatty liver phenotype with parallel insulin and leptin resistance. The kidneys were probed for mesangial cell activation and tubular inflammation that showed accelerated NASH phenotype and oxidative stress in the liver. Results showed that NAFLD kidneys had significant increases in α-SMA, a marker of mesangial cell activation, miR21 levels, tyrosine nitration and renal inflammation while they were significantly decreased in leptin and p47 phox knockout mice. Micro RNA21 knockout mice showed decreased tubular immunotoxicity and proinflammatory mediator release. Mechanistically, use of NOX2 siRNA or apocynin,phenyl boronic acid (FBA), DMPO or miR21 antagomir inhibited leptin primed-miR21-mediated mesangial cell activation in vitro suggesting a direct role of leptin-mediated NOX-2 in miR21-mediated mesangial cell activation. Finally, JAK-STAT inhibitor completely abrogated the mesangial cell activation in leptin-primed cells suggesting that leptin signaling in the mesangial cells depended on the JAK-STAT pathway. Taken together the study reports a novel mechanistic pathway of leptin-mediated renal inflammation that is dependent on NOX-2-miR21 axis in ectopic manifestations underlying NAFLD-induced co-morbidities. Topics: Animals; ATPases Associated with Diverse Cellular Activities; Diet, High-Fat; DNA Helicases; Humans; Inflammation; Janus Kinases; Kidney; Leptin; Mesangial Cells; Mice; Mice, Knockout; MicroRNAs; NADPH Oxidase 2; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Peroxynitrous Acid; Signal Transduction; STAT Transcription Factors | 2018 |
Self-reported dietary flavonoid intake and serum markers of inflammation: the multiethnic cohort.
To examine if dietary intake of foods rich in flavonoids, which have been shown to be inversely associated with chronic diseases, is associated with inflammatory processes.. This analysis includes controls of case-control studies nested within the Multiethnic Cohort (MEC) who completed a validated food frequency questionnaire at cohort entry. Biomarkers were assessed in blood donated during follow-up (mean = 9.6 years). We used multivariate linear regression adjusted for potential confounders to estimate associations between intake of flavanones, flavonols, and isoflavones and levels of adiponectin, leptin, C-reactive protein, interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α.. Among the 1,287 participants, the respective median intakes of flavanones, flavonols, and isoflavones were 26.5, 12.4, and 1.3 mg/day at cohort entry. With the exception of flavanone intake, which was statistically significantly inversely associated with adiponectin (p = 0.01) and IL-6 concentrations (p = 0.01), none of the examined flavonoids was related with levels of adipokines or inflammatory markers. Heterogeneity by ethnicity was only observed for flavonol intake and IL-10 (p. The current results do not support a consistent association between dietary intake of flavonoids and markers of inflammatory processes. Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Cohort Studies; Diet; Female; Flavanones; Flavonoids; Follow-Up Studies; Humans; Inflammation; Isoflavones; Leptin; Male; Middle Aged; Self Report; Tumor Necrosis Factor-alpha | 2018 |
Arginine pretreatment enhances circulating endothelial progenitor cell population and attenuates inflammatory response in high-fat diet-induced obese mice with limb ischemia.
Obesity is a global health problem with an up-regulated inflammatory reaction. Obesity-induced endothelial progenitor cells (EPCs) dysfunction is associated with vascular complications that may contribute to critical limb ischemia. Arginine (Arg) is an amino acid with immune-modulatory property and has been found to promote EPCs mobilization in disease conditions. Thus in the present investigation, we hypothesized that arginine given to a murine model of diet-induced obesity would increase circulating EPCs and mitigate the inflammatory reactions in response to limb ischemia. Mice were divided into normal group (NC), high-fat group (HC), and high-fat Arg group (HA). Mice in the HC group were fed with a diet containing 60% energy as fat for 8 weeks, while HA group were initially fed with the same high-fat diet for 4 weeks and later shifted to a high-fat diet enriched with 2% Arg for the remaining 4 weeks. Then mice in the HC and HA groups underwent ischemic operations and were euthanized at either day 1 or day 7 after limb ischemia. The results showed that, compared to the ischemic HC group, the ischemic HA group had higher circulating EPCs at day 1 post-ischemia and higher muscle stromal cell-derived factor-1 and interleukin (IL)-10 mRNA expressions at day 7 after ischemia. In contrast, plasma leptin concentration and expressions of IL-1β and tumor necrosis factor-α mRNAs by adipocytes were down-regulated. These findings suggest that obese mice treated with Arg-containing high-fat diet enhanced circulating EPCs percentage and attenuated inflammatory reaction in response to limb ischemia. Topics: Adipocytes; Adipose Tissue; Animals; Arginine; Cell Movement; Chemokine CXCL12; Diet, High-Fat; Endothelial Progenitor Cells; Endothelium, Vascular; Hindlimb; Inflammation; Interleukin-1beta; Ischemia; Leptin; Male; Mice, Inbred C57BL; Mice, Obese; Muscles; Obesity; Stem Cells | 2018 |
A role for TLR10 in obesity and adipose tissue morphology.
Toll like receptors (TLRs) are expressed in adipose tissue and promote adipose tissue inflammation during obesity. Recently, anti-inflammatory properties have been attributed to TLR10 in myeloid cells, the only member of the TLR family with inhibitory activity. In order to assess whether TLR10-induced inhibition of inflammation may be protective during the development of obesity and metabolic abnormalities we used transgenic human TLR10 mice (hTLR10tg) and wild type (WT) controls on a C57B6J background. HFD-feeding enhanced TLR10 expression in the adipose tissue, and HFD-fed hTLR10tg mice displayed reduced adipocyte size, adipose tissue weight, and a trend toward lower plasma insulin levels compared to WT mice. In humans, obese individuals with polymorphisms in the TLR10 gene displayed reduced macrophage infiltration in the adipose tissue accompanied by a trend to lower leptin levels and higher adiponectin levels in plasma. In healthy individuals with the same polymorphisms in the TLR10 gene we did not observe any difference in plasma concentrations of leptin and adiponectin. We conclude that TLR10 impacts adipose tissue morphology in obesity. Larger studies in humans are warranted to assess its potential value as therapeutic target in metabolic syndrome and type 2 diabetes. Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Animals; Biopsy; Cohort Studies; Gene Knock-In Techniques; Humans; Inflammation; Leptin; Macrophages; Male; Mice, Transgenic; Obesity; Paraffin Embedding; Polymorphism, Single Nucleotide; Toll-Like Receptor 10; Up-Regulation | 2018 |
Pleiotropic Associations of
Chemerin, an adipokine and inflammatory mediator, is associated with metabolic, inflammation- and immune-mediated diseases. The genetic, clinical, and biomarker correlates of circulating chemerin levels have not been completely elucidated. We analyzed the determinants and correlates of retinoic acid receptor responder 2 ( Topics: Adult; C-Reactive Protein; Chemokines; Female; Fibrinogen; Genotype; Glomerular Filtration Rate; Haplotypes; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Lipocalin-2; Logistic Models; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Triglycerides | 2018 |
The overweight increases circulating inflammatory mediators commonly associated with obesity in young individuals.
Obesity is a serious and growing world healthy problem affecting developed and developing countries. The new conception of obesity as a basal inflammatory condition has opened a new window of possibilities to identify inflammatory biomarkers to be used in the diagnosis or prognosis of obesity-associated comorbidities. This present work aims the identification of the adipokines (leptin and resistin), chemokines (CCL2, CCL5, CXCL16) and the BMP-2 and their association with the clinical, biochemical (fasting glucose, hemogram, cholesterol, T3, T4 and TSH) and anthropometric (weight, height, body circumferences, skinfold thickness and percentage of body fat) parameters in young adults (18-30 years old) presenting obesity and overweight. Our data showed increasing in anthropometric parameters and in the plasma inflammatory levels in those individuals presenting overweight and obesity. We observed a higher plasma levels of CCL2, CCL5, CXCL16, leptin and resistin in those overweigh and obese individuals. In addition, the CCL2, CCL5 presented a positive correlation with the body mass index and the body fat percentage. Assuming the obesity as a systemic inflammatory process, in this current study, the overweight individuals possess a close similar pattern of circulating inflammatory mediators which might be a potential risk of the development of obesity comorbidities. Further studies are still needed to precise the role of the biomarkers CCL2, CCL5, CXCL16 and BMP-2 in the clinical prognosis related to the overweight or obese individuals. Topics: Adipokines; Adiponectin; Adolescent; Adult; Biomarkers; Body Mass Index; Body Weight; Chemokines; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Obesity; Overweight; Resistin; Young Adult | 2018 |
Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study.
Among 365 Hertfordshire Cohort Study participants (aged 59-71 years at baseline), higher adiponectin and adiponectin to leptin ratios were associated with lower baseline lumbar spine and femoral neck bone mineral density (BMD). Lower IL-10 was associated with accelerated decline in lumbar spine BMD. This suggests that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis.. The aim of this study was to examine the association between indices of inflammation and BMD in a population-based cohort of older adults in the UK.. Analyses were based on a sample of 194 men and 171 women of the Hertfordshire Cohort Study (community-living, older adults). Dual energy X-ray absorptiometry (DXA) was performed at the lumbar spine and proximal femur at baseline and repeated at a median of 4.5 years (inter-quartile range 3.6 to 5.2). Inflammatory markers (CRP, TNF, IL-1β, IL-6, IL-8, IL-10, adiponectin and leptin) were ascertained at baseline using enzyme-linked immunosorbent assay (ELISA) techniques and Bio-Plex Pro Assays. Gender-adjusted linear regression was used to examine the associations between markers of inflammation and outcomes with and without adjustment for anthropometric and lifestyle factors.. The mean (SD) ages at baseline were 64.4 (2.5) and 66.5 (2.7) years for men and women respectively. Higher levels of adiponectin and adiponectin to leptin ratios were each associated with lower baseline lumbar spine and femoral neck BMD in gender-adjusted (p < 0.01) and fully adjusted (p < 0.05) analyses. Lower levels of IL-10 and TNF were each associated with accelerated decline in lumbar spine BMD in both gender-adjusted (p ≤ 0.05) and fully adjusted (p < 0.05) analyses.. In a cohort of older adults, high levels of adiponectin and adiponectin to leptin ratios were both associated with lower BMD at the lumbar spine and femoral neck at baseline, and lower IL-10 was associated with accelerated decline in BMD at the lumbar spine. This adds weight to the theory that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis. Topics: Absorptiometry, Photon; Adiponectin; Aged; Anthropometry; Biomarkers; Bone Density; Cohort Studies; Female; Femur Neck; Humans; Inflammation; Inflammation Mediators; Interleukin-10; Leptin; Lumbar Vertebrae; Male; Middle Aged | 2018 |
Leptin Promotes Allergic Airway Inflammation through Targeting the Unfolded Protein Response Pathway.
Allergic asthma and obesity are major public health problems in the world. Recent Meta-analysis studies implicated a positive relationship between serum leptin, which is elevated in obese individuals, and the risk of asthma. However, it is not well understood how obesity-associated elevation of leptin increases the risk of asthma. In the current study, we have found that leptin induces the unfolded protein response factor XBP1s in an mTOR- and MAPK-dependent manner in pro-allergic TH2 cells; in vivo, mice fed with high fat diet had increased serum leptin as observed in human obese population and exacerbated asthmatic symptoms, associated with increased XBP1s expression in splenic CD4 Topics: Animals; Asthma; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Inflammation; Leptin; Mice, Inbred C57BL; Th2 Cells; Unfolded Protein Response; X-Box Binding Protein 1 | 2018 |
Leptin alleviates intestinal mucosal barrier injury and inflammation in obese mice with acute pancreatitis.
Obesity is an independent risk factor for severe acute pancreatitis (AP). Leptin plays an important role in energy homeostasis. It has been reported that leptin might also participate in the regulation of the intestinal mucosal barrier and inflammatory response. This study aimed to evaluate the effects of leptin on the intestinal mucosal barrier and inflammatory injury in obese mice with AP.. AP was induced in leptin-deficient (ob/ob) or wild type (WT) mice by peritoneal injection of caerulein. The animals were divided into 4 groups: WT mice with or without exogenous leptin injection and ob/ob mice with or without leptin treatment. The inflammatory scoring of the pancreas and intestine were evaluated. Intestinal permeability, ileal interleukin (IL)-6 and IL-1β, proliferation, apoptosis and intestinal expression levels of claudin-1 and occludin were measured.. Pancreatic pathologic scores (8.50 ± 0.96 vs. 3.78 ± 1.35, p < 0.001), pancreatic levels of IL-6 (8.34 ± 3.21 ng/mg vs. 4.99 ± 0.53 ng/mg, p = 0.022), intestinal oedema scores (2.25 ± 0.46 vs. 1.14 ± 0.69, p = 0.001) and intestinal permeability to FD4 (0.78 ± 0.06 μg/ml vs. 0.53 ± 0.11 μg/ml, p < 0.001) were significantly higher in ob/ob mice than those in WT mice. Leptin replacement in ob/ob mice greatly improved the intestinal permeability (FD4 0.66 ± 0.03 μg/ml, vs. 0.78 ± 0.06 μg/ml, p = 0.012), increased the ileal expression of claudin-1(1.07 ± 0.08 vs. 0.83 ± 0.07 relative densitometry, p = 0.001) and reduced intestinal IL-6 and IL-1β to levels comparable to those in WT mice. The pancreatic level of IL-6 in ob/ob mice treated with leptin was also significantly decreased relative to that of untreated ob/ob mice (4.45 ± 1.71 ng/mg vs. 8.34 ± 3.21 ng/mg, p = 0.010).. Obesity may aggravate intestinal inflammation and increase intestinal permeability under the condition of acute pancreatitis. Exogenous leptin supplementation was in favour of anti-inflammation and improvement of intestinal mucosal barrier. Topics: Acute Disease; Animals; Inflammation; Intestinal Mucosa; Leptin; Male; Mice; Mice, Knockout; Mice, Obese; Obesity; Pancreas; Pancreatitis | 2018 |
ErbB4 deletion predisposes to development of metabolic syndrome in mice.
ErbB4, a member of the EGF receptor family, plays a variety of roles in physiological and pathological states. Genetic studies have indicated a link between ErbB4 and type 2 diabetes and obesity, but its role in metabolic syndrome (MetS) has not been reported. In the current study we found that mice with ErbB4 deletion developed MetS after 24 wk on a medium-fat diet (MFD), as indicated by development of obesity, dyslipidemia, hepatic steatosis, hyperglycemia, hyperinsulinemia, and insulin resistance, compared with wild-type mice. ErbB4 deletion mice also exhibited increased amounts of subcutaneous and visceral fat, with increased serum leptin levels, compared with wild-type mice, whereas levels of adiponectin were not significantly different. Histologically, severe inflammation, indicated by F4/80 immunostaining and M1 macrophage polarization, was detected in inguinal and epididymal white adipose tissue in ErbB4 deletion mice. ErbB4 expression decreased during 3T3-L1 preadipocyte differentiation. Administration of neuroregulin 4, a specific ligand for ErbB4, to 3T3-L1 adipocytes had no effect on adipogenesis and lipolysis but significantly inhibited lipogenesis, promoted browning, induced GLUT4 redistribution to the cell membrane, and increased glucose uptake. Neuroregulin 4 also significantly increased glucose uptake in adipocytes isolated from wild-type mice, while these effects were significantly decreased in adipocytes isolated from ErbB4 deletion mice. In conclusion, our results indicate that ErbB4 may play an important role in glucose homeostasis and lipogenesis. ErbB4 deficiency-related obesity and adipose tissue inflammation may contribute to the development of MetS. Topics: 3T3-L1 Cells; Adipogenesis; Adiponectin; Adipose Tissue, White; Animals; Dietary Fats; Dyslipidemias; Fatty Liver; Gene Deletion; Genetic Predisposition to Disease; Glucose Transporter Type 4; Hyperglycemia; Hyperinsulinism; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipogenesis; Macrophages; Male; Metabolic Syndrome; Mice; Neuregulins; Obesity; Receptor, ErbB-4; Subcutaneous Fat | 2018 |
The Influence of LPS-Induced Maternal Inflammation on Postnatal Collagen-Induced Arthritis.
Maternal health and nutritional status influence offspring health and the diseases that may develop in them. The effects of maternal inflammation on offspring from the perspective of the inflammatory response and immune changes are not fully understood. We hypothesized that maternal inflammation modulates immune and metabolic functions, affecting the pathophysiology of inflammatory diseases in offspring. This study investigated whether maternal inflammation affects the onset of collagen-induced arthritis (CIA), a murine model of human rheumatoid arthritis. Female DBA/1J mice received a single intraperitoneal injection of lipopolysaccharide (LPS) 5 days before conception. Male offspring of LPS-treated dams were placed in the maternal LPS group (MLG). To induce CIA, type II collagen (CII) was emulsified with Freund's complete adjuvant and injected twice into each mouse, at 13 and 16 weeks. The offspring were sacrificed at 26 weeks to analyze immunological and metabolic parameters. The degree of joint swelling at an early stage of CIA was lower in the MLG than in the control group. From histological analysis, the severity of joint destruction (severity of arthritis score) and CII-specific IgG titer were significantly lower in the MLG. However, at 26 weeks, serum interleukin (IL)-6 levels, an index of CIA disease activity, were significantly higher in the MLG. Moreover, serum leptin levels were lower in the MLG, and a negative correlation between leptin and serum IL-6 was observed. In conclusion, maternal inflammation does not merely suppress inflammation; it may delay CIA in offspring. The analysis of inflammatory cytokines and leptin concentrations at 26 weeks suggests that the pathophysiology of arthritis was worsening. This study also suggests that maternal inflammation modulates postnatal inflammatory response patterns in offspring. Topics: Animals; Arthritis, Experimental; Collagen Type II; Cytokines; Female; Inflammation; Leptin; Lipopolysaccharides; Male; Maternal Exposure; Mice; Pregnancy; Prenatal Exposure Delayed Effects | 2018 |
Exploring the potential of tocotrienol from Bixa orellana as a single agent targeting metabolic syndrome and bone loss.
Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienol has been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS. Topics: Adiponectin; Animals; Bixaceae; Bone Resorption; Cancellous Bone; Carotenoids; Diet, High-Fat; Dietary Carbohydrates; Hyperglycemia; Hypertension; Inflammation; Leptin; Male; Metabolic Syndrome; Osteoblasts; Plant Extracts; Rats, Wistar; Tocotrienols; X-Ray Microtomography | 2018 |
Recombinant leptin attenuates abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice.
Vascular disease can manifest as stenotic plaques or ectatic aneurysms. Human abdominal aortic aneurysms (AAA) comprise an inflammatory disease characterized by the predominance of T helper type 2 (Th2) cytokine expression. Leptin has been clearly demonstrated to play an important role in regulating Th0 cell to Th1. So, we hypothesize that leptin has a protective effect on aneurysm formation. In this study, we demonstrated that intraperitoneal injection of leptin attenuated Ang II-induced AAA formation in ApoE-/- mice with no effect on serum lipids and systolic blood pressure. To investigate the mechanisms involved, we found that leptin pretreatment exhibited decreased protein expression of matrix metalloproteinase 2 (MMP-2) and MMP-9 and increased transforming growth factor-β1 (TGF-β1). We also examined potential mechanism of leptin as a modulator of the immune response. Our results proved that pretreatment with leptin downregulated protein expression of Th2 cytokine IL-4 and mRNA levels of GATA-3, the key transcription factor for Th2 polarization, and upregulated Th1 cytokine INF-γ and T-bet, the key transcription factor for Th1 polarization. Taken together, leptin, with the effect of regulation of Th1/Th2 cytokines, may have therapeutic potential for the treatment of AAA. Leptin may constitute a novel therapeutic strategy to prevent AAA formation. Topics: Angiotensin II; Animals; Aortic Aneurysm, Abdominal; Apolipoproteins E; Inflammation; Injections, Intraperitoneal; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Recombinant Proteins; T-Lymphocytes; Th1 Cells | 2018 |
Circulating regulatory T cells (Treg), leptin and induction of proinflammatory activity in obese Labrador Retriever dogs.
Over-nutrition and obesity have been associated with impaired immunity and low-grade inflammation in humans and mouse models. In this context, a causal role for unbalanced T regulatory cell (Treg)-dependent mechanisms has been largely suggested. Obesity is the most common nutritional disorder in dogs. However, it is not defined whether canine obesity may influence circulating Treg as well as if their number variation might be associated with the occurrence of systemic inflammation. The present study investigated the immune profile of healthy adult obese dogs belonging to the Labrador Retriever breed, in comparison with the normal weight counterpart. Indeed, obesity has been described as particularly evident in this dogs. With this purpose, 26 healthy dogs were enrolled and divided into two groups based on body condition score (BCS): controls (CTR: BCS 4-5) and obeses (OB: BCS ≥ 7). Our data indicate that adult obese Labrador Retrievers are characterised by the inverse correlation between leptin serum concentration and circulating Treg (CD4 Topics: Animals; Dogs; Inflammation; Interferon-gamma; Leptin; Obesity; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory | 2018 |
Relationship between Obesity and Periodontal Diseases in Saudi Women (Asir Region): A Prospective Study.
The present study is undertaken to assess any possible association between obesity and periodontal diseases among Saudi women in Asir region.. A total number of 100 obese subjects in the age group between 16 and 35 years participated in the study. A questionnaire which consisted of anthropometric measurements [neck circumference (NC) ≥ 34 cm for women] and demographic features was used. Periodontal status was assessed for the subjects.. The periodontal disease shows significant association with anthropometric measurements (NC ≥ 34 cm for women) and demographic features.. The findings of this prospective study showed possible relationship between obesity and periodontal disease.. In view of changing lifestyle with dietary habits, there is a possibility of developing obesity. The results in this research show a direct relationship between obesity and periodontal diseases by measuring body mass index (BMI) and NC in the age group of 16 to 35 years females in Saudi Arabia. Thus, it helps in preventing and managing obesity, especially among youth. Topics: Adolescent; Adult; Anthropometry; Body Mass Index; C-Reactive Protein; Cetrimonium Compounds; Drug Combinations; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Myristates; Neck; Nicotinic Acids; Obesity; Periodontal Diseases; Prospective Studies; Saudi Arabia; Simethicone; Stearic Acids; Surveys and Questionnaires; Tumor Necrosis Factor-alpha; Young Adult | 2018 |
Contribution of systemic inflammation to permanence of K
Gain-of-function (GOF) mutations in the ATP-sensitive potassium (K Topics: Animals; Blood Glucose; Cytokines; Diabetes Mellitus; Glucagon; Glucagon-Like Peptide 1; Glyburide; Inflammation; Insulin; Insulin Resistance; Leptin; Mice; Mice, Transgenic; Mutation; Potassium Channels, Inwardly Rectifying | 2018 |
Histopathological Changes Caused by Inflammation and Oxidative Stress in Diet-Induced-Obese Mouse following Experimental Lung Injury.
Obesity has been identified as a risk factor for adverse outcomes of various diseases. However, information regarding the difference between the response of obese and normal subjects to pulmonary inflammation is limited. Mice were fed with the control or high-fat diet to establish the lean and diet-induced obese (DIO) mice. Escherichia coli was intranasally instilled to reproduce non-fatal acute pneumonia model. After infection, serum samples and lung tissues were obtained at 0, 12, 24, and 72 h. DIO mice exhibited increased serum triglyceride (TG) and total cholesterol (TC) contents as well as pulmonary resistin, IL-6, and leptin levels compared with lean mice. E. coli infection caused an acute suppurative inflammation in the lung with increased lung index and serum TG and TC contents; elevated pulmonary tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, and leptin levels; and oxidative stress in mice. Interestingly, almost all the above-mentioned parameters peaked at 12 h after infection in the lean-E. coli group but after 12 h in the DIO-E. coli group. These results indicated that the DIO mice presented a delayed inflammatory response and oxidative stress in non-fatal acute pneumonia induced by E. coli infection. Topics: Animals; Cholesterol; Cytokines; Diet, High-Fat; Disease Models, Animal; Escherichia coli; Humans; Inflammation; Interleukins; Leptin; Lung Injury; Mice; Obesity; Oxidative Stress; Pneumonia, Bacterial; Triglycerides; Tumor Necrosis Factor-alpha | 2018 |
Regulation of adipogenesis by ceramide 1-phosphate.
We showed previously that ceramide kinase (CerK) expression increases during adipogenesis pointing to a relevant role of intracellular C1P in this process. In the present work we demonstrate that administration of exogenous C1P inhibits the differentiation of 3T3-L1 pre-adipocytes into mature adipocytes through a mechanism involving activation of extracellularly regulated kinases (ERK) 1-2. Exogenous C1P reduced the accumulation of lipid droplets and the content of triacylglycerol in these cells, and potently inhibited the expression of the early and late adipogenic markers C/EBPβ and PPARγ, respectively. C1P also reduced the secretion of leptin, which is a crucial regulator of energy balance and appetite in the organism, and is considered to be a late marker of adipogenesis. Interestingly, all of these C1P actions were reversed by pertussis toxin, suggesting the intervention of a Gi protein-coupled receptor previously identified for C1P, in this process. Also, exogenous C1P significantly reduced CerK activity. Altogether, the data presented in this work suggest that exogenous C1P may balance adipogenesis, and that targeting CerK may be a novel way for potential applications in the treatment of obesity or other inflammation-associated diseases. Topics: 3T3-L1 Cells; Adipogenesis; Animals; CCAAT-Enhancer-Binding Protein-beta; Cell Differentiation; Ceramides; Gene Expression Regulation, Developmental; Humans; Inflammation; Leptin; Lipid Droplets; MAP Kinase Signaling System; Mice; Phosphotransferases (Alcohol Group Acceptor); PPAR gamma; Triglycerides | 2018 |
High-fat-diet-induced inflammation depresses the appetite of blunt snout bream (Megalobrama amblycephala) through the transcriptional regulation of leptin/mammalian target of rapamycin.
The aim of this article was to investigate the mechanism of appetite suppression induced by high-fat diets (HFD) in blunt snout bream (Megalobrama amblycephala). Fish (average initial weight 40·0 (sem 0·35) g) were fed diets with two fat levels (6 and 11 %) with four replicates. HFD feeding for 30 d could significantly increase the weight gain rate, but feeding for 60 d cannot. Food intake of M. amblycephala began to decline significantly in fish fed the HFD for 48 d. HFD feeding for 60 d significantly reduced the expression of neuropeptide Y and elevated the expression of cocaine- and amphetamine-regulated transcript (CART), actions both in favour of suppression of appetite. The activation of fatty acid sensing was partly responsible for the weakened appetite. In addition, inflammatory factors induced by the HFD may be involved in the regulation of appetite by increasing the secretion of leptin and then activating the mammalian target of rapamycin (mTOR). Lipopolysaccharide (LPS, 2·0 mg/kg of fish weight) was administered to induce inflammation, and sampling was performed after 3, 6, 9, 12, 18, 24 and 48 h of LPS injection. Within 6-24 h of LPS injection, the food intake and appetite of M. amblycephala decreased significantly, whereas the mRNA expression of leptin and mTOR increased significantly. Our results indicate that inflammatory cytokines may be the cause of appetite suppression in M. amblycephala fed a HFD. Topics: Animal Feed; Animals; Appetite; Cyprinidae; Diet, High-Fat; Eating; Fatty Acids; Fishes; Gene Expression Regulation; Inflammation; Leptin; Lipid Metabolism; Lipopolysaccharides; Liver; Nerve Tissue Proteins; RNA, Messenger; TOR Serine-Threonine Kinases | 2018 |
The potential anti-inflammatory role of adiponectin in food allergy: a case-control study on children.
We aimed to assess the possible relationship between food allergy and two key adipokines - leptin and adiponectin - in children with food allergy. A total of forty patients with definite diagnosis of food allergy according to clinical history and specific IgE (sIgE) for food allergens (group I) were enrolled in this pilot study. The control group (group II) included thirty children with no evidence of allergic symptoms. Serum levels of leptin and adiponectin were measured by ELISA. Meanwhile, sIgE was measured for the eight most common food allergens by the immunoblot method in all participants. The median ages in groups I and II were 18·5 and 23·5 months, respectively. The respective Caesarean section rate was 64·9 and 16·7 % in groups I and II (P<0·001). Serum levels of adiponectin were significantly higher in the patient group compared with controls (24·11 (sd 12·14) v. 10·67 (sd 12·23) μg/ml, P<0·001), whereas no statistically meaningful difference was detected in serum leptin concentrations (P=0·92). There was a significant inverse relationship between age and adiponectin levels in group I (P=0·002, r -0·479) and group II (P=0·04, r -0·365), and it was more significant in group I. The most common allergens in the patient group were wheat (52·5 %), hazelnut (52·5 %), cow's milk (50 %) and egg white (30 %). The results of this study suggest an essential link between adiponectin and food allergy that is probably unlikely to be affected by obesity as a confounding factor. Topics: Adiponectin; Allergens; Animals; Birth Weight; Case-Control Studies; Cesarean Section; Child, Preschool; Corylus; Cytokines; Egg Hypersensitivity; Egg White; Enzyme-Linked Immunosorbent Assay; Female; Food Hypersensitivity; Humans; Immunoglobulin E; Infant; Inflammation; Leptin; Male; Milk; Milk Hypersensitivity; Pilot Projects; Skin Tests; Triticum | 2018 |
Regulation of Leptin Methylation Not via Apoptosis by Melatonin in the Rescue of Chronic Programming Liver Steatosis.
We examined the mechanisms of chronic liver steatosis after prenatal dexamethasone exposure and whether melatonin rescues adult offspring with liver steatosis. Melatonin rescued prenatal dexamethasone-exposed livers with steatosis in young rats. Sprague-Dawley rats pregnant at gestational day 14⁻21 were administered with intraperitoneal dexamethasone (DEX) or prenatal dexamethasone and melatonin between gestational day 14 and postnatal day ~120 (DEX+MEL). Chronic programming effects in the liver were assessed at day ~120. Liver steatosis increased in the DEX compared with that in the vehicle group and decreased in the DEX+MEL group ( Topics: Acetylation; Animals; Apoptosis; Body Weight; DNA (Cytosine-5-)-Methyltransferases; Fatty Liver; Histones; Inflammation; Leptin; Liver; Methylation; Organ Size; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha | 2018 |
Time-restricted feeding mitigates high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice.
Erratic eating behavior disrupts the daily feeding and fasting pattern and leads to metabolic dysfunction and chronic diseases including cancer. In the present study, we tested the hypothesis that time-restricted feeding of a high-fat diet (HFD) to the dark phase does not enhance mammary tumorigenesis in MMTV-PyMT mice. Female mice were assigned to 3 groups and fed the standard AIN93G diet or an HFD with or without dark phase restricted feeding (12 hours). The duration of restricted feeding was 8 weeks. The HFD group had 24% more body fat mass than the AIN93G group; the body fat mass of the restricted group remained similar to that of the AIN93G group. Energy intake of the restricted group was similar to that of the HFD and AIN93G groups. The median mammary tumor latency was 5.8, 7.0, and 6.4 weeks for the AIN93G, HFD, and restricted groups, respectively. Mammary tumor progression was 241% higher in the HFD group than that in the AIN93G group; there was no significant difference in tumor progression between the restricted and AIN93G groups. Plasma concentrations of leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, angiopoietin-2, vascular endothelial growth factor, and hepatocyte growth factor were significantly higher in the HFD group than those in the control group; these measurements were similar between the restricted and control groups. In conclusion, feeding restricted to the dark phase mitigates the HFD-enhanced mammary tumorigenesis; this may be related to the lower body adiposity and associated inflammatory and angiogenic signals. Topics: Adipose Tissue; Adiposity; Angiopoietin-2; Animals; Breast Neoplasms; Carcinogenesis; Chemokine CCL2; Darkness; Diet, High-Fat; Fasting; Feeding Behavior; Female; Hepatocyte Growth Factor; Inflammation; Leptin; Mice, Inbred Strains; Neovascularization, Pathologic; Obesity; Plasminogen Activator Inhibitor 1; Vascular Endothelial Growth Factor A | 2018 |
The role of systemic inflammation in the pathogenesis of insulin resistance and metabolic syndrome in patients with chronic hepatitis C.
To determine the role of nonspecific inflammation in the formation of IR and metabolic syndrome in patients with chronic hepatitis C.. The study included 205 patients with CHC aged 18 to 69 years. Patients with CHC are randomized into two groups depending on the presence of IR: group 1 - patients with a HOMA index ≥2.77, which corresponded to IR (n=110); group 2 (n=95). The levels of serum iron, C-reactive protein (CRP), serum ferritin and adipose tissue hormones [leptin, resistin, adiponectin and tumor necrosis factor-α (TNF-α)] were additionally investigated.. At all stages of development of IR, nonspecific inflammation was detected (according to ferritin, CRP and serum iron), increasing with increasing HOMA index [Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)] (Matthews D., 1985), metabolic syndrome and its components. In the analysis of indicators in patients with chronic hepatitis C with a body mass index <25 kg/m2, conjugacy of IR with low-intensity inflammation, high viral load and hypersecretion of TNF-α was detected.. Given the high predictor role of CRP indicators in predicting IR, it should be used as a surrogate screening marker of IR in patients with chronic hepatitis C and should be actively treated for violations. Topics: Adiponectin; Adolescent; Adult; Aged; Hepatitis C, Chronic; Humans; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Random Allocation; Young Adult | 2018 |
Menopause Is a Determinant of Breast Aromatase Expression and Its Associations With BMI, Inflammation, and Systemic Markers.
Most estrogen-dependent breast cancers occur after menopause, despite low levels of circulating estrogens. Breast expression of the estrogen-biosynthetic enzyme, aromatase, is proposed to drive breast cancer development after menopause. However, the effects of menopause on breast aromatase expression are unknown.. To determine the effect of menopause on breast aromatase expression in relation to body mass index (BMI), white adipose tissue inflammation (WATi), and systemic markers of metabolic dysfunction.. Cross-sectional study of 102 premenopausal (age 27 to 56) and 59 postmenopausal (age 45 to 74) women who underwent mastectomy for breast cancer treatment/prevention.. Breast tissue was assessed for the presence of crown-like structures and the expression and activity of aromatase. Systemic markers examined include interleukin (IL)-6, insulin, glucose, leptin, adiponectin, high-sensitivity C-reactive protein (hsCRP), cholesterol, and triglycerides. Multivariable analysis was performed for aromatase messenger RNA (mRNA) in relation to BMI, WATi, and blood markers.. Postmenopausal women had higher BMI and more breast WATi than premenopausal women. Fasting levels of IL-6, glucose, leptin, hsCRP, and homeostatic model assessment 2 insulin resistance score were higher in the postmenopausal group. BMI was positively correlated with aromatase mRNA in both pre- and postmenopausal women. Aromatase levels were higher in breast tissue of postmenopausal women, with levels being higher in inflamed vs noninflamed, independent of BMI. Adipocyte diameter and levels of leptin, hsCRP, adiponectin, and high-density lipoprotein cholesterol were more strongly correlated with aromatase in postmenopausal than premenopausal women.. Elevated aromatase in the setting of adipose dysfunction provides a possible mechanism for the higher incidence of hormone-dependent breast cancer in obese women after menopause. Topics: Adiponectin; Adipose Tissue, White; Adult; Aged; Aromatase; Blood Glucose; Body Mass Index; Breast; Breast Neoplasms; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Gene Expression Regulation, Developmental; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Menopause; Middle Aged; Multivariate Analysis; Postmenopause; Premenopause; RNA, Messenger; Triglycerides | 2017 |
Obesity Modulates Inflammation and Lipid Metabolism Oocyte Gene Expression: A Single-Cell Transcriptome Perspective.
It is hypothesized that obesity adversely affects the ovarian environment, which can disrupt oocyte maturation and embryonic development.. This study aimed to compare oocyte gene expression profiles and follicular fluid (FF) content from overweight/obese (OW) women and normal-weight (NW) women who were undergoing fertility treatments.. Using single-cell transcriptomic analyses, we investigated oocyte gene expression using RNA sequencing.. Eleven OW women and 13 NW women undergoing fertility treatments were enrolled.. Oocyte messenger RNA profiles as well as serum and FF hormone and lipid levels were assessed.. OW women had significantly higher body mass index, body fat percentage, and serum homeostatic model assessment-insulin resistance index compared with NW women (P < 0.01). Serum leptin and C-reactive protein (CRP) levels as well as FF leptin, CRP, and triglyceride levels were increased (P < 0.05) in OW compared with NW women. Oocytes from OW women had increased expression of proinflammatory (CXCL2; P = 0.071) and oxidative stress-related (DUSP1; P = 0.051) genes but had decreased expression of GAS7 (fat metabolism; P = 0.065), TXNIP (oxidative stress; P = 0.055), and transcription factors ID3 (P = 0.075) and TWIST1 (P = 0.099) compared with NW women.. These findings provide evidence for the significant influence of body composition on oocyte transcript abundance in women undergoing hormonal induction to retrieve oocytes. They further identify the potential for maternal diet to influence oocyte gene expression. The preconception period is, therefore, an important window of opportunity to consider for lifestyle interventions. Topics: Adolescent; Adult; Body Composition; C-Reactive Protein; Carrier Proteins; Case-Control Studies; Chemokine CXCL2; Dual Specificity Phosphatase 1; Female; Follicular Fluid; Gene Expression Profiling; Humans; Inflammation; Inhibitor of Differentiation Proteins; Leptin; Lipid Metabolism; Neoplasm Proteins; Nerve Tissue Proteins; Obesity; Oocyte Retrieval; Oocytes; Overweight; Ovulation Induction; Sequence Analysis, RNA; Single-Cell Analysis; Triglycerides; Young Adult | 2017 |
Ideal cardiovascular health and inflammation in European adolescents: The HELENA study.
Inflammation plays a key role in atherosclerosis and this process seems to appear in childhood. The ideal cardiovascular health index (ICHI) has been inversely related to atherosclerotic plaque in adults. However, evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to assess the association between ICHI and inflammation in European adolescents.. As many as 543 adolescents (251 boys and 292 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional multi-center study including 9 European countries, were measured. C-reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell counts were used to compute an inflammatory score. Multilevel linear models and multilevel logistic regression were used to assess the association between ICHI and inflammation controlling by covariates. Higher ICHI was associated with a lower inflammatory score, as well as with several individual components, both in boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal components of the ICHI had significantly lower inflammatory score and lower levels of the study biomarkers, except CRP. Finally, the multilevel logistic regression showed that for every unit increase in the ICHI, the probability of having an inflammatory profile decreased by 28.1% in girls.. Results from this study suggest that a better ICHI is associated with a lower inflammatory profile already in adolescence. Improving these health behaviors, and health factors included in the ICHI, could play an important role in CVD prevention. Topics: Adolescent; Age Factors; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Complement C3; Complement C4; Cross-Sectional Studies; Diet; Europe; Female; Health Status; Humans; Inflammation; Inflammation Mediators; Leptin; Leukocyte Count; Life Style; Linear Models; Logistic Models; Male; Multivariate Analysis; Nutrition Surveys; Odds Ratio; Risk Assessment; Risk Factors; Risk Reduction Behavior | 2017 |
High-fat diet induced leptin and Wnt expression: RNA-sequencing and pathway analysis of mouse colonic tissue and tumors.
Obesity, an immense epidemic affecting approximately half a billion adults, has doubled in prevalence in the last several decades. Epidemiological data support that obesity, due to intake of a high-fat, western diet, increases the risk of colon cancer; however, the mechanisms underlying this risk remain unclear. Here, utilizing next generation RNA sequencing, we aimed to determine the high-fat diet (HFD) mediated expression profile in mouse colon and the azoxymethane/dextran sulfate sodium model of colon cancer. Mice on HFD had significantly higher colonic inflammation, tumor burden, and a number of differentially expressed transcripts compared to mice on regular diet (RD). We identified 721 transcripts differentially expressed in mouse HFD colon that were in a shared pattern with colonic tumors (RD and HFD). Importantly, in mouse colon, HFD stimulated an expression signature strikingly similar to human colon cancer, especially those with inflammatory microsatellite instability. Furthermore, pathway analysis of these transcripts demonstrated their association with active inflammation and colon cancer signaling, with leptin and Wnt as the top two transcripts elevated in mouse HFD colon shared with tumors. Moreover, in mouse colon, HFD-stimulated tumorigenic Wnt pathway activation was further validated by upregulation of β-catenin transcriptional targets. Finally, in human colon cancer, upregulation of leptin pathway members was shown with a large network of dysregulated transcripts being linked with worse overall survival. Topics: Animals; beta Catenin; Colon; Colonic Neoplasms; Diet, High-Fat; Gene Expression Regulation, Neoplastic; High-Throughput Nucleotide Sequencing; HT29 Cells; Humans; Inflammation; Inflammation Mediators; Leptin; Mice; Mice, Inbred C57BL; Obesity; Signal Transduction; Wnt Signaling Pathway | 2017 |
Unfavorable cytokine and adhesion molecule profiles during and after pregnancy, in women with gestational diabetes mellitus.
Gestational diabetes mellitus is a significant risk factor for metabolic syndrome and cardiovascular disease.. To assess the relationships between components of the metabolic syndrome and cytokine and adhesion molecule levels in women with GDM during pregnancy and after delivery.. A prospective case-control study on a sample of 126 pregnant women (63 with and 63 without gestational diabetes mellitus). In an intra-subject analysis, 41 women with history of gestational diabetes mellitus and 21 controls were re-assessed in the postpartum period. Clinical data and levels of cytokines and adhesion molecules were recorded during weeks 24-29 of pregnancy and 12 months after delivery.. In the postpartum period, there were significantly higher levels of tumor necrosis factor alpha in both cases and controls, and of adiponectin in controls. Cases showed higher leptin levels, with no significant differences during and after pregnancy. No significant differences were seen in adhesion molecules and interleukin-6 between cases and controls during pregnancy and in the postpartum period, but levels of both were higher in cases. During pregnancy and after delivery, adiponectin decreased in cases and increased in controls. Significant positive correlations were seen between adiponectin and fasting blood glucose levels and vascular cell adhesion molecule-1, and also between leptin and tumor necrosis factor alpha levels.. The results suggest that increased inflammation and transient hyperglycemia during pregnancy would represent a latent form of metabolic syndrome, with an increased risk for type 2 diabetes mellitus and future cardiovascular disease. Topics: Adiponectin; Adult; Blood Glucose; Cardiovascular Diseases; Case-Control Studies; Cell Adhesion Molecules; Cytokines; Diabetes, Gestational; Disease Susceptibility; Female; Humans; Hyperglycemia; Inflammation; Leptin; Metabolic Syndrome; Postpartum Period; Prediabetic State; Pregnancy; Prospective Studies; Tumor Necrosis Factor-alpha; Young Adult | 2017 |
Body composition and inflammatory markers in pubertal girls: Comparison between athletes and non-athletic controls.
Various inflammation parameters are increased with childhood obesity, but few comparable data are found in lean growing athletes. This study aims to characterize differences in 12 simultaneously measured inflammatory parameters between pubertal rhythmic gymnasts (RG) and untrained controls (UC), and to examine the relationship between body composition and inflammatory markers. Sixty 10-12-year-old girls were divided into RG (n = 30) and UC (n = 30). Fat mass (FM) and fat free mass (FFM) were measured by dual-energy X-ray absorptiometry. Leptin and 12 inflammatory parameters (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor, interferon-gamma [IFN-γ], tumor necrosis factor-alpha, IL-1α, IL-1β, monocyte chemotactic protein-1 and epidermal growth factor) were measured from fasting blood samples. No differences were seen in 12 inflammatory markers between studied groups. As expected, leptin (RG: 2.4 ± 1.1; UC: 7.6 ± 4.2 ng ml Topics: Athletes; Biomarkers; Body Composition; Child; Cytokines; Female; Humans; Inflammation; Interferon-gamma; Interleukins; Leptin; Puberty | 2017 |
Chronic diabetic states worsen Alzheimer neuropathology and cognitive deficits accompanying disruption of calcium signaling in leptin-deficient APP/PS1 mice.
The coincidences between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are so compelling that it is attractive to speculate that diabetic conditions might aggravate AD pathologies by calcium dysfunction, although the understanding of the molecular mechanisms involved remains elusive. The present work was undertaken to investigate whether calcium dyshomeostasis is associated with the exacerbated Alzheimer-like cognitive dysfunction observed in diabetic conditions in APP/PS1-ob/ob mice, which were generated by crossing ob/ob mice with APP/PS1 mice. We confirmed that the diabetic condition can aggravate not only Aβ deposition but also tau phosphorylation, synaptic loss, neuronal death, and inflammation, exacerbating cognitive impairment in AD mice. More importantly, we found that the diabetic condition dramatically elevated calcium levels in APP/PS1 mice, thereby stimulating the phosphorylation of the calcium-dependent kinases. Our findings suggest that controlling over-elevation of intracellular calcium may provide novel insights for approaching AD in diabetic patients and delaying AD progression. Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Calcium Signaling; Cognitive Dysfunction; Diabetes Mellitus, Type 2; Disease Models, Animal; Humans; Inflammation; Leptin; Male; Memory Disorders; Mice; Mice, Transgenic; Phosphorylation; Protein Aggregation, Pathological; Signal Transduction; Synapses; tau Proteins | 2017 |
Ablation of β,β-carotene-9',10'-oxygenase 2 remodels the hypothalamic metabolome leading to metabolic disorders in mice.
β,β-Carotene-9',10'-oxygenase 2 (BCO2) is a protein localized to the inner membrane of mitochondria. It was initially discovered as an enzyme that catalyzes the asymmetric cleavage of carotenoids. Systemic depletion of BCO2 causes increased food intake and impaired hepatic lipid metabolism in mice. The aim of this current study was to determine the extent to which BCO2 exerts its role in hypothalamic nutrient metabolism and feeding behavior through remodeling the hypothalamic metabolome in mice. Male BCO2 knockout (KO) and the isogenic wild-type 129S6 (WT) mice at 6 weeks of age were used for metabolic and cytokine and hypothalamic metabolomics and biochemical analysis. Compared to the WT, BCO2 KO mice exhibited widespread disruptions in metabolism and metabolite homeostasis, an increase in fasting blood glucose, a decrease in circulating glucagon and leptin, an elevation of plasma interleukin 1 beta and tumor necrosis factor alpha, and impaired AMP-activated protein kinase signaling. The global hypothalamic metabolomic results revealed that depletion of BCO2 resulted in striking metabolic changes, including suppression of long-chain fatty acids transport into mitochondria, inhibition of the metabolism of dipeptides and sulfur-containing amino acids, and stimulation of local oxidative stress and inflammation in the hypothalamus of BCO2 KO mice. These findings suggest that BCO2 regulates hypothalamic mitochondrial function, nutrient metabolism, and local oxidative stress and inflammation. Complex interplay between the hormone signaling and impaired lipid and glucose metabolism could account for initiation of oxidative stress, inflammation and eventual metabolic disorders in BCO2 KO mice. Topics: Animals; Blood Glucose; Cytokines; Dioxygenases; Energy Metabolism; Fatty Acids; Feeding Behavior; Glucagon; Hypothalamus; Inflammation; Leptin; Male; Metabolome; Mice, Inbred Strains; Mice, Knockout; Mitochondria; Oxidative Stress; Principal Component Analysis | 2017 |
Normalization of adiponectin concentrations by leptin replacement in ob/ob mice is accompanied by reductions in systemic oxidative stress and inflammation.
The circulating concentrations of adiponectin, an antidiabetic adipokine, have been shown to be reduced in obesity, in relation to an increase in inflammation. The aim of the present work was to assess the effect of leptin replacement on adiponectin levels and expression as well as on markers of oxidative stress and inflammation in leptin-deficient ob/ob mice. Twelve-week-old male mice (n = 7-10 per group) were treated with either saline (wild type and ob/ob mice) or leptin (ob/ob mice) for 18 days. A third group of ob/ob mice was treated with saline and pair-fed to the amount of food consumed by the leptin-treated group. Leptin replacement restored values of adiponectin (P < 0.001), reduced circulating 8-isoprostane and serum amyloid A (SAA) levels (P < 0.05 for both), and significantly downregulated the increased gene expression of osteopontin (Spp1, P < 0.05), Saa3 (P < 0.05), Cd68 (P < 0.01), Il6 (P < 0.01) and NADPH oxidase (Nox1 and Nox2, P < 0.01) in the perirenal WAT and Spp1 (P < 0.05) in the liver of ob/ob mice. In cultured adipocytes from ob/ob mice, leptin increased (P < 0.05) the mRNA expression and secretion of adiponectin. We concluded that circulating concentrations of adiponectin are positively regulated by leptin and ameliorate obesity-associated oxidative stress and inflammation in mice. Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Biomarkers; Inflammation; Leptin; Mice; Mice, Obese; Oxidative Stress | 2017 |
Nonalcoholic fatty liver disease in chronic obstructive pulmonary disease.
Nonalcoholic fatty liver disease (NAFLD) is independently linked to cardiometabolic morbidity and mortality. Low-grade inflammation, oxidative stress and ectopic fat, common features of chronic obstructive pulmonary disease (COPD), might contribute to the development of NAFLD.We aimed to investigate the prevalence of NAFLD and to evaluate the relationship between various types of liver damage and COPD severity, comorbidities and circulating inflammatory cytokines. Validated noninvasive tests (FibroMax: SteatoTest, NashTest and FibroTest) were used to assess steatosis, nonalcoholic steatohepatitis (NASH) and liver fibrosis. Patients underwent an objective assessment of COPD comorbidities, including sleep studies. Biological parameters included a complete lipid profile and inflammatory markers.In COPD patients the prevalence of steatosis, NASH and fibrosis were 41.4%, 36.9% and 61.3%, respectively. In multivariate analysis, SteatoTest and FibroTest were significantly associated with sex, body mass index (BMI), untreated sleep apnoea and insulin resistance, and, in addition, COPD Global Initiative for Chronic Obstructive Lung Disease stage for SteatoTest. Patients with steatosis had higher tumour necrosis factor-α levels and those with NASH or a combination of liver damage types had raised leptin levels after adjustment for age, sex and BMI.We concluded that NAFLD is highly prevalent in COPD and might contribute to cardiometabolic comorbidities. Topics: Adiponectin; Aged; Body Mass Index; C-Reactive Protein; Cohort Studies; Comorbidity; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Liver Cirrhosis; Male; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Resistin; Tumor Necrosis Factor-alpha | 2017 |
Effects of mild calorie restriction on lipid metabolism and inflammation in liver and adipose tissue.
Calorie restriction (CR) has been reported to improve lipid metabolism and to decrease inflammatory diseases. However, most existing CR models use 30-50% calorie reduction, which is hard to achieve in humans. We investigated the effects of mild CR on lipid metabolism and inflammatory responses. Male C57BL/6 mice were fed control diet (10% kcal fat, Control) or high fat diet (60% kcal fat, HFD) ad libitum or reduced amount of control diet to achieve 15% CR for 16 wks. Body weights, white adipose tissue weights, liver triacylglycerol levels, and serum fetuin-A levels were lower in CR than in the Control. Serum adiponectin levels were higher in CR and lower in HFD compared with the Control. Liver and adipose tissue Mcp-1 mRNA levels were significantly lower in CR compared with the Control. Adipose tissue mRNA levels of Mcp-1, Il-6, Tnf-α and Socs3 were significantly higher in HFD than in the Control and CR, and levels of these negatively correlated with serum adiponectin levels. CR group had the lowest leptin levels and the highest liver Lepr expression, and Lepr mRNA levels positively correlated with liver Socs3 mRNA levels. Our findings showed that mild CR lowered adiposity which resulted in higher adiponectin and lower fetuin-A levels, and might have contributed to alleviation of inflammatory status in the liver and adipose tissue. Furthermore, mild CR might have affected leptin sensitivity by up-regulating Lepr expression. Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Body Weight; Caloric Restriction; Gene Expression Regulation; Inflammation; Leptin; Lipid Metabolism; Lipids; Liver; Male; Mice, Inbred C57BL; Signal Transduction; Transaminases | 2017 |
Administration of a leptin antagonist during the neonatal leptin surge induces alterations in the redox and inflammatory state in peripubertal /adolescent rats.
The importance of the neonatal leptin surge in rodents in neurodevelopmental processes has aroused curiosity in its implication in other physiological systems. Given the role of leptin in neuro-immune interactions, we hypothesized that the neonatal leptin surge could have an effect on the oxidative and inflammatory stress situations of both systems. We blocked the neonatal leptin surge by a leptin antagonist and measured several parameters of oxidative and inflammatory stress in the spleen, hypothalamus and adipose tissue of peripubertal/adolescent rats. The treated rats showed lower activity of several antioxidant enzymes in the spleen and their leukocytes released lower levels of mitogen-stimulated IL-10 and IL-13 and higher levels of TNF-alpha. In conclusion, the neonatal leptin surge may have a key role in the establishment of adequate redox and inflammatory states in the immune system, which is important for the generation of adequate immune responses and to obtain and maintain good health. Topics: Adipose Tissue, White; Animals; Animals, Newborn; Body Weight; Catalase; Cytokines; Female; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Hypothalamus; Inflammation; Leptin; Male; Organ Size; Oxidation-Reduction; Oxidative Stress; Rats, Wistar; RNA, Messenger; Sexual Maturation; Superoxide Dismutase | 2017 |
Protein-Tyrosine Phosphatase-1B Mediates Sleep Fragmentation-Induced Insulin Resistance and Visceral Adipose Tissue Inflammation in Mice.
Sleep fragmentation (SF) is highly prevalent and has emerged as an important contributing factor to obesity and metabolic syndrome. We hypothesized that SF-induced increases in protein tyrosine phosphatase-1B (PTP-1B) expression and activity underlie increased food intake, inflammation, and leptin and insulin resistance.. Wild-type (WT) and ObR-PTP-1b-/- mice (Tg) were exposed to SF and control sleep (SC), and food intake was monitored. WT mice received a PTP-1B inhibitor (RO-7d; Tx) or vehicle (Veh). Upon completion of exposures, systemic insulin and leptin sensitivity tests were performed as well as assessment of visceral white adipose tissue (vWAT) insulin receptor sensitivity and macrophages (ATM) polarity.. SF increased food intake in either untreated or Veh-treated WT mice. Leptin-induced hypothalamic STAT3 phosphorylation was decreased, PTP-1B activity was increased, and reduced insulin sensitivity emerged both systemic and in vWAT, with the latter displaying proinflammatory ATM polarity changes. All of the SF-induced effects were abrogated following PTP-1B inhibitor treatment and in Tg mice.. SF induces increased food intake, reduced leptin signaling in hypothalamus, systemic insulin resistance, and reduced vWAT insulin sensitivity and inflammation that are mediated by increased PTP-1B activity. Thus, PTP-1B may represent a viable therapeutic target in the context of SF-induced weight gain and metabolic dysfunction. Topics: Adipose Tissue, White; Animals; Eating; Hypothalamus; Inflammation; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Macrophages; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Receptor, Insulin; Signal Transduction; Sleep Deprivation; STAT3 Transcription Factor; Tyrosine; Weight Gain | 2017 |
Vaspin prevents leptin‑induced inflammation and catabolism by inhibiting the activation of nuclear factor‑κB in rat chondrocytes.
The present study aimed to investigate the function and possible underlying mechanism of various concentrations of visceral adipose tissue‑derived serine protease inhibitor (vaspin) on leptin‑induced inflammatory and metabolic responses in rat chondrocytes. Rat articular chondrocytes were isolated and treated with different concentrations of vaspin, which was followed by stimulation with leptin. The expression of genes, secretion of nitric oxide and tumor necrosis factor‑α, and activation of the nuclear factor (NF)‑κB pathway were analyzed by reverse transcription‑quantitative polymerase chain reaction, ELISA and western blotting. The results demonstrated that vaspin inhibited the leptin‑induced upregulated gene expression levels of leptin receptor (OB‑Rb), a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)‑4, ADAMTS‑5, matrix metalloproteinase (MMP)‑2 and MMP‑9, and the secretion of NO and TNF‑α, in a dose‑dependent manner. The phosphorylation of inhibitor of NF‑κB (IκB), IκB kinase (IKK)α, IKKβ and NF‑κB were also promoted by leptin in the chondrocytes, which were also suppressed by increased concentration of vaspin. Taken together, results demonstrated that vaspin prevented leptin‑induced inflammation and catabolism by inhibiting the activation of NF‑κB in rat chondrocytes. Topics: Animals; Cells, Cultured; Chondrocytes; Gene Expression Regulation; Inflammation; Leptin; NF-kappa B; Nitric Oxide; Rats; Rats, Sprague-Dawley; Serpins; Tumor Necrosis Factor-alpha | 2017 |
Voluntary running of defined distances reduces body adiposity and its associated inflammation in C57BL/6 mice fed a high-fat diet.
This study investigated the effect of voluntary running of defined distances on body adiposity in male C57BL/6 mice fed a high-fat diet. Mice were assigned to 6 groups and fed a standard AIN93G diet (sedentary) or a modified high-fat AIN93G diet (sedentary; unrestricted running; or 75%, 50%, or 25% of unrestricted running) for 12 weeks. The average running distance was 8.3, 6.3, 4.2, and 2.1 km/day for the unrestricted, 75%, 50%, and 25% of unrestricted runners, respectively. Body adiposity was 46% higher in sedentary mice when fed the high-fat diet instead of the standard diet. Running decreased adiposity in mice fed the high-fat diet in a dose-dependent manner but with no significant difference between sedentary mice and those running 2.1 km/day. In sedentary mice, the high-fat instead of the standard diet increased insulin resistance, hepatic triacylglycerides, and adipose and plasma concentrations of leptin and monocyte chemotactic protein-1 (MCP-1). Running reduced these variables in a dose-dependent manner. Adipose adiponectin was lowest in sedentary mice fed the high-fat diet; running raised adiponectin in both adipose tissue and plasma. Running 8.3 and 6.3 km/day had the greatest, but similar, effects on the aforementioned variables. Running 2.1 km/day did not affect these variables except, when compared with sedentariness, it significantly decreased MCP-1. The findings showed that running 6.3 kg/day was optimal for reducing adiposity and associated inflammation that was increased in mice by feeding a high-fat diet. The findings suggest that voluntary running of defined distances may counteract the obesogenic effects of a high-fat diet. Topics: Adiposity; Animals; Biomarkers; Chemokine CCL2; Diet, High-Fat; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Physical Conditioning, Animal; Running | 2017 |
Effects of intravenous lipopolysaccharide administration on feed intake, ruminal forage degradability, and liquid parameters and physiological responses in beef cattle.
This experiment compared DMI, ruminal forage degradability, and liquid parameters as well as physiological responses in beef cattle receiving a lipopolysaccharide (LPS) challenge or not. Eight ruminally cannulated Angus × Hereford steers (485 ± 16 kg BW) were housed in individual pens on d -7, ranked by BW, and allocated to 1 of 2 treatments administered on d 0: 1) an intravenous (i.v.) bolus dose (0.5 μg/kg of BW, diluted in 5 mL of 0.9% sterile saline) of bacterial LPS ( 0111:B4) or 2) a 5-mL i.v. injection of 0.9% sterile saline (CON). Steers had free-choice access to mixed alfalfa-grass hay, water, and a commercial vitamin + mineral mix during the experiment (d -7 to 6). Hay DMI was evaluated daily from d -5 to 6. Immediately prior to treatment administration (h 0), polyester bags containing 4 g of ground dietary hay (DM basis) were immersed into the rumen of each steer and incubated for 0, 4, 8, 12, 24, 36, and 48 h for DM and NDF degradability evaluation. Steers were also intraruminally pulse-dosed with 5 g of Co-EDTA immediately prior to treatment administration, and rumen fluid samples were collected at 0, 2, 4, 6, 8, 12, 16, and 24 h for ruminal liquid volume and dilution rate calculations. Blood was collected every 2 h from -2 to 8 h, every 4 h from 8 to 16 h, every 12 h from 24 to 72 h, and every 24 h from 96 to 144 h relative to treatment administration. Values obtained before treatment administration were used as a covariate within each respective analysis. Steers receiving LPS had less ( ≤ 0.03) DMI on d 0 and 1 compared with CON steers. Steers receiving LPS had reduced ( ≤ 0.05) rumen liquid volume and dilution rate as well as ruminal disappearance rate and effective degradability of DM and NDF compared with CON steers. Steers receiving LPS had greater ( ≤ 0.05) plasma tumor necrosis factor α at 2 h, greater plasma haptoglobin from 24 to 72 h, greater plasma cortisol from 12 to 16 h, greater serum NEFA from 6 to 48 h, greater plasma insulin and glucose at 2 h, reduced plasma glucose from 4 to 12 h, greater plasma cholecystokinin at 16 h, and greater plasma leptin concentrations at 8, 12, 16, 36, 48, and 60 h after treatment administration compared with CON steers. Hence, LPS administration transiently reduced DMI in steers via physiological reactions that modulate gastrointestinal motility and satiety centers in the central nervous system, in addition to potential host-microbiome endocrine interactions that impaired ruminal hay DM and NDF d Topics: Administration, Intravenous; Animal Feed; Animals; Cattle; Diet; Digestion; Eating; Gastrointestinal Motility; Haptoglobins; Inflammation; Leptin; Lipopolysaccharides; Male; Medicago sativa; Poaceae; Rumen | 2017 |
Role of Thyroid Deficiency on Adiponectin, Leptin, and Metabolic Status in Visceral Obesity: A Cross-Sectional Study.
Hypothyroidism results in disturbances of metabolism influencing many regulatory systems and active molecules as adipocytokines. Objective of the study was to investigate leptin and adiponectin in patients with visceral obesity and hypothyroidism in relation to metabolic status, insulin resistance and systemic inflammation. A total of 118 patients (59 hypothyroid and 59 euthyroid) were enrolled divided into four age-matched groups according to body wеight (BMI) and thyroid function. Laboratory panel includes TSH, FT4, FT3 (CMIA), adiponectin and leptin (ELISA), IL- 6 (ECLIA), CRP, insulin, glucose, apolipoprotein B and lipoprotein (a) - Lp(a). Hypothyroid patients revealed significant positive correlations of TSH, adiponectin and Lp(a). Their medians of 10.4 mU/l, 12.5 µg/ml and 116.3 mg/l respectively were significantly higher than in euthyroid patients- 1.5 mU/l, 6.26 µg/ml and 32.0 mU/l (p < 0.0001). Leptin in both obese groups was significantly higher than in patients with normal weight. Leptin in hypothyroid patients was lower but not significant to euthyroid ones (9.7 ng/ml vs 13.4 ng/ml respectively, p = 0.16), correlated negatively to TSH and positively to CRP, IL-6, ApoB, Lp(a) and BMI. HOMA-IR and serum insulin at 120 min in OGTT were significantly higher in hypothyroid than in euthyroid patients independent of BMI (p < 0.001). Adiponectin, insulin resistance and chronic inflammation indices in hypothyroid patients correlated positively to TSH, BMI and atherogenic lipoproteins subclasses ApoB/Lp(a). Increased adiponectin in thyroid deficiency could be due to secondary resistance of adiponectin receptors or appeared as a compensatory pathogenetic factor in hypothyroidism. Topics: Adiponectin; Adult; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypothyroidism; Inflammation; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity, Abdominal; Thyroid Gland | 2017 |
Predictors of Subclinical Inflammatory Obesity: Plasma Levels of Leptin, Very Low-Density Lipoprotein Cholesterol and CD14 Expression of CD16+ Monocytes.
Predictors of subclinical inflammatory obesity (SIO) can be important tools for early therapeutic interventions in obesity-related comorbidities. Waist circumference (WC) and BMI have different SIO sensitivity. We aimed to i) identify SIO predictors and ii) investigate whether CD16+ monocytes are associated with BMI- (generally) or WC-defined (centrally) obesity.. Anthropometric and metabolic/endocrine (namely catecholamines, adrenaline and noradrenaline) parameters were evaluated, and CD16+ monocytes were studied by flow cytometry in the peripheral blood from 63 blood donors, and compared and correlated to each other. Multiple linear regression analysis was performed to identify variables that best predict SIO.. CD16+ monocyte counts were similar in BMI and WC groups. CD16+ monocytes from centrally obese (CO) showed a more inflammatory pattern, as compared to non-CO subjects. WC was sensitive to lipidemia and, in CO subjects, lipidemia was associated with a more inflammatory phenotype of CD16+ monocytes. These differences were not noticed between BMI groups. Adrenaline was correlated with CD16+ monocyte expansion with a lower inflammatory pattern. Leptin, very low-density lipoprotein cholesterol (VLDL-C), and CD14 expression of CD16+ monocytes were found to be CO predictors.. WC-, but not BMI-defined obesity, was associated with a more inflammatory pattern of CD16+ monocytes, without monocyte expansion, suggesting that a monocyte maturation process rather than an independent arise of CD16+ monocytes occurs in CO. Thus, in a population with low cardiovascular risk, leptin, VLDL-C, and CD14 expression of CD16+ monocytes predict CO, constituting a putative tool for screening of SIO. Topics: Anthropometry; Antigens, CD; Body Mass Index; Cardiovascular Diseases; Cholesterol, VLDL; Female; GPI-Linked Proteins; Humans; Inflammation; Leptin; Leukocyte Count; Lipopolysaccharide Receptors; Male; Monocytes; Obesity; Receptors, Immunologic; Risk Factors; Waist Circumference | 2017 |
Xuefu Zhuyu decoction ameliorates obesity, hepatic steatosis, neuroinflammation, amyloid deposition and cognition impairment in metabolically stressed APPswe/PS1dE9 mice.
Metabolic syndrome and vascular dysfunction was suggested to be the risk factors for Alzheimer's disease (AD). Xuefu Zhuyu decoction (XZD) is a traditional Chinese medicine used to treat metabolic syndrome and cardiac-cerebral vascular disease. The effects of XZD on ameliorating metabolic syndrome, amyloid-related pathologies and cognitive impairment in an animal model of AD with metabolic stress was investigated.. The animal model of AD with metabolic stress was created by administrating high-fat diet and a low-dose injection of streptozotocin prior to the appearance of senile plaques in APP/PS1 transgenic mice. The diabesity-associated metabolic changes and AD-related pathological alterations were examined.. We found that XZD reduced body weight, insulin and leptin level, HOMA-IR, hepatic triglyceride, serum Aβ42 in the metabolic stressed AD animal. XZD also ameliorated oral glucose tolerant, Aβ deposition, astrocyte and microglia activation in the vicinity of plaques, and nesting behavior in the metabolic stressed AD animal.. The results of this study suggest that XZD is able to reduce the peripheral metabolic stress-mediated vascular hypoperfusion, neuroinflammation and AD-related pathology in APP/PS1 mice. Topics: Alzheimer Disease; Amyloid; Amyloid beta-Protein Precursor; Animals; Blood Glucose; Cognitive Dysfunction; Drugs, Chinese Herbal; Fatty Liver; Homeostasis; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Mice; Mice, Transgenic; Obesity; Stress, Physiological; Triglycerides | 2017 |
Involvement of the leptin-adiponectin axis in inflammation and oxidative stress in the metabolic syndrome.
The aim of the present work was to study whether the leptin-adiponectin axis may have a pathophysiological role in the increased systemic inflammation and oxidative stress observed in patients with the metabolic syndrome (MS). Leptin, adiponectin, and markers of inflammation and oxidative stress were measured in a sample of 140 Caucasian subjects (74 males/66 females), aged 28-82 years, 60 with and 80 without the MS. Total concentrations of adiponectin as well as its multimeric forms HMW, MMW and LMW were significantly lower in individuals with the MS. The ratio adiponectin/leptin, a marker of dysfunctional adipose tissue, was dramatically decreased in the MS group. Systemic oxidative stress, as evidenced by levels of thiobarbituric acid reactive substances (TBARS), as well as markers of inflammation such as serum amyloid A (SAA), C-reactive protein (CRP) and osteopontin were significantly increased in subjects with the MS. Total adiponectin concentrations were negatively correlated with levels of TBARS and CRP levels. Furthermore, the ratio adiponectin/leptin was negatively correlated with SAA concentrations as well as with CRP levels. We concluded that a dysfunctional adipose tissue as suggested by a low adiponectin/leptin ratio may contribute to the increased oxidative stress and inflammation, hallmarks of the MS. Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Chemical Analysis; Female; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress | 2017 |
Serum levels of soluble urokinase plasminogen activator receptor as a new inflammatory marker in adolescent obesity.
Obesity is known for low-grade inflammatory state with enhanced production of inflammatory mediators in children and adolescents. Soluble urokinase plasminogen activator receptor (suPAR) can be generated as a pro-inflammatory marker. This study was conducted to evaluate the role of suPAR, and its association with leptin, adiponectin, interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP) and fibrinogen in adolescent obesity.. A total of 98 participants, 55 obese individuals and 43 healthy controls, aged between 10 and 17 yr, were included in the study. Serum suPAR, IL-6, leptin and adiponectin were measured using ELISA method.. Serum suPAR, IL-6, fibrinogen, hsCRP and leptin levels in obese individuals were significantly higher than those of controls (P<0.05 & P<0.001). Serum adiponectin levels in obese individuals were significantly lower than those of controls (P<0.01).. Our findings showed that suPAR, IL-6, fibrinogen, hsCRP and leptin were significantly higher in the obese individuals than those of controls. suPAR may be a good novel biomarker for systemic subclinical inflammation and immune activation linked to adolescent obesity. Topics: Adiponectin; Adolescent; Biomarkers; C-Reactive Protein; Child; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Pediatric Obesity; Receptors, Urokinase Plasminogen Activator | 2017 |
Elucidating the role of leptin in systemic inflammation: a study targeting physiological leptin levels in rats and their macrophages.
Topics: Animals; Cytokines; Fever; Food Deprivation; Inflammation; Leptin; Lipopolysaccharides; Macrophages; Male; Rats, Wistar | 2017 |
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Topics: Adult; Biomarkers; Body Mass Index; Female; Gene Expression Regulation; Humans; Inflammation; Leptin; Leukocytes, Mononuclear; Male; Metabolome; Middle Aged; Obesity, Abdominal; Receptors, Adrenergic, beta; Triglycerides; Waist Circumference | 2017 |
The Beneficial Effect of Anthocyanidin-Rich Vitis vinifera L. Grape Skin Extract on Metabolic Changes Induced by High-Fat Diet in Mice Involves Antiinflammatory and Antioxidant Actions.
We hypothesized that a polyphenol-rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high-fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. GSE prevented weight gain; dyslipidemia; insulin resistance; the alterations in plasma levels of leptin, adiponectin, and resistin; and the deregulation of leptin and adiponectin expression in adipose tissue. These beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio, and GLUT4 expression in muscle and adipose tissue. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an anti-inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF-α, IL-6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF-fed mice by regulating insulin sensitivity and GLUT4 expression as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright © 2017 John Wiley & Sons, Ltd. Topics: Adiponectin; Adipose Tissue; Animals; Anthocyanins; Anti-Inflammatory Agents; Antioxidants; Body Weight; Diet, High-Fat; Fruit; Glucose Transporter Type 4; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Obesity; Oxidative Stress; Phosphatidylinositol 3-Kinases; Plant Extracts; Polyphenols; Tumor Necrosis Factor-alpha; Vitis | 2017 |
Interleukin 6 (IL-6) and Tumor Necrosis Factor α (TNF-α) Single Nucleotide Polymorphisms (SNPs), Inflammation and Metabolism in Gestational Diabetes Mellitus in Inner Mongolia.
BACKGROUND Gestational diabetes mellitus (GDM) is common all over the world. GDM women are with inflammatory and metabolisms abnormalities. However, few studies have focused on the association of IL-65-72C/G and TNF-α -857C/T single nucleotide polymorphisms (SNPs), inflammatory biomarkers, and metabolic indexes in women with GDM, especially in the Inner Mongolia population. The aim of this study was to investigate the associations of IL-65-72C/G and TNF-α -857C/T SNPs, and inflammation and metabolic biomarkers in women with GDM pregnancies. MATERIAL AND METHODS Blood samples and placentas from 140 women with GDM and 140 women with healthy pregnancies were collected. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and MassARRAY-IPLEX were performed to analyze IL-65-72C/G and TNF-α -857C/T SNPs. Enzyme linked immunosorbent assay (ELISA) was performed to analyze inflammatory biomarkers and adipokines. RESULTS Distribution frequency of TNF-α -857CT (OR=3.316, 95% CI=1.092-8.304, p=0.025) in women with GDM pregnancies were obviously higher than that in women with healthy pregnancies. Women with GDM were of older maternal age, had higher BMI, were more nulliparous, and had T2DM and GDM history, compared to women with healthy pregnancies (p<0.05). Inflammatory biomarkers in serum (hs-CRP, IL-6, IL-8, IL-6/IL-10 ratio) and placental (NF-κB, IL-6, IL-8, IL-6/IL-10 ratio, IL-1b, TNF-α) were significantly different (p<0.05) between women with GDM and women with healthy pregnancies. Differences were found for serum FBG, FINS, HOMA-IR, and HOMA-β, and placental IRS-1, IRS-2, leptin, adiponectin, visfatin, RBP-4, chemerin, nesfatin-1, FATP-4, EL, LPL, FABP-1, FABP-3, FABP-4, and FABP-5. CONCLUSIONS TNF-α -857C/T SNP, hs-CRP, IL-6, IL-8, and IL-6/IL-10 were associated with GDM in women from Inner Mongolia, as was serious inflammation and disordered lipid and glucose metabolisms. Topics: Adipokines; Adult; Biomarkers; Blood Glucose; China; Diabetes, Gestational; Female; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Placenta; Polymorphism, Single Nucleotide; Pregnancy; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumor Necrosis Factor-alpha | 2017 |
Exogenous leptin protects rat models of sodium taurocholate‑induced severe acute pancreatitis through endocrinal and immunological pathways.
Acute pancreatitis (AP) is a common non‑bacterial disease compromising pancreatic tissues. Adipocyte‑derived leptin is closely associated with the severity and clinical outcome of pancreatitis. The potential protective effects of exogenous leptin administration on a rat model of severe AP (SAP) remain to be elucidated, and were examined in the present study. Male Wistar rats were divided into a sham operation group (SO), SAP model group (SAP) and leptin group (LEP). Each group was divided into three sub‑groups by observation time (24, 48 and 72 h). The SAP models were prepared by retrograde injection of 6% sodium taurocholate into the pancreatic‑bile duct. Following model establishment, exogenous leptin was intraperitoneally injected into mice at 50 mg/kg in the LEP group. Subsequently, serum amylase, lipase and glucose levels at particular time‑points were analyzed using a fully‑automatic biochemical analyzer, and serum levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑10 were detected using an enzyme‑linked immunosorbent assay. The pathological changes in pancreatic tissues were observed using hematoxylin and eosin staining, and the pancreatic expression of the long form of the leptin receptor (OB‑Rb) was detected and evaluated using Nest‑polymerase chain reaction analysis. The mortality rates of the model rats were compared between the groups. Following the administration of exogenous leptin, the serum level of amylase in the LEP group was significantly decreased at 48 h, compared with that in the SAP group, with serum lipase levels decreased at 48 and 72 h, and blood glucose levels decreased at 72 h. Regarding the serum inflammatory factors, the level of TNF‑α in the LEP group was significantly lower, compared with that in the SAP group at 24 h; whereas no significant difference was observed in the serum level of IL‑10 between the two groups. Regarding the pathological changes in the pancreas, the tissues in the LEP group showed significantly alleviated pancreatic inflammation. In addition, the pancreatic expression of OB‑Rb in the LEP group was significantly higher, compared with that in the SAP group at 24 and 48 h. No significant difference in 3‑day mortality rates were observed between the SAP group and the LEP group. Taken together, exogenous leptin administration regulated inflammatory factors and the expression of OB‑Rb at the early stage of AP, which exerted protective effects by through the immunological and endocrinal pathways. Topics: Acute Disease; Amylases; Animals; Blood Glucose; Disease Models, Animal; Inflammation; Interleukin-10; Leptin; Lipase; Male; Pancreas; Pancreatitis; Protective Agents; Rats; Rats, Wistar; Receptors, Leptin; Severity of Illness Index; Taurocholic Acid; Tumor Necrosis Factor-alpha | 2017 |
A high fat-high sucrose diet enriched in blue mussels protects against systemic inflammation, metabolic dysregulation and weight gain in C57BL/6 mice.
High fat-high sucrose (HF-HS) diet, known as the western diet, has been shown to induce the onset of obesity via increasing metabolic inflammation, insulin resistance and adipose tissue dysfunction. Hyperleptinemia, hyperglycemia and dyslipidemia are also the primary observations of obesogenic diet induced obesity. We have previously reported anti-adipogenic and insulin sensitizing effects of blue mussels (BM) using 3T3-L1 cells. BM is a rich source of omega-3 polyunsaturated fatty acids, phytosterols and other micronutrients that has been shown to elicit benefits under obese conditions using in-vitro cell culture models. However, no studies to date have established the anti-obesity effects, safety and efficacy of BM in an in-vivo animal model. In the present study, we fed a HF-HS diet supplemented with different concentrations of BM freeze-dried powder (1.25, 2.5 and 5% w/w) to C57BL/6 mice for 12weeks. A HF-HS diet caused rapid weight gain, hyperglycemia, dyslipidemia, hyperleptinemia, and increased plasma levels of inflammatory cytokines; interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Incorporating 2.5% BM in the HF-HS diet prevented weight gain, dyslipidemia, hyperglycemia and reduced the levels of inflammatory cytokines and leptin mRNA expression. Furthermore, plasma from 2.5% BM increased cholesterol efflux capacity of J774 macrophage cells, compared to plasma from HF-HS diet. There was no effect of 1.25% BM on any tested parameters, while 5% BM was not palatable after four weeks. In conclusion, our findings have established the efficacy and safety of BM using C57BL/6 mice, demonstrating that BM has the potential to target obesity and related complications. Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Biomarkers; Cholesterol; Cytokines; Diet, High-Fat; Diet, Western; Dietary Sucrose; Dietary Supplements; Dyslipidemias; Hyperglycemia; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Macrophages; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Models, Animal; Mytilus edulis; Obesity; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Gain | 2017 |
The impact of the Standard American Diet in rats: Effects on behavior, physiology and recovery from inflammatory injury.
Obesity is a significant health concern in the Western world and the presence of comorbid conditions suggests an interaction. The overlapping distributions of chronic pain populations and obesity suggests that an interaction may exist. Poor quality diet (high carbohydrates, saturated fats, omega-6 polyunsaturated fatty acids) can lead to increased adiposity which can activate immune cells independent of the activating effect of the diet components themselves. This dual action can contribute to chronic inflammation that may alter susceptibility to chronic pain and prolong recovery from injury. However, traditional examinations of diet focus on high-fat diets that often contain a single source of fat, that is not reflective of an American diet. Thus, we examined the impact of a novel human-relevant (high-carbohydrate) American diet on measures of pain and inflammation in rats, as well as the effect on recovery and immune cell activation.. We developed a novel, human-relevant Standard American Diet (SAD) to better model the kilocalorie levels and nutrient sources in an American population. Male and female rats were fed the SAD over the course of 20 weeks prior to persistent inflammatory pain induction with Complete Freund's Adjuvant (CFA). Mechanical and thermal sensitivity were measured weekly. Spontaneous pain, open field locomotion and blood glucose levels were measured during diet consumption. Body composition was assessed at 20 weeks. Following full recovery from CFA-induced hypersensitivity, blood was analyzed for inflammatory mediators and spinal cords were immunohistochemically processed for microglial markers.. Chronic consumption of the SAD increased fat mass, decreased lean mass and reduce bone mineral density. SAD-fed rats had increased leptin levels and pro-inflammatory cytokines in peripheral blood serum. Following CFA administration, mechanical sensitivity was assessed and recovery was delayed significantly in SAD-fed animals. Sex differences in the impact of the SAD were also observed. The SAD increased body weight and common T-cell related inflammatory mediators in female, but not male, animals. In males, the SAD had a greater effect on bone mineral density and body composition. Long-term consumption of the SAD resulted in elevated microglial staining in the dorsal horn of the spinal cord, but no sex differences were observed.. We demonstrate the negative effects of an American diet on physiology, behavior and recovery from injury. SAD consumption elevated pro-inflammatory mediators and increased microglial activation in the spinal cord. While there were sex differences in weight gain and inflammation, both sexes showed prolonged recovery from injury.. These data suggest that poor quality diet may increase susceptibility to chronic pain due to persistent peripheral and central immune system activation. Furthermore, consumption of a diet that is high in carbohydrates and omega-6 polyunsaturated fatty acid is likely to lead to protracted recovery following trauma or surgical procedures. These data suggest that recovery of a number of patients eating a poor quality diet may be expedited with a change in diet to one that is healthier. Topics: Adipose Tissue; Animals; Behavior, Animal; Blood Glucose; Bone Density; Cytokines; Diet, Western; Female; Inflammation; Leptin; Male; Microglia; Pain; Rats; Rats, Sprague-Dawley; Sex Factors; Spinal Cord | 2017 |
Biomarkers of inflammation and breast cancer risk: a case-control study nested in the EPIC-Varese cohort.
Breast cancer (BC) is the leading cause of cancer death in women. Adipokines, and other inflammation molecules linked to adiposity, are suspected to be involved in breast carcinogenesis, however prospective findings are inconclusive. In a prospective nested case-control study within the EPIC-Varese cohort, we used conditional logistic regression to estimate rate ratios (RRs) for BC, with 95% confidence intervals (CI), in relation to plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6, leptin, and adiponectin, controlling for BC risk factors. After a median 14.9 years, 351 BC cases were identified and matched to 351 controls. No marker was significantly associated with BC risk overall. Significant interactions between menopausal status and CRP, leptin, and adiponectin were found. Among postmenopausal women, high CRP was significantly associated with increased BC risk, and high adiponectin with significantly reduced risk. Among premenopausal women, high TNF-α was associated with significantly increased risk, and high leptin with reduced risk; interleukin-6 was associated with increased risk only in a continuous model. These findings constitute further evidence that inflammation plays a role in breast cancer. Interventions to lower CRP, TNF-α, and interleukin-6 and increase adiponectin levels may contribute to preventing BC. Topics: Adiponectin; Adult; Aged; Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; C-Reactive Protein; Female; Genetic Association Studies; Humans; Inflammation; Interleukin-6; Leptin; Middle Aged; Postmenopause; Risk Factors; Tumor Necrosis Factor-alpha | 2017 |
Weight loss-dependent and -independent effects of moderate calorie restriction on endothelial cell markers in obesity.
Endothelial cell dysfunction in obesity can be reduced by calorie restriction (CR), however it is unclear whether this benefit requires a concomitant weight loss or is it simply related to the reduced calorie intake per se. In our study serum was drawn from 41 obese women who were undergoing an 8-week dietary intervention with 15 - 30% energy deficit, and from 48 age- and sex-matched controls of normal weight. Serum was analysed for biomarkers of endothelial cell function, oxidative stress and inflammation. Compared with non-obese individuals, the obese patients had lower serum levels of nitric oxide (NO), adiponectin, and decreased serum antioxidant status. They also had significantly higher levels of adhesive molecules, thrombomodulin (TM), von Wilebrand factor (vWF), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and leptin. To further characterize the effect of moderate CR, the patients were ranked into two comparable groups according to the extent of weight loss - below and above the median (-5.8 kg). A moderate dietary intervention did not correct adiponectin, antioxidant status, vWF, TM, and plasminogen activator inhibitor-1 (PAI-1) but ameliorated changes in other parameters. Only changes in NO and - to a lesser degree - in sE-selectin showed a clear relationship with the magnitude of weight reduction. By contrast, a beneficial reduction in TNF-α occurred equally in patients who lost more or less weight after caloric restriction. We concluded that moderate calorie restriction could still improve several parameters of endothelial cell function irrespective of whether it was accompanied by changes in body mass. However, a significant improvement in nitric oxide, a key mediator of endothelial well-being, requires a substantial reduction in body weight. Topics: Adiponectin; Adult; Antioxidants; Biomarkers; Body Weight; Caloric Restriction; Endothelial Cells; Endothelium, Vascular; Female; Humans; Inflammation; Leptin; Nitric Oxide; Obesity; Oxidative Stress; Weight Loss | 2017 |
Short-Term High-Fat Diet Feeding Provides Hypothalamic but Not Hippocampal Protection against Acute Infection in Male Mice.
Obesity is associated with increased fever and sickness behavior in response to infection. The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the reaction to immune stimuli. Bacterial infection, or bacterial lipopolysaccharide (LPS), induces the expression of peripheral cytokines that stimulate the hypothalamus and the hippocampus and activate the HPA axis. In this study, we explored whether the hypothalamic and hippocampal responses to infection are altered during the development of diet-induced obesity. Male mice were exposed to a high-fat diet (HFD) or a low-fat diet (LFD) for 15 days. They were then administered a single intraperitoneal injection of bacterial LPS or vehicle and sacrificed 24 h later. LPS increased circulating levels of insulin and leptin, but only in LFD animals. LPS induced a significant decrease in hypothalamic corticotrophin-releasing hormone and glucocorticoid receptor mRNA levels in LFD animals but exerted the opposite effect in HFD-fed mice. LPS increased the hypothalamic expression of molecules involved in the leptin signaling pathway (SOCS3 and STAT3), nuclear factor-κB pathway members, inflammatory mediators (tumor necrosis factor-α and interleukin-6) and glial proliferation markers (Emr1 and CD68) in LFD animals. These effects were dampened in HFD-fed mice. In contrast, the hippocampal responses to LPS were largely insensitive to HFD. These results suggest that HFD feeding reduced the inflammatory response induced by LPS in the hypothalamus but not in the hippocampus. Topics: Adiponectin; Analysis of Variance; Animals; Body Weight; Corticotropin-Releasing Hormone; Cytokines; Diet, High-Fat; Dietary Fats; Disease Models, Animal; Eating; Gene Expression Regulation; Hippocampus; Hypothalamus; Inflammation; Insulin; Leptin; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Obesity; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor | 2017 |
Two opposite extremes of adiposity similarly reduce inflammatory response of antigen-induced acute joint inflammation.
Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known about the acute inflammatory response in joints that results from diet-induced adipose tissue remodeling. The objective of this study was to determine whether alterations in adipose tissue mass arising from food consumption modify the inflammatory response of antigen-induced joint inflammation in mice.. Male BALB/c mice were fed a chow diet, a highly refined carbohydrate-containing (HC) diet for 8 wk. They were then immunized and, after 2 wk, received a knee injection of methylated bovine serum albumin (mBSA). They were sacrificed at 6, 24, and 48 h after injection. The effect of the cafeteria diet for 8 wk, which also increases adipose tissue, or conjugated linoleic acid (CLA) supplementation for 4 wk, a model of lipodystrophy, was evaluated 24 h after knee challenge with mBSA.. Cellular influx, predominantly neutrophils, in synovial fluid was attenuated in the HC diet group, as were levels of myeloperoxidase and IL-1β in periarticular tissue and histopathological analysis. These responses were associated with reduced adiponectin and increased leptin in serum, which was pronounced in mice fed the HC diet. Cafeteria diet and CLA supplementation induced a profile similar to that seen with the HC diet in terms of inflammation, disease response, and metabolic alteration. Interestingly, after the injection of mBSA, the area of adipocytes in the infrapatellar fat pad increased in mice fed with chow diet similar to those fed the HC and cafeteria diet.. We demonstrated that attenuation of joint response induced by diet was independent of adipose tissue remodeling but could be associated with metabolic alterations. Topics: Adipocytes; Adiponectin; Adipose Tissue; Adiposity; Animals; Arthritis; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Supplements; Inflammation; Interleukin-1beta; Knee Joint; Leptin; Linoleic Acids, Conjugated; Lipid Metabolism; Lipodystrophy; Male; Metabolome; Mice, Inbred BALB C; Neutrophils; Obesity; Peroxidase; Serum Albumin, Bovine | 2017 |
The relationship between sleep apnea, metabolic dysfunction and inflammation: The gender influence.
Obstructive sleep apnea (OSA) has been associated with increased risk of cardiovascular morbidity and mortality. Although inflammatory markers may mediate this association, it is unknown the influence of gender in this mechanism. Thus, we aimed to evaluate the interaction effects between OSA and gender on metabolic and inflammatory profile in a population sample. This study is part of EPISONO cohort, in which 1042 participants underwent polysomnography, answered questionnaires, and had their blood collected for analysis of fasting glucose, total cholesterol and fractions, leptin, ghrelin, liver transaminases, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C-reactive protein. The results showed that men with OSA had higher leptin levels, shorter sleep latency and lower N3 sleep stage compared to men control (CTRL). They also presented higher apnea index and number of central apneas compared to both CTRL men and OSA women. In women, OSA was related to longer REM sleep latency, higher apnea-hypopnea index (AHI) during REM sleep and increased TNF-α levels compared to CTRL women. A multivariate model showed that male gender, ghrelin and total cholesterol were negatively associated with TNF-α, while IL-6, triglycerides and hypopnea index were positively associated (R Topics: Adult; Body Mass Index; Cohort Studies; Cross-Sectional Studies; Female; Ghrelin; Humans; Inflammation; Leptin; Male; Metabolic Diseases; Polysomnography; Sex Characteristics; Sleep Apnea Syndromes; Sleep Stages; Sleep, REM; Socioeconomic Factors; Tumor Necrosis Factor-alpha | 2017 |
Association Between Serum Leptin Level and Mortality in Kidney Transplant Recipients.
Leptin is a hormone made by adipocytes and associated with hypertension, inflammation, and coronary artery disease. Low serum leptin level was associated with higher risk of death in patients with advanced chronic kidney disease. Little is known about the association of serum leptin with outcomes in kidney transplant recipients.. Prospective prevalent cohort.. We collected sociodemographic and clinical parameters, medical and transplant history, and laboratory data of 979 prevalent kidney transplant recipients. Associations between serum leptin level and death with a functioning graft, all-cause death, and death-censored graft loss over a 6-year follow-up period were examined in survival models.. Serum leptin levels showed moderate negative correlation with eGFR (R = -0.21, P < .001) and positive correlations with BMI (R = 0.48, P < .001) and C-reactive protein (R = 0.20, P < .001). Each 10 ng/mL higher serum leptin level was associated with 7% lower risk of death with functioning graft (hazard ratio [HR] (95% confidence interval [CI]), 0.93 (0.87-0.99)), and this association persisted after adjustment for confounders: HR (95% CI), 0.90 (0.82-0.99). Similar associations were found with all-cause death as outcome. The association between serum leptin level and risk of graft loss was nonlinear, and only low serum leptin level was associated with higher risk of graft loss.. In prevalent kidney transplant recipients, lower serum leptin was an independent predictor of death. Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Female; Follow-Up Studies; Graft Rejection; Humans; Inflammation; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Socioeconomic Factors; Treatment Outcome | 2017 |
Leptin resistance elicits depressive-like behaviors in rats.
There is a growing appreciation that the complications of obesity extend to the central nervous system (CNS) and include increased risk for development of neuropsychiatric co-morbidities such as depressive illness. The neurological consequences of obesity may develop as a continuum and involve a progression of pathological features which is initiated by leptin resistance. Leptin resistance is a hallmark feature of obesity, but it is unknown whether leptin resistance or blockage of leptin action is casually linked to the neurological changes which underlie depressive-like phenotypes. Accordingly, the aim of the current study was to examine whether chronic administration of a pegylated leptin receptor antagonist (Peg-LRA) elicits depressive-like behaviors in adult male rats. Peg-LRA administration resulted in endocrine and metabolic features that are characteristic of an obesity phenotype. Peg-LRA rats also exhibited increased immobility in the forced swim test, depressive-like behaviors that were accompanied by indices of peripheral inflammation. These results demonstrate that leptin resistance elicits an obesity phenotype that is characterized by peripheral immune changes and depressive-like behaviors in rats, supporting the concept that co-morbid obesity and depressive illness develop as a continuum resulting from changes in the peripheral endocrine and metabolic milieu. Topics: Animals; Behavior, Animal; Body Weight; Depression; Inflammation; Leptin; Male; Obesity; Rats, Sprague-Dawley | 2017 |
Location and gene-specific effects of methylprednisolone acetate on mitigating IL1β-induced inflammation in mature ovine explant knee tissue.
To determine the ability of methylprednisolone acetate (MPA) to influence interleukin 1β (IL1β)-induced gene expression in ovine knee joint tissues.. Ovine articular cartilage, synovium, and infrapatellar fat pad (IPFP) explants.. Explants were treated with 10. Explant treatment groups: (1) control (DMEM); (2) inflammation (IL1β); (3) IL1β + 10. Except for IL8 in a subset of cartilage locations, matrix metalloproteinases (MMPs) were the only genes consistently affected by MPA. MPA mitigated IL1β-induced MMP3 expression levels in all regions of the articular cartilage, and in the synovium and IPFP, while MMP1 mRNA expression levels were significantly decreased with MPA after IL1β in the tibial plateau and synovium, but paradoxical increases in the IPFP. MMP13 mRNA expression levels exhibited significant decreases with MPA after IL1β in the femoral condyles, tibial plateau, synovium, and IPFP.. MPA treatment suppressed IL1β-induced mRNA levels for MMPs in articular cartilage, synovium, and IPFP and was found to be tissue-, location-, and gene-specific. Topics: Adiponectin; Adipose Tissue; Animals; Cartilage, Articular; Cytokines; Female; Inflammation; Knee Joint; Leptin; Matrix Metalloproteinases; Methylprednisolone; Methylprednisolone Acetate; Nicotinamide Phosphoribosyltransferase; RNA, Messenger; Sheep; Synovial Membrane; Toll-Like Receptor 4 | 2017 |
Muscular fitness and metabolic and inflammatory biomarkers in adolescents: Results from LabMed Physical Activity Study.
This study aimed to evaluate the associations between muscular fitness and inflammatory biomarkers and to investigate the relationship between muscular fitness and selected clustered inflammatory biomarkers in adolescents. This is a cross-sectional analysis with 529 adolescents (267 girls) aged 12-18 years. Handgrip strength and standing long jump tests assessed MF. Continuous scores of clustered inflammatory biomarkers (sum of Z-scores of C-reactive protein [CRP], C3, C4, fibrinogen, and leptin); metabolic risk factor (MRF) score (sum of Z-scores of SBP, triglycerides, ratio total cholesterol [TC]/HDL, HOMA-IR, and waist circumference [WC]) were computed. Regression analyses showed an inverse association between muscular fitness score (β=-.204; P<.021) and clustered score of inflammatory biomarkers, adjusted for age, sex, pubertal stage, socioeconomic status, adherence to the Mediterranean diet, cardiorespiratory fitness (CRF), MRF score, and body fat. Analysis of covariance showed that adolescents with an adverse inflammatory profile with low levels of muscular fitness exhibit the poorest MRF score (F Topics: Adolescent; Biomarkers; Body Mass Index; C-Reactive Protein; Child; Cholesterol; Cross-Sectional Studies; Female; Fibrinogen; Health Status; Humans; Inflammation; Leptin; Male; Muscle Strength; Physical Fitness; Prospective Studies; Risk Factors; Triglycerides; Waist Circumference | 2017 |
Leptin/OB-R signaling is elevated in mice with Sjögren's syndrome and is implicated in disease pathogenesis.
Sjögren's syndrome (SjS) is a systemic autoimmune disease resulting in a severe dry mouth and dry eyes. Currently, care for patients with SjS is palliative, as no established therapeutics target the disease directly, and its pathogenetic mechanisms are uncertain. Leptin activates B cells to induce the secretion of proinflammatory and anti-inflammatory cytokines and is elevated in several autoimmune diseases. In this study, we found the expression of leptin and its receptor OB-R in mouse models of SjS are elevated both locally and systemically during SjS progression. Recombinant serotype 2 adeno-associated viral (rAAV2) vectors expressing either OB-R shRNA (rAAV2-shOB-R) or none (rAAV2-null) were injected into 4 or 16 week-old BALB/c NOD/LtJ (NOD) mice and resulted in a modest reduction in glandular inflammation in the SjS model. In conclusion, Leptin/OB-R signaling may be pathogenically involved in SjS and may serve as a new marker and a potential therapeutic target. Topics: Animals; Disease Models, Animal; Female; Humans; Inflammation; Leptin; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Receptors, Leptin; Signal Transduction; Sjogren's Syndrome; Up-Regulation | 2017 |
Toll-like receptor 4 signalling mediates inflammation in skeletal muscle of patients with chronic kidney disease.
Inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia but why uremia up-regulates pro-inflammatory cytokines is unknown. Toll-like receptors (TLRs) regulate locally the innate immune responses, but it is unknown whether in chronic kidney disease (CKD) TLR4 muscle signalling is altered. The aim of the study is to investigate whether in CKD muscle, TLRs had abnormal function and may be involved in transcription of pro-inflammatory cytokine.. TLR4, phospho-p65, phospho-ikBα, tumour necrosis factor (TNF)-α, phospho p38, Murf 1, and atrogin were studied in skeletal muscle from nondiabetic CKD stage 5 patients (n = 29) and controls (n = 14) by immunohistochemistry, western blot, and RT-PCR. Muscle cell cultures (C2C12) exposed to uremic serum were employed to study TLR4 expression (western blot and RT-PCR) and TLR-driven signalling. TLR4 signalling was abrogated by a small molecule chemical inhibitor or TLR4 siRNA. Phospho AKT and phospho p38 were evaluated by western blot.. CKD subjects had elevated TLR4 gene and protein expression. Also expression of NFkB, p38 MAPK and the NFkB-regulated gene TNF-α was increased. At multivariate analysis, TLR4 protein content was predicted by eGFR and Subjective Global Assessment, suggesting that the progressive decline in renal function and wasting mediate TLR4 activation. In C2C12, uremic serum increased TLR4 as well as TNF-α and down-regulated pAkt. These effects were prevented by blockade of TLR4.. CKD promotes muscle inflammation through an up-regulation of TLR4, which may activate downward inflammatory signals such as TNF-α and NFkB-regulated genes. Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Animals; C-Reactive Protein; Cell Line; Cytokines; Female; Humans; Inflammation; Leptin; Male; Mice; Middle Aged; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; Rectus Abdominis; Renal Insufficiency, Chronic; Resistin; Signal Transduction; Toll-Like Receptor 4; Transcription Factor RelA; Uremia | 2017 |
Cancer anorexia: hypothalamic activity and its association with inflammation and appetite-regulating peptides in lung cancer.
Energy homeostasis is mediated by the hypothalamus, whose inflammation-induced functional derangements contribute to the onset of anorexia in cancer. By using functional magnetic resonance imaging (fMRI), we determined the patterns of hypothalamic activation after oral intake in anorexic (A), non-anorexic (NA) cancer patients, and in controls (C).. Lung cancer patients were considered. Hypothalamic activation was recorded in A and NA patients and in C by fMRI, before (T0), immediately after (T1) the administration of an oral nutritional supplement, and after 15 min (T2). The grey of the hypothalamus and Blood Oxygen Level Dependent (BOLD) intensity were calculated and normalized for basal conditions. Interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, ghrelin, and leptin plasma levels were measured. A statistical parametric mapping was used.. Thirteen lung cancer patients (7 M, 6 F; 9A, 4NA) and 2 C (1 M, 1 F) were enrolled. Controls had the lowest BOLD intensity. At all-time points, anorexic patients showed lower hypothalamic activity compared with NA (P < 0.001) (T0: 585.57 ± 55.69 vs. 667.92 ± 33.18, respectively; T1: 536.50 ± 61.70 vs. 624.49 ± 55.51, respectively; T2: 556.44 ± 58.51 vs. 615.43 ± 71.50, respectively). Anorexic patients showed greater BOLD signal reduction during T0-T1 than NA (-8.5% vs. -6.80%, P < 0.001). Independently from the presence of anorexia, BOLD signals modification before and after oral challenge correlated with basal values of IL-1 and ghrelin (P < 0.001).. Hypothalamic activity in A cancer patients is reduced respect to NA and responds differently to oral challenges. This suggests a central control of appetite dysregulation during cancer anorexia, before, and after oral intake. Topics: Aged; Aged, 80 and over; Anorexia; Appetite; Carcinoma, Non-Small-Cell Lung; Cytokines; Dietary Supplements; Female; Ghrelin; Humans; Hypothalamus; Inflammation; Leptin; Lung Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged | 2017 |
Inhibiting Microglia Expansion Prevents Diet-Induced Hypothalamic and Peripheral Inflammation.
Cell proliferation and neuroinflammation in the adult hypothalamus may contribute to the pathogenesis of obesity. We tested whether the intertwining of these two processes plays a role in the metabolic changes caused by 3 weeks of a high-saturated fat diet (HFD) consumption. Compared with chow-fed mice, HFD-fed mice had a rapid increase in body weight and fat mass and specifically showed an increased number of microglia in the arcuate nucleus (ARC) of the hypothalamus. Microglia expansion required the adequate presence of fats and carbohydrates in the diet because feeding mice a very high-fat, very low-carbohydrate diet did not affect cell proliferation. Blocking HFD-induced cell proliferation by central delivery of the antimitotic drug arabinofuranosyl cytidine (AraC) blunted food intake, body weight gain, and adiposity. AraC treatment completely prevented the increase in number of activated microglia in the ARC, the expression of the proinflammatory cytokine tumor necrosis factor-α in microglia, and the recruitment of the nuclear factor-κB pathway while restoring hypothalamic leptin sensitivity. Central blockade of cell proliferation also normalized circulating levels of the cytokines leptin and interleukin 1β and decreased peritoneal proinflammatory CD86 immunoreactive macrophage number. These findings suggest that inhibition of diet-dependent microglia expansion hinders body weight gain while preventing central and peripheral inflammatory responses due to caloric overload. Topics: Adiposity; Animals; Antimitotic Agents; Arabinonucleosides; Arcuate Nucleus of Hypothalamus; Body Weight; Cell Proliferation; Cytarabine; Cytidine; Diet, High-Fat; Eating; Hypothalamus; Inflammation; Interleukin-1beta; Leptin; Macrophages, Peritoneal; Male; Mice; Microglia; NF-kappa B; Obesity; Tumor Necrosis Factor-alpha; Weight Gain | 2017 |
AAV-mediated IL-10 gene transfer counteracts inflammation in the hypothalamic arcuate nucleus and obesity induced by high-fat diet.
Consumption of high-fat diet (HFD) induces energy imbalance and consequently obesity. In the pathogenesis of obesity, HFD triggers inflammation in the hypothalamus including arcuate nucleus (ARC). Interleukin-10 (IL-10) is a representative anti-inflammatory cytokine, known to ameliorate the adipose tissue inflammation and insulin resistance in obesity. However, the effect of IL-10 on the hypothalamic inflammation remains less defined. We here report the effect of over-expression of murine IL-10 using adeno-associated virus (AAV) vector on the inflammation in ARC and feeding behavior in HFD-induced obese (DIO) mice. DIO mice exhibited reduced POMC expression and elevated IKKs (IκB kinases) and SOCS3 expression in ARC. Overexpression of mIL-10 using AAV vector ameliorated obesity in parallel with restoration of ARC POMC expression in DIO mice. Moreover, IL-10 treatment suppressed IKKs activation and SOCS3 expression in ARC of DIO mice. These results suggest that IL-10 gene transfer provides an effective approach for counteracting HFD-induced inflammation and leptin resistance in ARC to prevent progression of obesity. Topics: Adipose Tissue; Animals; Arcuate Nucleus of Hypothalamus; Dependovirus; Diet, High-Fat; Eating; Inflammation; Insulin Resistance; Interleukin-10; Leptin; Male; Mice; Obesity | 2017 |
Physical Activity and Adiposity-related Inflammation: The MESA.
Physical activity is associated with decreased adiposity-related inflammation in adults. Whether this association is independent of central obesity is unknown but important for understanding the mechanisms associated with reducing cardiometabolic disease risk through physical activity. This study examined whether associations of physical activity and obesity-related inflammatory markers were independent of central adiposity.. Between 2002 and 2005, 1970 participants from the Multi-Ethnic Study of Atherosclerosis completed detailed health history and physical activity questionnaires, underwent physical measurements including computed tomography to quantify abdominal visceral and subcutaneous fat, and measurements of adiponectin, leptin, interleukin-6, tumor necrosis factor-alpha, and resistin. Statistical analyses included analysis of covariance and multivariable-adjusted regression.. The mean (range) age of participants was 64.7 (55-84) yr and 50% were women. After adjustment for age and sex, and compared with the lowest quartile, inflammatory markers in the highest quartile of moderate-to-vigorous physical activity were 16% higher for adiponectin and 30%, 26%, and 9% lower for leptin, interleukin-6, and resistin, respectively (P < 0.05 for all). In linear regression adjusted for demographics, dyslipidemia, hypertension, diabetes, smoking, glomerular filtration rate, renin, and aldosterone, each standard deviation increment of moderate-to-vigorous physical activity was associated with significantly higher levels of adiponectin (β = 0.04) and lower levels of leptin (β = -0.06), interleukin-6 (β = -0.08), and resistin (β = -0.05, P < 0.05 for all). The associations with leptin, interleukin-6, and resistin were independent of total and central adiposity (P < 0.05), whereas the association between moderate-to-vigorous physical activity and adiponectin was attenuated by central adiposity (P > 0.05). There were no significant interactions by race/ethnicity or sex.. Moderate-to-vigorous physical activity was associated with a more favorable profile of inflammatory markers, independent of relevant cardiometabolic disease risk factors including central obesity. Topics: Adiponectin; Adiposity; Aged; Aged, 80 and over; Biomarkers; Exercise; Female; Humans; Inflammation; Interleukin-6; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity, Abdominal; Resistin; Risk Factors; Tumor Necrosis Factor-alpha | 2017 |
Thermogenesis, fatty acid synthesis with oxidation, and inflammation in the brown adipose tissue of ob/ob (-/-) mice.
Brown adipose tissue (BAT) is specialized in heat production, but its metabolism in ob/ob mice is still a matter of debate. We aimed to verify ob/ob mice BAT using C57Bl/6 male mice (as the wild-type, WT) and leptin-deficient ob/ob mice (on the C57Bl/6 background strain), at three months of age (n=10/group). At euthanasia, animals had their interscapular BAT weighed, and prepared for analysis (Western blot, and RT-qPCR). In comparison with the WT group, the ob/ob group showed reduced thermogenic signaling markers (gene expression of beta 3-adrenergic receptor, beta3-AR; PPARgamma coactivator 1 alpha, PGC1alpha, and uncoupling protein 1, UCP1). The ob/ob group also showed impaired gene expression for lipid utilization (perilipin was increased, while other markers were diminished: carnitine palmitoyltransferase-1b, CPT-1b; cluster of differentiation 36, CD36; fatty acid binding protein 4, FABP4; fatty acid synthase, FAS, and sterol regulatory element-binding protein 1c, SREBP1c), and altered protein expression of insulin signaling (diminished pAKT, TC10, and GLUT-4). Lastly, the ob/ob group showed increased gene expression of markers of inflammation (interleukin 1 beta, IL-1beta; IL-6, tumor necrosis factor alpha, TNFalpha; and monocyte chemotactic protein-1, MCP-1). In conclusion, the ob/ob mice have decreased thermogenic markers associated with reduced gene expression related to fatty acid synthesis, mobilization, and oxidation. There were also alterations in insulin signaling and protein and gene expressions of inflammation. The findings suggest that the lack of substrate for thermogenesis and the local inflammation negatively regulated thermogenic signaling in the ob/ob mice. Topics: Adipose Tissue, Brown; Animals; Body Weight; Fatty Acids; Genetic Markers; Glucose; Inflammation; Leptin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Oxidation-Reduction; Thermogenesis | 2017 |
Interrelations among the adipocytokines leptin and adiponectin, oxidative stress and aseptic inflammation markers in pre- and early-pubertal normal-weight and obese boys.
Presumed interrelationships among deleterious aspects of adipose tissue metabolism, inflammation, and cellular oxidative stress could be influenced by pubertal hormonal changes. They were investigated in pre- and early pubertal normal-weight and obese boys before and after an exercise bout employed as an energy demanding stimulator.. Cross-sectional study. Seventy-six healthy pre- (mean ± SD, 10.6 ± 0.2 years old, 28 normal-weight, and 11 obese) and early-(11.4 ± 0.2 years old, 25 normal-weight, and 12 obese) pubertal boys, were blood-sampled before and after a bout of exercise at 70% VO. Baseline and post-exercise adiponectin was greater and leptin and high-sensitivity C-reactive protein were lower in normal-weight than in obese pre- and early pubertal boys, while high sensitivity IL-6 was greater in obese than in normal-weight pre-pubertal boys. In pre-pubertal obese boys: at baseline, high-sensitivity C-reactive protein correlated negatively with catalase; high sensitivity IL-6 correlated positively with protein carbonyls; Δ (difference during exercise) adiponectin correlated positively with Δcatalase. In all boys: at baseline, high sensitivity IL-6 correlated positively with leptin and was the best negative and the second best positive predictor for post-exercise glutathione/oxidized glutathione and protein carbonyls, respectively; leptin was the best negative predictor for post-exercise glutathione; waist to height ratio was the best positive predictor for post-exercise thiobarbitouric acid reactive substances; body mass index z-score and adiponectin were, respectively, the best positive predictor for post-exercise protein carbonyls and catalase.. In all subjects, leptin and adiponectin predict negatively and positively anti-oxidation, respectively, while high sensitivity IL-6 predicts positively and negatively pro- and anti-oxidation, respectively. High-sensitivity C-reactive protein is increased and negatively associated with anti-oxidation in pre-pubertal obese boys, suggesting that childhood obesity is associated with aseptic inflammation and oxidative stress. Topics: Adiponectin; Biomarkers; C-Reactive Protein; Child; Exercise; Humans; Inflammation; Interleukin-6; Leptin; Male; Obesity; Oxidative Stress; Puberty | 2017 |
Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice.
Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes remarkable improvements in cardiometabolic health, including hypertension remission. However, the mechanisms responsible remain undefined and poorly studied. Therefore, we developed and validated the first murine model of VSG that recapitulates the blood pressure-lowering effect of VSG using gold-standard radiotelemetry technology. We used this model to investigate several potential mechanisms, including body mass, brain endoplasmic reticulum (ER) stress signaling and brain inflammatory signaling, which are all critical contributors to the pathogenesis of obesity-associated hypertension. Mice fed on a high-fat diet underwent sham or VSG surgery and radiotelemeter implantation. Sham mice were fed Topics: Animals; Blood Pressure; Body Weight; Cecum; Endoplasmic Reticulum Stress; Energy Intake; Fasting; Gastrectomy; Gastrointestinal Microbiome; Ghrelin; Hypothalamus; Inflammation; Leptin; Male; Mice, Inbred C57BL; Norepinephrine; Signal Transduction | 2017 |
Is Leptin A Key to Metabolic Inflammation in Trauma and Sepsis?
Topics: Humans; Inflammation; Leptin; Sepsis | 2017 |
Anti-inflammatory role of Leptin in glial cells through p38 MAPK pathway inhibition.
In the present work, we studied the modulatory effect of Leptin (Lep) against pro-inflammatory cytokines, tumour necrosis factor-alpha (TNFα), interleukin 1-beta (IL1β) and interferon-gamma (IFNγ), in primary glial cell cultures.. Glial cultures were treated with pro-inflammatory cytokines (TNFα, 20ng/ml; IL1β, 20ng/ml; IFNγ 20ng/ml). Cells were pre-treated with Lep 500nM, 1h prior to cytokine treatment. NO released from glial cells was determined using the Griess reaction. Cell viability was determined by the MTT method. Protein expression was determined by western blot.. Pre-treatment with 500nM Lep produced an inhibitory effect on inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production after glial cells exposure to pro-inflammatory cytokines. Anti-inflammatory effect can be related to a decrease in P38 MAP Kinase (MAPK) pathway activity. Treatment of glial cell cultures with Lep also reduced the intrinsic apoptotic pathway (cytochrome c release and caspase-3 activation).. We suggest that Lep would act as an anti-inflammatory factor in glial cells exposed to pro-inflammatory cytokines, exerting its function on p38 MAPK pathway and reducing NO production. Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cell Survival; Cells, Cultured; Cytokines; Disease Models, Animal; Inflammation; Interferon-gamma; Interleukin-1beta; Leptin; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Neuroglia; Nitric Oxide; p38 Mitogen-Activated Protein Kinases; Tumor Necrosis Factor-alpha | 2017 |
Biomarkers of systemic inflammation in pathogenesis of syntropic occupational bronchial asthma and metabolic syndrome.
In search of inflammatory molecular markers helpful in detection of increased risk and prognosis of severity of syntropic occupational bronchial asthma and metabolic syndrome, the authors conducted a study covering 140 examinees with confirmed occupational bronchial asthma. According to IDF criteria (2005), the patients were assigned into a group with combined occupational bronchial asthma and metabolic syndrome, and a group of occupational bronchial asthma without metabolic syndrome. All the examinees underwent studies of inflammation markers - biochemical (C-reactive protein, leptine) and molecular-genetic ( polymorphism of Gln223Arg gene of leptine receptor (LEPR), polymorphism of C174G gene of interleukin-6 (IL-6), polymorphism of G308A gene of (TNF-a) tumor necrosis factor alpha). Evidences are that the patients with combined bronchial asthma and metabolic syndrome demonstrate higher activity of inflammatory processes (higher level of C-reactive protein, leptine) - that manifests in clinically more severe course of bronchopulmonary disease. Moleculary-genetic markers revealed are associated with higher activity of inflammation and therefore with increased risk of occupational bronchial asthma associated with metabolic syndrome and diabetess mellitus 2 type (polymorphisms of LEPR gene, IL-6 gene). Topics: Air Pollutants, Occupational; Asthma, Occupational; Biomarkers; C-Reactive Protein; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Russia | 2016 |
Effect of Aging on Adipose Tissue Inflammation in the Knee Joints of F344BN Rats.
The infrapatellar fat pad (IFP) secretes inflammatory mediators in osteoarthritic knees, but the effect of aging on IFP inflammation is unknown. We tested the hypothesis that aging increases basal and interleukin-1β (IL-1β)-stimulated IFP inflammation in 10-, 20-, and 30-month-old male F344BN F1-hybrid rats. IFPs were cultured ex vivo for 24 hours and treated ±1ng/mL IL-1β to simulate injury-induced inflammation. IFP inflammation was evaluated by measuring secreted cytokine concentrations and by quantitative expression of immunoregulatory and pro- and anti-adipogenic genes. With age, osteoarthritis pathology increased and IFP mass decreased. Although adipocyte size did not change with age, variation in adipocyte size was positively associated with synovial thickness independent of age whereas associations with cartilage damage were age dependent. In the absence of IL-1β, aging was associated with a significant increase in IFP secretion of tumor necrosis factor α by 67% and IL-13 by 35% and a reduction in the expression of immunoregulatory M2 macrophage genes. However, following an IL-1β challenge, adipogenesis markers decreased and pro- and anti-inflammatory cytokines increased independent of age. The lone exception was leptin, which decreased >70% with age. Thus, although aging promotes osteoarthritis risk by increasing basal inflammation, our findings also revealed a potentially protective effect of aging by decreasing IL-1β-stimulated leptin production. Topics: Adipogenesis; Adipose Tissue; Aging; Animals; Biomarkers; In Vitro Techniques; Inflammation; Interleukin-13; Interleukin-1beta; Knee Joint; Leptin; Male; Osteoarthritis, Knee; Predictive Value of Tests; Rats; Rats, Inbred F344; Sensitivity and Specificity; Severity of Illness Index; Tumor Necrosis Factor-alpha | 2016 |
Sebocytes differentially express and secrete adipokines.
In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte-associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression profile of adipokines [adiponectin, interleukin (IL) 6, resistin, leptin, serpin E1, visfatin, apelin, chemerin, retinol-binding protein 4 (RBP4) and monocyte chemoattractant protein 1 (MCP1)] in sebaceous glands of healthy and various disease-affected (acne, rosacea, melanoma and psoriasis) skin samples. Sebaceous glands in all examined samples expressed adiponectin, IL6, resistin, leptin, serpin E1 and visfatin, but not apelin, chemerin, RBP4 and MCP1. Confirming the presence of the detected adipokines in the human SZ95 sebaceous gland cell line we further characterized their expression and secretion patterns under different stimuli mimicking bacterial invasion [by using Toll-like receptor (TLR)2 and 4 activators], or by 13-cis retinoic acid (13CRA; also known as isotretinoin), a key anti-acne agent. With the exception of resistin, the expression of all of the detected adipokines (adiponectin, IL6, leptin, serpin E1 and visfatin) could be further regulated at the level of gene expression, showing a close correlation with the secreted protein levels. Besides providing further evidence on similarities between adipocytes and sebocytes, our results strongly suggest that sebocytes are not simply targets of inflammation but may exhibit initiatory and modulatory roles in the inflammatory processes of the skin through the expression and secretion of adipokines. Topics: Adipocytes; Adipokines; Adiponectin; Cell Line; Gene Expression Regulation; Humans; Inflammation; Interleukin-6; Leptin; Lipid Metabolism; Resistin; Sebaceous Glands; Sebum; Skin | 2016 |
The effect of obesity on inflammatory cytokine and leptin production following acute mental stress.
Obesity may contribute to cardiovascular disease (CVD) risk by eliciting chronic systemic inflammation and impairing the immune response to additional stressors. There has been little assessment of the effect of obesity on psychological stress, an independent risk factor for CVD. Therefore, it was of interest to examine interleukin-6, tumor necrosis factor-α, interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), and leptin following an acute mental stress task in nonobese and obese males. Twenty college-aged males (21.3 ± 0.56 years) volunteered to participate in a 20-min Stroop color-word and mirror-tracing task. Subjects were recruited for obese (body mass index: BMI > 30) and nonobese (BMI < 25) groups, and blood samples were collected for enzyme-linked immunosorbent assay analysis. The acute mental stress task elicited an increase in heart rate, catecholamines, and IL-1β in all subjects. Additionally, acute mental stress increased cortisol concentrations in the nonobese group. There was a significant reduction in leptin in obese subjects 30 min posttask compared with a decrease in nonobese subjects 120 min posttask. Interestingly, the relationship between the percent change in leptin and IL-1Ra at 120 min posttask in response to an acute mental stress task was only observed in nonobese individuals. This is the first study to suggest that adiposity in males may impact leptin and inflammatory signaling mechanisms following acute mental stress. Topics: Cytokines; Heart Rate; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Interleukin-6; Leptin; Male; Neuropsychological Tests; Obesity; Stress, Psychological; Tumor Necrosis Factor-alpha; Young Adult | 2016 |
Cranberries (Oxycoccus quadripetalus) inhibit pro-inflammatory cytokine and chemokine expression in 3T3-L1 adipocytes.
Oxidative stress and inflammation are involved in the development of obesity, type 2 diabetes and vascular complications. Systemic inflammation, as seen in obesity, is associated with high plasmatic levels of pro-inflammatory, pro-atherogenic and pro-thrombotic adipokines. Here we studied the effects of lyophilized cranberries (LCB) on the secretion and expression of PAI-1, IL-6, MCP-1 and leptin in mature 3T3-L1 adipocytes under baseline conditions and excessive inflammatory response elicitation by stimulation with H2O2. Our data demonstrated that LCB significantly reduced the expression and secretion of IL-6, MCP-1 and leptin, as well as suppressed the overexpression of PAI-1 induced by H2O2. Our findings suggested that LCB counteracted the stimulatory effect of H2O2 on secretion and expression of pro-inflammatory adipokines, implying a potential anti-inflammatory effect during the inflammatory process induced via oxidative stress in adipose tissue. Topics: 3T3-L1 Cells; Adipocytes; Animals; Anti-Inflammatory Agents; Cytokines; Fruit; Hydrogen Peroxide; Inflammation; Leptin; Mice; Plant Preparations; Serpin E2; Vaccinium | 2016 |
Total Western Diet Alters Mechanical and Thermal Sensitivity and Prolongs Hypersensitivity Following Complete Freund's Adjuvant in Mice.
Obesity and chronic pain are often comorbid and their rates are increasing. It is unknown whether increased pain is caused by greater weight or poor diet quality or both. Therefore, we utilized a Total Western Diet (TWD) to investigate the functional and physiologic consequences of nutritionally poor diet in mice. For 13 weeks on the commercially available TWD, based on the National Health and Nutrition Examination Survey, thresholds of TWD-fed mice significantly increased in both thermal and mechanical tests. Quantitative magnetic resonance imaging revealed a significant increase in fat mass with a concomitant decrease in lean mass in the TWD-fed mice. In addition, there were significant increases in levels of serum leptin and inflammatory cytokines. After chronic pain induction using complete Freund's adjuvant, hypersensitivity was more pronounced and significantly prolonged in the TWD-fed mice. Therefore, prolonged exposure to poor diet quality resulted in altered acute nociceptive sensitivity, systemic inflammation, and persistent pain after inflammatory pain induction.. These results highlight the negative effects of poor diet quality with respect to recovery from hypersensitivity and susceptibility to chronic pain. A complete understanding of the impact of diet can aid in treatment and recovery dynamics in human clinical patients. Topics: Animals; Chronic Pain; Cytokines; Diet, Western; Freund's Adjuvant; Hyperalgesia; Inflammation; Leptin; Male; Mice; Obesity; Pain Threshold | 2016 |
Body condition score and plane of nutrition prepartum affect adipose tissue transcriptome regulators of metabolism and inflammation in grazing dairy cows during the transition period.
Recent studies demonstrating a higher incidence of metabolic disorders after calving have challenged the management practice of increasing dietary energy density during the last ~3 wk prepartum. Despite our knowledge at the whole-animal level, the tissue-level mechanisms that are altered in response to feeding management prepartum remain unclear. Our hypothesis was that prepartum body condition score (BCS), in combination with feeding management, plays a central role in the peripartum changes associated with energy balance and inflammatory state. Twenty-eight mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to 1 of 4 treatment groups in a 2 × 2 factorial arrangement: 2 prepartum BCS categories (4.0 and 5.0, based on a 10-point scale; BCS4, BCS5) obtained via differential feeding management during late-lactation, and 2 levels of energy intake during the 3 wk preceding calving (75 and 125% of estimated requirements). Subcutaneous adipose tissue was harvested via biopsy at -1, 1, and 4 wk relative to parturition. Quantitative polymerase chain reaction was used to measure mRNA and microRNA (miRNA) expression of targets related to fatty acid metabolism (lipogenesis, lipolysis), adipokine synthesis, and inflammation. Both prepartum BCS and feeding management had a significant effect on mRNA and miRNA expression throughout the peripartum period. Overfed BCS5 cows had the greatest prepartum expression of fatty acid synthase (FASN) and an overall greater expression of leptin (LEP); BCS5 was also associated with greater overall adiponectin (ADIPOQ) and peroxisome proliferator-activated receptor gamma (PPARG), whereas overfeeding upregulated expression of proadipogenic miRNA. Higher postpartum expression of chemokine ligand 5 (CCL5) and the cytokines interleukin 6 (IL6) and tumor necrosis factor (TNF) was detected in overfed BCS5 cows. Feed-restricted BCS4 cows had the highest overall interleukin 1 (IL1B) expression. Prepartum feed restriction resulted in greater chemokine ligand 2 (CCL2) expression. Overall, changes in mRNA expression were consistent with the expression pattern of inflammation-related miRNA. These data shed light on molecular mechanisms underlying the effect of prepartum BCS and feeding management on metabolic and inflammatory status of adipose tissue during the peripartum period. Data support the use of a controlled feed restriction prepartum in optimally conditioned cows, as well as the use of a higher level of diet Topics: Adiponectin; Adipose Tissue; Animal Feed; Animals; Breeding; Cattle; Chemokine CCL2; Chemokine CCL5; Diet; Energy Intake; Energy Metabolism; Fatty Acid Synthases; Female; Inflammation; Interleukin-1beta; Interleukin-6; Leptin; Lipid Metabolism; Lipogenesis; Lipolysis; MicroRNAs; Nutritional Status; Overnutrition; Peripartum Period; PPAR gamma; RNA, Messenger; Subcutaneous Fat; Transcriptome; Tumor Necrosis Factor-alpha; Up-Regulation | 2016 |
Differential methylation in inflammation and type 2 diabetes genes in siblings born before and after maternal bariatric surgery.
Siblings born before (BMS) and after (AMS) maternal biliopancreatic diversion (BPD) show differences in the methylome. The objective was to use a sibling-pair design to examine the effects from interpregnancy weight loss as a consequence of maternal bariatric surgery, other than BPD, on the methylome comparing BMS and AMS.. Women with at least one child born before and one after bariatric surgery were identified in Swedish national registers. Whole blood samples from BMS (N = 31) and AMS (N = 31) siblings were collected for epigenetic methylation analysis while maternal information was collected from antenatal medical records.. In total 3,074 genes, with corresponding 23,449 CpG methylation sites, were differently methylated and associated with an overrepresentation of differently methylated CpG sites in genes involved with insulin receptor signaling, type 2 diabetes signaling, and leptin signaling in obesity, while the most significant differently methylated genes were HLA-DQA1, HLA-DQB1, and TSPAN18, when comparing BMS and AMS siblings.. These results suggest that maternal bariatric surgery, with subsequent weight loss between pregnancies, is associated with alterations in the methylome of genes involved in insulin receptor signaling, type 2 diabetes signaling, and leptin signaling in obesity in a comparison of BMS and AMS siblings. Topics: Adult; Bariatric Surgery; Biliopancreatic Diversion; Child; Child, Preschool; Diabetes Mellitus, Type 2; Diseases in Twins; DNA Methylation; Female; HLA-DQ alpha-Chains; HLA-DQ beta-Chains; Humans; Infant; Infant, Newborn; Inflammation; Leptin; Male; Obesity; Pregnancy; Sweden; Tetraspanins | 2016 |
Zinc transporter Slc39a14 regulates inflammatory signaling associated with hypertrophic adiposity.
Zinc is a signaling molecule in numerous metabolic pathways, the coordination of which occurs through activity of zinc transporters. The expression of zinc transporter Zip14 (Slc39a14), a zinc importer of the solute carrier 39 family, is stimulated under proinflammatory conditions. Adipose tissue upregulates Zip14 during lipopolysaccharide-induced endotoxemia. A null mutation of Zip14 (KO) revealed that phenotypic changes in adipose include increased cytokine production, increased plasma leptin, hypertrophied adipocytes, and dampened insulin signaling. Adipose tissue from KO mice had increased levels of preadipocyte markers, lower expression of the differentiation marker (PPARγ), and activation of NF-κB and STAT3 pathways. Our overall hypothesis was that ZIP14 would play a role in adipocyte differentiation and inflammatory obesity. Global Zip14 KO causes systemic endotoxemia. The observed metabolic changes in adipose metabolism were reversed when oral antibiotics were administrated, indicating that circulating levels of endotoxin were in part responsible for the adipose phenotype. To evaluate a mechanism, 3T3-L1 cells were differentiated into adipocytes and treated with siRNA to knock down Zip14. These cells had an impaired ability to mobilize zinc, which caused dysregulation of inflammatory pathways (JAK2/STAT3 and NF-κB). The Zip14 deletion may limit the availability of intracellular zinc, yielding the unique phenotype of inflammation coupled with hypertrophy. Taken together, these results suggest that aberrant zinc distribution observed with Zip14 ablation impacts adipose cytokine production and metabolism, ultimately increasing fat deposition when exposed to endotoxin. To our knowledge, this is the first investigation into the mechanistic role of ZIP14 in adipose tissue regulation and metabolism. Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Adipose Tissue, White; Adiposity; Animals; Blotting, Western; Cation Transport Proteins; Cell Differentiation; Cytokines; Endotoxemia; Gene Knockdown Techniques; Hypertrophy; Inflammation; Janus Kinase 2; Leptin; Lipopolysaccharides; Mice; Mice, Knockout; Microscopy, Confocal; NF-kappa B; PPAR gamma; Signal Transduction; STAT3 Transcription Factor | 2016 |
Is sebocyte-derived leptin the missing link between hyperseborrhea, ductal hypoxia, inflammation and comedogenesis in acne vulgaris?
Topics: Acne Vulgaris; Animals; Cell Proliferation; Dermatitis, Seborrheic; Humans; Hypoxia; Inflammation; Keratinocytes; Leptin; Mechanistic Target of Rapamycin Complex 1; Mice; Multiprotein Complexes; Sebaceous Glands; TOR Serine-Threonine Kinases | 2016 |
Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer.
Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance.. WAT inflammation was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS) of the breast. Two independent groups were examined in cross-sectional (cohort 1) and retrospective (cohort 2) studies. Cohort 1 included 100 women undergoing mastectomy for breast cancer risk reduction (n = 10) or treatment (n = 90). Metabolic syndrome-associated circulating factors were compared by CLS-B status. The association between CLS of the breast and the metabolic syndrome was validated in cohort 2, which included 127 women who developed metastatic breast cancer. Distant recurrence-free survival (dRFS) was compared by CLS-B status.. In cohorts 1 and 2, breast WAT inflammation was detected in 52 of 100 (52%) and 52 of 127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and IL6 and lower high-density lipoprotein cholesterol and adiponectin (P < 0.05) in cohort 1. In cohort 2, breast WAT inflammation was associated with hyperlipidemia, hypertension, and diabetes (P < 0.05). Compared with patients without breast WAT inflammation, the adjusted HR for dRFS was 1.83 (95% CI, 1.07-3.13) for patients with inflammation.. WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis. Clin Cancer Res; 22(9); 2283-9. ©2015 AACR. Topics: Adipocytes; Adipose Tissue, White; Adult; Aged; Breast; Breast Neoplasms; C-Reactive Protein; Cross-Sectional Studies; Female; Glucose; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Macrophages; Metabolic Syndrome; Middle Aged; Obesity; Retrospective Studies; Triglycerides | 2016 |
Type 2 diabetes mellitus coincident with pulmonary or latent tuberculosis results in modulation of adipocytokines.
Type 2 diabetes mellitus (T2DM) is recognized as major risk factor for the progress of active pulmonary tuberculosis (PTB), although the mechanistic link between diabetes and tuberculosis remains poorly characterized. Moreover, the influence of poorly controlled diabetes on the baseline levels of adipocytokines in the context of tuberculosis has not been explored in detail. To characterize the influence of coexistent DM on adipocytokine levels in pulmonary or latent TB (LTB), we examined circulating levels of adipocytokines in the plasma of individuals with PTB-DM or LTB-DM and compared them with those without DM (PTB or LTB). PTB-DM or LTB-DM is characterized by diminished circulating levels of adiponectin and adipsin and/or heightened circulating levels of leptin, visfatin and PAI-1. In addition, adiponectin and adipsin exhibit a significant negative correlation, whereas leptin, visfatin and PAI-1 display a significant positive correlation with HbA1C levels and random blood glucose levels. Therefore, our data reveal that PTB-DM or LTB-DM is characterized by alterations in the systemic levels of adipocytokines, indicating that altered adipose tissue inflammation underlying Type 2 diabetes potentially contributes to pathogenesis of TB disease. Topics: Adipokines; Adiponectin; Adipose Tissue; Adult; Aged; Blood Glucose; Complement Factor D; Cytokines; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Inflammation; Latent Tuberculosis; Leptin; Male; Middle Aged; Mycobacterium tuberculosis; Nicotinamide Phosphoribosyltransferase; Plasminogen Activator Inhibitor 1; Tuberculosis, Pulmonary | 2016 |
Early cardiac changes induced by a hypercaloric Western-type diet in "subclinical" obesity.
"Obesity cardiomyopathy" effects have been widely described; however, the specific contribution of metabolic changes and altered adipokine secretion are still uncharacterized. Moreover, a diagnosis based on body mass index might not be the most accurate to identify increased adiposity and its outcomes. In this study, we aimed to determine the impact of a Western-type diet [hypercaloric diet (HCD)] ingestion on biventricular structure and function, as well as the metabolic and endocrine changes that occur before the establishment of overt obesity. Wistar rats were fed for 6 wk with a regular diet or HCD. At the end of the protocol, metabolic tests, cardiac structure, and functional evaluation were performed, and blood and tissue samples collected to perform histological, molecular biology, and functional studies. The animals that ingested the HCD presented increased adiposity and larger adipocyte cross-sectional area, but similar body weight compared with the regular diet group. At the cardiac level, HCD induced biventricular cardiomyocyte hypertrophy, fibrosis, increased stiffness, and impaired relaxation. Galectin-3 plasma expression was likewise elevated in the same animals. The nutritional modulation also altered the secretory pattern of the adipose tissue, originating a proinflammatory systemic environment. In this study, we observed that before "clinical" overweight or frank obesity is established, the ingestion of a HCD-induced cardiac remodeling manifests by increased biventricular stiffness and diastolic dysfunction. The mechanism triggering the cardiac alterations appears to be the proinflammatory environment promoted by the adipose tissue dysfunction. Furthermore, galectin-3, a profibrotic molecule, might be a potential biomarker for the myocardial alterations promoted by the HCD before overweight or obesity. Topics: Adipocytes; Adipose Tissue; Animals; Body Weight; Cardiomyopathies; Cell Size; Collagen Type I; Collagen Type III; Diastole; Diet, Western; Echocardiography; Extracellular Matrix; Fibrosis; Galectin 3; Glucose Tolerance Test; Inflammation; Insulin Resistance; Interleukin-1beta; Leptin; Myocardium; Myocytes, Cardiac; Obesity; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Resistin; RNA, Messenger; Tumor Necrosis Factor-alpha; Ventricular Dysfunction; Ventricular Remodeling | 2016 |
Cardiometabolic Health in Submariners Returning from a 3-Month Patrol.
Confined space, limited exercise equipment, rotating shift work and reduced sleep may affect cardiometabolic health in submariners. To test this hypothesis, 53 male U.S. Submariners (20-39 years) were studied before and after a 3-month routine submarine patrol. Measures included anthropometrics, dietary and physical activity, biomarkers of cardiometabolic health, energy and appetite regulation, and inflammation. Before deployment, 62% of submariners had a body fat % (BF%) ≥ 25% (obesity), and of this group, 30% met the criteria for metabolic syndrome. In obese volunteers, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), leptin, the leptin/adiponectin ratio, and pro-inflammatory chemokines growth-related oncogene and macrophage-derived chemokine were significantly higher compared to non-obese submariners. Following the patrol, a significant mean reduction in body mass (5%) and fat-mass (11%) occurred in the obese group as a result of reduced energy intake (~2000 kJ) during the patrol; and, independent of group, modest improvements in serum lipids and a mean reduction in interferon γ-induced protein 10 and monocyte chemotactic protein 1 were observed. Since 43% of the submariners remained obese, and 18% continued to meet the criteria for metabolic syndrome following the patrol, the magnitude of weight loss was insufficient to completely abolish metabolic dysfunction. Submergence up to 3-months, however, does not appear to be the cause of obesity, which is similar to that of the general population. Topics: Adiponectin; Adipose Tissue; Adult; Blood Glucose; Body Mass Index; Chemokines; Energy Intake; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Military Personnel; Obesity; Sedentary Behavior; Ships; Sleep; Weight Loss; Work; Young Adult | 2016 |
Linoleic acid and stearic acid elicit opposite effects on AgRP expression and secretion via TLR4-dependent signaling pathways in immortalized hypothalamic N38 cells.
The regulation of food intake is a promising way to combat obesity. It has been implicated that various fatty acids exert different effects on food intake and body weight. However, the underlying mechanism remains poorly understood. The aim of the present study was to investigate the effects of linoleic acid (LA) and stearic acid (SA) on agouti-related protein (AgRP) expression and secretion in immortalized mouse hypothalamic N38 cells and to explore the likely underlying mechanisms. Our results demonstrated that LA inhibited, while SA stimulated AgRP expression and secretion of N38 cells in a dose-dependent manner. In addition, LA suppressed the protein expression of toll-like receptor 4 (TLR4), phosphorylation levels of JNK and IKKα/β, suggesting the inhibition of TLR4-dependent inflammation pathway. However, the above mentioned inhibitory effects of LA were eliminated by TLR4 agonist lipopolysaccharide (LPS). In contrast, SA promoted TLR4 protein expression and activated TLR4-dependent inflammation pathway, with elevated ratio of p-JNK/JNK. While TLR4 siRNA reversed the stimulatory effects of SA on AgRP expression and TLR4-dependent inflammation. Moreover, we found that TLR4 was also involved in LA-enhanced and SA-impaired leptin/insulin signal pathways in N38 cells. In conclusion, our findings indicated that LA elicited inhibitory while SA exerted stimulatory effects on AgRP expression and secretion via TLR4-dependent inflammation and leptin/insulin pathways in N38 cells. These data provided a better understanding of the mechanism underlying fatty acids-regulated food intake and suggested the potential role of long-chain unsaturated fatty acids such as LA in reducing food intake and treating obesity. Topics: Agouti-Related Protein; Animals; Eating; Hypothalamus; I-kappa B Kinase; Inflammation; Leptin; Linoleic Acid; Lipopolysaccharides; Mice; Obesity; Phosphorylation; RNA, Small Interfering; Signal Transduction; Stearic Acids; Toll-Like Receptor 4 | 2016 |
Advanced Glycation End Products Induce Obesity and Hepatosteatosis in CD-1 Wild-Type Mice.
AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the "multiple hit hypothesis" of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis. Topics: Adipose Tissue; Animals; Diet, High-Fat; Fatty Liver; Glycation End Products, Advanced; Humans; Inflammation; Interleukin-6; Leptin; Liver; Mice; Non-alcoholic Fatty Liver Disease; Obesity; Oxidation-Reduction; Peroxidase; Tumor Necrosis Factor-alpha; Weight Gain | 2016 |
Subacute inhalation exposure to ozone induces systemic inflammation but not insulin resistance in a diabetic mouse model.
Epidemiological studies suggest that diabetics may be more susceptible to the adverse health effects from exposure to high ambient concentrations of ozone, the primary oxidant gas in photochemical smog. While increased morbidity and mortality from ozone inhalation has been linked to disruption of normal cardiovascular and airway functions, potential effects on glucose and insulin homeostasis are not understood. We tested the hypothesis that ozone exposure would worsen metabolic homeostasis in KKAy mice, a genetic diabetic animal model. Male KKAy mice were exposed to 0.5 ppm ozone for 13 consecutive weekdays, and then assessed for airway, adipose and systemic inflammation, glucose homeostasis, and insulin signaling. Ozone exposure increased plasma TNFα, as well as expression of VCAM-1, iNOS and IL-6 in both pulmonary and adipose tissues. Pro-inflammatory CD11b(+)Gr-1(lo)7/4(hi) macrophages were increased by 200% in adipose tissue, but unchanged in blood. Interestingly, glucose levels were not significantly different in the insulin tolerance test between air- and ozone-exposed mice, whereas fasting insulin levels and HOMA-IR in ozone-exposed animals were significantly reduced. These changes were accompanied by increased insulin signaling in skeletal muscle and liver, but not adipose tissues. Ozone also caused decrease in body weight and plasma leptin. Our results show that in addition to marked local and systemic inflammation, ozone increases insulin sensitivity that may be related to weight loss/leptin sensitization-dependent mechanisms in KKAy mice, warranting further study on the role of hyperglycemia in mediating cardiometabolic effects of ozone inhalation. Topics: Adiponectin; Adipose Tissue; Administration, Inhalation; Animals; Blood Glucose; Diabetes Mellitus; Disease Models, Animal; Inflammation; Insulin; Insulin Resistance; Leptin; Liver; Male; Mice; Muscle, Skeletal; Sulfuric Acids | 2016 |
Cycle-phase dependent associations between CRP, leptin, and reproductive hormones in an urban, Canadian sample.
To assess the relationships among reproductive hormones, follicular development, inflammation, and adiposity in a sample of urban, Canadian women.. Participants (n = 41) had blood collected every 3 days through one interovulatory interval (IOI) to measure estradiol, progesterone, LH, FSH, leptin, and C-reactive protein (CRP). Participants underwent daily transvaginal ultrasound examinations during the IOI to quantify all follicles > 2 mm. CRP and leptin tertiles were used to compare conditions of high and low inflammatory processes and adiposity, respectively.. Luteal phase estradiol, luteal phase LH, and follicular phase progesterone were lower among individuals in the highest CRP tertile (adjusted r(2) = 0.63, 0.70, 0.76, respectively). Luteal and follicular phase follicle diameter was greatest in the high CRP tertile (adjusted r(2) = 0.68, 0.71). Follicular phase progesterone was lowest among individuals in the highest leptin tertile, and follicular phase FSH was lowest among individuals in the lowest leptin tertile (adjusted r(2) = 0.54, 0.45). Luteal phase follicle diameter was highest among those in the moderate leptin tertile (adjusted r(2) = 0.49).. This study is a first comprehensive assessment of the relationship between multiple ovarian function components and inflammatory biomarkers. The results are interpreted to mean that inflammatory and energetic stressors produce differential effects depending on population, adiposity, and cycle phase. Am J Phys Anthropol 160:389-396, 2016. © 2016 Wiley Periodicals, Inc. Topics: Adult; Biomarkers; C-Reactive Protein; Canada; Cohort Studies; Estradiol; Female; Gonadotropins, Pituitary; Humans; Inflammation; Leptin; Menstrual Cycle; Ovarian Follicle; Progesterone; Urban Population; Young Adult | 2016 |
Leptin Mediates High-Fat Diet Sensitization of Angiotensin II-Elicited Hypertension by Upregulating the Brain Renin-Angiotensin System and Inflammation.
Obesity is characterized by increased circulating levels of the adipocyte-derived hormone leptin, which can increase sympathetic nerve activity and raise blood pressure. A previous study revealed that rats fed a high-fat diet (HFD) have an enhanced hypertensive response to subsequent angiotensin II administration that is mediated at least, in part, by increased activity of brain renin-angiotensin system and proinflammatory cytokines. This study tested whether leptin mediates this HFD-induced sensitization of angiotensin II-elicited hypertension by interacting with brain renin-angiotensin system and proinflammatory cytokine mechanisms. Rats fed an HFD for 3 weeks had significant increases in white adipose tissue mass, plasma leptin levels, and mRNA expression of leptin and its receptors in the lamina terminalis and hypothalamic paraventricular nucleus. Central infusion of a leptin receptor antagonist during HFD feeding abolished HFD sensitization of angiotensin II-elicited hypertension. Furthermore, central infusion of leptin mimicked the sensitizing action of HFD. Concomitant central infusions of the angiotensin II type 1 receptor antagonist irbesartan, the tumor necrosis factor-α synthesis inhibitor pentoxifylline, or the inhibitor of microglial activation minocycline prevented the sensitization produced by central infusion of leptin. RT-PCR analysis indicated that either HFD or leptin administration upregulated mRNA expression of several components of the renin-angiotensin system and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus. The leptin antagonist and the inhibitors of angiotensin II type 1 receptor, tumor necrosis factor-α synthesis, and microglial activation all reversed the expression of these genes. The results suggest that HFD-induced sensitization of angiotensin II-elicited hypertension is mediated by leptin through upregulation of central renin-angiotensin system and proinflammatory cytokines. Topics: Angiotensin II; Animals; Blood Pressure Determination; Cytokines; Diet, High-Fat; Disease Models, Animal; Hypertension; Inflammation; Leptin; Male; Paraventricular Hypothalamic Nucleus; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Renin-Angiotensin System; RNA, Messenger; Up-Regulation | 2016 |
Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice.
Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. Topics: Adipokines; AMP-Activated Protein Kinases; Animals; Asthma; Collagen Type I; Diet, High-Fat; Female; Inflammation; Insulin; Interleukins; Lactation; Leptin; Lung; Male; Mice, Inbred C57BL; Obesity; Signal Transduction; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein | 2016 |
Bisphenol A Promotes Adiposity and Inflammation in a Nonmonotonic Dose-response Way in 5-week-old Male and Female C57BL/6J Mice Fed a Low-calorie Diet.
A growing body of epidemiological research show that Bisphenol A (BPA) is positively correlated with obesity and metabolic disorders. However, the mechanisms of BPA on adiposity remain largely unknown. In this study, we found that 5-week-old male and female C57BL/6J mice exposed to four dosages of BPA (5, 50, 500, and 5000 μg/kg/d) by oral intake for 30 days showed significantly increased body weight and fat mass in a nonmonotonic dose-dependent manner when fed a chow diet. The effect occurred even at the lowest concentration (5μg/kg/d), lower than the tolerable daily intake of 50 μg/kg/day for BPA. However, no significant difference in body weight and fat mass was observed in either male or female mice fed a high-fat diet, suggesting that BPA may interact with diet in promoting obesity risk. In vitro study showed that BPA treatment drives the differentiation of white adipocyte progenitors from the stromal vascular fraction, partially through glucocorticoid receptor. BPA exposure increased circulating inflammatory factors and the local inflammation in white adipose tissues in both genders fed a chow diet, but not under high-fat diet. We further found that BPA concentration was associated with increased circulating inflammatory factors, including leptin and TNFα, in lean female subjects (body mass index < 23.0 kg/m(2)) but not in lean male subjects or in both sexes of overweight/obese subjects (body mass index > 25.0 kg/m(2)). In conclusion, we demonstrated the nonmonotonic dose effects of BPA on adiposity and chronic inflammation in 5-week-old mice, which is related to caloric uptake. Topics: Adiposity; Aged; Animals; Benzhydryl Compounds; Body Weight; Caloric Restriction; Cell Differentiation; Diet, High-Fat; Female; Humans; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Middle Aged; Obesity; Phenols; Real-Time Polymerase Chain Reaction; Receptors, Glucocorticoid | 2016 |
Salidroside improves glucose homeostasis in obese mice by repressing inflammation in white adipose tissues and improving leptin sensitivity in hypothalamus.
Salidroside is a functionally versatile natural compound from the perennial flowering plant Rhodiola rosea L. Here, we examined obese mice treated with salidroside at the dosage of 50 mg/kg/day for 48 days. Mice treated with salidroside showed slightly decreased food intake, body weight and hepatic triglyceride content. Importantly, salidroside treatment significantly improved glucose and insulin tolerance. It also increased insulin singling in both liver and epididymal white adipose tissue (eWAT). In addition, salidroside markedly ameliorated hyperglycemia in treated mice, which is likely due to the suppression of gluconeogenesis by salidroside as the protein levels of a gluconeogenic enzyme G6Pase and a co-activator PGC-1α were all markedly decreased. Further analysis revealed that adipogenesis in eWAT was significantly decreased in salidroside treated mice. The infiltration of macrophages in eWAT and the productions of pro-inflammatory cytokines were also markedly suppressed by salidroside. Furthermore, the leptin signal transduction in hypothalamus was improved by salidroside. Taken together, these euglycemic effects of salidroside may due to repression of adipogenesis and inflammation in eWAT and stimulation of leptin signal transduction in hypothalamus. Thus, salidroside might be used as an effective anti-diabetic agent. Topics: Adipose Tissue, White; Animals; Body Weight; Eating; Epididymis; Glucose-6-Phosphatase; Glucosides; Hyperglycemia; Hypothalamus; Inflammation; Leptin; Liver; Male; Mice; Mice, Obese; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phenols; Triglycerides | 2016 |
Action of nicotinic acid on the reversion of hypoxic-inflammatory link on 3T3-L1 adipocytes.
Hypoxia resulting from adipocyte expansion is considered the basis of the inflammatory milieu observed in Metabolic Syndrome. Nicotinic acid can act on adipocytes interfering on the inflammatory response. In this study, we investigated the role of HIF-1 α (hypoxia-inducible factor -1 alpha) in the inflammatory process induced by hypoxia. The effect of nicotinic acid on the PPARs (peroxisome proliferator-activated receptors) expression during the inflammatory response was assessed over its action under HIF-1 α in 3T3-L1 adipocytes submitted to hypoxia.. 3T3-L1 adipocytes were pre-treated with nicotinic acid and incubated under hypoxic conditions. The level of adipokines and HIF-1 α were quantified using immunoassays. Adipokine expression was measured using real-time PCR, whereas PPARs and HIF-1 α expression were analyzed by western blot. The statistical significance of the differences between variables studied was determined by analysis of variance (ANOVA) complemented by Bonferroni's test.. The results demonstrated an increase in leptin and PAI-1 (plasminogen activator inhibitor-1) expression, while adiponectin production decreased under hypoxia. In parallel, induction with hypoxia enhanced HIF-1 α expression, despite causing reduced expression of PPAR α and PPAR γ. However, nicotinic acid reversed adipokine modulation under hypoxic conditions, leading to decreased HIF-1 α expression and increased PPARs expression.. Our findings suggest that nicotinic acid blunt the inflammatory response resulting from hypoxia by the reduction of HIF-1 α expression and concomitant increase of PPARs α and γ expression in 3T3-L1 adipocytes. Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Animals; Cell Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Leptin; Mice; Niacin; PPAR alpha; PPAR gamma; Serpin E2 | 2016 |
Obesity enhances sepsis-induced liver inflammation and injury in mice.
How obesity affects the response to sepsis was not completely understood. It was hypothesized that obesity alters adipose and hepatic tissue inflammation through signal transducer and activator of transcription (STAT3) activation.. Male C57BL/6 mice at 6 weeks of age were randomized to a high-fat diet (60% kcal fat) or normal diet (16% kcal fat) for 6 to 7 weeks. Sepsis was then induced by cecal ligation and puncture, and animals were monitored for survival or sacrificed and tissue collected.. High-fat diet-fed mice gained more weight, had increased fat mass, and were glucose intolerant compared with normal diet-fed mice. Obesity increased hepatic neutrophil infiltration and injury after sepsis. Mice with obesity had higher plasma leptin levels compared with mice without obesity. Adipose tissue expression of adiponectin receptor 2, tumor necrosis factor-α, and peroxisome proliferator activated receptor gamma was altered during sepsis and affected by obesity, but the greatest change in adipose tissue expression was in leptin. Septic mice with obesity had lower plasma interleukin-17a, interleukin-23, and tumor necrosis factor-α levels and increased hepatic STAT3 and activator protein-1 activation compared with septic mice without obesity. Ultimately, mice with obesity had a lower probability of survival following sepsis.. Mice with obesity are more susceptible to sepsis and have higher mortality, in part, through activation of the STAT3 signaling pathway and through activator protein-1 activation. Topics: Adipose Tissue; Animals; Cecum; Diet, High-Fat; Hepatitis; Inflammation; Interleukin-17; Interleukin-23; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; PPAR gamma; Sepsis; Signal Transduction; STAT3 Transcription Factor; Transcription Factor AP-1; Tumor Necrosis Factor-alpha | 2016 |
Low expression of the GILZ may contribute to adipose inflammation and altered adipokine production in human obesity.
The glucocorticoid-induced leucine zipper (GILZ), a primary target of glucocorticoids, is expressed in human adipocytes, but its importance in adipocyte function is unknown. Because TNFα is increased in obese adipose tissue and antagonizes a number of glucocorticoid actions, we investigated the interplay of these pathways. GILZ knockdown increased and GILZ overexpression decreased interleukin-6 (IL-6) and leptin mRNA and protein secretion. GILZ knockdown increased the magnitude of the glucocorticoid effect on leptin secretion, but did not affect the glucocorticoid suppression of IL-6. Although GILZ silencing decreased adiponectin mRNA levels, it did not affect the amount of adiponectin secreted. GILZ negatively modulated pro-inflammatory signaling pathways, blocking basal and TNFα-stimulated (1 h) p65 nuclear factor κB nuclear translocation and transcriptional activity by binding to p65 in the cytoplasm. GILZ silencing increased basal ERK1/2 and JNK phosphorylation, and decreased MAPK phosphatase-1 protein levels. Longer term TNFα (4 h or 24 h) treatment decreased GILZ expression in human adipocytes. Furthermore, adipose tissue GILZ mRNA levels were reduced in proportion to the degree of obesity and expression of inflammatory markers. Overall, these results suggest that GILZ antagonizes the pro-inflammatory effects of TNFα in human adipocytes, and its downregulation in obesity may contribute to adipose inflammation and dysregulated adipokine production, and thereby systemic metabolism. Topics: Adipokines; Adipose Tissue; Adult; Biopsy; Dual Specificity Phosphatase 1; Female; Gene Expression Regulation; Gene Knockdown Techniques; Humans; Inflammation; Interleukin-6; Leptin; Male; MAP Kinase Signaling System; NF-kappa B; Obesity; RNA, Messenger; Transcription Factor RelA; Transcription Factors; Tumor Necrosis Factor-alpha | 2016 |
Central leptin resistance and hypothalamic inflammation are involved in letrozole-induced polycystic ovary syndrome rats.
Accumulating evidence indicates that leptin acts as an important mediator in energy homeostasis and reproduction. Since dysfunction of reproduction and metabolism are major characteristics of polycystic ovarian syndrome (PCOS), the role of leptin in pathogenesis of PCOS needs further research. Many studies have shown that central leptin resistance existed in obesity rats through leptin intracerebroventricular (icv) injection; however, central leptin resistance in PCOS rats has not been reported. This study aimed to investigate whether there was a state of central leptin resistance in PCOS rats, as well as explore the possible association of hypothalamic inflammation with central leptin resistance. First, letrozole was used to induce the PCOS model, 24 h food intake, 24 h body weight changes and the expression of p-STAT3 were determined following leptin or artificial cerebrospinal fluid (aCSF) icv injection in rats. Second, we further evaluated the expressions of IL-1β, IL-6, TNF-α, p-IKKβ, NF-κB, p-NF-κB, IκBα, p-IκBα and SOCS3 in hypothalamus. The results showed that 24 h food intake and body weight were decreased, while the expression of p-STAT3 was increased in control group rats following leptin icv injection compared with aCSF icv injection; however, both of them showed no significant difference in PCOS rats. Furthermore, inflammatory markers were upregulated in the hypothalami of PCOS rats. Taken together, our data indicated that there was a state of chronic low-grade inflammation in hypothalamus which might be the possible mechanism for central leptin resistance in PCOS rats. Topics: Animals; Body Weight; Eating; Female; Hypothalamus; Inflammation; Leptin; Letrozole; Nitriles; Ovary; Polycystic Ovary Syndrome; Rats, Sprague-Dawley; Suppressor of Cytokine Signaling 3 Protein; Triazoles | 2016 |
Leptin inhibitors from fungal endophytes (LIFEs): Will be novel therapeutic drugs for obesity and its associated immune mediated diseases.
Treatment of obesity and its associated immune mediated diseases is challenging due to impaired function of leptin system. Thus leptin is providing an interesting target for therapeutic intervention. Leptin, an adipose tissue-derived adipokine, displays a variety of immune functions, and regulate both innate and adaptive immune responses. The increased secretion of leptin (hyperleptinemia) and production of proinflammatory cytokines has been implicated in the pathogenesis of obesity-related immune diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer, systemic lupus erythematosus, rheumatoid arthritis, crohn's disease and multiple sclerosis. These disorders are managed through antibiotics and by cytokines replacement. However, the effectiveness of cytokines coupled to the complexity of the cytokine network leads to severe side-effects, which can still occur after careful preclinical evaluation. In addition, synthetic immunotherapeutics carries a degree of risk, is time-consuming and expensive. Hence, the complexity of existing therapy and adverse effects emphasizes the need of an alternative approach for the management of immune dysfunction associated with obesity and its related diseases. For the aforementioned diseases that are related to leptin overabundance, new drugs blocking leptin signaling need to be generated. The research on the discovery of clinically important novel compounds from natural source is expanding due to their safety and no side effect. The fungal endophytes are the microbes that colonize internal tissue of plants without causing negative effects to the host. They produce plethora of substances of potential use to modern medicinal and pharmaceutical industry. The increasing body of evidence associated with application of bioactive metabolites derived from fungal endophytes in diverse disease states merits its use as therapeutic drugs. In particular, the saponins have been extensively proved to modulate the immune system, which has raised a significant interest in their potential as immunomodulators. Thus, our hypothesis is that the saponins derived from fungal endophytes can be explored as clinical applicable leptin inhibitors for treating immune mediated diseases. Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Cytokines; Endophytes; Fungi; Humans; Immune System; Immune System Diseases; Immunologic Factors; Immunotherapy; Inflammation; Leptin; NF-kappa B; Obesity; Translational Research, Biomedical | 2016 |
Cytokines, adipocytokines and inflammatory markers in patients on continuous ambulatory peritoneal dialysis and hemodialysis.
Cytokines are essential mediators of immune response. Chronic renal failure patients suffer from chronic inflammation that results from factors such as impaired renal function, accumulation of uremic toxins and bio incompatibility of dialyzer membranes. These patients are also at increased risk of cardiovascular diseases. We have evaluated cytokines, adipocytokines and inflammatory markers in patients with chronic renal failure undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD).. We have determined serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), leptin and ghrelin levels of chronic renal failure patients treated with either HD (n = 20) or CAPD (n = 20). TNF-α, IL-6, ghrelin and leptin measurements were performed by commercially available kits based on enzyme-linked immunosorbent assay (ELISA) method. hsCRP levels were determined by turbidimetric methods.. Serum TNF-α and IL-6 levels of patients on HD were significantly higher than those of the ones on CAPD (p < 0.05). Ghrelin, leptin and hsCRP concentrations were similar in both groups.. We can conclude that cytokine production is more obvious in HD process. Topics: Adipokines; Adult; Aged; Biomarkers; C-Reactive Protein; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Tumor Necrosis Factor-alpha | 2016 |
IL-6 mediates differentiation disorder during spermatogenesis in obesity-associated inflammation by affecting the expression of Zfp637 through the SOCS3/STAT3 pathway.
Zfp637 is a recently identified zinc finger protein, and its functions remain largely unknown. Here, we innovatively demonstrate the effects of Zfp637 on the differentiation of mouse spermatogonia and on its downstream target gene SOX2 in vitro. Obesity has been recognized as a chronic inflammatory disease that leads to decreased sexual function and sexual development disorders. We observed higher levels of IL-6 in serum and testis homogenates from obese mice compared with control mice. We also demonstrated that high levels of IL-6 inhibited Zfp637 expression, and we elucidated the underlying mechanisms. SOCS3 overexpression and STAT3 phosphorylation inhibitor (AG490) were used to investigate the function of the SOCS3/STAT3 pathway during this process. Our results showed that exposure of mouse spermatogonial cells to high levels of IL-6 inhibited Zfp637 expression by increasing SOCS3 expression and inhibiting the phosphorylation of STAT3, further reducing cellular differentiation. Consistent with the in vitro results, we observed increasing expression levels of SOCS3 and SOX2, but a reduction of Zfp637 expression, in obese mouse testes. In conclusion, Zfp637 plays a crucial role in spermatogenesis by downregulating SOX2 expression, and IL-6 can decrease the expression of Zfp637 through the SOCS3/STAT3 signaling pathway. Topics: Animals; Cell Line; DNA-Binding Proteins; Down-Regulation; Inflammation; Interleukin-6; Leptin; Male; Mice; Mice, Obese; Obesity; Phosphorylation; RNA Interference; Signal Transduction; SOXB1 Transcription Factors; Spermatogenesis; Spermatogonia; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Testis; Tyrphostins | 2016 |
Bardoxolone methyl prevents obesity and hypothalamic dysfunction.
High-fat (HF) diet-induced obesity is associated with hypothalamic leptin resistance and low grade chronic inflammation, which largely impairs the neuroregulation of negative energy balance. Neuroregulation of negative energy balance is largely controlled by the mediobasal and paraventricular nuclei regions of the hypothalamus via leptin signal transduction. Recently, a derivative of oleanolic acid, bardoxolone methyl (BM), has been shown to have anti-inflammatory effects. We tested the hypothesis that BM would prevent HF diet-induced obesity, hypothalamic leptin resistance, and inflammation in mice fed a HF diet. Oral administration of BM via drinking water (10 mg/kg daily) for 21 weeks significantly prevented an increase in body weight, energy intake, hyperleptinemia, and peripheral fat accumulation in mice fed a HF diet. Furthermore, BM treatment prevented HF diet-induced decreases in the anorexigenic effects of peripheral leptin administration. In the mediobasal and paraventricular nuclei regions of the hypothalamus, BM administration prevented HF diet-induced impairments of the downstream protein kinase b (Akt) pathway of hypothalamic leptin signalling. BM treatment also prevented an increase in inflammatory cytokines, tumour necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in these two hypothalamic regions. These results identify a potential novel neuropharmacological application for BM in preventing HF diet-induced obesity, hypothalamic leptin resistance, and inflammation. Topics: Animals; Anti-Obesity Agents; Body Weight; Diet, High-Fat; Energy Intake; Energy Metabolism; Hypothalamus; Inflammation; Leptin; Male; Mice, Inbred C57BL; Obesity; Oleanolic Acid; Signal Transduction | 2016 |
Differential body weight, blood pressure and placental inflammatory responses to normal versus high-fat diet in melanocortin-4 receptor-deficient pregnant rats.
Although obesity increases the risk for hypertensive disorders of pregnancy, the mechanisms remain unclear. Neural melanocortin-4 receptor (MC4R) deficiency causes hyperphagia and obesity. Effects of MC4R deficiency on body weight, blood pressure (BP) and placental inflammatory responses to high-fat diet (HFD) are unknown. We tested two hypotheses: MC4R deficiency results in higher body weight, BP and placental inflammation under normal-fat diet (NFD) conditions and HFD exaggerates these responses in MC4R-deficient pregnant rats.. MC4R and MC4R rats were maintained on NFD (13% kcal fat) or HFD (40% kcal fat) for ∼15 weeks, then measurements made on gestational day 19.. MC4R pregnant rats had greater body mass and total body fat and visceral adipose tissue weights along with greater circulating total cholesterol (TC) and leptin levels than MC4R rats regardless of diet. On NFD, circulating adiponectin levels were lower and placental TNFα levels and BP (conscious with carotid catheter) were higher in these heavier rats. Circulating adiponectin levels were lower and placental TNFα levels and BP were higher in MC4R rats compared with NFD controls. These parameters were not affected by HFD in the already heavier and hypertensive MC4R pregnant rats.. Obesity in MC4R deficiency and HFD in MC4R rats result in higher BP and placental inflammation during pregnancy. However, HFD did not exaggerate these responses in already obese MC4R pregnant rats. These data suggest that obesity and HFD are independently related to hypertension and placental inflammation in pregnancy. Topics: Adiponectin; Adiposity; Animals; Blood Pressure; Body Weight; Cholesterol; Diet, High-Fat; Female; Hypertension; Inflammation; Intra-Abdominal Fat; Leptin; Obesity; Placenta; Pregnancy; Rats; Receptor, Melanocortin, Type 4; Tumor Necrosis Factor-alpha | 2016 |
Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation.
Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptin-sufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease. Topics: Animals; Autoantibodies; Autoimmunity; Disease Models, Animal; Humans; Immunity, Innate; Inflammation; Leptin; Lupus Erythematosus, Systemic; Mice; Mice, Inbred NZB; T-Lymphocytes, Regulatory; Terpenes | 2016 |
Changes of Regulatory T Cells in the Early Stage of Obesity Mice and Their Modulation on Macrophage Subtypes in Visceral Adipose Tissue.
Objective To investigate the changes of regulatory T cells (Tregs) and whether Tregs can modulate the distribution of macrophage subtypes in visceral adipose tissue in the early stage of obesity.Methods After C57BL/6 mice obesity models were successfully established,metabolic parameters and numbers of Tregs and M1/M2 macrophage were measured at 4,10,and 20 weeks.The changes of metabolic parameters and adipose tissue inflammation in obesity mice after rapamycin intervention were evaluated. Results The early-stage obesity models were successfully established.Compared with normal diet mice,high fat diet mice had significantly higher epididymal adipose tissue mass and serum leptin levels(P<0.05).However,there was no statistical difference in blood glucose and insulin levels between these two groups(All P>0.05). Macrophages infiltration in adipose tissue in high fat diet mice gradually increased with time,coincident with decrease in Treg numbers. Increased numbers of Treg,improved metabolic parameters,and decreased ratio of M1/M2 can be seen after rapamycin intervention in mice.Conclusion The decrease of Tregs in the early stage of obesity may contribute to abnormal distribution of macrophage subtypes in visceral adipose. Topics: Animals; Blood Glucose; Diet, High-Fat; Inflammation; Intra-Abdominal Fat; Leptin; Macrophages; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; T-Lymphocytes, Regulatory | 2016 |
Association of Vitamin B12 with Pro-Inflammatory Cytokines and Biochemical Markers Related to Cardiometabolic Risk in Saudi Subjects.
This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population.. A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m² and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m²) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer.. Vitamin B12 was negatively associated with TNF-α (r = -0.14, p < 0.05), insulin (r = -0.230, p < 0.01) and HOMA-IR (r = -0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = -0.160, p < 0.01), insulin (r = -0.248, p < 0.01), HOMA-IR (r = -0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = -0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r² = -0.17, p < 0.05) and in children (r² = -0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r² = -0.78, p < 0.05).. Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population. Topics: Adiponectin; Adolescent; Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Humans; Inflammation; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Resistin; Risk Factors; Saudi Arabia; Tumor Necrosis Factor-alpha; Vitamin B 12; Waist Circumference | 2016 |
Intermittent hypoxia in obese Zucker rats: cardiometabolic and inflammatory effects.
What is the central question of this study? This study addresses the relative impact of obesity and intermittent hypoxia in the pathophysiological process of obstructive sleep apnoea by investigating the metabolic, inflammatory and cardiovascular consequences of intermittent hypoxia in lean and obese Zucker rats. What is the main finding and its importance? We found that obesity and intermittent hypoxia have mainly distinct consequences on the investigated inflammatory and cardiometabolic parameters in Zucker rats. This suggests that, for a given severity of sleep apnea, the association of obesity and obstructive sleep apnoea may not necessarily be deleterious. Obstructive sleep apnoea is associated with obesity with a high prevalence, and both co-morbidities are independent cardiovascular risk factors. Intermittent hypoxia (IH) is thought to be the main factor responsible for the obstructive sleep apnoea-related cardiometabolic alterations. The aim of this study was to assess the respective impact of obesity and IH on the inflammatory and cardiometabolic state in rats. Lean and obese Zucker rats were exposed to normoxia or chronic IH, and we assessed metabolic and inflammatory parameters, such as plasma lipids and glucose, serum leptin and adiponectin, liver cytokines, nuclear factor-κB activity and cardiac endothelin-1 levels. Myocardial infarct size was also evaluated following in vitro ischaemia-reperfusion. Circulating lipids, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin and adiponectin levels were higher in obese versus lean rats. Chronic IH did not have a significant impact on metabolic parameters in lean rats. In obese rats, IH increased glycaemia and HOMA-IR. Liver interleukin-6 and tumour necrosis factor-α levels were elevated in lean rats exposed to IH; obesity prevented the increase in interleukin-6 but not in tumour necrosis factor-α. Finally, IH exposure enhanced myocardial sensitivity to infarction in both lean and obese rats and increased cardiac endothelin-1 in lean but not obese rats. In conclusion, this study shows that the dyslipidaemia and insulin resistance induced by obesity of genetic origin does not enhance the deleterious cardiovascular response to IH and may even partly protect against IH-induced inflammation. Topics: Adiponectin; Animals; Blood Glucose; Cardiovascular Diseases; Cytokines; Disease Models, Animal; Endothelin-1; Hypoxia; Inflammation; Insulin; Interleukin-6; Leptin; Lipids; Liver; Male; Myocardium; NF-kappa B; Obesity; Rats; Rats, Zucker; Tumor Necrosis Factor-alpha | 2016 |
Inflammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents.
Only a handful of studies, primarily in clinical samples, have reported an association between obesity, inflammation, and obstructive sleep apnea (OSA) in children and adolescents. No studies, however, have examined the pathogenetic link between visceral adiposity, systemic inflammation, and incident OSA in a large general population sample using objective measures of sleep and body fat. Adolescents (n = 392; mean age 17.0 ± 2.2 yr, 54.0% male) from the Penn State Child Cohort (PSCC) underwent 9-h overnight polysomnography; a DXA scan to assess body fat distribution; and a single fasting blood draw for the assessment of plasma interleukin-6 (IL-6), IL-6 soluble receptor (IL-6 sR), tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1A (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels via ELISA. Visceral fat area was significantly elevated in moderate OSA (AHI ≥ 5), especially in boys. IL-6, CRP, and leptin were highest in adolescents with moderate OSA, even after adjusting for BMI percentile. Mediation analysis revealed that 42% of the association between visceral fat and OSA in adolescents was mediated by IL-6 (p = 0.03), while 82% of the association was mediated by CRP (p = 0.01). These data are consistent with the model of a feed-forward, vicious cycle, in which the release of proinflammatory cytokines by visceral adipocytes largely explains the association between central obesity and OSA; in turn, inflammation is also elevated in OSA independent of BMI. These findings, in a large, representative, non-clinical sample of young people, add to our understanding of the developmental pathogenesis of sleep apnea. Topics: Absorptiometry, Photon; Adipokines; Adiponectin; Adolescent; Body Fat Distribution; C-Reactive Protein; Comorbidity; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Obesity, Abdominal; Polysomnography; Receptors, Cytokine; Receptors, Interleukin-6; Receptors, Tumor Necrosis Factor, Type I; Sex Factors; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha; Young Adult | 2016 |
Inflammation: Leptin deficiency protects against SLE.
Topics: Adiponectin; Humans; Inflammation; Leptin; Lupus Erythematosus, Systemic | 2016 |
Adiponectin, leptin, nitric oxide, and C-reactive protein levels in kidney transplant recipients: comparison with the hemodialysis and chronic renal failure.
Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with chronic kidney disease (CKD) including kidney transplant recipients (KTR). Secondary lipid metabolism disorders, endothelial dysfunction, and inflammation enhance the risk of CVD development in these patients. The aim of the present study was to investigate the lipid profile, adiponectin, leptin, nitric oxide (NO), and high sensitivity C-reactive protein (hs-CRP) levels in KTR and to compare these parameters with those of the patients with chronic renal failure (CRF), hemodialysis (HD) patients, and healthy controls.. Serum adiponectin and leptin levels were measured by radioimmunoassay; hs-CRP was determined immunoturbidimetrically. Determination of NO was based on the Griess reaction.. Compared with the control group, serum NO and adiponectin levels were significantly higher in the KTR, CRF, and HD groups; hs-CRP levels were significantly higher in the KTR and HD groups; leptin levels were significantly higher in the KTR. In addition, serum NO level was significantly higher in the KTR compared to CRF cases. Adiponectin correlated positively with high density lipoprotein-cholesterol in the control and patient groups. A positive correlation was observed between hs-CRP and NO in the KTR and the patients with CRF. Serum adiponectin levels were inversely correlated with hs-CRP and leptin in the HD group.. KTR suffer from inflammation and accompanying changes in levels of adipocytokines and NO which contribute to the increased risk of CVD in these patients. Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Inflammation; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Middle Aged; Nitric Oxide; Renal Dialysis; Transplant Recipients; Turkey | 2016 |
A Novel Selective Inhibitor of Delta-5 Desaturase Lowers Insulin Resistance and Reduces Body Weight in Diet-Induced Obese C57BL/6J Mice.
Obesity is now recognized as a state of chronic low-grade inflammation and is called as metabolic inflammation. Delta-5 desaturase (D5D) is an enzyme that metabolizes dihomo-γ-linolenic acid (DGLA) to arachidonic acid (AA). Thus, D5D inhibition increases DGLA (precursor to anti-inflammatory eicosanoids) while decreasing AA (precursor to pro-inflammatory eicosanoids), and could result in synergistic improvement in the low-grade inflammatory state. Here, we demonstrate reduced insulin resistance and the anti-obesity effect of a D5D selective inhibitor (compound-326), an orally active small-molecule, in a high-fat diet-induced obese (DIO) mouse model. In vivo D5D inhibition was confirmed by determining changes in blood AA/DGLA profiles. In DIO mice, chronic treatment with compound-326 lowered insulin resistance and caused body weight loss without significant impact on cumulative calorie intake. Decreased macrophage infiltration into adipose tissue was expected from mRNA analysis. Increased daily energy expenditure was also observed following administration of compound-326, in line with sustained body weight loss. These data indicate that the novel D5D selective inhibitor, compound-326, will be a new class of drug for the treatment of obese and diabetic patients. Topics: 8,11,14-Eicosatrienoic Acid; Adiponectin; Adipose Tissue; Animals; Arachidonic Acid; Body Weight; Delta-5 Fatty Acid Desaturase; Diet, High-Fat; Energy Metabolism; Enzyme Inhibitors; Fatty Acid Desaturases; Gene Expression; Hep G2 Cells; Humans; Inflammation; Insulin Resistance; Leptin; Macrophages; Male; Mice, Inbred C57BL; Obesity; Pyrimidinones; Pyrrolidinones; Reverse Transcriptase Polymerase Chain Reaction; Weight Loss | 2016 |
High-fat Western diet-induced obesity contributes to increased tumor growth in mouse models of human colon cancer.
Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth. Homozygous Rag1 Topics: Adipose Tissue, White; Animals; Chemokine CCL2; Colonic Neoplasms; Diet, High-Fat; Diet, Western; Dietary Fats; Disease Models, Animal; Epididymis; Heterografts; Humans; Inflammation; Insulin; Insulin Resistance; Intra-Abdominal Fat; JNK Mitogen-Activated Protein Kinases; Leptin; Male; Mice, Inbred Strains; Obesity; Phosphorylation; Receptor Protein-Tyrosine Kinases; Signal Transduction | 2016 |
Neuroendocrine Inflammatory Responses in Overweight/Obese Infants.
Childhood obesity is related to a cascade of neuroendocrine inflammatory changes. However, there remains a gap in the current literature regarding the possible occurrence of these changes in overweight/obese infants. The objective of this study was to evaluate adipokines, cortisol, brain-derived neurotrophic factor (BDNF) and redox status in overweight/obese infants versus normal-weight peers. A cross-sectional study was conducted with 50 infants (25 in the overweight/obese group and 25 in the normal-weight group) between 6 and 24 months. Plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor (TNF) receptors, chemokines, BDNF, serum cortisol and redox status were measured. Unpaired Student's t-test was used to analyze the results and a probability of p<0.05 was acceptable for rejection of the null hypothesis. The Pearson correlation was used to verify the association between the biomarkers analyzed in each group. Plasma levels of leptin (p = 0.0001), adiponectin (p = 0.0007) and BDNF (p = 0.003), and serum cortisol (p = 0.048) were significantly higher in overweight/obese infants than normal-weight infants. In contrast, the concentration of thiobarbituric acid reactive substances (TBARS) (p = 0.004), and catalase (p = 0.045) and superoxide dismutase activity (p = 0.02) were lower in overweight/obese infants than normal-weight peers. All the results together indicate neuroendocrine inflammatory response changes in overweight/obese infants between 6 and 24 months. Although there is already an environment that predisposes for a subsequent pro-inflammatory response, neuroendocrine secretion changes that permit the control of the inflammatory process in this age interval can be observed. Topics: Adipokines; Adiponectin; Biomarkers; Body Composition; Body Weight; Brain-Derived Neurotrophic Factor; Cross-Sectional Studies; Humans; Hydrocortisone; Infant; Inflammation; Leptin; Neurosecretory Systems; Obesity; Overweight; Oxidation-Reduction | 2016 |
Lunasin Attenuates Obesity-Associated Metastasis of 4T1 Breast Cancer Cell through Anti-Inflammatory Property.
Obesity prevalence is increasing worldwide and is accompanied by low-grade inflammation with macrophage infiltration, which is linked with a poorer breast cancer prognosis. Lunasin is a natural seed peptide with chemopreventive properties and multiple bioactivities. This is the first study to explore the chemopreventive effects of lunasin in the obesity-related breast cancer condition using 4T1 breast cancer cells, 3T3-L1 adipocytes, and conditioned media. An obesity-related environment, such as leptin-treatment or adipocyte-conditioned medium (Ad-CM), promoted 4T1 cell proliferation and metastasis. Lunasin treatment inhibited metastasis of breast cancer cells, partially through modestly inhibiting production of the angiogenesis-mediator vascular endothelial growth factor (VEGF) and significantly by inhibiting secretion in the Ad-CM condition. Subsequently, two adipocytes inflammation models, 3T3-L1 adipocytes were stimulated by tumor necrosis factor (TNF)-α, and RAW 264.7 cell-conditioned medium (RAW-CM) was used to mimic the obese microenvironment. Lunasin significantly inhibited interleukin (IL)-6 and macrophage chemoattractant protein (MCP)-1 secretion by TNF-α stimulation, and MCP-1 secretion in the RAW-CM model. This study highlights that lunasin suppressed 3T3-L1 adipocyte inflammation and inhibited 4T1 breast cancer cell migration. Interestingly, lunasin exerted more effective anti-metastasis activity in the obesity-related condition models, indicating that it possesses anti-inflammatory properties and blocks adipocyte-cancer cell cross-talk. Topics: 3T3-L1 Cells; Adipocytes; Animals; Anti-Inflammatory Agents; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Culture Media, Conditioned; Cytokines; Female; Inflammation; Inflammation Mediators; Leptin; Lipid Metabolism; Mammary Neoplasms, Animal; Mice; Mice, Inbred BALB C; Models, Biological; Neoplasm Metastasis; Obesity; Peptides; RAW 264.7 Cells; Vascular Endothelial Growth Factor A | 2016 |
High Thyroid-stimulating Hormone Levels Increase Proinflammatory and Cardiovascular Markers in Patients with Extreme Obesity.
Obesity is an important health problem worldwide and many studies have suggested a relationship between obesity and thyroid function, with controversial results. Interestingly, high TSH levels have been involved with the presence of inflammatory state and risk for developing cardiovascular diseases in hypothyroid and obese patients. The aim in this work was to determine the prevalence of hypothyroidism in patients with extreme obesity and to determine whether their TSH levels were related to increased serum levels of inflammatory and cardiovascular markers.. A cross-sectional study in 101 patients with extreme obesity (BMI ≥40) was performed. Anthropometric (weight, height and waist circumference) and biochemical (fasting glucose, glycosylated hemoglobin, triglycerides, total cholesterol, LDL-C, HDL-C and insulin) parameters were measured. TSH and FT4 levels as well as clinical exploration for diagnosis of hypothyroidism were carried out. Serum concentration of IL-10, IL-6, adiponectin, resistin, leptin, ICAM-1, VCAM-1 and E-selectin were determined.. A high prevalence for diabetes (37.6%), prediabetes (50.5%), dyslipidemia (74.3%), hypertension (61.4%) and hypothyroidism (48.5%) was observed in patients with extreme obesity. The presence of hypothyroidism increased serum concentration of proinflammatory cytokines IL-6 and leptin and decreased the antiinflammatory cytokine adiponectin. In addition, serum TSH levels showed a correlation for waist circumference, weight, BMI, A1c, insulin, IL-6, leptin, ICAM-1 and E-selectin.. There is a high prevalence for hypothyroidism in patients with extreme obesity. High levels of TSH contribute to elevate proinflammatory and cardiovascular risk markers, increasing the risk for development of cardiovascular diseases. Topics: Adiponectin; Adult; Biomarkers; Body Weight; Cardiovascular Diseases; Cross-Sectional Studies; E-Selectin; Female; Humans; Hypothyroidism; Inflammation; Insulin; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-6; Leptin; Male; Middle Aged; Obesity, Morbid; Prevalence; Resistin; Risk Factors; Thyrotropin; Triglycerides; Vascular Cell Adhesion Molecule-1; Waist Circumference | 2016 |
Testosterone Deficiency Induces Changes of the Transcriptomes of Visceral Adipose Tissue in Miniature Pigs Fed a High-Fat and High-Cholesterol Diet.
Testosterone deficiency causes fat deposition, particularly in visceral fat, and its replacement might reverse fat accumulation, however, the underlying mechanisms of such processes under diet-induced adiposity are largely unknown. To gain insights into the genome-wide role of androgen on visceral adipose tissue (VAT), RNA-Seq was used to investigate testosterone deficiency induced changes of VAT in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT) treatments. The results showed that testosterone deficiency significantly increased VAT deposition and serum leptin concentrations. Moreover, a total of 1732 differentially expressed genes (DEGs) were identified between any two groups. Compared with gene expression profiles in IM and CMT pigs, upregulated genes in CM pigs, i.e., Topics: Adiposity; Animals; Castration; Cell Adhesion; Cell Differentiation; Cholesterol; Diet, High-Fat; Gene Expression Profiling; Hypercholesterolemia; Inflammation; Intra-Abdominal Fat; Leptin; Male; Obesity; Oxidation-Reduction; Swine; Swine, Miniature; Testosterone; Transcriptome | 2016 |
The Effects of the Combination of a Refined Carbohydrate Diet and Exposure to Hyperoxia in Mice.
Obesity is a multifactorial disease with genetic, social, and environmental influences. This study aims at analyzing the effects of the combination of a refined carbohydrate diet and exposure to hyperoxia on the pulmonary oxidative and inflammatory response in mice. Twenty-four mice were divided into four groups: control group (CG), hyperoxia group (HG), refined carbohydrate diet group (RCDG), and refined carbohydrate diet + hyperoxia group (RCDHG). The experimental diet was composed of 10% sugar, 45% standard diet, and 45% sweet condensed milk. For 24 hours, the HG and RCDHG were exposed to hyperoxia and the CG and RCDG to ambient air. After the exposures were completed, the animals were euthanized, and blood, bronchoalveolar lavage fluid, and lungs were collected for analyses. The HG showed higher levels of interferon- Topics: Adipocytes; Adiposity; Animals; Antioxidants; Biomarkers; Blood Glucose; Bronchoalveolar Lavage Fluid; Cell Count; Cholesterol; Dietary Carbohydrates; Epididymis; Feeding Behavior; Hyperoxia; Immunoassay; Inflammation; Leptin; Lung; Male; Mice, Inbred BALB C; Oxidation-Reduction; Oxidative Stress; Weight Gain | 2016 |
A Single Bout of Fasting (24 h) Reduces Basal Cytokine Expression and Minimally Impacts the Sterile Inflammatory Response in the White Adipose Tissue of Normal Weight F344 Rats.
Sterile inflammation occurs when inflammatory proteins are increased in blood and tissues by nonpathogenic states and is a double-edged sword depending on its cause (stress, injury, or disease), duration (transient versus chronic), and inflammatory milieu. Short-term fasting can exert a host of health benefits through unknown mechanisms. The following experiment tested if a 24 h fast would modulate basal and stress-evoked sterile inflammation in plasma and adipose. Adult male F344 rats were either randomized to Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Corticosterone; Cytokines; Fatty Acids, Nonesterified; Food Deprivation; Inflammation; Insulin; Interleukin-10; Interleukin-1beta; Interleukin-6; Leptin; Male; Random Allocation; Rats; Rats, Inbred F344; Tumor Necrosis Factor-alpha | 2016 |
The interplay among iron metabolism, endothelium and inflammatory cascade in dysmetabolic disorders.
Metabolic syndrome (MetS) is considered as a proinflammatory and prothrombotic state with atherogenic risk factors including dyslipidemia, obesity and glucose intolerance. Oxidative stress is a unifying basis of several disorders including diabetes mellitus (DM) and MetS. We therefore designed this cross-sectional study to investigate the potential interaction among iron metabolism, inflammation and endothelial plexus in MetS and DM patients.. A total of 62 patients [median age 54 (23-76) years; male/female 16/46] and 18 healthy controls [median age 38 (30-64) years; male/female 6/12] were included in the study. Patient population was classified as MetS (n = 30) and DM (n = 32).. Leukocyte count (p = 0.002) and osteopontin (OPN) levels (p = 0.008) were significantly higher, while C-reactive protein (CRP) (p = 0.056) and IL-6 (p = 0.059) represented a relative increase in the patient group. Leptin, endothelin 1 (ET1), hepcidin, nitric oxide synthase (NOS), erythrocyte sedimentation rate (ESR), iron, transferrin saturation (TS) and ferritin levels were not significantly different between the patient and control groups. Endothelin 1 was found to be higher in the DM group compared to MetS group (p = 0.15, p = 0.049). Leukocyte count, leptin, hepcidin, OPN, NOS, IL-6, ESR, CRP, iron, TS and ferritin levels were not different between DM and MetS groups. A positive correlation was demonstrated between leptin and OPN (p = 0.001, r = 0.360), ferritin and hepcidin (p < 0.01, r = 0.633), IL-6 and CRP (p = 0.023, r = 0.319), leptin and NOS (p = 0.005, r = 0.309) and OPN and NOS (p < 0.001, r = 0.803). There was a negative correlation between hepcidin and NOS (p = 0.009, r = -0.289). When the study cohort was divided into two particular groups based on median ferritin and hepcidin levels, hepcidin (p = 0.002), ALT (p = 0.001) and LDL (p = 0.049) levels were higher in the high-ferritin group. Nitric oxide synthase levels (p = 0.033) were lower, whereas ferritin levels (p = 0.004) were higher in the high-hepcidin group.. Mechanisms involved in the vicious circle of MetS including inflammation, endothelial vasculature and iron metabolism remain to be elucidated. The role of iron metabolism in this complex interaction should be confirmed with further studies. Topics: Adult; Aged; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus; Endothelium, Vascular; Female; Ferritins; Glucose Intolerance; Hepcidins; Humans; Inflammation; Interleukin-6; Iron; Leptin; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Young Adult | 2015 |
Protein tyrosine phosphatase-1B contributes to LPS-induced leptin resistance in male rats.
Leptin resistance is induced by the feedback inhibitors tyrosine phosphatase-1B (PTP1B) and decreased Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) signaling. To investigate the participation of PTP1B and SHP-2 in LPS-induced leptin resistance, we injected repeated (6-LPS) intraperitoneal LPS doses (100 μg/kg ip) for comparison with a single (1-LPS) treatment and evaluated the expression of SHP-2, PTP1B, p-ERK1/2, and p-STAT3 in the hypothalamus of male Wistar rats. The single LPS treatment increased the expression of p-STAT3 and PTP1B but not SHP-2. The repeated LPS treatment reduced SHP-2, increased PTP1B, and did not change p-STAT3. We observed that the PTP1B expression induced by the endotoxin was highly colocalized with leptin receptor cells in the hypothalamus of LepRb-IRES-Cre-tdTomato reporter mice. The single, but not the repeated, LPS treatment decreased the food intake and body weight. Leptin had no stimulatory effect on the hypophagia, body weight loss, or pSTAT3 expression in 6-LPS rats, indicating leptin unresponsiveness. Notably, the PTP1B inhibitor (3.0 nmol/rat in 5 μl icv) restored the LPS-induced hypophagia in 6-LPS rats and restored the ability of leptin to reduce food intake and body weight as well as to phosphorylate STAT3 in the arcuate, paraventricular, and ventromedial nuclei of the hypothalamus. The present data suggest that an increased PTP1B expression in the hypothalamus underlies the development of leptin resistance during repeated exposure to LPS. Our findings contribute to understanding the mechanisms involved in leptin resistance during low-grade inflammation as seen in obesity. Topics: Animals; Drug Resistance; Hypothalamus; Inflammation; Leptin; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Rats; Rats, Wistar; Receptors, Leptin | 2015 |
Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children.
Accumulation of fat mass in obesity may result from hypertrophy and/or hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in adults. Here we assessed early alterations in AT biology and function by comprehensive experimental and clinical characterization of 171 AT samples from lean and obese children aged 0 to 18 years. We show an increase in adipocyte size and number in obese compared with lean children beginning in early childhood. These alterations in AT composition in obese children were accompanied by decreased basal lipolytic activity and significantly enhanced stromal vascular cell proliferation in vitro, potentially underlying the hypertrophy and hyperplasia seen in obese children, respectively. Furthermore, macrophage infiltration, including the formation of crown-like structures, was increased in AT of obese children from 6 years on and was associated with higher hs-CRP serum levels. Clinically, adipocyte hypertrophy was not only associated with leptin serum levels but was highly and independently correlated with HOMA-IR as a marker of insulin resistance in children. In summary, we show that adipocyte hypertrophy is linked to increased inflammation in AT in obese children, thereby providing evidence that obesity-associated AT dysfunction develops in early childhood and is related to insulin resistance. Topics: Adipocytes; Adipose Tissue; Adolescent; Blood Glucose; Cell Differentiation; Cell Proliferation; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Inflammation; Insulin; Insulin Resistance; Leptin; Macrophages; Male; Obesity | 2015 |
Roux-en-Y gastric bypass decreases pro-inflammatory and thrombotic biomarkers in individuals with extreme obesity.
The low-grade inflammatory state in obesity leads to insulin resistance and endothelial dysfunction, which promote cardiovascular diseases in individuals with obesity. The purpose of this study was to evaluate the early effects of weight loss achieved through bariatric surgery on the inflammatory and prothrombotic states. This study also aimed to identify the role of hyperleptinemia on the prothrombotic state.. The sample was composed of 41 extremely obese who underwent Roux-en-Y gastric bypass (RYGB). Anthropometric and clinical data, and biochemical markers of inflammation were collected prior to surgery and 6 months post-RYGB.. It was found that plasminogen activator inhibitor-1 (PAI-1) concentrations were higher among extremely obese individuals with hyperleptinemia than in those without hyperleptinemia (p < 0.01).In relation to the baseline, post-surgery body mass index (BMI) was reduced by 12.9 kg/m(2), corresponding to 63.50 % of excess weight loss. Additionally, waist circumference was found to decrease significantly from 126.2 to 101.4 cm. Plasma total cholesterol (p < 0.01), LDL cholesterol (p = 0.02), triglycerides (p < 0.01), and glucose (p = 0.01) were also found to decrease. Pro-inflammatory biomarkers were observed to decrease: PAI-1 by 55.9 ± 6.0 % (p < 0.01), C-reactive protein (CRP) by 18.8 ± 3.4 % (p < 0.01), intercellular adhesion molecule-1 (ICAM-1) by 89.9 ± 5.7 % (p < 0.01), leptin by 27.9 ± 3.2 % (p < 0.01), and resistin by 69.3 ± 5.8 % (p < 0.01). Additionally, significant decreases of tumor necrosis factor alpha (TNF-α) and leptin/adiponectin ratio were observed. Anti-inflammatory cytokines adiponectin and interleukin-10 (IL-10) were significantly increased (170.7 ± 82.5 %, p < 0.01; 122.7 ± 55.1 %, p = 0.02). CRP levels were predictive of ICAM-1 (p = 0.04), and changes in leptin concentrations were associated with decreased PAI-1 levels (p = 0.03).. We observed that individuals with obesity that have hyperleptinemia have higher circulating PAI-1 levels, which could indicate increased risk for cardiovascular disease. The biomarkers of inflammation and thrombosis measured in this study decreased after RYGB, suggesting that the surgery may be effective in reducing pro-inflammatory and thrombotic risk in individuals with extreme obesity. Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Female; Gastric Bypass; Humans; Inflammation; Insulin Resistance; Intercellular Adhesion Molecule-1; Interleukin-10; Leptin; Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Treatment Outcome; Triglycerides; Weight Loss; Young Adult | 2015 |
Novel coronary heart disease risk factors at 60-64 years and life course socioeconomic position: the 1946 British birth cohort.
Social disadvantage across the life course is associated with a greater risk of coronary heart disease (CHD) and with established CHD risk factors, but less is known about whether novel CHD risk factors show the same patterns. The Medical Research Council National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and markers of inflammation (C-reactive protein, interleukin-6), endothelial function (E-selectin, tissue-plasminogen activator), adipocyte function (leptin, adiponectin) and pancreatic beta cell function (proinsulin) measured at 60-64 years. Life course models representing sensitive periods, accumulation of risk and social mobility were compared with a saturated model to ascertain the nature of the relationship between social class across the life course and each of these novel CHD risk factors. For interleukin-6 and leptin, low childhood socioeconomic position alone was associated with high risk factor levels at 60-64 years, while for C-reactive protein and proinsulin, cumulative effects of low socioeconomic position in both childhood and early adulthood were associated with higher (adverse) risk factor levels at 60-64 years. No associations were observed between socioeconomic position at any life period with either endothelial marker or adiponectin. Associations for C-reactive protein, interleukin-6, leptin and proinsulin were reduced considerably by adjustment for body mass index and, to a lesser extent, cigarette smoking. In conclusion, socioeconomic position in early life is an important determinant of several novel CHD risk factors. Body mass index may be an important mediator of these relationships. Topics: Adipocytes; Adiponectin; Biomarkers; Body Mass Index; C-Reactive Protein; Coronary Disease; E-Selectin; Endothelium; Female; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Male; Middle Aged; Proinsulin; Risk Factors; Smoking; Social Class; Socioeconomic Factors; Tissue Plasminogen Activator; United Kingdom | 2015 |
Prolonged REM sleep restriction induces metabolic syndrome-related changes: Mediation by pro-inflammatory cytokines.
Chronic sleep restriction in human beings results in metabolic abnormalities, including changes in the control of glucose homeostasis, increased body mass and risk of cardiovascular disease. In rats, 96h of REM sleep deprivation increases caloric intake, but retards body weight gain. Moreover, this procedure increases the expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which may be involved with the molecular mechanism proposed to mediate insulin resistance. The goal of the present study was to assess the effects of a chronic protocol of sleep restriction on parameters of energy balance (food intake and body weight), leptin plasma levels and its hypothalamic receptors and mediators of the immune system in the retroperitoneal adipose tissue (RPAT). Thirty-four Wistar rats were distributed in control (CTL) and sleep restriction groups; the latter was kept onto individual narrow platforms immersed in water for 18h/day (from 16:00h to 10:00h), for 21days (SR21). Food intake was assessed daily, after each sleep restriction period and body weight was measured daily, after the animals were taken from the sleep deprivation chambers. At the end of the 21day of sleep restriction, rats were decapitated and RPAT was obtained for morphological and immune functional assays and expression of insulin receptor substrate 1 (IRS-1) was assessed in skeletal muscle. Another subset of animals was used to evaluate blood glucose clearance. The results replicated previous findings on energy balance, e.g., increased food intake and reduced body weight gain. There was a significant reduction of RPAT mass (p<0.001), of leptin plasma levels and hypothalamic leptin receptors. Conversely, increased levels of TNF-α and IL-6 and expression of phosphorylated NFκ-β in the RPAT of SR21 compared to CTL rats (p<0.01, for all parameters). SR21 rats also displayed reduced glucose clearance and IRS-1 expression than CTL rats (p<0.01). The present results indicated that 21days of sleep restriction by the platform method induced metabolic syndrome-related alterations that may be mediated by inflammation of the RPAT. Topics: Adipose Tissue; Animals; Body Weight; Cytokines; Eating; Hypothalamus; Inflammation; Insulin Receptor Substrate Proteins; Leptin; Male; Metabolic Syndrome; Muscle, Skeletal; Phosphorylation; Rats; Rats, Wistar; Receptors, Leptin; Sleep Deprivation | 2015 |
Gender differences in the association of sleep apnea and inflammation.
Over the last 15years, many studies have established an association of sleep apnea with inflammation and metabolic aberrations. However, no controlled studies have examined potential gender effects in this association. We recruited 120 middle-aged, predominantly non-obese mild-to-moderate sleep apneics and controls (62 males, 58 females). All participants underwent a clinical history, physical examination, and 1-night 8-h polysomnography recording and provided a single fasting blood sample for assessment of interleukin-6 (IL-6), tumor necrosis factor receptor 1 (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels. Among non-sleep apneics, females had higher levels of TNFR1 (p=0.01), CRP (p=0.005), leptin (p<0.001), and adiponectin (p<0.001) compared to males, independent of age and body mass index. When analyzed separately by gender, sleep apneic men had elevated TNFR1 (p=0.04), CRP (p=0.06) and IL-6 (p=0.11) relative to control men; in sleep apneic females, only CRP was elevated (p=0.04). Furthermore, CRP was associated with apnea severity in a dose-response manner (p-linear=0.04 in both genders) and was independently associated with comorbid hypertension in apnea (p-linear=0.005 for women; p-linear=0.09 for men). In conclusion, although women have naturally higher levels of inflammatory and metabolic markers than men, sleep apneic men appear to have a more severe inflammatory profile compared to women. Our findings suggest that these markers should be analyzed and interpreted separately in men and women, and that a single measure of plasma CRP appears to be a clinically-useful marker of apnea severity and comorbid cardiovascular morbidity. Topics: Adiponectin; C-Reactive Protein; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Polysomnography; Receptors, Tumor Necrosis Factor, Type I; Sex Characteristics; Sleep Apnea Syndromes | 2015 |
Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice.
Fsp27 is a lipid droplet-associated protein almost exclusively expressed in adipocytes where it facilitates unilocular lipid droplet formation. In mice, Fsp27 deficiency is associated with increased basal lipolysis, 'browning' of white fat and a healthy metabolic profile, whereas a patient with congenital CIDEC deficiency manifested an adverse lipodystrophic phenotype. Here we reconcile these data by showing that exposing Fsp27-null mice to a substantial energetic stress by crossing them with ob/ob mice or BATless mice, or feeding them a high-fat diet, results in hepatic steatosis and insulin resistance. We also observe a striking reduction in adipose inflammation and increase in adiponectin levels in all three models. This appears to reflect reduced activation of the inflammasome and less adipocyte death. These findings highlight the importance of Fsp27 in facilitating optimal energy storage in adipocytes and represent a rare example where adipose inflammation and hepatic insulin resistance are disassociated. Topics: Adipose Tissue, White; Animals; Blotting, Western; Crosses, Genetic; Diet, High-Fat; Energy Metabolism; Glucose Clamp Technique; Glucose Tolerance Test; Inflammasomes; Inflammation; Insulin Resistance; Leptin; Mice; Mice, Knockout; Microarray Analysis; Proteins | 2015 |
Thyroid autoimmunity as a window to autoimmunity: An explanation for sex differences in the prevalence of thyroid autoimmunity.
Autoimmune thyroid diseases (AITDs), predominately Graves׳ disease and Hashimoto׳s thyroiditis, comprise the most common autoimmune diseases in humans. Both have the production of anti-thyroid antibody as an important aspect and both are much more prevalent in females, being at least 10 times more common than in males. Using these two clues, a hypothesis for the initiation of thyroid autoimmunity is proposed that helps to make the case that the thyroid is one of the most sensitive sites for autoimmunity and helps account for the prevalence and the observed sex differences in AITDs and associated diseases, such as type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA). The primary mechanisms proposed involve the underlying state of inflammation as a result of the adipokines, especially leptin, TNF-α, and IL-6, and the receptors able to recognize pathogen-associated molecular patterns (PAMP׳s) and damage-associated molecular patterns (DAMP׳s) through Toll-like receptors (TLR) and others receptors present on thyrocytes. The adipokines are produced by adipose tissue, but have hormone-like and immune modulating properties. As the levels of leptin are significantly higher in females, an explanation for the sex difference in thyroid autoimmunity emerges. The ability of the thyrocytes to participate in innate immunity through the TLR provides an adjuvant-like signal and allows for the action of other agents, such as environmental factors, viruses, bacteria, and even stress to provide the initiation step to break tolerance to thyroid self-antigens. Seeing the thyroid as one of the most sensitive sites for autoimmunity, means that for many autoimmune disorders, if autoimmunity is present, it is likely to also be present in the thyroid - and that that condition in the thyroid was probably earlier. The evidence is seen in multiple autoimmune syndrome. Topics: Adipokines; Animals; Autoantibodies; Autoantigens; Autoimmunity; Diabetes Mellitus, Type 1; Female; Graves Disease; Hashimoto Disease; Humans; Immunity, Innate; Inflammation; Leptin; Male; Mice; Prevalence; Receptors, Pattern Recognition; Sex Factors; Thyroid Gland | 2015 |
Helichrysum and Grapefruit Extracts Boost Weight Loss in Overweight Rats Reducing Inflammation.
Obesity is characterized by an increased production of inflammatory markers. High levels of circulating free fatty acids and chronic inflammation lead to increased oxidative stress, contributing to the development of insulin resistance (IR). Recent studies have focused on the potential use of flavonoids for obesity management due to their antioxidant and anti-inflammatory properties. This study was designed to investigate the antioxidant and anti-inflammatory effects of helichrysum and grapefruit extracts in overweight insulin-resistant rats. Thirty-eight male Wistar rats were randomly distributed in two groups: control group (n=8) and high-fat sucrose (HFS) group (n=30). After 22 days of ad libitum water and food access, the rats fed HFS diet changed to standard diet and were reassigned into three groups (n=10 each group): nonsupplemented, helichrysum extract (2 g/kg bw), and grapefruit extract (1 g/kg bw) administered for 5 weeks. Rats supplemented with both extracts gained less body weight during the 5-week period of treatment, showed lower serum insulin levels and liver TBARS levels. Leptin/adiponectin ratio, as an indicator of IR, was lower in both extract-administered groups. These results were accompanied by a reduction in TNFα gene expression in epididymal adipose tissue and intestinal mucosa, and TLR2 expression in intestinal mucosa. Helichrysum and grapefruit extracts might be used as complement hypocaloric diets in weight loss treatment. Both extracts helped to reduce weight gain, hyperinsulinemia, and IR, improved inflammation markers, and decreased the HFS diet-induced oxidative stress in insulin-resistant rats. Topics: Adiponectin; Animals; Antioxidants; Blood Glucose; Body Weight; Citrus paradisi; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Helichrysum; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Overweight; Plant Extracts; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Treatment Outcome; Weight Loss | 2015 |
Difference in inflammatory cytokine production by mononuclear cells from obese and non-obese schizophrenic patients.
Schizophrenic patients have an increased risk for obesity compared with the general population. Evidence suggests the existence of an inflammatory process in the etiology of both obesity and schizophrenia. Our study compares in vitro secretion of inflammatory cytokines by peripheral blood mononuclear cells (PBMC) obtained from obese and non-obese schizophrenic patients.. Mononuclear cells were isolated from 20 obese (BMI >27) and 20 non-obese (BMI <24) schizophrenic in-patients. The levels of TNF-α, IL-1β, IL-6, IL-1ra, IL-10 or IL-2 and IFN-γ in the supernatants of stimulated PBMC, as well as leptin and adiponectin serum values were evaluated.. Peripheral blood mononuclear cells from patients in the obese group showed a significantly increased TNF-α and IL-1β production, whereas the release of IL-1ra was decreased as compared with the non-obese group. In the obese group, the serum concentration of leptin was significantly higher and that of adiponectin was significantly lower. The results of the remaining cytokines did not differ between the two groups.. Our study indicates the existence of a difference between obese and non-obese schizophrenic subjects as for inflammatory cytokine production and serum leptin and adiponectin levels, suggesting a 'subclinical inflammatory state' in obese schizophrenic patients that may contribute to a predisposition to inflammation and infections. Topics: Adiponectin; Adult; Body Mass Index; Cytokines; Disease Susceptibility; Humans; Inflammation; Leptin; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Middle Aged; Obesity; Schizophrenia | 2015 |
Nutritional ingredients modulate adipokine secretion and inflammation in human primary adipocytes.
Nutritional factors such as casein hydrolysates and long chain polyunsaturated fatty acids have been proposed to exert beneficial metabolic effects. We aimed to investigate how a casein hydrolysate (eCH) and long chain polyunsaturated fatty acids could affect human primary adipocyte function in vitro. Incubation conditions with the different nutritional factors were validated by assessing cell vitality with lactate dehydrogenase (LDH) release and neutral red incorporation. Intracellular triglyceride content was assessed with Oil Red O staining. The effect of eCH, a non-peptidic amino acid mixture (AA), and long-chain polyunsaturated fatty acids (LC-PUFAs) on adiponectin and leptin secretion was determined by enzyme-linked immunosorbent assay (ELISA). Intracellular adiponectin expression and nuclear factor-κB (NF-κB) activation were analyzed by Western blot, while monocyte chemoattractant protein-1 (MCP-1) release was explored by ELISA. The eCH concentration dependently increased adiponectin secretion in human primary adipocytes through its intrinsic peptide bioactivity, since the non-peptidic mixture, AA, could not mimic eCH's effects on adiponectin secretion. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and DHA combined with arachidonic acid (ARA) upregulated adiponectin secretion. However, only DHA and DHA/ARA exerted a potentanti-inflammatory effect reflected by prevention of tumor necrosis factor-α (TNF-α) induced NF-κB activation and MCP-1 secretion in human adipocytes. eCH and DHA alone or in combination with ARA, may hold the key for nutritional programming through their anti-inflammatory action to prevent diseases with low-grade chronic inflammation such as obesity or diabetes. Topics: Adipocytes; Adipokines; Caseins; Cell Culture Techniques; Chemokine CCL2; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Humans; Inflammation; L-Lactate Dehydrogenase; Leptin; Milk Proteins; NF-kappa B; Tumor Necrosis Factor-alpha | 2015 |
Temporal relationship between diet-induced steatosis and onset of insulin/leptin resistance in male Wistar rats.
Rats fed with high-fat-high-sucrose (HFHS) diet are known to manifest metabolic syndrome including hyperinsulinemia, hyperleptinemia, hyperglycemia, diabetic dyslipidemia, and hepatic steatosis. The aim of the current study is to determine the temporal relationships between the development of hepatic steatosis and the onset of insulin and leptin resistance in hypothalamus and liver in male Wistar rats (six weeks of age) fed chow or HFHS diet for up to 8 weeks. Fasting plasma glucose, lipids/lipoproteins, insulin and leptin levels were quantified, histopathologic score of hepatic steatosis and inflammation were assessed, and the responses of common checkpoints of insulin and leptin signalling responsible for lipogenesis and gluconeogenesis were analyzed. In addition, acute insulin or leptin administration was performed at different stages of HFHS dieting to determine the responsiveness of the respective signalling pathways. Hyperinsulinemia, hyperglycemia, dyslipidemia, and increased homeostasis model assessment of basal insulin resistance occurred 1-week after HFHS dieting, coinciding with upregulation of suppressor of cytokine signalling 3 in both hypothalamus and liver. However, hepatosteatosis, accompanied with increased expression of sterol regulatory element binding protein 1c and phosphoenolpyruvate carboxykinase, did not manifest until 4- to 8-week after HFHS dieting. Lowered insulin sensitivity (shown by decreased insulin receptor substrate 1 and protein kinase B phosphorylation) occurred approximately 2 weeks prior to leptin resistance (shown by impaired signal transducer and activator of transcription 3 activation) in both the liver and hypothalamus. Acute insulin/leptin administration also demonstrated the impaired insulin or leptin signalling transduction. These data suggest that lowered insulin sensitivity and leptin resistance occurred at least 2-3 weeks earlier than the manifestation of hepatosteatosis in rats fed HFHS diet. Topics: Animals; Blood Glucose; Diet, High-Fat; Dietary Sucrose; Dyslipidemias; Fatty Liver; Hyperglycemia; Hyperinsulinism; Hypothalamus; Inflammation; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Lipids; Lipoproteins; Liver; Male; Rats, Wistar | 2015 |
Endogenous hormones, inflammation, and body size in premenopausal Mexican women: results from the Mexican Teachers' Cohort (MTC, ESMaestras).
Obesity is a major risk factor for several cancers, including female cancers. Endogenous hormones and inflammatory factors may mediate the association between anthropometric measures and cancer risk, although these associations have been studied mainly in Caucasians. The aim of the current study was to explore the association of circulating hormones, adipokines, and inflammatory factors with obesity and overweight in premenopausal Mexican women.. We conducted a cross-sectional analysis of 504 premenopausal women from the large Mexican Teachers' Cohort (MTC, ESMaestras) study to determine the association of insulin-like growth factor I (IGF-I), its major circulating binding protein (IGFBP-3), leptin, adiponectin, C-peptide, and C-reactive protein with comprehensive measures of body size. Biomarkers were measured by immunoassays. Multivariate regression analyses were performed to compare geometric mean biomarker concentrations with measured markers of body size and adiposity.. Mean IGF-I and IGFBP-3 concentrations significantly increased with increasing height and leg length. Concentrations of IGF-I, adiponectin, and the IGF-I/IGFBP-3 ratio strongly decreased with increasing BMI, weight, waist and hip circumferences, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), while CRP, leptin, C-peptide concentrations, and the leptin/adiponectin ratio strongly increased. Adiponectin and the leptin/adiponectin ratio remained significantly related to measures of central adiposity (waist circumference, WHpR, and WHtR) after adjustment by body mass index.. The results of our study suggest a strong relation between biomarkers and body size in this study population and suggest that different fat depots may have different metabolic properties. Topics: Adiposity; Adult; Biomarkers; Body Mass Index; Body Size; Body Weight; C-Peptide; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Female; Humans; Immunoassay; Inflammation; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Mexico; Middle Aged; Multivariate Analysis; Obesity; Overweight; Premenopause; Waist Circumference; Waist-Hip Ratio | 2015 |
Overweight across the life course and adipokines, inflammatory and endothelial markers at age 60-64 years: evidence from the 1946 birth cohort.
There is growing evidence that early development of obesity increases cardiovascular risk later in life, but less is known about whether there are effects of long-term excess body weight on the biological drivers associated with the atherosclerotic pathway, particularly adipokines, inflammatory and endothelial markers. This paper therefore investigates the influence of overweight across the life course on levels of these markers at retirement age.. Data from the Medical Research Council National Survey of Health and Development (n=1784) were used to examine the associations between overweight status at 2, 4, 6, 7, 11, 15, 20, 26, 36, 43, 53 and 60-64 years (body mass index (BMI)⩾25 kg m(-2) for adult ages and gender-specific cut-points for childhood ages equivalent to BMI⩾25 kg m(-2)) and measurements of adipokines (leptin and adiponectin), inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6)) and endothelial markers (E-selectin, tissue plasminogen activator (t-PA) and von Willebrand factor) at 60-64 years. In addition, the fit of different life course models (sensitive periods/accumulation) were compared using partial F-tests.. In age- and sex-adjusted models, overweight at 11 years and onwards was associated with higher leptin, CRP and IL-6 and lower adiponectin; overweight at 15 years and onwards was associated with higher E-selectin and t-PA. Associations between overweight at all ages earlier than 60-64 with leptin, adiponectin, CRP and IL-6 were reduced but remained apparent after adjustment for overweight at 60-64 years; whereas those with E-selectin and t-PA were entirely explained. An accumulation model best described the associations between overweight across the life course with adipokines and inflammatory markers, whereas for the endothelial markers, the sensitive period model for 60-64 years provided a slightly better fit than the accumulation model.. Overweight across the life course has a cumulative influence on adipokines, inflammatory and possibly endothelial markers. Avoidance of overweight from adolescence onwards is likely important for cardiovascular disease prevention. Topics: Adiponectin; Adolescent; Adult; Age of Onset; Aging; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Child; Child, Preschool; Diabetes Mellitus, Type 2; E-Selectin; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Risk Factors; United Kingdom; von Willebrand Factor | 2015 |
Relationship between relative interdialytic weight gain and serum leptin levels, nutrition, and inflammation in chronic hemodialysis patients.
Excessive relative interdialytic weight gain (RIDWG, %) is an important risk factor for long-term adverse cardiovascular outcomes in chronic hemodialysis (HD) patients. On the other hand, it may also be an index of good appetite and nutritional status. We aimed to assess the relationship between RIDWG and appetite, nutrition, inflammation parameters of chronic HD patients.. 100 chronic anuric HD patients were enrolled in this prospective study between January 2013 and January 2014. Patients with hospitalization, major surgery, obvious infectious/inflammatory disease, end-stage liver disease, malignancies, and malabsorption syndromes were excluded. Patients were divided into 3 groups according to their RIDWG levels; group 1 = RIDWG < 3%, group 2 = RIDWG: 3 - 5%, and group 3 = RIDWG > 5%.. Group 3 patients were younger (p = 0.011) and had a lower body mass index (BMI) (p = 0.014). Nutrition and inflammation parameters including malnutrition inflammation score (MIS), serum albumin, prealbumin, triceps skinfold thickness, hs-CRP, and TNF-α ere not significantly different between the groups. Leptin and leptin/BMI ratio were significantly lower in group 3 (p = 0.001). RIDWG was negatively correlated with age (p = 0.001, r = -0.371), BMI (p = 0.001, r = -0.372), leptin (p = 0.001, r = -0.369), leptin/BMI (p = 0.001, r = -0.369). After adjustment for BMI in linear regression analyis, leptin/BMI remained significantly correlated with RIDWG (p = 0.024).. This study revealed that RIDWG was associated with younger age, lower BMI and dry weight, and lower serum leptin levels. More detailed studies are needed to validate and dissect the mechanisms of these findings. Topics: Adult; Aged; Body Mass Index; Female; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Prospective Studies; Renal Dialysis; Serum Albumin; Weight Gain | 2015 |
Increasing fat content from 20 to 45 wt% in a complex diet induces lower endotoxemia in parallel with an increased number of intestinal goblet cells in mice.
The impacts of high-fat diets (HFDs) on the onset of metabolic endotoxemia and low-grade inflammation are well established in rodent models. However, the dose-effect of dietary lipid intakes on these parameters is not known. We hypothesized that increasing dietary lipid amounts could be linked to parallel increases of endotoxemia, low-grade inflammation, and metabolic and intestinal alterations. Six-week-old male C57BL/6J mice were fed a low-fat diet (LFD, 2.6 wt% of lipids), a moderate HFD (mHFD, 22 wt% of lipids), or a very HFD (vHFD, 45 wt% of lipids) formulated mainly using chow ingredients and milk fat. After 12 weeks, white adipose tissues, liver, intestine, distal colon contents, and plasma were collected. Only vHFD mice significantly increased body weight and fat mass vs LFD mice. This was associated with increases of plasma concentrations of triglycerides, leptin and adiponectin, and liver lipids. No such differences were observed between LFD and mHFD mice. However, mHFD developed metabolic endotoxemia and inflammation, unlike vHFD mice. In turn, vHFD mice showed more goblet cells in all intestine segments vs both other groups and a decrease of Bacteroides-Prevotella in their microbiota vs LFD mice. Finally, mHFD mice colon exhibited a decrease in lactobacilli and in the levels of occludin phosphorylation. Altogether, using complex HFD, no associations were observed between dietary lipid amounts and the magnitude of endotoxemia, inflammation, and physiological alterations developed. These results reveal the impact of the diet composition on intestinal goblet cells and mucus coat, bringing new insights about further consequences on HFD-induced metabolic disorders. Topics: Adiponectin; Adipose Tissue, White; Animals; Colon; Diet, Fat-Restricted; Diet, High-Fat; Dietary Fats; Endotoxemia; Goblet Cells; Inflammation; Interleukin-6; Intestinal Mucosa; Intestines; Leptin; Lipopolysaccharides; Liver; Male; Mice; Mice, Inbred C57BL; Occludin; Triglycerides; Weight Gain; Zonula Occludens-1 Protein | 2015 |
SOCS3 promotes inflammation and apoptosis via inhibiting JAK2/STAT3 signaling pathway in 3T3-L1 adipocyte.
The suppressor of cytokine signaling 3 (SOCS3) is an established negative feedback regulation transcription factor associated with leptin, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and growth hormone (GH). However, the regulatory mechanism of SOCS3 on inflammation and apoptosis of adipocyte is still not clear. In this study, we found an increased expression of adipocyte inflammatory cytokines TNF-α and IL-6 due to leptin treatment. Meanwhile Caspase3, a key executioner of apoptosis, was also elevated in this process. In addition, we observed that SOCS3 could promote inflammation whereas SOCS3 interference reversed this effect in LPS-induced adipocytes inflammatory model. Moreover, the expression of apoptosis-associated genes Bax, cleaved-Caspase9 and cleaved-Caspase3 were elevated along with decreased Bcl-2 expression as detected with Western blot and ELISA assay. The phosphorylation level of JAK2/STAT3 signal was inhibited by SOCS3 along with the elevated expression of IL-6, TNF-α and Caspase3. We also demonstrated that stable knockdown of SOCS3 along with SD1008, a specific inhibitor of JAK2/STAT3 signaling pathway, could significantly inhibit inflammation and apoptosis of adipocyte. Altogether, these results inferred that SOCS3 promotes adipocyte apoptosis by both aggravating inflammation and inhibiting the activity of JAK2/STAT3 signaling pathway. Topics: 3T3-L1 Cells; Adipocytes; Animals; Apoptosis; Caspase 3; Gene Expression Regulation; Inflammation; Interferon-gamma; Interleukin-6; Janus Kinase 2; Leptin; Mice; Phosphorylation; Signal Transduction; STAT3 Transcription Factor; Suppressor of Cytokine Signaling Proteins; Tropanes; Tumor Necrosis Factor-alpha | 2015 |
Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice.
The consumption of diets rich in saturated fat largely contributes to the development of obesity in modern societies. A diet high in saturated fats can induce inflammation and impair leptin signaling in the hypothalamus. However, the role of saturated fatty acids on hypothalamic leptin signaling, and hepatic glucose and lipid metabolism remains largely undiscovered. In this study, we investigated the effects of intracerebroventricular (icv) administration of a saturated fatty acid, palmitic acid (PA, C16:0), on central leptin sensitivity, hypothalamic leptin signaling, inflammatory molecules and hepatic energy metabolism in C57BL/6J male mice. We found that the icv administration of PA led to central leptin resistance, evidenced by the inhibition of central leptin's suppression of food intake. Central leptin resistance was concomitant with impaired hypothalamic leptin signaling (JAK2-STAT3, PKB/Akt-FOXO1) and a pro-inflammatory response (TNF-α, IL1-β, IL-6 and pIκBa) in the mediobasal hypothalamus and paraventricular hypothalamic nuclei. Furthermore, the pre-administration of icv PA blunted the effect of leptin-induced decreases in mRNA expression related to gluconeogenesis (G6Pase and PEPCK), glucose transportation (GLUT2) and lipogenesis (FAS and SCD1) in the liver of mice. Therefore, elevated central PA concentrations can induce pro-inflammatory responses and leptin resistance, which are associated with disorders of energy homeostasis in the liver as a result of diet-induced obesity. Topics: Animals; Glucose; Hypothalamus; Inflammation; Leptin; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Palmitic Acid; Signal Transduction; Tyrosine 3-Monooxygenase | 2015 |
Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients.
Obesity and type 2 diabetes (T2D) are associated with low-grade inflammation, activation of immune cells, and alterations of the gut microbiota. Mucosal-associated invariant T (MAIT) cells, which are innate-like T cells that recognize bacterial ligands, are present in blood and enriched in mucosal and inflamed tissues. Here, we analyzed MAIT cells in the blood and adipose tissues of patients with T2D and/or severe obesity. We determined that circulating MAIT cell frequency was dramatically decreased in both patient groups, and this population was even undetectable in some obese patients. Moreover, in both patient groups, circulating MAIT cells displayed an activated phenotype that was associated with elevated Th1 and Th17 cytokine production. In obese patients, MAIT cells were more abundant in adipose tissue than in the blood and exhibited a striking IL-17 profile. Bariatric surgery in obese patients not only improved their metabolic parameters but also increased circulating MAIT cell frequency at 3 months after surgery. Similarly, cytokine production by blood MAIT cells was strongly decreased after surgery. This study reveals profound MAIT cell abnormalities in patients harboring metabolic disorders, suggesting their potential role in these pathologies. Topics: Adiponectin; Adipose Tissue; Adult; Bariatric Surgery; Blood Cells; Cytokines; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interleukin-17; Leptin; Lymphocyte Count; Male; Middle Aged; Natural Killer T-Cells; Obesity; Omentum; Organ Specificity; Postoperative Period; Subcutaneous Tissue; T-Lymphocyte Subsets | 2015 |
Effects of adenotonsillectomy on plasma inflammatory biomarkers in obese children with obstructive sleep apnea: A community-based study.
Obesity and obstructive sleep apnea syndrome (OSA) are highly prevalent and frequently overlapping conditions in children that lead to systemic inflammation, the latter being implicated in the various end-organ morbidities associated with these conditions.. To examine the effects of adenotonsillectomy (T&A) on plasma levels of inflammatory markers in obese children with polysomnographically diagnosed OSA who were prospectively recruited from the community.. Obese children prospectively diagnosed with OSA, underwent T&A and a second overnight polysomnogram (PSG) after surgery. Plasma fasting morning samples obtained after each of the two PSGs were assayed for multiple inflammatory and metabolic markers including interleukin (IL)-6, IL-18, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), adiponectin, apelin C, leptin and osteocrin.. Out of 122 potential candidates, 100 obese children with OSA completed the study with only one-third exhibiting normalization of their PSG after T&A (that is, apnea-hypopnea index (AHI) ≤1/hour total sleep time). However, overall significant decreases in MCP-1, PAI-1, MMP-9, IL-18 and IL-6, and increases in adropin and osteocrin plasma concentrations occurred after T&A. Several of the T&A-responsive biomarkers exhibited excellent sensitivity and moderate specificity to predict residual OSA (that is, AHI⩾5/hTST).. A defined subset of systemic inflammatory and metabolic biomarkers is reversibly altered in the context of OSA among community-based obese children, further reinforcing the concept on the interactive pro-inflammatory effects of sleep disorders such as OSA and obesity contributing to downstream end-organ morbidities. Topics: Adenoidectomy; Adiponectin; Adolescent; Biomarkers; Chemokine CCL2; Child; Child, Preschool; Female; Humans; Inflammation; Interleukin-18; Interleukin-6; Leptin; Male; Matrix Metalloproteinase 9; Muscle Proteins; Pediatric Obesity; Plasminogen Activator Inhibitor 1; Polysomnography; Sleep Apnea, Obstructive; Tonsillectomy; Transcription Factors | 2015 |
Relationship of leptin with adiposity and inflammation and resistin with disease severity in psoriatic patients undergoing anti-TNF-alpha therapy.
Altered secretion patterns of proinflammatory adipokines may influence the increased risk of cardiovascular mortality observed in patients with chronic inflammatory diseases.. To determine whether two adipokines, leptin and resistin, correlate with metabolic syndrome features and disease severity in psoriatic patients who underwent anti-TNF-α therapy.. Prospective study of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α- adalimumab. Patients with kidney disease, hypertension or body mass index ≥35 Kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of anti-TNF-α treatment and at month 6.. Twenty-nine patients were assessed. A correlation between adiposity and leptin was observed (waist circumference and leptin levels after 6 months of therapy: r = 0.43; P = 0.030). Leptin concentration also correlated with blood pressure before adalimumab onset (systolic: r = 0.48; P = 0.013 and diastolic blood pressure: r = 0.50; P = 0.010 ). A marginally significant negative correlation between insulin sensitivity (QUICKI) and leptin levels was also observed. CRP levels correlated with leptin prior to the onset of adalimumab (r = 0.45; P = 0.020) and with resistin both before (r = 0.45; P = 0.020) and after 6 months of therapy (r = 0.55; P = 0.004). A positive association between parameters of disease activity such as BSA (r = 0.60; P = 0.001) and PASI (r = 0.63; P = 0.001) prior to the onset of adalimumab therapy and resistin concentrations was also disclosed. No significant changes in leptin and resistin concentrations following the 6-month treatment with adalimumab were seen.. In patients with moderate-to-severe psoriasis leptin correlates with metabolic syndrome features and inflammation whereas resistin correlate with inflammation and disease severity. Topics: Adalimumab; Adiposity; Adult; Anti-Inflammatory Agents; Blood Pressure; Body Surface Area; C-Reactive Protein; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Psoriasis; Resistin; Severity of Illness Index; Sex Factors; Tumor Necrosis Factor-alpha; Waist Circumference | 2015 |
Microparticles release by adipocytes act as "find-me" signals to promote macrophage migration.
Macrophage infiltration of adipose tissue during weight gain is a central event leading to the metabolic complications of obesity. However, what are the mechanisms attracting professional phagocytes to obese adipose tissue remains poorly understood. Here, we demonstrate that adipocyte-derived microparticles (MPs) are critical "find-me" signals for recruitment of monocytes and macrophages. Supernatants from stressed adipocytes stimulated the attraction of monocyte cells and primary macrophages. The activation of caspase 3 was required for release of these signals. Adipocytes exposed to saturated fatty acids showed marked release of MPs into the supernatant while common genetic mouse models of obesity demonstrate high levels of circulating adipocyte-derived MPs. The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase. Further analysis identified these MPs as a central chemoattractant in vitro and in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice. These data identify adipocyte-derived MPs as novel "find me" signals that contributes to macrophage infiltration associated with obesity. Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Animals; Caspase 3; Cell Movement; Cell-Derived Microparticles; Chemotactic Factors; Chemotaxis; Inflammation; Leptin; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes; Obesity; Phagocytes; rho-Associated Kinases | 2015 |
Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice.
Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood.. We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks.. Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [ΜIP-1β]), compared with sham-operated mice. Plasma IL-17 and MIP-1β concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n = 40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations.. Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice. Topics: Adipocytes; Adiponectin; Adiposity; Animals; Body Composition; Cytokines; Diet, High-Fat; Eating; Gluconeogenesis; Glucose; Glucose Intolerance; Inflammation; Insulin; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Subcutaneous Fat; Triglycerides | 2015 |
The role of multicomponent therapy in the metabolic syndrome, inflammation and cardiovascular risk in obese adolescents.
Obesity is characterised by low-grade inflammation, which increases the metabolic syndrome (MetS) and cardiovascular risks. The aim of the present study was to verify the role of multicomponent therapy in controlling the MetS, inflammation and carotid intima-media thickness (cIMT) in obese adolescents. The second aim was to investigate the relationships between adipokines, the MetS parameters and cIMT. A total of sixty-nine obese adolescents participated in the present study and completed 1 year of multicomponent therapy (a combination of strategies involving nutrition, psychology, physical exercise and clinical therapy), and were divided according to their MetS diagnosis as follows: MetS (n 19); non-MetS (n 50). Blood analyses of glucose, lipid and adipokine concentrations (adiponectin, leptin, plasminogen activator inhibitor 1 (PAI-1) and C-reactive protein) were collected. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance, quantitative insulin sensitivity check index and homeostasis model assessment-adiponectin. cIMT and visceral and subcutaneous fat were estimated using ultrasonography. At baseline, the MetS group presented higher waist circumference, glucose and insulin levels, and systolic and median blood pressures compared with the non-MetS group. After therapy, both groups showed improvements in the anthropometric profile, body composition, insulin level, insulin resistance, insulin sensibility, TAG and VLDL-cholesterol, adiponectin, leptin and PAI-1 levels, blood pressure and cIMT. The prevalence of the MetS was reduced from 27·5 to 13·0 %. Metabolic syndrome patients showed resistance in the attenuation of total cholesterol and LDL-cholesterol (LDL-C) levels and leptin:adiponectin and adiponectin:leptin ratios. In the MetS group, the variation in the adiponectin:leptin ratio was correlated with variations in glucose, insulin sensibility, total cholesterol, LDL-c and systolic blood pressure. Additionally, the number of MetS parameters was correlated with the carotid measurement. Moreover, the variation in cIMT was correlated with the variations in insulin sensibility, total cholesterol and LDL-c. For the entire group, the number of MetS alterations was correlated with the leptin level and leptin:adiponectin ratio and adiponectin:leptin ratio after therapy. In conclusion, multicomponent therapy was effective in controlling the MetS, inflammation and cIMT in the obese adolescents. However, the MetS patie Topics: Adipokines; Adiponectin; Adiposity; Adolescent; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; Brazil; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Combined Modality Therapy; Diet; Exercise; Female; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Nutrition Therapy; Obesity; Plasminogen Activator Inhibitor 1; Psychotherapy; Risk Factors; Treatment Outcome; Waist Circumference | 2015 |
Expression of Selenoprotein Genes Is Affected by Obesity of Pigs Fed a High-Fat Diet.
Relations of the 25 mammalian selenoprotein genes with obesity and the associated inflammation remain unclear.. This study explored impacts of high-fat diet-induced obesity on inflammation and expressions of selenoprotein and obesity-related genes in 10 tissues of pigs.. Plasma and 10 tissues were collected from pigs (n = 10) fed a corn-soy-based control diet or that diet containing 3-7% lard from weanling to finishing (180 d). Plasma concentrations (n = 8) of cytokines and thyroid hormones and tissue mRNA abundance (n = 4) of 25 selenoprotein genes and 16 obesity-related genes were compared between the pigs fed the control and high-fat diets. Stepwise regression was applied to analyze correlations among all these measures, including the previously reported body physical and plasma biochemical variables.. The high-fat diet elevated (P < 0.05) plasma concentrations of tumor necrosis factor α, interleukin-6, leptin, and leptin receptor by 29-42% and affected (P < 0.05-0.1) tissue mRNA levels of the selenoprotein and obesity-related genes in 3 patterns. Specifically, the high-fat diet up-regulated 12 selenoprotein genes in 6 tissues, down-regulated 13 selenoprotein genes in 7 tissues, and exerted no effect on 5 genes in any tissue. Body weights and plasma triglyceride concentrations of pigs showed the strongest regressions to tissue mRNA abundances of selenoprotein and obesity-related genes. Among the selenoprotein genes, selenoprotein V and I were ranked as the strongest independent variables for the regression of phenotypic and plasma measures. Meanwhile, agouti signaling protein, adiponectin, and resistin genes represented the strongest independent variables of the obesity-related genes for the regression of tissue selenoprotein mRNA.. The high-fat diet induced inflammation in pigs and affected their gene expression of selenoproteins associated with thioredoxin and oxidoreductase systems, local tissue thyroid hormone activity, endoplasmic reticulum protein degradation, and phosphorylation of lipids. This porcine model may be used to study interactive mechanisms between excess fat intake and selenoprotein function. Topics: Adiponectin; Agouti Signaling Protein; Animals; Body Weight; Diet, High-Fat; Disease Models, Animal; Down-Regulation; Inflammation; Interleukin-6; Leptin; Obesity; Receptors, Leptin; Resistin; RNA, Messenger; Selenoproteins; Swine; Thyroid Hormones; Tumor Necrosis Factor-alpha; Up-Regulation | 2015 |
GlycA, a biomarker of inflammatory glycoproteins, is more closely related to the leptin/adiponectin ratio than to glucose tolerance status.
Plasma GlycA is a recently developed biomarker whose nuclear magnetic resonance signal originates from glycosylated acute-phase proteins. The aim of our study was to determine potential relationships between GlycA and adiposity, insulin resistance (HOMA(ir)), high sensitive C-reactive protein (hs-CRP), leptin, adiponectin, and the leptin/adiponectin ratio, and to test whether GlycA is elevated in subjects with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM).. Plasma GlycA, hs-CRP, leptin, adiponectin, the leptin/adiponectin ratio, and insulin resistance (HOMA(ir)) were measured in 103 fasting subjects (30 with normal fasting glucose, 25 with IFG and 48 with T2DM).. In all subjects combined, plasma GlycA was correlated positively with body mass index (BMI), HOMA(ir), hs-CRP, leptin and the leptin/adiponectin ratio, and inversely with adiponectin (p < 0.05 to p < 0.001). GlycA did not significantly vary according to glucose tolerance category (p = 0.060). GlycA was related positively to the leptin/adiponectin ratio (p = 0.049), independent of BMI (p = 0.056) and HOMA(ir) (p = 0.50).. High plasma GlycA reflects a pro-inflammatory state. Adipose tissue-associated inflammatory processes could contribute to increased circulating levels of glycosylated acute-phase proteins. Topics: Adiponectin; Biomarkers; Blood Glucose; C-Reactive Protein; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Glycoproteins; Glycosylation; Humans; Inflammation; Leptin; Linear Models; Male; Middle Aged; Nuclear Magnetic Resonance, Biomolecular | 2015 |
Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?
The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes. Topics: Adipocytes; Adipose Tissue; Animals; Cell Hypoxia; Cell Line; Diabetes Mellitus, Type 2; Epididymis; Ethanol; Glucose Intolerance; Glucose Tolerance Test; Glucose Transporter Type 1; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Leptin; Lipid Metabolism; Male; Mice; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A | 2015 |
Diet-induced obesity causes peripheral and central ghrelin resistance by promoting inflammation.
Ghrelin, a stomach-derived orexigenic peptide, transmits starvation signals to the hypothalamus via the vagus afferent nerve. Peripheral administration of ghrelin does not induce food intake in high fat diet (HFD)-induced obese mice. We investigated whether this ghrelin resistance was caused by dysfunction of the vagus afferent pathway. Administration (s.c.) of ghrelin did not induce food intake, suppression of oxygen consumption, electrical activity of the vagal afferent nerve, phosphorylation of ERK2 and AMP-activated protein kinase alpha in the nodose ganglion, or Fos expression in hypothalamic arcuate nucleus of mice fed a HFD for 12 weeks. Administration of anti-ghrelin IgG did not induce suppression of food intake in HFD-fed mice. Expression levels of ghrelin receptor mRNA in the nodose ganglion and hypothalamus of HFD-fed mice were reduced. Inflammatory responses, including upregulation of macrophage/microglia markers and inflammatory cytokines, occurred in the nodose ganglion and hypothalamus of HFD-fed mice. A HFD blunted ghrelin signaling in the nodose ganglion via a mechanism involving in situ activation of inflammation. These results indicate that ghrelin resistance in the obese state may be caused by dysregulation of ghrelin signaling via the vagal afferent. Topics: AMP-Activated Protein Kinases; Animals; Diet, High-Fat; Eating; Ghrelin; Hypothalamus; Inflammation; Leptin; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Nodose Ganglion; Obesity; Phosphorylation; Proto-Oncogene Proteins c-fos; Receptors, Ghrelin; RNA, Messenger; Signal Transduction | 2015 |
The thymoprotective function of leptin is indirectly mediated via suppression of obesity.
Leptin is an adipokine that regulates metabolism and plays an important role as a neuroendocrine hormone. Leptin mediates these functions via the leptin receptor, and deficiency in either leptin or its receptor leads to obesity in humans and mice. Leptin has far reaching effects on the immune system, as observed in obese mice, which display decreased thymic function and increased inflammatory responses. With expression of the leptin receptor on T cells and supporting thymic epithelium, aberrant signalling through the leptin receptor has been thought to be the direct cause of thymic involution in obese mice. Here, we demonstrate that the absence of leptin receptor on either thymic epithelial cells or T cells does not lead to the loss of thymic function, demonstrating that the thymoprotective effect of leptin is mediated by obesity suppression rather than direct signalling to the cellular components of the thymus. Topics: Adipogenesis; Animals; Cell Differentiation; Epithelial Cells; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Mice, Transgenic; Obesity; Receptors, Leptin; T-Lymphocytes; Thymus Gland | 2015 |
Omega-3-Acid Ethyl Esters Block the Protumorigenic Effects of Obesity in Mouse Models of Postmenopausal Basal-like and Claudin-Low Breast Cancer.
Obesity induces chronic inflammation and is an established risk and progression factor for triple-negative breast cancers, including basal-like (BL) and claudin-low (CL) subtypes. We tested the effects of dietary supplementation with ethyl esters of the marine-derived anti-inflammatory omega-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA+DHA; Lovaza) on growth of murine BL and CL mammary tumors. Female ovariectomized C57BL/6 mice were fed a control diet or a diet-induced obesity (DIO) diet with or without EPA+DHA (0.025%, resulting in blood levels of EPA and DHA comparable with women taking Lovaza 4 g/d) for 6 weeks. All mice were then orthotopically injected with Wnt-1 cells (a BL tumor cell suspension derived from MMTV-Wnt-1 transgenic mouse mammary tumors) or M-Wnt cells (a CL tumor cell line cloned from the Wnt-1 tumor cell suspension). Mice were killed when tumors were 1 cm in diameter. EPA+DHA supplementation did not significantly affect Wnt-1 or M-Wnt mammary tumor growth in normoweight control mice. However, EPA+DHA supplementation in DIO mice reduced growth of Wnt-1 and M-Wnt tumors; reduced leptin:adiponectin ratio and proinflammatory eicosanoids in the serum; improved insulin sensitivity; and decreased tumoral expression of COX-2 and phospho-p65. Thus, EPA+DHA supplementation in mouse models of postmenopausal BL and CL breast cancer offsets many of the protumorigenic effects of obesity. These preclinical findings, in combination with results from parallel biomarker studies in women, suggest that EPA+DHA supplementation may reduce the burden of BL and CL breast cancer in obese women. Topics: Adiponectin; Animals; Body Composition; Cell Line, Tumor; Claudin-1; Cyclooxygenase 2; Eicosanoids; Erythrocytes; Esters; Fatty Acids, Omega-3; Female; Glucose Tolerance Test; Inflammation; Leptin; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Obesity; Pilot Projects; Postmenopause; Transcription Factor RelA; Wnt1 Protein | 2015 |
Dysregulation of Autonomic Nervous System in Chagas' Heart Disease Is Associated with Altered Adipocytokines Levels.
Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD.. Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group.. We found increased adiponectin levels in Chagas' heart disease with systolic dysfunction and in patients with ECG abnormalities and normal systolic function at rest. Adipocytokines levels (adiponectin and leptin) were associated with ANS parameters in Chagas' heart disease. Topics: Adipokines; Adiponectin; Adult; Autonomic Nervous System; Chagas Cardiomyopathy; Electrocardiography; Female; Heart; Heart Rate; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Male; Middle Aged; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left | 2015 |
Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk.
Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited.. In a case-cohort analysis nested within the Women's Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, hepatocyte growth factor, and plasminogen activator inhibitor-1, and for C-reactive protein (CRP), an inflammatory marker. Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels. All statistical tests were two-sided.. The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy (HT) use at baseline (P interaction = .003). In a model that controlled for multiple breast cancer risk factors including body mass index (BMI), estradiol, and insulin, CRP level was positively associated with breast cancer risk among HT nonusers (hazard ratio for high vs low CRP levels = 1.67, 95% confidence interval = 1.04 to 2.68, P trend = .029). None of the other adipokines were statistically significantly associated with breast cancer risk. Following inclusion of CRP, insulin, and estradiol in a multivariable model, the association of BMI with breast cancer was attenuated by 115%.. These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers. Inflammatory mediators, together with insulin and estrogen, may play a role in the obesity-breast cancer relation. Topics: Adipokines; Adiponectin; Aged; Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; C-Reactive Protein; Estradiol; Female; Hepatocyte Growth Factor; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Middle Aged; Obesity; Odds Ratio; Plasminogen Activator Inhibitor 1; Postmenopause; Proportional Hazards Models; Prospective Studies; Resistin; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha | 2015 |
Concentrating carbohydrates before sleep improves feeding regulation and metabolic and inflammatory parameters in mice.
New evidance highlights the importance of food timing. Recently, we showed that a low-calorie diet with carbohydrates eaten mostly at dinner changed diurnal hormone secretion and led to greater weight loss and improved metabolic status in obese people. Herein, we set out to test whether concentrated-carbohydrates diet (CCD), in which carbohydrates are fed only before sleep, leads to an improved metabolic status in mouse hypothalamus and peripheral tissues. Diet-induced obese mice were given concentrated or distributed carbohydrate diet for 6 weeks. Obese mice fed CCD ate 8.3% less, were 9.3% leaner and had 39.7% less fat mass. Leptin, ghrelin and adiponectin displayed altered secretion. In addition, these mice exhibited an improved biochemical and inflammatory status. In the hypothalamus, anorexigenic signals were up-regulated and orexigenic signals were down-regulated. In peripheral tissues, CCD promoted adiponectin signaling, repressed gluconeogenesis, enhanced lipid oxidation and lowered inflammation, thus ameliorating the major risk factors of obesity. Topics: Adiponectin; Animals; Appetite Regulation; Body Weight; Dietary Carbohydrates; Disease Models, Animal; Feeding Behavior; Gene Expression Regulation; Ghrelin; Gluconeogenesis; Hypothalamus; Inflammation; Leptin; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Obesity; Sleep | 2015 |
Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice.
Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived. Median longevity is also increased in mice with deletion of hypothalamic GH-releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6-week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR(-/-) mice lead to reduced formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18-month-old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF-1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF-1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early-life disruption of GH signaling produces long-term hypothalamic changes that may contribute to the longevity of GH-deficient and GH-resistant mice. Topics: Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Carrier Proteins; Dwarfism, Pituitary; Growth Hormone; Inflammation; Insulin; Insulin-Like Growth Factor I; Leptin; Liver; Longevity; Male; Mediodorsal Thalamic Nucleus; Mice; Mice, Inbred C57BL; Mice, Knockout; Paraventricular Hypothalamic Nucleus; Pro-Opiomelanocortin; STAT3 Transcription Factor | 2015 |
Combined Training Reduces Subclinical Inflammation in Obese Middle-Age Men.
We investigated the effects of 24 wk of combined training on proinflammatory and anti-inflammatory markers associated with obesity in obese middle-age men.. Thirty obese men (48.73 ± 1.04 yr; body mass index, 31.00 ± 0.29 kg·m) underwent 24 wk of combined training [CT (N = 17), aerobic (50%-85% of V˙O2peak) and resistance (6-10 maximum repetition [RM]) training)] three times per week, 60 min per session, or a control group (N = 13). Anthropometric measures, maximal strength for leg press and bench press, peak oxygen uptake (V˙O2peak) and serum concentrations of C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), IL-10, IL-15, resistin, leptin, and adiponectin were determined before (M1) and after 8 (M2), 16 (M3), and 24 (M4) wk of the experimental design.. Significant increases were observed in the maximal strength for bench press and leg press, V˙O2peak, and serum concentrations of adiponectin and IL-15 for CT. Concomitantly, significant decreases were observed in percentage body fat and serum concentrations of CRP, resistin, and leptin for CT after the experimental period.. Twenty-four weeks of moderate- to high-intensity CT reduced markers of subclinical inflammation associated with obesity and improved insulin resistance and functional capabilities of obese middle-age men, regardless of dietary intervention and weight loss. Topics: Adiponectin; Biomarkers; Blood Glucose; Body Fat Distribution; C-Reactive Protein; Exercise Therapy; Humans; Inflammation; Insulin Resistance; Interleukin-15; Leg; Leptin; Male; Middle Aged; Muscle Strength; Obesity; Oxygen Consumption; Physical Fitness; Resistance Training; Resistin; Tumor Necrosis Factor-alpha | 2015 |
The role of Ad-36 as a risk factor in males with gynecomastia.
Gynecomastia is highly prevalent worldwide and Adenovirus-36 (Ad-36), recently implicated in increased adipose tissue deposition due to its affinity for adipose tissue, is a potential etiological agent in the development of obesity and therefore we hypothesized that Ad-36 may also play a role in the development of gynecomastia by possibly accompanying increased regional adiposity. To support our hypothesis, we conducted a study that included 33 adult males with gynecomastia (PG) and 15 adult males as the patient control group (HCG). Leptin and adiponectin levels were monitored using ELISA. A significant difference in Ad-36 antibody positivity was found between the groups (p<0.05). Average leptin levels were found to be higher, but average adiponectin levels were found to be lower in Ad-36 Ab(+) patient group. No Ad-36 DNA was detected in any tissue samples. In conclusion, we hypothesize that low-grade chronic inflammation, which was caused by Ad-36 infection, possibly caused an increase in circulating leptin. This in turn may have caused an increase in local or circulating estrogens and/or the estrogen/androgen ratio by stimulating the aromatase enzyme activity in adipose stromal cells and breast tissues. We suggest that gynecomastia may develop following an increase in aromatase enzyme activity, by which more oestrogen is produced and the estrogen-androgen balance disrupted. Also, regional adipose tissue enlargements may cause the excessive production of estrogens leading to gynecomastia. Adipose tissue has been recognized as a major endocrine organ in recent years. Another plausible explanation is excessive aromatization of androgens to estrogens by peripheral adipose tissue may promote gynecomastia in males. Moreover, our results suggest that there might be a relationship between Ad-36 and gynecomastia. Topics: Adenoviridae; Adiponectin; Adipose Tissue; Adult; Case-Control Studies; DNA, Viral; Enzyme-Linked Immunosorbent Assay; Gynecomastia; Humans; Inflammation; Leptin; Male; Obesity; Risk Factors | 2015 |
Excessive eccentric exercise leads to transitory hypothalamic inflammation, which may contribute to the low body weight gain and food intake in overtrained mice.
Low body weight gain and food intake are related to exhaustive training and overtraining; however, the molecular mechanisms responsible for these alterations remain unknown. The main aim of this study was to evaluate the effects of running overtraining (OT) protocols performed downhill, uphill and without inclination on the inflammatory pathway in the mouse hypothalamus. The rodents were randomized into the control (C), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR) groups. The body weights and food intake were recorded daily. The incremental load, exhaustive, rotarod and grip force tests were used to measure performance. At 36 h after the grip force test was performed at the end of OT protocols (i.e., week eight) and/or after a 2-week total recovery period (i.e., week 10), the hypothalamus and gastrocnemius were extracted for immunoblotting analysis. In addition, the serum was used to determine cytokine and leptin concentrations. From week 0 to week 8, the OTR/down group exhibited decreased body weight and food intake, and the OTR/up group increased their food intake. At week 10, the OTR/down group exhibited increased body weight, while the OTR group decreased their food intake. The OTR/down group exhibited increased IL-1beta, IL-6, TNF-alpha, pSAPK/JNK and SOCS3 levels at week eight. The OTR/down, OTR/up and OTR groups exhibited increased IL-10 levels at week 10. The OTR/up group displayed increased pJAK2 levels at week eight. While the OTR/down group exhibited increased IL-1beta levels, the OTR/down and OTR/up groups exhibited increased IL-6 and TNF-alpha levels, but decreased IL-10 levels in the gastrocnemius at week eight. The three OT protocols increased the IL-1beta and IL-6 levels, but only the OTR/down and OTR/up groups had increased TNF-alpha levels in serum at week eight. The serum leptin levels were lower for the OTR group compared with the CT group at week eight. In conclusion, the OTR/down protocol induced transitory hypothalamic inflammation with concomitant reductions in the body weight and food intake. After the 2-week total recovery period, the OTR/down group had reversed the hypothalamic inflammation, with the concomitant normalization of the body weight and food intake. Topics: Animals; Body Weight; Cytokines; Eating; Hand Strength; Hypothalamus; Inflammation; Leptin; Male; Mice, Inbred C57BL; Motor Activity; Muscle, Skeletal; Random Allocation; Rotarod Performance Test; Running; Sedentary Behavior | 2015 |
Serum cytokine, chemokine and hormone levels in Saudi adults with pre-diabetes: a one-year prospective study.
Approximately 5-10% of subjects with pre-diabetes eventually progress to diabetes every year. While inflammation is thought to be involved in the development of obesity-related type 2 diabetes mellitus (T2DM), the relation between inflammation and pre-diabetes remains largely unexplored. In this study we examined a comprehensive panel of 10 serum biomarkers involved in overweight and obese subjects with pre-diabetes. A total of 98 subjects (23 males, 75 females) were advised to reduce total intake of fat, increase fiber intake and physical activity. Serum cytokines, MCP and other hormones were assessed by multiplex cytokine profiling. Results show that CRP, IL-6, leptin, IL-10, MCP, resistin, serpin, and TNF-α were significantly lower after 12-months than baseline. Serum concentrations of other adipocytokines, including adipsin and leptin were modestly lower in the 12-month follow-up than baseline, but failed to reach statistical significance. Changes in HbA1c was found to be positively correlated with adipsin, CRP, IL-6, IL-10, resistin, serpin, and TNF-α. The results suggest that promotion of lifestyle changes for one year among overweight and obese subjects modestly changes several circulating inflammatory biomarkers which maybe favorable in reducing risk for T2DM progression. Topics: Adipokines; Adult; Biomarkers; Chemokines; Cytokines; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Inflammation; Leptin; Male; Middle Aged; Obesity; Overweight; Prospective Studies; Saudi Arabia | 2015 |
Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals.
We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA) in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and synovial tissue of subjects at risk of RA.. Fifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA), without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27). Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry.. The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2); p = 0.020), also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5); p = 0.016). This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529) and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520) and ESR (leptin r = 0.512, chemerin r = 0.708), p-value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis.. In this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals. Topics: Adiponectin; Adult; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Body Mass Index; Demography; Follow-Up Studies; Humans; Inflammation; Leptin; Middle Aged; Proportional Hazards Models; Serpins; Synovial Membrane | 2015 |
Association of cystatin C with leptin and TNF-α in elderly Japanese women.
Determinants of cystatin C, a novel marker of mortality in the elderly, have not been extensively studied in Asian elderly population.. Associations of cystatin C with anthropometric, cardiometabolic, hematological, nutritional variables and inflammatory markers were examined in 159 community-living elderly Japanese women whose BMI averaged 22.6±2.9 (SD) kg/m2.. Serum creatinine and cystatin C averaged 0.73±0.16 mg/dL and 0.85±0.20 mg/L, respectively. Creatinine-based estimated glomerular filtration rate (standardized β, -0.538, p<0.001), age (standardized β, 0.274, p<0.001), serum leptin (standardized β, 0.218, p<0.001) and tumour necrosis factor-α (TNF-α, standardized β, 0.165, p=0.002) emerged as significant predictors of serum cystatin C independent of percentage body fat, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, systolic blood pressure and HDL cholesterol (cumulative R2=0.674).. Elevated serum levels of leptin and TNF-α contributed to elevated cystatin C independent of kidney function, fat mass, insulin resistance and inflammation in community-living elderly women and may represent confounders of associations between cystatin C and mortality in this population.. 背景與目的:胱蛋白C 為一個老年死亡的新標記,其決定因子在亞洲老年族 群尚未被大規模的探討。方法與研究設計:評估159 名BMI 平均值為 22.6±2.9 (SD) kg/m2 的日本社區老年女性,其胱蛋白C 與體位測量值、心血管 代謝、血液資料、營養狀況及發炎標記之相關。結果:血清肌酸酐與胱蛋白C 平均值分別為0.73±0.16 mg/dL 及0.85±0.20 mg/L。肌酸酐評估腎絲球過濾率 ( 標準化迴歸係數-0.538 , p<0.001 ) 、年齡( 標準化迴歸係數0.274 , p<0.001)、血清瘦體素(標準化迴歸係數0.218,p<0.001)及腫瘤壞死因子-α (TNF-α 標準化迴歸係數0.165,p=0.0021)顯示為血清胱蛋白C 的顯著預測 因子,且此結果獨立於體脂肪百分比、胰島素抗性之恆定模式評估、高敏感度 C 反應蛋白、收縮壓及高密度脂蛋白膽固醇(累積R2=0.674)。結論:社區老 年女性血清瘦體素及TNF-α 的增加導致胱蛋白C 的提高,此相關獨立於腎功 能、體脂質量、胰島素阻抗性及發炎反應。這個族群之胱蛋白C 與死亡率的 相關,可能是干擾因子造成的相關。. Topics: Aged; Aged, 80 and over; Blood Pressure; Body Composition; Body Mass Index; Cholesterol, HDL; Creatinine; Cystatin C; Female; Glomerular Filtration Rate; Humans; Inflammation; Insulin Resistance; Japan; Leptin; Middle Aged; Tumor Necrosis Factor-alpha | 2015 |
Long-term effects of early overnutrition in the heart of male adult rats: role of the renin-angiotensin system.
To analyze the long-term effects of early overfeeding on the heart and coronary circulation, the effect of ischemia-reperfusion (I/R) and the role of the renin-angiotensin system (RAS) was studied in isolated hearts from control and overfed rats during lactation. On the day of birth litters were adjusted to twelve pups per mother (controls) or to three pups per mother (overfed). At 5 months of age, the rats from reduced litters showed higher body weight and body fat than the controls. The hearts from these rats were perfused in a Langendorff system and subjected to 30 min of ischemia followed by 15 min of reperfusion (I/R). The myocardial contractility (dP/dt) and the coronary vasoconstriction to angiotensin II were lower, and the expression of the apoptotic marker was higher, in the hearts from overfed rats compared to controls. I/R reduced the myocardial contractily, the coronary vasoconstriction to angiotensin II and the vasodilatation to bradykinin, and increased the expression of (pro)renin receptor and of apoptotic and antiapoptotic markers, in both experimental groups. I/R also increased the expression of angiotensinogen in control but not in overfed rats. In summary, the results of this study suggest that early overnutrition induces reduced activity of the RAS and impairment of myocardial and coronary function in adult life, due to increased apoptosis. Ischemia-reperfusion produced myocardial and coronary impairment and apoptosis, which may be related to activation of RAS in control but not in overfed rats, and there may be protective mechanisms in both experimental groups. Topics: Aging; Angiotensin II; Animals; Apoptosis; Biomarkers; Bradykinin; Feeding Behavior; Gene Expression Regulation; Heart; Hemodynamics; In Vitro Techniques; Inflammation; Leptin; Male; Myocardium; Organ Size; Overnutrition; Perfusion; Rats, Sprague-Dawley; Renin-Angiotensin System; Time Factors; Vasoconstriction; Vasodilation | 2014 |
MiR-335, an adipogenesis-related microRNA, is involved in adipose tissue inflammation.
During the development of obesity, adipose tissue releases a host of different adipokines and inflammatory cytokines, such as leptin, resistin, tumor necrosis factor α (TNF-α), Interleukin-6 (IL-6), and adiponectin, which mediate insulin resistance. Recently, some microRNAs (miRNAs) regulated by adiponectin were identified as novel targets for controlling adipose tissue inflammation. Therefore, the relationship between adipokines and miRNA is worth studying. MiR-335 is an adipogenesis-related miRNA and implicated in both fatty acid metabolism and lipogenesis. In this study, we focused on the association of miR-335 and adipokines, and examined the expression trend of miR-335 during human adipocyte differentiation. Our results showed that miR-335 is significantly upregulated with treatment of leptin, resistin, TNF-α, and IL-6 in human mature adipocytes, and its expression elevated in the process of adipocyte differentiation. Interestingly, the transcriptional regulation of miR-335 by these adipokines seems independent of its host gene (mesoderm-specific transcript homolog, MEST). Thus, we cloned and identified potential promoter of miR-335 within the intron of MEST. As a result, a fragment about 600-bp length upstream sequences of miR-335 had apparent transcription activity. These findings indicated a novel role for miR-335 in adipose tissue inflammation, and miR-335 might play an important role in the process of obesity complications via its own transcription mechanism. Topics: Adipogenesis; Adipokines; Adipose Tissue; Cells, Cultured; HEK293 Cells; Humans; Inflammation; Interleukin-6; Leptin; MicroRNAs; Obesity; Promoter Regions, Genetic; Resistin; Tumor Necrosis Factor-alpha; Up-Regulation | 2014 |
Muscular fitness, fatness and inflammatory biomarkers in adolescents.
Muscular fitness, cardiorespiratory fitness (CRF) and fatness are mutually related with chronic inflammation.. To examine the independent association of muscular fitness with inflammatory biomarkers in adolescents from nine European countries.. A total of 639 adolescents (296 boys) aged from 12.5 to 17.5 year were included in this report. Data collection took place in 2006-2007 and analyses in 2012. A muscular fitness score was computed from handgrip strength and standing long jump. CRF was measured using the 20 m shuttle run test. Z-scores of C-reactive protein, complement factors C3 and C4, leptin and white blood cell counts were summed to create a cluster of inflammatory biomarkers. Sex, age, pubertal stage and centre were used as main confounders. Additional models were further adjusted for insulin resistance (HOMA-IR) and sum of four skinfolds.. Muscular fitness was negatively associated with single and clustered inflammatory biomarkers (standardized β from -0.399 to -0.100, all P-values < 0.05). Additional adjustments for CRF and HOMA-IR weakened the associations, but they still remained significant. The association was no longer significant when adjusting for skinfolds. Decreasing values of inflammatory score were observed across incremental levels of muscular fitness in both non-overweight and overweight adolescents (P ≤ 0.05).. Adolescents with higher levels of muscular fitness present a lower chronic inflammation, and this seems to be explained by lower levels of fatness. Yet, overweight and obese adolescents may exhibit a less adverse profile if they maintain appropriate levels of muscular fitness. Topics: Adolescent; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cholesterol; Cross-Sectional Studies; Exercise; Exercise Test; Female; Hand Strength; Humans; Inflammation; Insulin Resistance; Leptin; Lipoproteins, HDL; Male; Motor Activity; Muscle Strength; Muscle, Skeletal; Overweight; Physical Endurance; Physical Fitness; Risk Factors | 2014 |
Hyperleptinemia: implications on the inflammatory state and vascular protection in obese adolescents submitted to an interdisciplinary therapy.
The low-grade systemic inflammation seen in obesity may affect the actions of some adipose tissue-derived adipokines that are involved in the regulation of vascular function. We sought to verify whether hyperleptinemia may influence the inflammatory and atherogenic responses in obese adolescents undergoing interdisciplinary therapy. Thirty-four obese adolescents underwent interdisciplinary therapy for 1 year. Subjects were considered hyperleptinemic if they had baseline values of leptin above 20 ng/mL for boys and 24 ng/mL for girls. Both groups showed an improvement in body composition and a reduction in carotid intima-media thickness. However, only subjects in the non-hyperleptinemic group showed an increase in adiponectin concentration after therapy. Moreover, leptin concentration was positively correlated with adiponectin and inversely correlated with PAI-1 in this group. Hyperleptinemic state may impair the attenuation of inflammation in obese adolescents undergoing interdisciplinary therapy, particularly by impeding the increase in adiponectin concentration, which is directly involved in vascular protection. Topics: Adiponectin; Adipose Tissue; Adiposity; Adolescent; Blood Glucose; Carotid Intima-Media Thickness; Female; Humans; Inflammation; Insulin Resistance; Leptin; Life Style; Male; Obesity; Plasminogen Activator Inhibitor 1; Weight Reduction Programs | 2014 |
Irisin in patients with nonalcoholic fatty liver disease.
Irisin is a recently discovered myokine proposed to increase thermogenesis-related energy expenditure and improve metabolism. We aimed to comparatively evaluate serum irisin levels in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) vs. controls and study their association with disease severity.. Fifteen and 16 consecutively enrolled patients with biopsy-proven nonalcoholic simple steatosis (NAFL) and steatohepatitis (NASH), respectively, and 24 lean and 28 obese controls without NAFLD were recruited. Irisin, established adipokines and biochemical tests were measured.. Serum irisin levels were statistically different in obese controls (33.7±2.7 ng/mL; p<0.001) and patients with NAFL (30.5±1.5 ng/mL; p<0.001) and NASH (35.8±1.9 ng/mL; p=0.001) compared with lean controls (47.7±2.0 ng/mL), but were similar among patients with NAFL, NASH and obese controls. This difference remained significant after adjustment for body mass index (or waist circumference), gender, age, insulin resistance (assessed by HOMA-IR or QUICKI), exercise and time since blood collection. Serum leptin and adiponectin, but not irisin, levels were independently from BMI correlated with insulin resistance and cardiometabolic factors. Serum irisin tended to be higher in patients with (36.7±2.4 ng/mL) than without (30.8±1.2 ng/mL; p=0.02) portal inflammation and independently associated with the latter; these data need to be confirmed by future studies.. Serum irisin levels differ between lean controls and obese controls or NAFLD patients. Despite similar circulating irisin levels between NAFL and NASH groups, irisin may be independently and positively associated with the presence of portal inflammation. Future clinical and mechanistic studies are needed to confirm and extend these data. Topics: Adipokines; Adiponectin; Adult; Aged; Biomarkers; Body Mass Index; Case-Control Studies; Chemokines; Fatty Liver; Female; Fibronectins; Humans; Inflammation; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Portal Vein; Retinol-Binding Proteins, Plasma; Risk Factors; Severity of Illness Index; Thinness | 2014 |
Plasma leptin and adiponectin concentrations correlate with cardiometabolic risk and systemic inflammation in healthy, non-obese children.
Plasma adipocytokines are associated with metabolic profile and cardiovascular risk in obese children.. To investigate the association of plasma leptin and adiponectin concentrations with cardiometabolic risk profile and systemic inflammation in non-obese children.. We studied 170 healthy, non-obese children (86 males, mean age 10±2 years).. Children's current body mass index (BMI), plasma leptin and adiponectin concentrations, lipid profile, fasting plasma glucose and high sensitivity C reactive protein (hsCRP) were measured.. After adjustment for age, gender and BMI, plasma leptin concentrations were positively associated with hsCRP (t=2.72, p=0.009) and fasting plasma glucose (t=4.27, p<0.0001); plasma adiponectin concentrations were negatively associated with hsCRP (t=-3.31, p=0.0016); and positively with high density lipoprotein cholesterol (t=2.32, p=0.02). Children in the highest quartile of leptin/adiponectin (L/A) ratio demonstrated significantly higher BMI, systolic blood pressure, hsCRP, triglycerides and fasting glucose and the lowest high density lipoprotein (HDL) compared to lower L/A ratio quartiles.. Alterations in plasma leptin and adiponectin may help to reclassify non-obese children, detecting those with more unfavorable risk profiles independent of BMI status. Topics: Adiponectin; Body Mass Index; Child; Female; Healthy Volunteers; Humans; Inflammation; Leptin; Male; Metabolic Diseases | 2014 |
Subclinical inflammation during third trimester of pregnancy was not associated with markers of the metabolic syndrome in young adult offspring.
Growing evidence indicates that the metabolic syndrome (MS) is rooted in adverse exposures during fetal life. The aim of this study was to assess the possible associations between biomarkers of inflammation during third trimester of pregnancy and markers of MS in adult offspring.. High-sensitive C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleuki-6 (IL-6) were measured in serum samples obtained in gestational week 30. Offspring were clinically examined at age 20 years. Analyses based on 439 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, prepregnancy body mass index (BMI), education, and offspring's sex. Offspring MS markers included waist circumference, BMI, blood pressure, HOMA insulin resistance, and plasma levels of fasting glucose, triglycerides, cholesterol fractions, insulin, and leptin.. The median level was 2.8 (interquartile range = 3.3) µg/ml for CRP, for TNF-α: 5.7 (3.2) pg/ml, for IL-1β: 0.5 (0.4) pg/ml, and for IL-6: 1.1 (0.7) pg/ml. Concentrations were not significantly associated with MS markers in the offspring. The results remained essentially unchanged after correction for potential confounding.. Markers for subclinical inflammation in third trimester in healthy women were not associated with components of MS in their adult offspring. Topics: Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Cholesterol; Female; Follow-Up Studies; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-1beta; Interleukin-6; Leptin; Linear Models; Longitudinal Studies; Male; Metabolic Syndrome; Multivariate Analysis; Pregnancy; Pregnancy Trimester, Third; Triglycerides; Tumor Necrosis Factor-alpha; Waist Circumference; Young Adult | 2014 |
Bone marrow leptin signaling mediates obesity-associated adipose tissue inflammation in male mice.
Obesity is characterized by an increased recruitment of proinflammatory macrophages to the adipose tissue (AT), leading to systemic inflammation and metabolic disease. The pathogenesis of this AT inflammation, however, remains to be elucidated. The circulating adipokine leptin is increased in obesity and is involved in immune cell function and activation. In the present study, we investigated the role of leptin in the induction of obesity-associated inflammation. We generated radiation chimeric C57BL/6J mice reconstituted with either leptin receptor-deficient (db/db) or wild-type (WT) bone marrow and challenged them with a high-fat diet (HFD) for 16 weeks. Mice reconstituted with db/db bone marrow (WT/db), had significantly lower body weight and adiposity compared with mice with WT bone marrow (WT/WT). Gonadal AT in WT/db mice displayed a 2-fold lower expression of the inflammatory genes Tnfa, Il6, and Ccl2. In addition, gonadal fat of WT/db mice contained significantly fewer crown-like structures compared with WT/WT mice, and most of their AT macrophages expressed macrophage galactose-type C type lectin 1 (MGL1) and were C-C chemokine receptor type 2 (CCR2)-negative, indicative of an anti-inflammatory phenotype. Moreover, WT/db mice exhibited greater insulin sensitivity compared with WT/WT mice. These data show that disrupted leptin signaling in bone marrow-derived cells attenuates the proinflammatory conditions that mediate many of the metabolic complications that characterize obesity. Our findings establish a novel mechanism involved in the regulation of obesity-associated systemic inflammation and support the hypothesis that leptin is a proinflammatory cytokine. Topics: Adipose Tissue; Animal Feed; Animals; Body Composition; Bone Marrow; Diet, High-Fat; Disease Models, Animal; Gene Expression Profiling; Gene Expression Regulation; Immunohistochemistry; Inflammation; Leptin; Macrophages; Male; Mice; Mice, Inbred C57BL; Obesity; Receptors, Leptin; Signal Transduction | 2014 |
Changes in central and peripheral inflammatory responses to lipopolysaccharide in ovariectomized female rats.
Obesity leads to increases in inflammatory responses in a site-specific manner. Ovariectomized animals, usually used as menopause models, exhibit obesity; however, their inflammatory responses have not been fully examined. In the present study, we investigated whether ovariectomy had site-specific effects on inflammatory responses. First, fever and anorectic responses to systemic injections of lipopolysaccharide (LPS) (500μg/kg, i.p.) were compared between ovariectomized rats (OVX) and sham-operated female rats (Sham). Inflammatory cytokines at the central and peripheral levels were also compared under saline-injected and LPS-injected conditions. Body weight in OVX was significantly higher than in Sham. The anorectic responses (reduction of body weight and food intake) to LPS were higher in OVX than in Sham. In the hypothalamus, all of the examined cytokine (IL-1β, TNF-α and IL-6) mRNA levels in OVX were higher than in Sham under the LPS-injected condition. On the other hand, in serum and adipose tissue, only IL-6, not IL-1β and TNF-α, levels in OVX were significantly higher than those in Sham under the LPS-injected condition. Second, responses to central (intracerebroventricular) injections of LPS (500ng) were compared between OVX and Sham. The result was that the fever response in OVX was more evident than in Sham. Finally, responses to systemic injections of LPS (500μg/kg, i.p.) were compared between OVX (OVX-oil) and OVX with estradiol (E) and progesterone (P) supplementation (OVX-EP). The anorectic responses and hypothalamic cytokine mRNA levels under LPS-injected condition were not different between OVX-oil and OVX-EP. These results indicate that ovariectomy enhances inflammatory responses, especially at the central level compared with the peripheral level. As supplementation of E and P could not attenuate the anorectic and cytokine responses to LPS, the deficiency of gonadal steroids might not be directly involved in the increase of inflammatory responses in OVX. Topics: Adipose Tissue; Animals; Body Weight; Estradiol; Female; Inflammation; Interleukin-1beta; Interleukin-6; Leptin; Lipopolysaccharides; Obesity; Ovariectomy; Progesterone; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tumor Necrosis Factor-alpha | 2014 |
Modifications of mesenteric adipose tissue during moderate experimental colitis in mice.
Adipose tissue secretes various proteins referred to as adipokines, being involved in inflammation. It was recognized that mesenteric adipose tissue (MAT) is altered by inflammation, and pathologies such as inflammatory bowel disease (IBD). The aim of this study was to investigate the alterations of the mesenteric adipose tissue in two experimental colitis models in mice adapted to obtain moderate colonic inflammation.. Colonic inflammation was obtained using two models, either DSS dissolved in drinking water or intra-colonic instillation of DNBS. The expression of adipokines (leptin and adiponectin) and inflammatory markers (IL-6, MCP-1, F4/80) was studied by qRT-PCR in the MAT of treated and control mice.. Observations of the colon and IL-6 plasma level determination demonstrated that DNBS treatment led to stronger inflammation. Colitis induced a decrease of mRNA encoding to leptin and adiponectin in MAT. In contrast, colonic inflammation led to an increase of mRNA encoding to IL-6, MCP-1 and F4/80, a specific marker of macrophages.. The mesenteric adipose tissue, in two models of moderate colitis, shows a loss of adipose profile and a strong increase of inflammatory pattern, close to the observations made in MAT of IBD patients. These data suggest that these pro-inflammatory modifications of MAT have to be taken into account in the pathophysiology of IBD. Topics: Adiponectin; Adipose Tissue; Animals; Colitis; Dextran Sulfate; Dinitrofluorobenzene; Disease Models, Animal; Inflammation; Inflammation Mediators; Inflammatory Bowel Diseases; Leptin; Male; Mice; Mice, Inbred BALB C; Proteasome Endopeptidase Complex; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger | 2014 |
Aerobic plus resistance training improves bone metabolism and inflammation in adolescents who are obese.
Obesity is a worldwide epidemic with a high prevalence of comorbidities, including alterations in bone mineral metabolism. The purpose of this yearlong study was to evaluate the role of 2 types of exercise training (aerobic and aerobic plus resistance exercise) on adipokines parameters and bone metabolism in adolescents who are obese. This was a clinical trial study with interdisciplinary weight loss therapy. Forty-two postpubertal adolescents who are obese were subjected to interdisciplinary weight loss therapy with physical exercise, medical monitoring, nutritional intervention, and psychological intervention. Data were collected from serum analyses of leptin, ghrelin, adiponectin, glucose, and insulin. Anthropometric measurements of body composition, bone mineral density, visceral, and subcutaneous fat were also performed. Statistical tests were applied using repeated-measures analysis of variance. Correlations were established using the Pearson test, and dependencies of variables were established using simple linear regression test. Both training types promoted reductions in body mass index, total central, visceral and subcutaneous fat, insulin concentration, and homeostasis model assessment insulin resistance (HOMA-IR) index, but only aerobic plus resistance training showed statistical improvements in the bone mineral content, adiponectin concentration, and lean tissue. Effective reduction in the visceral/subcutaneous ratio, central/peripheral ratio, and leptin concentration was observed. Insulin and the HOMA-IR index were negative predictors of bone mineral content in the combined training group. Moreover, fat distribution was a negative predictor for bone mineral density in both groups. Aerobic plus resistance training promotes a protective role in bone mineral content associated with an improvement in adiponectin and leptin concentrations, favoring the control of the inflammatory state related to obesity in adolescents. Aerobic plus resistance training combined with interdisciplinary interventions provides important strategies to approach obesity, and these strategies may contribute to clinical practice. Topics: Adiponectin; Adolescent; Blood Glucose; Body Fat Distribution; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Diet; Exercise; Female; Ghrelin; Homeostasis; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Obesity; Patient Education as Topic; Resistance Training; Weight Reduction Programs | 2014 |
Glycemic load is associated with oxidative stress among prevalent maintenance hemodialysis patients.
High glycemic index (GI) and glycemic load (GL) are associated with increased levels of oxidative stress and systemic inflammation in the general population. Maintenance hemodialysis (MHD) patients are known to have excessive oxidative stress burden and inflammation. In this study, we examined the relationship between dietary GI or GL and markers of oxidative stress or inflammation among prevalent MHD patients.. A registered dietitian obtained GI, GL and other dietary data from 58 MHD patients. Two separate 24-h diet recalls (a hemodialysis day and a non-hemodialysis day) were analyzed using the Nutrition Data System for Research (NDS-R) software. Plasma or serum concentrations of F2-isoprostanes, high sensitivity C-reactive protein (hsCRP), leptin and adiponectin (ADPN) were measured in fasting state. Fat mass was measured by dual-energy X-ray absorptiometry (DEXA). Cross-sectional associations between GI, GL and markers of interest were examined by multiple regression analysis with adjustment for potential covariates.. Mean (±SD) age, body mass index (BMI) and total trunk fat were 47 ± 12 years, 29.5 ± 6.8 kg/m(2) and 16.4 ± 8.8 kg, respectively. Dietary GI was associated with trunk fat (r = -0.182, P = 0.05) but not with F2-isoprostanes and hsCRP. In contrast, GL was significantly associated with F2-isoprostanes (P = 0.002), in unadjusted analysis, which remained in adjusted analyses, adjusting for age and sex (P = 0.005), and after adjusting for BMI, trunk fat and waist/hip ratio (P = 0.004). Addition of leptin or ADPN did not alter the significance of the association. GL also correlated with hsCRP (P = 0.03), but this association was modified by BMI and trunk fat.. Dietary GL is significantly associated with markers of oxidative stress and inflammation among prevalent MHD patients, independent of the body composition and adipocytokines. These data indicate the importance of the contents of dietary nutrient intake composition and its potential role in determining the metabolic disturbances in MHD patients. Topics: Absorptiometry, Photon; Adiponectin; Adult; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diet; Female; Glycemic Index; Humans; Inflammation; Leptin; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Retrospective Studies | 2014 |
Relationship between serum leptin level and disease activity in patients with systemic sclerosis.
To determine the relationship between serum leptin levels and disease activity in systemic sclerosis (SSc). A total of 60 subjects (30 controls and 30 patients) were included. The inflammatory markers and leptin levels were evaluated and body mass index (BMI) was measured for both groups. The assessment of the skin involvement was performed based on the modified Rodnan skin score (mRSS). Disease activity was evaluated according to the Valentini scleroderma disease activity index. There was a significant difference between the patient and control groups in terms of BMI (p < 0.05); however there was no difference with regards to age and gender (p > 0.05). Valentini scores and mRSS were determined to be significantly higher in active patients (n = 14) than in inactive patients (n = 16) (p < 0.05). No significant difference was determined between groups in terms of leptin levels (p > 0.05). However, leptin levels were significantly lower in active patients than in inactive patients (p < 0.05). We found a significant positive correlation between serum leptin and BMI (p < 0.05), and leptin and serum C3 levels (p < 0.05); no relationship was detected between leptin and other parameters. Leptin can be used as an activity marker in SSc. Further studies, including larger series, should be carried out to clarify this relationship. Topics: Adult; Biomarkers; Body Mass Index; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Scleroderma, Systemic; Severity of Illness Index | 2014 |
Cluster of cardiometabolic risk factors in children with GH deficiency: a prospective, case-control study.
Growth hormone (GH) deficiency (GHD) in adults is associated with increased cardiovascular (CV) risk. Although some authors have documented the presence of early CV risk factors in untreated GHD children, results are still inconsistent. Aim of this study was to evaluate the effects of GHD and GH therapy on early cardiometabolic risk factors in a large cohort of children.. Waist-to-height ratio (WHtR), triglycerides, total-, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol, atherogenic index (AI = total /HDL cholesterol), homocysteine, leptin, adiponectin, high-sensitivity C-reactive protein (hsCRP) and fibrinogen were evaluated in seventy-one GHD children (9·8 ± 3·6 years) before and after 2 years of GH therapy. Seventy-one healthy controls comparable with patients for age, sex and body mass index (BMI) were enrolled.. Compared with controls, GHD children at study entry had higher WHtR (0·52 ± 0·05 vs 0·45 ± 0·19, P = 0·004), triglycerides (0·44 ± 0·98 vs -0·03 ± 0·73 SDS, P = 0·012), total cholesterol (0·28 ± 1·08 vs -0·46 ± 0·98 SDS, P < 0·001), LDL cholesterol (0·20 ± 0·90 vs -0·39 ± 1·06 SDS, P = 0·007), AI (3·19 ± 0·73 vs 2·77 ± 0·53, P = 0·001), homocysteine (8·45 ± 1·8 vs 7·72 ± 1·6 μm, P = 0·003), leptin (8·03 ± 4·2 vs 5·09 ± 1·9 ng/ml, P = 0·001) and fibrinogen (292·6 ± 33 vs 268 ± 31·4 mg/dl, P = 0·011). No differences were found in adiponectin or hsCRP. GH therapy was associated with a significant reduction in WHtR (P < 0·001), total cholesterol (P < 0·001), LDL cholesterol (P = 0·002), homocysteine (P = 0·044) leptin (P = 0·022) and fibrinogen (P = 0·001). Moreover, GH therapy was associated with a significant increase in adiponectin levels (P = 0·001).. Our data suggest that children with untreated GHD exhibit a cluster of early cardiovascular risk factors and that GH treatment exerts beneficial effects on these abnormalities. Topics: Adipokines; Adiponectin; Biomarkers; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Child; Cholesterol; Female; Fibrinogen; Homocysteine; Human Growth Hormone; Humans; Inflammation; Leptin; Male; Prospective Studies; Risk Factors; Treatment Outcome | 2014 |
High-fat diet induces leptin resistance in leptin-deficient mice.
The occurrence of type II diabetes is highly correlated with obesity, although the mechanisms linking the two conditions are incompletely understood. Leptin is a potent insulin sensitiser and, in leptin-deficient, insulin insensitive, Lep(ob/ob) mice, leptin improves glucose tolerance, indicating that leptin resistance may link obesity to insulin insensitivity. Leptin resistance occurs in response to a high-fat diet (HFD) and both hyperleptinaemia and inflammation have been proposed as causative mechanisms. Scrutinising the role of hyperleptinaemia in this process, central hyperleptinaemia in Lep(ob/ob) mice was induced by chronic i.c.v. infusion of leptin (4.2 μg/day) over 10 days. This treatment led to a dramatic decline in body weight and food intake, as well as an improvement in glucose tolerance. Transfer to HFD for 4 days markedly arrested the beneficial effects of leptin on these parameters. Because Lep(ob/ob) mice are exquisitely sensitive to leptin, the possibility that leptin could reverse HFD-induced glucose intolerance in these animals was investigated. HFD led to increased body weight and glucose intolerance compared to a low-fat diet (LFD). Older and heavier Lep(ob/ob) mice were used as body weight-matched controls. Mice in each group received either i.p. leptin (1.25 mg/kg) or vehicle, and glucose tolerance, food intake and the number of phosphorylated signal transducer and activator of transcription (pSTAT)3 immunoreactive cells in the arcuate nucleus (ARC) and ventromedial hypothalamus (VMH) were analysed. Leptin improved glucose tolerance (P = 0. 019) and reduced food intake in Lep(ob/ob) mice on LFD (P ≤ 0.001) but was ineffective in mice on HFD. Furthermore, when leptin was administered centrally, the glucose tolerance of Lep(ob/ob) mice on HFD was significantly impaired (P = 0.007). Although leptin induced the number of pSTAT3 immunoreactive cells in the ARC and VMH of Lep(ob/ob) mice on LFD, HFD was associated with elevated pSTAT3 immunoreactivity in vehicle-treated Lep(ob/ob) mice that was unaffected by leptin treatment, suggesting central leptin resistance. Negating central inflammation by co-administering a c-Jun n-terminal kinase (JNK) inhibitor reinstated the glucose-lowering effects of leptin. These findings demonstrate that Lep(ob/ob) mice develop leptin resistance on a HFD independent of hyperleptinaemia and also indicate that the JNK inflammatory pathway plays a key role in the induction of diet-induced glucose intolerance. Topics: Animals; Diet, High-Fat; Inflammation; Leptin; Mice; Mice, Transgenic; Phosphorylation; STAT3 Transcription Factor | 2014 |
Bilirubin increases insulin sensitivity in leptin-receptor deficient and diet-induced obese mice through suppression of ER stress and chronic inflammation.
Obesity-induced endoplasmic reticulum (ER) stress causes chronic inflammation in adipose tissue and steatosis in the liver, and eventually leads to insulin resistance and type 2 diabetes (T2D). The goal of this study was to understand the mechanisms by which administration of bilirubin, a powerful antioxidant, reduces hyperglycemia and ameliorates obesity in leptin-receptor-deficient (db/db) and diet-induced obese (DIO) mouse models. db/db or DIO mice were injected with bilirubin or vehicle ip. Blood glucose and body weight were measured. Activation of insulin-signaling pathways, expression of inflammatory cytokines, and ER stress markers were measured in skeletal muscle, adipose tissue, and liver of mice. Bilirubin administration significantly reduced hyperglycemia and increased insulin sensitivity in db/db mice. Bilirubin treatment increased protein kinase B (PKB/Akt) phosphorylation in skeletal muscle and suppressed expression of ER stress markers, including the 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein, X box binding protein (XBP-1), and activating transcription factor 4 in db/db mice. In DIO mice, bilirubin treatment significantly reduced body weight and increased insulin sensitivity. Moreover, bilirubin suppressed macrophage infiltration and proinflammatory cytokine expression, including TNF-α, IL-1β, and monocyte chemoattractant protein-1, in adipose tissue. In liver and adipose tissue of DIO mice, bilirubin ameliorated hepatic steatosis and reduced expression of GRP78 and C/EBP homologous protein. These results demonstrate that bilirubin administration improves hyperglycemia and obesity by increasing insulin sensitivity in both genetically engineered and DIO mice models. Bilirubin or bilirubin-increasing drugs might be useful as an insulin sensitizer for the treatment of obesity-induced insulin resistance and type 2 diabetes based on its profound anti-ER stress and antiinflammatory properties. Topics: Animals; Bilirubin; Body Weight; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Glucose Tolerance Test; Heme Oxygenase-1; Inflammation; Insulin; Insulin Resistance; Leptin; Liver; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle, Skeletal; Obesity; Protein Denaturation; Receptors, Leptin | 2014 |
Hyperleptinemia is associated with CRP, but not apolipoprotein E, and is reduced by exercise training.
The purpose of this study was to examine whether leptin levels affect the response of leptin to exercise training (ET) and whether this is also affected by C-reactive protein (CRP) or the three common Apolipoprotein E genotypes (APOE). Ninety-seven (male = 45, female = 52) sedentary individuals underwent 6 months of supervised ET. Blood was sampled before the initiation of ET, and again 24 and 72 hr after completion of the final training session. ET resulted in a small reduction in body mass (80.47 ± 18.03 vs 79.42 ± 17.34 kg, p < .01). Leptin was reduced 24 hr after the final exercise session (p < .01), but returned to normal after 72 hr (p > .05)--Pre: 13.51 ± 12.27, 24hr: 12.14 ± 12.34, 72 hr: 12.98 ± 11.40 ng/ml. The most hyperleptinemic individuals had a greater initial response, which was sustained through to 72 hr after the final session in the pooled study population (p < .01), and in both males (p < .05) and females (p < .05) separately. CRP was related to leptin independently of body weight and positively related to the reductions in leptin. APOE genotype was not related to leptin levels and did not affect the response to ET. Leptin levels may only be reduced by ET in those with hyperleptinemia. In addition, both the initial extent of hyperleptinemia and the subsequent reduction in leptin may be related to low grade chronic systemic inflammation. Topics: Adult; Apolipoproteins E; Body Weight; C-Reactive Protein; Exercise; Female; Genotype; Humans; Inflammation; Leptin; Male; Middle Aged; Physical Conditioning, Human; Sedentary Behavior | 2014 |
Effects of varying degrees of intermittent hypoxia on proinflammatory cytokines and adipokines in rats and 3T3-L1 adipocytes.
Intermittent hypoxia (IH), resulted from recurring episodes of upper airway obstruction, is the hallmark feature and the most important pathophysiologic pathway of obstructive sleep apnea (OSA). IH is believed to be the most important factor causing systemic inflammation. Studies suggest that insulin resistance (IR) is positively associated with OSA. In this study, we hypothesized that the recurrence of IH might result in cellular and systemic inflammation, which was manifested through the levels of proinflammatory cytokines and adipokines after IH exposure, and because IR is linked with inflammation tightly, this inflammatory situation may implicate an IR status.. We developed an IH 3T3-L1 adipocyte and rat model respectively, recapitulating the nocturnal oxygen profile in OSA. In IH cells, nuclear factor kappa B (NF-κB) DNA binding reactions, hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (Glut-1), necrosis factor alpha (TNF-α), interleukin (IL) -6, leptin, adiponectin mRNA transcriptional activities and protein expressions were measured. In IH rats, blood glucose, insulin, TNF-α, IL-6, leptin and adiponectin levels were analyzed.. The insulin and blood glucose levels in rats and NF-κB DNA binding activities in cells had significantly statistical results described as severe IH>moderate IH>mild IH>sustained hypoxia>control. The mRNA and protein levels of HIF-1α and Glut-1 in severe IH group were the highest. In cellular and animal models, both the mRNA and protein levels of TNF-α, IL-6 and leptin were the highest in severe IH group, when the lowest in severe IH group for adiponectin.. Oxidative stress and the release of pro-inflammatory cytokines/adipokines, which are the systemic inflammatory markers, are associated with IH closely and are proportional to the severity of IH. Because IR and glucose intolerance are linked with inflammation tightly, our results may implicate the clinical relationships between OSA and IR. Topics: Adipocytes; Adipokines; Adiponectin; Animals; Blood Glucose; Cytokines; Glucose Transporter Type 1; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Models, Animal; NF-kappa B; Oxidative Stress; Oxygen; Rats; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha | 2014 |
Leptin is involved in age-dependent changes in response to systemic inflammation in the rat.
Obesity contributes to a state of subclinical peripheral and central inflammation and is often associated with aging. Here we investigated the source and contribution of adipose tissue derived cytokines and the cytokine-like hormone leptin to age-related changes in lipopolysaccharide (LPS)-induced brain-controlled sickness-responses. Old (24 months) and young (2 months) rats were challenged with LPS or saline alone or in combination with a neutralizing leptin antiserum (LAS) or control serum. Changes in the sickness-response were monitored by biotelemetry. Additionally, ex vivo fat-explants from young and old rats were stimulated with LPS or saline and culture medium collected and analyzed by cytokine-specific bioassays/ELISAs. We found enhanced duration/degree of the sickness-symptoms, including delayed but prolonged fever in old rats. This response was accompanied by increased plasma-levels of interleukin (IL)-6 and IL-1ra and exaggerated expression of inflammatory markers in brain and liver analyzed by RT-PCR including inhibitor κBα, microsomal prostaglandin synthase and cyclooxygenase 2 (brain). Moreover, for the first time, we were able to show prolonged elevated plasma leptin-levels in LPS-treated old animals. Treatment with LAS in young rats tended to attenuate the early- and in old rats the prolonged febrile response. Fat-explants exhibited unchanged IL-6 but reduced IL-1ra and tumor necrosis factor (TNF)-α release from adipose tissue of aged compared to young animals. In addition, we found increased expression of the endogenous immune regulator microRNA146a in aged animals suggesting a role for these mediators in counteracting brain inflammation. Overall, our results indicate a role of adipose tissue and leptin in “aging-related-inflammation” and age-dependent modifications of febrile-responses. Topics: Adipose Tissue; Aging; Animals; Cyclooxygenase 2; Cytokines; Hypothalamus; Inflammation; Leptin; Lipopolysaccharides; Liver; Male; MicroRNAs; Oxidative Stress; Rats; Rats, Wistar | 2014 |
Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm.
The pathogenesis of diabetic retinopathy (DR) in metabolic syndrome (MetS) and type 2 diabetes (T2D) is not well studied, partly because an appropriate model has not been developed. Recently, we introduced a novel model of spontaneous T2D and MetS that replicates the relevant features of the human disease. In the current study, we investigated the retinal vascular changes in these animals. Experimental DR in streptozotocin (STZ)-injected rodents is described as an inflammatory disease, in which intercellular adhesion molecule 1 (ICAM-1) plays a key role. In comparison, advanced diabetes (HbA1c>10%) in the Nile grass rat (NGR) was associated with lower ICAM-1 protein expression when compared with that in normal or moderately diabetic animals. Vascular cell adhesion molecule 1 (VCAM-1) expression, however, was unaffected by the disease state. As opposed to the STZ-induced model of DR, in diabetic NGRs, most leukocytes accumulated in the retinal arteries. Consistent with the ICAM-1 reduction, leukocyte accumulation was significantly reduced in advanced disease. Similarly, leukocyte adhesions were significantly lower, with elevated plasma triglycerides (>200 mg/dl), and cholesterol (>240 mg/dl). However, these adhesions were significantly higher in animals with higher plasma insulin (>5 μIU/ml) and leptin (>20 ng/ml), suggesting a role for these hormones in diabetic retinal leukostasis. Diabetic NGRs showed substantial retinal endothelial injury, primarily in the microvessels, including vascular tortuosity, obliterated acellular capillaries, and pericyte ghosts. The NGR provides a convenient and realistic model for investigation of retinal changes in MetS/T2D with convincing advantages over the commonly used STZ-induced T1D. Topics: Adiponectin; Animals; Blood-Retinal Barrier; Cell Adhesion; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Models, Animal; Female; Glycated Hemoglobin; Inflammation; Insulin; Intercellular Adhesion Molecule-1; Leptin; Leukocytes; Lipids; Male; Metabolic Syndrome; Rats; Retina; Retinal Vessels; Streptozocin; Triglycerides; Vascular Cell Adhesion Molecule-1 | 2014 |
Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver.
To explore lipocalin-2 (LCN-2) expression and its possible role and mechanism(s) of production in rat models of diet-inducible fatty liver.. Fatty liver was triggered in male Sprague-Dawley rats fed either with liquid Lieber-DeCarli (LDC) or LDC + 70% cal fructose (L-HFr) diet for 4 or 8 wk. Chow-nourished animals served as controls. Hepatic expression of LCN-2 and other metabolic and inflammatory mediators was assessed by quantitative reverse transcription polymerase chain reaction and Western blotting. Serum LCN-2, fasting leptin, and lipid profile were evaluated via Enzyme-Linked Immunosorbent Assay, Radioimmunoassay, and colorimetric assays, respectively. The localization of LCN-2 in the liver was detected by using immunofluorescence staining. Furthermore, HE stain was used to evaluate hepatic fat degeneration and inflammation.. Both LDC-fed and L-HFr-fed rat histologically featured fatty liver. In the liver, mRNA transcriptions of Mcp-1, a2-m, Il-8 and Glut5 were increased in the L-HFr group at both time points (P < 0.001), while the transcription of Tlr4, Inos, and Tnf-α was significantly up-regulated at week 4. Interestingly, hepatic Lcn-2 expression was 90-fold at week 4 and 507-fold at week 8 higher in L-HFr-subjected rats vs control (P < 0.001). In contrast to HDL-cholesterol, systemic levels of LCN-2, fasting leptin and triglycerides were elevated in the L-HFr regimen (P < 0.001). Moreover, protein expression of hepatic LCN-2, CD14, phospho-MAPK, caspase-9, cytochrome c and 4-hydroxynonenal was increased in the L-HFr group. Conversely, the hepatic expression of PGC-1α (a mitochondrial-biogenic protein) was reduced in the L-HFr category at week 8. The localization of LCN-2 in the liver was predominantly restricted to MPO⁺ granulocytes.. Fructose diet up-regulates hepatic LCN-2 expression, which correlates with the increased indicators of oxidative stress and mitochondrial dysfunction. The LCN-2 may be involved in liver protection. Topics: Animal Feed; Animals; Apoptosis; Chemokine CCL2; Colorimetry; Enzyme-Linked Immunosorbent Assay; Fatty Liver; Fructose; Gene Expression Regulation; Glucose Transporter Type 5; Inflammation; Interleukin-8; Leptin; Lipid Peroxidation; Lipocalin-2; Lipocalins; Liver; Male; Oxidative Stress; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Toll-Like Receptor 4 | 2014 |
Leptin does not induce an inflammatory response in the murine placenta.
Leptin is described as a pro-inflammatory signal in fat tissue, which is released from adipocytes and in turn activates immune cells. Also, leptin levels are known to be increased in pregnancies complicated with enhanced inflammatory processes in the placenta. Hence, we assumed that increased leptin amounts might contribute to inducing an inflammatory response in the placenta. To test this hypothesis, pregnant mice were continuously infused with recombinant murine leptin s. c. from day g13 to g16, resulting in a 3-fold increase of maternal circulating serum leptin levels. Dissected placentas were examined for the expression of pro-inflammatory cytokines IL-6 and TNF-alpha and the anti-inflammatory cytokine IL-10 using qPCR analysis. No changes were found except for TNF-alpha, which was slightly elevated upon leptin stimulation. However, TNF-alpha protein levels were not significantly higher in placentas from leptin treated mice. Also, leukocyte infiltration in the labyrinth section of placentas was not increased. In summary, our data demonstrate for the first time that elevated leptin levels alone do not induce an inflammatory response in the placenta. Topics: Animals; Cytokines; Feeding Behavior; Female; Inflammation; Leptin; Leukocytes; Matrix Metalloproteinase 9; Mice, Inbred C57BL; Placenta; Pregnancy; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins | 2014 |
Relationship between retinol-binding protein-4/adiponectin and leptin/adiponectin ratios with insulin resistance and inflammation.
There is much data supporting a role for adipokines in both obesity and metabolic syndrome. Insulin resistance and low-grade inflammation are crucial in the genesis of both disorders. Although data suggest that the ratio of leptin/adiponectin correlates with insulin resistance and predicts cardiovascular disease (CVD), there is scanty data on the relationship between the retinol-binding protein-4 (RBP4)/adiponectin ratio with insulin resistance and inflammation. We tested the relationship of both these ratios with measures of insulin resistance and inflammation.. In 72 individuals, including controls and patients with metabolic syndrome, we calculated the homeostasis model assessment of insulin resistance (HOMA-IR) and assayed high-sensitivity C-reactive protein (hsCRP) and the adipokines, adiponectin, leptin, and RBP4.. Whereas both the leptin/adiponectin and RBP4/adiponectin ratios did not correlate with HOMA-IR, both correlated significantly with the prototypic biomarker of inflammation, hsCRP. Also in patients with metabolic syndrome following adjustment for adiposity, only the RBP4/adiponectin ratio was significantly increased.. Hence it appears that whereas both the leptin/adiponectin and RBP4/adiponectin ratios correlate with inflammation, only the RBP4/adiponectin ratio was significantly increased in metabolic syndrome and would be more useful to predict CVD, especially in metabolic syndrome. Topics: Adiponectin; Adult; Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Retinol-Binding Proteins, Plasma | 2014 |
Obesity-induced hyperleptinemia improves survival and immune response in a murine model of sepsis.
Obesity is a growing health problem and associated with immune dysfunction. Sepsis is defined as systemic inflammatory response syndrome that occurs during infection. Excessive inflammation combined with immune dysfunction can lead to multiorgan damage and death.. The authors investigated the influence of a class 1 obesity (body mass index between 30 and 34.9) on immune function and outcome in sepsis and the role of leptin on the immune response. The authors used a long-term high-fat-diet feeding model (12 weeks) on C57Bl/6 mice (n = 100) and controls on standard diet (n = 140) followed by a polymicrobial sepsis induced by cecal ligation and puncture.. The authors show that class 1 obesity is connected to significant higher serum leptin levels (data are mean ± SEM) (5.7 ± 1.2 vs. 2.7 ± 0.2 ng/ml; n = 5; P = 0.033) and improved innate immune response followed by significant better survival rate in sepsis (71.4%, n = 10 vs. 10%, n = 14; P < 0.0001). Additional sepsis-induced increases in leptin levels stabilize body temperature and are associated with a controlled immune response in a time-dependent and protective manner. Furthermore, leptin treatment of normal-weight septic mice with relative hypoleptinemia (n = 35) also significantly stabilizes body temperature, improves cellular immune response, and reduces proinflammatory cytokine response resulting in improved survival (30%; n = 10).. Relative hyperleptinemia of class 1 obesity or induced by treatment is protective in sepsis. Leptin seems to play a regulatory role in the immune system in sepsis, and treatment of relative hypoleptinemia could offer a new way of an individual sepsis therapy. Topics: Animals; Body Temperature; Bronchoalveolar Lavage Fluid; Cecum; Colony Count, Microbial; Cytokines; Dietary Fats; Eating; Flow Cytometry; Immunity, Cellular; Inflammation; Injections, Intraperitoneal; Leptin; Leukocyte Count; Ligation; Mice; Mice, Inbred C57BL; Neutrophils; Obesity; Respiratory Burst; Sepsis; Survival | 2014 |
[Adipocytes and macrophages functional morphology in obese humans: correlation with plasma leptins level].
White adipose tissue macrophages and both in peripheral blood simples obtained in biopsies from male (n=14) and female (n=11) gluteal depots, were observes by light and electron microscopic methods, in obese in patients with BMI (35,2±7,9 and 31,3±8,5) in female and men, consequently. The data indicates on the positive correlation between adipocytes death, macrophages local activization and leptins level in obese individuals. Recent evidence indicates the correlation between increased leptin prodaction level and adipocytes necrotic foci in WAT, which is trigger lipid tissue persistans necrotic foci and formation chronic inflammation response in obese individuals. Topics: Adipocytes; Adipose Tissue, White; Adult; Body Mass Index; Female; Humans; Inflammation; Insulin Resistance; Leptin; Macrophages; Male; Middle Aged; Obesity | 2014 |
Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet.
A low-grade pro-inflammatory state is at the pathogenic core of obesity and type 2 diabetes. We tested the hypothesis that the plant terpenoid compound ginsenoside Rb1 (Rb1), known to exert anti-inflammatory effects, would ameliorate obesity, obesity-associated inflammation and glucose intolerance in the high-fat diet-induced obese mouse model. Furthermore, we examined the effect of Rb1 treatment on central leptin sensitivity and the leptin signaling pathway in the hypothalamus. We found that intraperitoneal injections of Rb1 (14 mg/kg, daily) for 21 days significantly reduced body weight gain, fat mass accumulation, and improved glucose tolerance in obese mice on a HF diet compared to vehicle treatment. Importantly, Rb1 treatment also reduced levels of pro-inflammatory cytokines (TNF-α, IL-6 and/or IL-1β) and NF-κB pathway molecules (p-IKK and p-IκBα) in adipose tissue and liver. In the hypothalamus, Rb1 treatment decreased the expression of inflammatory markers (IL-6, IL-1β and p-IKK) and negative regulators of leptin signaling (SOCS3 and PTP1B). Furthermore, Rb1 treatment also restored the anorexic effect of leptin in high-fat fed mice as well as leptin pSTAT3 signaling in the hypothalamus. Ginsenoside Rb1 has potential for use as an anti-obesity therapeutic agent that modulates obesity-induced inflammation and improves central leptin sensitivity in HF diet-induced obesity. Topics: Adiposity; Animals; Body Weight; Diet, High-Fat; Energy Metabolism; Ginsenosides; Glucose; Glucose Tolerance Test; Hormones; Hypothalamus; Inflammation; Leptin; Male; Mice; Mice, Obese; Neuropeptides; Obesity; Signal Transduction; Time Factors | 2014 |
Regular exercise coupled to diet regimen accelerates reduction of hepatic steatosis and associated pathological conditions in nonalcoholic fatty liver disease.
A diet regimen focusing on weight loss is still the most efficient treatment for nonalcoholic fatty liver disease (NAFLD). Recently, specific benefits of exercise against NAFLD independent of weight loss have been reported. Hence, combining exercise with diet-induced weight loss can be expected to have an additive benefit for NAFLD management. We evaluated the effectiveness of diet in conjunction with exercise (DE) compared with that of diet alone (D) on hepatic steatosis and its underlying pathophysiology.. Data obtained from 72 obese, middle-aged men with NAFLD who completed a 3-month program of DE or D in 2011 and 2012 were analyzed. Subjects went through a comprehensive parameters analysis for the pathophysiology of NAFLD.. Subjects in the DE group, compared with those in the D group, elicited additive effects on the degree of hepatic steatosis (-82.6% vs. -60.0%) and body weight (-13.3% vs. -8.9%) accompanied by an improvement in serum marker levels: inflammation, ferritin (-16.1% vs. -2.1%); oxidative stress, lipid peroxidation (-31.8% vs. +4.8%); adipokine imbalance, adiponectin, and leptin (+27.4% vs. +2.6% and -74.4% vs. -30.2%). Consequently, subjects in the DE group achieved further attenuation of insulin resistance [homeostatsis model assessment of insulin resistance (HOMA-IR) (-63.6% vs. -40.0%)]. These observed additive benefits in the DE group were closely associated with the increased volume of physical activity.. The addition of exercise to a diet regimen potentiates the benefits in NAFLD management through further improvement of hepatic steatosis, inflammatory and oxidative stress levels, and adipokine imbalance, thereby attenuating insulin resistance independent of detectable weight loss. Topics: Adipokines; Adiponectin; Adiposity; Adult; Aged; Anthropometry; Body Mass Index; Diet; Diet, Reducing; Exercise; Fatty Liver; Ferritins; Humans; Inflammation; Insulin Resistance; Leptin; Lipid Peroxidation; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress | 2014 |
Serum adipokine and inflammatory markers before and after liver transplantation in recipients with major cardiovascular events.
In the nontransplant setting, aberrant serum adipokine levels are associated with cardiovascular (CV) disease. The effects of liver transplantation (LT) on serum adipokine levels and their association with post-LT CV disease have not been studied. A nested case-control study of 77 patients with major CV events more than 4 months after LT analyzed serum adiponectin, resistin, leptin, C-reactive protein, and apolipoprotein levels measured before transplantation and 4, 12, and 24 months after LT. Adiponectin and resistin levels decreased dramatically after LT in all patients. Recipients with CV disease had lower levels of adiponectin and higher levels of resistin, leptin, C-reactive protein, and apolipoprotein B100 than controls. The pre-LT adiponectin level was associated with a 16% increased risk for CV events for every 1 μg/mL decrease in adiponectin [hazard ratio (HR) = 0.84, P = 0.046]. Pre-LT C-reactive protein levels (HR = 1.03, P = 0.047) and 12-month C-reactive protein levels (HR = 1.03, P = 0.03) were associated with CV events after LT. Pre-LT Diabetes (HR = 2.14, P = 0.09), and post-LT resistin (HR = 1.07, P = 0.07), and apolipoprotein B (HR = 1.08, P = 0.08) were associated with a nonsignificantly increased risk of CV events in this small sample size. In conclusion, pre- and post-LT changes in serum adipokine and inflammatory markers may be signals of an increased risk of CV events after LT, but further study is needed. Topics: Adipokines; Adiponectin; Adult; Aged; Apolipoprotein B-100; Apolipoproteins; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; End Stage Liver Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Leptin; Liver Transplantation; Male; Middle Aged; Proportional Hazards Models; Resistin; Risk Factors; Time Factors | 2014 |
Association of chemerin with oxidative stress, inflammation and classical adipokines in non-diabetic obese patients.
The prevalence of obesity has been increasing worldwide. Chemerin is a recently discovered adipokine secreted by the enlarged adipose tissue with diverse biological effects that are not well detailed yet. This study aimed to elucidate the potential role of chemerin in oxidative stress and inflammation that are characteristics for excess weight and may eventually lead to insulin resistance and atherosclerotic complications. We also analysed the associations between chemerin and classical adipokines, namely leptin and adiponectin. Therefore, we investigated non-diabetic obese patients without manifest cardiovascular disease and compared their data to healthy lean individuals. Chemerin correlated positively with markers of oxidative stress and inflammation, while it showed a negative correlation with the measure of antioxidant status, characterized by the HDL-linked paraoxonase-1 enzyme. Chemerin also correlated positively with leptin and negatively with adiponectin respectively. In our study population, oxidized low-density lipoprotein and high-sensitivity C-reactive protein were found to be the strongest predictors of chemerin level. We conclude that chemerin may contribute to chronic inflammation and increased oxidative stress in obese individuals, even in the absence of manifest insulin resistance. Topics: Adipokines; Adiponectin; Adipose Tissue; Aryldialkylphosphatase; Biomarkers; Case-Control Studies; Chimerin Proteins; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation; Insulin Resistance; Leptin; Lipoproteins, LDL; Obesity; Oxidative Stress | 2014 |
Regulation of NAMPT in human gingival fibroblasts and biopsies.
Adipokines, such as nicotinamide phosphoribosyltransferase (NAMPT), are molecules, which are produced in adipose tissue. Recent studies suggest that NAMPT might also be produced in the tooth-supporting tissues, that is, periodontium, which also includes the gingiva. The aim of this study was to examine if and under what conditions NAMPT is produced in gingival fibroblasts and biopsies from healthy and inflamed gingiva. Gingival fibroblasts produced constitutively NAMPT, and this synthesis was significantly increased by interleukin-1β and the oral bacteria P. gingivalis and F. nucleatum. Inhibition of the MEK1/2 and NFκB pathways abrogated the stimulatory effects of F. nucleatum on NAMPT. Furthermore, the expression and protein levels of NAMPT were significantly enhanced in gingival biopsies from patients with periodontitis, a chronic inflammatory infectious disease of the periodontium, as compared to gingiva from periodontally healthy individuals. In summary, the present study provides original evidence that gingival fibroblasts produce NAMPT and that this synthesis is increased under inflammatory and infectious conditions. Local synthesis of NAMPT in the inflamed gingiva may contribute to the enhanced gingival and serum levels of NAMPT, as observed in periodontitis patients. Moreover, local production of NAMPT by gingival fibroblasts may represent a possible mechanism whereby periodontitis may impact on systemic diseases. Topics: Adiponectin; Adolescent; Adult; Biopsy; Cells, Cultured; Cytokines; Female; Fibroblasts; Gene Expression Regulation, Enzymologic; Gingiva; Humans; Inflammation; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Periodontitis; Resistin; Young Adult | 2014 |
Myeloid-specific deletion of SIRT1 increases hepatic steatosis and hypothalamic inflammation in mice fed a high-fat diet.
Obesity-induced fatty liver disease is associated with increased hypothalamic inflammation. Previous reports have demonstrated that the deletion of SIRT1 in hepatocytes increases hepatic steatosis and inflammation. Using myeloid cell-specific SIRT1 knockout (KO) mice, we investigated whether ablation of SIRT1 in macrophages plays a role in regulating hepatic steatosis and hypothalamic inflammation. When challenged with a high-fat diet (HFD) for 24 weeks, hyperleptinemia, hyperinsulinemia, hepatic steatosis and macrophage infiltrations in HFD-fed KO mice were increased compared with HFD-fed WT mice. Hypothalamic expression levels of iba1 were increased in HFD-fed KO mice compared with HFD-fed WT mice. In particular, the expression levels of choline acetyltransferase were decreased in the hypothalamus of HFD-fed KO mice compared with HFD-fed WT mice. Thus, our findings suggest that SIRT1 plays a key role for hepatic steatosis and hypothalamic inflammation and that anti-inflammatory effect of SIRT1 may be important for the prevention of obesity-induced metabolic syndromes. Topics: Animals; Diet, High-Fat; Fatty Liver; Glucose Tolerance Test; Hypothalamus; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Mice; Mice, Knockout; Myeloid Cells; Sirtuin 1 | 2014 |
Leptin-mediated increases in catecholamine signaling reduce adipose tissue inflammation via activation of macrophage HDAC4.
Obesity promotes systemic insulin resistance through inflammatory changes that lead to the release of cytokines from activated macrophages. Although the mechanism is unclear, the second messenger cAMP has been found to attenuate macrophage activity in response to a variety of hormonal signals. We show that, in the setting of acute overnutrition, leptin triggers catecholamine-dependent increases in cAMP signaling that reduce inflammatory gene expression via the activation of the histone deacetylase HDAC4. cAMP stimulates HDAC4 activity through the PKA-dependent inhibition of the salt-inducible kinases (SIKs), which otherwise phosphorylate and sequester HDAC4 in the cytoplasm. Following its dephosphorylation, HDAC4 shuttles to the nucleus where it inhibits NF-κB activity over proinflammatory genes. As variants in the Hdac4 gene are associated with obesity in humans, our results indicate that the cAMP-HDAC4 pathway functions importantly in maintaining insulin sensitivity and energy balance via its effects on the innate immune system. Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Catecholamines; Cholera Toxin; Cyclic AMP; Energy Metabolism; Histone Deacetylases; Humans; Inflammation; Insulin Resistance; Leptin; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; Panniculitis; Pertussis Toxin; Phosphorylation; Polymorphism, Single Nucleotide; Protein Serine-Threonine Kinases; Signal Transduction; Transcription Factor RelA; Viper Venoms | 2014 |
Regulatory effects of resveratrol on glucose metabolism and T-lymphocyte subsets in the development of high-fat diet-induced obesity in C57BL/6 mice.
High-fat diet (HFD)-induced obesity is often associated with immune dysfunction. Resveratrol (trans-3,5,4'-trihydroxystilbene), which has well-founded immunity-related beneficial properties, was used to elucidate the regulatory effect on glucose metabolism and T-lymphocyte subsets in the development of HFD-induced obesity. Resveratrol, being associated with decreases of plasma leptin and plasma lipids and the release of oxidative stress, significantly decreased the body weight and fat masses in HF mice after 26 weeks of feeding. Furthermore, resveratrol decreased the fasting blood glucose and fasting plasma insulin and increased the CD3(+)CD4(+)/CD3(+)CD8(+) subsets percentages and the regulatory T cells (Tregs) production after 13 and 26 weeks of feeding. The results indicate that resveratrol, as an effective supplement for HFD, maintained glucose homeostasis by activating the PI3K and SIRT1 signaling pathways. Moreover, resveratrol activated the Nrf2 signaling pathway-mediated antioxidant enzyme expression to alleviate inflammation by protecting against oxidative damage and T-lymphocyte subset-related chronic inflammatory response in the development of HFD-induced obesity. Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Blood Glucose; Body Weight; Diet, High-Fat; Fasting; Female; Inflammation; Insulin; Leptin; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Obesity; Oxidative Stress; Phosphatidylinositol 3-Kinases; Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes; T-Lymphocyte Subsets | 2014 |
Maternal pregravid obesity changes gene expression profiles toward greater inflammation and reduced insulin sensitivity in umbilical cord.
Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC).. UCs from 12 lean (pregravid BMI < 24.9) and 10 overweight/obese (pregravid BMI ≥ 25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays. Metabolic parameters were assayed in mother's plasma and cord blood.. Although offspring birth weight and adiposity (at 2 wk) did not differ between groups, expression of 232 transcripts was affected in UC from overweight/obese compared with those of lean mothers. Gene-set enrichment analysis revealed an upregulation of genes related to metabolism, stimulus and defense response, and inhibitory to insulin signaling in the overweight/obese group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from overweight/obese mothers, while endothelin receptor B, KLF10, PEG3, and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST, and SOCS1 were positively correlated (P < 0.05) with mother's first-trimester body fat mass (%).. Our data suggest a positive association between maternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life. Topics: Adiposity; Adult; Analysis of Variance; Anthropometry; Blotting, Western; Cell Adhesion Molecules; DNA Primers; Early Growth Response Protein 1; Female; Gene Expression Profiling; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Maternal Nutritional Physiological Phenomena; Microarray Analysis; Obesity; Proto-Oncogene Proteins c-fos; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Umbilical Cord | 2014 |
Tissue iron deficiency and adiposity-related inflammation in disadvantaged preschoolers from NE Brazil.
Earlier we reported an association between iron deficiency and overweight in Brazilian preschoolers. Here, we investigate whether this is the result of adipose-related inflammation.. Fasting serum C-reactive protein, α-1-acid glycoprotein (AGP), hepcidin, interleukin-6 (IL-6) and leptin, together with two iron biomarkers (serum ferritin and transferrin receptor (sTfR)), were measured in 364 disadvantaged preschoolers with a mean BMIZ (standardised Z-score for BMI) of 0.015, aged 3-6 years and attending day care in Salvador, Brazil. The role of genetic haemoglobin (Hb) disorders, intestinal parasites and dietary iron supply (calculated from serving sizes of 20 weekday menus) were also examined.. Forty-eight children (13%) were overweight (BMIZ >1). Prevalence of tissue iron deficiency (sTfR >113.3 nmol/l; 30.6 vs 12.5%; P=0.002) and chronic inflammation (AGP >25 μmol/l; 19 vs 10%; P=0.025) were higher in overweight than in normal-weight children. From multiple regression, BMIZ was a positive predictor of log serum sTfR, ferritin and leptin, but not of log hepcidin or IL-6. Instead, major positive predictors of log hepcidin were log IL-6, followed by an elevated AGP and sex (male), whereas for log IL-6 elevated AGP was the only significant predictor. Besides BMIZ, sex (female) was also a major positive predictor of leptin. Heterozygous variant of sickle cell Hb (n=20), but not helminths, was also a positive predictor of log sTfR. Median dietary iron supply (mg/day) was above the WHO Recommended Nutrient Intake assuming moderate bioavailability and appeared adequate.. The role of adiposity-related inflammation in tissue iron deficiency should be considered even when the prevalence of overweight is relatively low. Topics: Adipose Tissue; Adiposity; Anemia, Iron-Deficiency; Biomarkers; Brazil; Child; Child, Preschool; Female; Ferritins; Hepcidins; Humans; Inflammation; Interleukin-6; Iron Deficiencies; Iron, Dietary; Leptin; Male; Obesity; Orosomucoid; Prevalence; Receptors, Transferrin; Sex Factors; Vulnerable Populations | 2014 |
Serum leptin and adiponectin levels in Korean patients with psoriasis.
Psoriasis is a disorder caused by genetic and immunological factors. Leptin, a peptide hormone secreted predominantly from adipose tissue, regulates energy intake and expenditure, as well as the T-helper response. There have been conflicting reports regarding serum levels of leptin and adiponectin in patients with psoriasis. In the present study, we measured serum levels of leptin and adiponectin in Korean patients with psoriasis. Twenty-four patients with psoriasis and fifteen control subjects were included in the study. Serum leptin and adiponectin levels were determined by an immunometric sandwich enzyme-linked immunosorbent assay (ELISA). The mean serum leptin concentration in patients with psoriasis was higher than in controls, and the difference was statistically significant. In contrast, serum adiponectin levels in patients with psoriasis were significantly decreased compared with healthy controls. Leptin levels in vitamin D-deficient patients were statistically significantly higher than in vitamin D-sufficient patients. Serum adiponectin concentrations showed a negative correlation with body mass index (BMI) and psoriasis area and severity index (PASI) in patients with psoriasis. In conclusion, the present study demonstrated that leptin and adiponectin may play a role in the immunopathogenesis of psoriasis and may be useful biomarkers indicating severity of psoriasis in Korean patients. Topics: Adiponectin; Adult; Aged; Biomarkers; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Psoriasis; Republic of Korea; Risk; Severity of Illness Index; Vitamin D; Vitamin D Deficiency; Young Adult | 2014 |
Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational-age outcomes in Tanzania.
We sought to investigate the relationship between a panel of angiogenic and inflammatory biomarkers measured in midpregnancy and small-for-gestational-age (SGA) outcomes in sub-Saharan Africa.. Concentrations of 18 angiogenic and inflammatory biomarkers were determined in 432 pregnant women in Dar es Salaam, Tanzania, who participated in a trial examining the effect of multivitamins on pregnancy outcomes. Infants falling below the 10th percentile of birthweight for gestational age relative to the applied growth standards were considered SGA. Multivariate binomial regression models with the log link function were used to determine the relative risk of SGA associated with increasing quartiles of each biomarker. Restricted cubic splines were used to test for nonlinearity of these associations.. A total of 60 participants (13.9%) gave birth to SGA infants. Compared to those in the first quartile, the risk of SGA was reduced among those in the fourth quartiles of vascular endothelial growth factor-A (adjusted risk ratio [RR], 0.38; 95% confidence interval [CI], 0.19-0.74), placental growth factor (adjusted RR, 0.28; 95% CI, 0.12-0.61), soluble fms-like tyrosine kinase-1 (adjusted RR, 0.48; 95% CI, 0.23-1.01), monocyte chemoattractant protein-1 (adjusted RR, 0.48; 95% CI, 0.25-0.92), and leptin (adjusted RR, 0.46; 95% CI, 0.22-0.96).. Our findings provide evidence of altered angiogenic and inflammatory mediators, at midpregnancy, in women who went on to deliver SGA infants. Topics: Adolescent; Adult; Angiopoietins; Antigens, CD; Biomarkers; Birth Weight; C-Reactive Protein; Complement System Proteins; Cytokines; Endoglin; Female; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Multivariate Analysis; Neovascularization, Physiologic; Placenta Growth Factor; Pregnancy; Pregnancy Proteins; Pregnancy Trimester, First; Pregnancy Trimester, Second; Receptors, Cell Surface; Receptors, Tumor Necrosis Factor, Type II; Regression Analysis; Tanzania; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Young Adult | 2014 |
The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity.
Metabolic disorders, including obesity and insulin resistance, have their basis in dysregulated lipid metabolism and low-grade inflammation. In a microarray search of unique lipase-related genes whose expressions are associated with obesity, we found that two secreted phospholipase A2s (sPLA2s), PLA2G5 and PLA2G2E, were robustly induced in adipocytes of obese mice. Analyses of Pla2g5(-/-) and Pla2g2e(-/-) mice revealed distinct roles of these sPLA2s in diet-induced obesity. PLA2G5 hydrolyzed phosphatidylcholine in fat-overladen low-density lipoprotein to release unsaturated fatty acids, which prevented palmitate-induced M1 macrophage polarization. As such, PLA2G5 tipped the immune balance toward an M2 state, thereby counteracting adipose tissue inflammation, insulin resistance, hyperlipidemia, and obesity. PLA2G2E altered minor lipoprotein phospholipids, phosphatidylserine and phosphatidylethanolamine, and moderately facilitated lipid accumulation in adipose tissue and liver. Collectively, the identification of "metabolic sPLA2s" adds this gene family to a growing list of lipolytic enzymes that act as metabolic coordinators. Topics: Adipose Tissue, White; Animals; Cells, Cultured; Diet, High-Fat; Female; Glucose Tolerance Test; Group II Phospholipases A2; Group V Phospholipases A2; Humans; Inflammation; Insulin; Leptin; Lipoproteins; Liver; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; Proto-Oncogene Proteins c-akt; RNA, Messenger; Time Factors | 2014 |
Adiposity, chronic inflammation, and the prepubertal decline of sex hormone binding globulin in children: evidence for associations with the timing of puberty (Earlybird 58).
The regulation and role of SHBG in children are poorly defined. Here we investigated whether adiposity-related mechanisms regulate SHBG and whether SHBG levels are associated with the age of puberty.. Longitudinal modelling of annual physiological and endocrine measurements from age 5 to 15 years in a cohort of 347 Plymouth schoolchildren.. SHBG levels were highest at age 5 years and then declined. Mean (SE) SHBG levels were higher in boys than girls at age 5 years [mean (SE) difference 7.68 (3.80) nmol/L; P = .045] but lower in boys by age 15 years [difference 12.19 (3.4) nmol/L; P < .001]. SHBG correlated inversely with adiposity [body mass index SD score (BMI SDS)], insulin, IGF-I, C-reactive protein (CRP), and leptin and positively with adiponectin but not with dehydroepiandrosterone sulphate, androstenedione, or T. In linear mixed models, five adiposity-related covariates (insulin, leptin, adiponectin, IGF-I, and CRP) all exerted significant main effects on SHBG (boys P = .04 to < .001; girls P = .007 to < .001). However, the further addition of BMI SDS rendered the effects of leptin, insulin, and adiponectin nonsignificant, whereas CRP and IGF-I remained significant. In separate models, the individual effects on SHBG of insulin, leptin, IGF-I, and adiponectin, but not CRP, were displaced by BMI SDS. Finally, in linear regression, BMI SDS little affected R(2) resulting from the five adiposity-related signals. Girls with lower SHBG levels at age 5 years reached Tanner stage 2 earlier, tended to have earlier LH secretion, and earlier age at peak height velocity and menarche. In contrast, boys with lower SHBG levels at age 5 years reached Tanner stage 2 earlier, but there were no relationships between SHBG and earlier onset of LH secretion or age at peak height velocity.. Adiposity-related endocrine mechanisms and chronic inflammation were associated with the prepubertal decline of SHBG, and lower SHBG levels anticipated earlier puberty. These findings may be relevant to the occurrence of earlier puberty in recent decades. Topics: Adiposity; Adolescent; Age Factors; Androgens; Body Mass Index; C-Reactive Protein; Child; Child, Preschool; Chronic Disease; Female; Humans; Inflammation; Insulin; Insulin-Like Growth Factor I; Leptin; Longitudinal Studies; Luteinizing Hormone; Male; Puberty; Sex Hormone-Binding Globulin | 2014 |
Synovial fluid levels of adipokines in osteoarthritis: Association with local factors of inflammation and cartilage maintenance.
The role of body weight in the pathogenesis of osteoarthritis (OA) - previously considered the sole factor in the association between obesity and OA - is being re-evaluated as the contribution of adiposity to the cartilage degenerative process becomes clearer. The current study has been undertaken to better understand the role of adipose-derived proteins, namely adipokines, in OA. For this purpose, we investigated in patients with OA the relationships between the joint levels of leptin, adiponectin and resistin and those of factors involved in inflammation and cartilage maintenance. The sandwich enzyme-linked immunosorbent assays were used to determine in the synovial fluid (SF) from 35 OA patients, the concentrations of adipokines, interleukin-6 (IL-6) and transforming growth factor-β (TGF-β). The soluble form of leptin receptor (sOb-R) was also examined to evaluate the biological active free form of leptin. Correlation analysis indicate that IL-6 levels are positively related to the levels of resistin and adiponectin. Surprisingly, the free form of leptin, but not the total leptin, is negatively associated with IL-6. Beside, adiponectin is the single adipokine that is correlated with TGF-β. Interestingly, a sexual dimorphism is observed in the study as correlations between adipokines and IL-6 or TGF-β are found only with female OA patients. Taken together, these findings suggest that only adiponectin may contribute to the metabolic changes associated with OA. The three adipokines may also be involved in inflammation, but with opposite effects. Both resistin and adiponectin may exhibit pro-inflammatory activity while the free form of leptin may down-regulate the inflammation. Topics: Adiponectin; Aged; Aged, 80 and over; Arthroplasty, Replacement, Knee; Cartilage; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Osteoarthritis, Knee; Receptors, Leptin; Resistin; Synovial Fluid; Transforming Growth Factor beta | 2014 |
Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling.
Chronic inflammation constitutes an important link between obesity and its pathophysiological sequelae. In contrast to the belief that inflammatory signals exert a fundamentally negative impact on metabolism, we show that proinflammatory signaling in the adipocyte is in fact required for proper adipose tissue remodeling and expansion. Three mouse models with an adipose tissue-specific reduction in proinflammatory potential were generated that display a reduced capacity for adipogenesis in vivo, while the differentiation potential is unaltered in vitro. Upon high-fat-diet exposure, the expansion of visceral adipose tissue is prominently affected. This is associated with decreased intestinal barrier function, increased hepatic steatosis, and metabolic dysfunction. An impaired local proinflammatory response in the adipocyte leads to increased ectopic lipid accumulation, glucose intolerance, and systemic inflammation. Adipose tissue inflammation is therefore an adaptive response that enables safe storage of excess nutrients and contributes to a visceral depot barrier that effectively filters gut-derived endotoxin. Topics: Adipogenesis; Adiponectin; Adipose Tissue, White; Adrenergic Agonists; Animals; Body Weight; Diet, High-Fat; Fatty Acid-Binding Proteins; Fatty Liver; Female; Glucose Tolerance Test; Inflammation; Intra-Abdominal Fat; Leptin; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Animal; Recombinant Proteins; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha | 2014 |
Effect of Sipjeondaebo-tang on cancer-induced anorexia and cachexia in CT-26 tumor-bearing mice.
Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- α (TNF- α). In addition, glucagon like peptide-1 (GIP-1), peptide YY (PYY), ghrelin, and leptin plays a crucial role in food intake. In this study, we investigated the therapeutic effects of one of the traditional herbal medicines, Sipjeondaebo-tang (Juzen-taiho-to in Japanese; SJDBT), on cancer anorexia and cachexia in a fundamental mouse cancer anorexia/cachexia model, CT-26 tumor-bearing mice. SJDBT was more significantly effective in a treatment model where it was treated after anorexia and cachexia than in a prevention model where it was treated before anorexia and cachexia on the basis of parameters such as weights of muscles and whole body and food intakes. Moreover, SJDBT inhibited a production of IL-6, MCP-1, PYY, and GLP-1 and ameliorated cancer-induced anemia. Therefore, our in vivo studies provide evidence on the role of SJDBT in cancer-associated anorexia and cachexia, thereby suggesting that SJDBT may be useful for treating cancer-associated anorexia and cachexia. Topics: Animals; Anorexia; Body Weight; Cachexia; Cell Line, Tumor; Chemokine CCL2; Drugs, Chinese Herbal; Ghrelin; Glucagon-Like Peptide 1; Inflammation; Interleukin-6; Intestinal Mucosa; Leptin; Male; Mice; Mice, Inbred BALB C; Muscles; Neoplasm Transplantation; Neoplasms; Peptide YY; Plant Preparations; Tumor Necrosis Factor-alpha | 2014 |
Effect of increased leptin and C-reactive protein levels on mortality: results from the National Health and Nutrition Examination Survey.
Leptin and C-reactive protein (CRP) have each been linked to adverse cardiovascular events, and prior cross-sectional research suggests that increased levels of both biomarkers pose an even greater risk. The effect of increased levels of both leptin and CRP on mortality has not, however, been previously assessed.. We used data from the third National Health and Nutrition Examination Survey (NHANES III) to estimate the mortality effect of high leptin and high CRP levels. Outcomes were compared with the use of inverse-probability-weighting adjustment. Among 6259 participants included in the analysis, 766 were in their sex-specific, population-weighted highest quartiles of both leptin and CRP. Median follow-up time was 14.3 years.. There was no significant difference in adjusted all-cause mortality between the groups (risk ratio 1.22, 95% confidence interval [CI], 0.97-1.54). Similar results were noted with the use of several different analytic methods and in many subgroups, though high leptin and CRP levels may increase all-cause mortality in males (hazard ratio, 1.80, 95% CI, 1.32-2.46; P for interaction, 0.011). A significant difference in cardiovascular mortality was also noted (risk ratio, 1.54, 95% CI, 1.08-2.18), though that finding was not confirmed in all sensitivity analyses... In this observational study, no significant difference in overall all-cause mortality rates in those with high leptin and high CRP levels was found, though high leptin and CRP levels appear associated with increased mortality in males. High leptin and CRP levels also likely increase risk for cardiovascular death.. Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Cardiovascular Diseases; Cause of Death; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus; Dyslipidemias; Ethnicity; Female; Follow-Up Studies; Health Surveys; Humans; Inflammation; Kidney Diseases; Leptin; Lung Diseases; Male; Middle Aged; Mortality; Risk Factors; Sex Factors; Smoking; United States; Young Adult | 2014 |
Adiponectin levels are reduced while markers of systemic inflammation and aortic remodelling are increased in intrauterine growth restricted mother-child couple.
To investigate the relationships between the adipocytokine levels, markers of inflammation, and vascular remodelling in pregnancies complicated by intrauterine growth restriction (IUGR).. This was a retrospective study. One hundred and forty pregnant patients were enrolled. Adiponectin, leptin, tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and C reactive protein (CRP) were assessed in IUGR, small for gestational age (SGA), and appropriate for gestational age (AGA) mother-child couples at delivery. IUGR and SGA fetuses were defined as fetuses whose estimated fetal weight (EFW) was below 10th percentile for gestational age with and without umbilical artery (UA) Doppler abnormalities, respectively. Fetal aorta intima media thickness (aIMT) was evaluated by ultrasound in the same fetal groups. Data were analyzed by R (version 2.15.2).. There were 37 IUGR mother-child couples, 33 SGA, and 70 AGA. Leptin, TNFα, IL-6, and CRP serum levels were higher in IUGR pregnant patients (P < 0.05). Adiponectin levels were significantly reduced in IUGR fetuses compared to SGA and AGA, while leptin, TNFα, and IL-6 levels were higher in IUGR group (P ≤ 0.05). Fetal aIMT was significantly higher in IUGR (P < 0.05) and in this group there was a negative correlation between aIMT and adiponectin/leptin ratio (A/L ratio) (P < 0.05) and between adiponectin and IL-6 levels (P < 0.05).. In conclusion, compared to SGA and AGA, IUGR fetuses had reduced circulating levels of adiponectin and elevated measures of aIMT and several inflammatory markers. Moreover, adiponectin levels were negatively correlated with aIMT in IUGR fetuses suggesting a possible causal link between reduced adiponectin and vessel remodelling. Topics: Adiponectin; Adult; Aorta; Biomarkers; C-Reactive Protein; Female; Fetal Growth Retardation; Humans; Inflammation; Interleukin-6; Leptin; Mother-Child Relations; Pregnancy; Tumor Necrosis Factor-alpha; Tunica Media | 2014 |
Association of adiponectin and leptin with relative telomere length in seven independent cohorts including 11,448 participants.
Oxidative stress and inflammation are major contributors to accelerated age-related relative telomere length (RTL) shortening. Both conditions are strongly linked to leptin and adiponectin, the most prominent adipocyte-derived protein hormones. As high leptin levels and low levels of adiponectin have been implicated in inflammation, one expects adiponectin to be positively associated with RTL while leptin should be negatively associated. Within the ENGAGE consortium, we investigated the association of RTL with adiponectin and leptin in seven independent cohorts with a total of 11,448 participants. We performed partial correlation analysis on Z-transformed RTL and LN-transformed leptin/adiponectin, adjusting for age and sex. In extended models we adjusted for body mass index (BMI) and C-reactive protein (CRP). Adiponectin showed a borderline significant association with RTL. This appeared to be determined by a single study and when the outlier study was removed, this association disappeared. The association between RTL and leptin was highly significant (r = -0.05; p = 1.81 × 10(-7)). Additional adjustment for BMI or CRP did not change the results. Sex-stratified analysis revealed no difference between men and women. Our study suggests that high leptin levels are associated with short RTL. Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Oxidative Stress; Telomere | 2014 |
Obesity and low-grade inflammation increase plasma follistatin-like 3 in humans.
Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation.. To elucidate the association between plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans.. Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS), TNF-α, or interleukin-6 (IL-6) as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans.. Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans.. Plasma fstl3 is increased in obese subjects and associated with fat mass and low-grade inflammation. Furthermore, TNF-α increased plasma fstl3, suggesting that TNF-α is one of the inflammatory drivers of increased systemic levels of fstl3. Topics: Adiponectin; Adult; Cross-Sectional Studies; Follistatin-Related Proteins; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Lipopolysaccharides; Male; Obesity; Tumor Necrosis Factor-alpha | 2014 |
Leptin-mediated inflammatory signaling crucially links visceral fat inflammation to obesity-associated β-cell dysfunction.
This study aimed to examine the causal relationship between adipokines released from visceral fat and pancreatic β-cell dysfunction in the state of obesity inflammation.. Adipose tissue and adipocyte conditioned medium were obtained from epididymal fat of B6 mice on regular or high fat diet for 16 weeks. The latter were classified into two groups: overweight (OW, 40±2g) and obese (OB, 50±2g). Isolated mouse islets and NIT-1 cells were used to evaluate β-cell function.. Fasting glucose, leptin, and interleukin-6 levels were increased in OW mice and were further elevated in OB mice. Adipocyte size and number of adipose macrophage infiltrations showed a similar trend. The augmentation of homeostasis model assessment of insulin resistance, islet hyperplasia and macrophage infiltration was noted only in OB mice. The stimulation index was lower, but reactive oxygen species production was higher in islets isolated from OB mice than from controls. In epididymal fat conditioned medium, the increases in leptin, IL-6 and TNF-α production in OW mice were further elevated in OB mice except TNF-α. Adipose tissue conditioned medium suppressed the stimulation index of islets isolated from B6 mice but not from db/db mice. The suppressive effect was also reversed by co-treatment with N-acetylcysteine or NS-398 (a selective cyclooxygenase-2 inhibitor).. A markedly elevated leptin production from inflamed visceral fat could deteriorate β-cell function via leptin receptor-mediated oxidative stress and cyclooxygenase-2 activation in the development of obesity. Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Cyclooxygenase 2; Diet, High-Fat; Glucose; Inflammation; Insulin-Secreting Cells; Interleukin-6; Intra-Abdominal Fat; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Overweight; Oxidative Stress; Receptors, Leptin; Signal Transduction; Tumor Necrosis Factor-alpha | 2014 |
Persistent inflammation and its relationship to leptin and insulin in phases of bipolar disorder from acute depression to full remission.
A proinflammatory phase with various immunomodulatory mechanisms has been noted in bipolar mania and major depression. Weight gain and increased production of leptin may be associated with immunomodulation and insulin resistance in bipolar disorder. However, immunomodulation and its linkage with leptin and insulin in the depressive episode of bipolar disorder remain unclear. We investigated alterations in inflammatory markers and their relationship with leptin and insulin levels in patients with phases of bipolar disorder from acute depression to full remission.. Thirty-two physically healthy bipolar I depressed patients aged <45 years and age- and sex-matched healthy controls participated in this study. We measured their circulating levels of leptin, insulin, high-sensitivity C-reactive protein (hs-CRP), soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 1 (sTNF-R1), and interleukin-1 receptor antagonist (IL-1Ra) in three phases, i.e., acute depression, subsequent partial remission, and full remission.. In acute depression, subsequent partial remission, and full remission, patients with bipolar disorder had significantly higher mean levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R compared with control subjects. The IL-1Ra and sTNF-R1 levels in various affective phases were significantly correlated to body mass index, leptin level, circulating lipids, and medication status. The sIL-2R levels in the three affective phases were all independent of other inflammatory markers and clinical and laboratory variables. Patients showed no alteration of sIL-6R levels through the depressive episode.. Patients with bipolar disorder in depressive episodes may exhibit persistent inflammation with elevated levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R but not sIL-6R from the acute phases to full remission. Only sIL-2R production seems to be tightly linked with the pathophysiology of bipolar depression and is independent of insulin and leptin levels. Topics: Adult; Bipolar Disorder; Body Weight; C-Reactive Protein; Case-Control Studies; Cytokines; Disease Progression; Female; Humans; Inflammation; Insulin; Leptin; Male; Psychiatric Status Rating Scales; Recurrence; Smoking; Statistics as Topic; Young Adult | 2014 |
Effects of Ilex paraguariensis (yerba mate) treatment on leptin resistance and inflammatory parameters in obese rats primed by early weaning.
We evaluated the effects of yerba mate treatment over 30 days on body weight, food intake, hypothalamic leptin action and inflammatory profile in adult rats that were weaned early.. To induce early weaning, the teats of lactating rats were blocked with a bandage to interrupt milk access for the last 3 days of lactation (EW group). Control offspring had free access to milk throughout lactation. On postnatal day (PN) 150, EW offspring were subdivided into: EW and M groups were treated with water and mate aqueous solution (1g/kg BW/day, gavage), respectively, for 30 days. Control offspring received water by gavage. On PN180, offspring were killed.. EW group presented hyperphagia; higher adiposity; higher NPY and TNF-α expression in the ARC nucleus; higher TNF-α and IL-1β levels in the adipose tissue; and lower IL-10 levels in the adipose tissue. These characteristics were normal in M group. As expected, the leptin injection in control offspring caused lower food intake. However, EW group exhibited no change in food intake after the leptin injection, indicating leptin resistance. In contrast, M group had a normal response to the leptin injection.. Thirty days of mate treatment prevented the development of hyperphagia, overweight, visceral obesity and central leptin resistance. This beneficial effect on the satiety of M offspring most likely occurred after the improvement of inflammatory markers in the hypothalamus and adipocytes, which suggests that Ilex paraguariensis plays an important role in the management of obesity by acting on the inflammatory profile. Topics: Adiposity; Animals; Body Weight; Drug Resistance; Eating; Female; Hypothalamus; Ilex paraguariensis; Inflammation; Injections; Leptin; Male; Obesity; Phytotherapy; Plant Preparations; Rats; Rats, Wistar; Weaning | 2014 |
Relationship between leptin and chronic inflammatory state in uremic patients.
To explore the relation between high leptin and inflammation in uremic patients.. A group of 73 uremic patients in dialysis center of our Department were assigned as uremic group; a group of 30 healthy persons who were examined over the same period were regarded as control group. The level of body mass index (BMI), serum creatinine (SCr), blood urea nitrogen (BUN), leptin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, and the neutrophils phagocytosis function were compared in two groups.. BMI and IL-10 of uremic group were lower than the control group. The levels of SCr, BUN, leptin, TNF-α, IL-6 of uremic group were higher than the control group (p < 0.05). The neutrophils phagocytosis function in uremic group significantly decreases, compared to control group (p < 0.05). Using one-way ANOVA analysis, serum leptin was positively correlated with the level of TNF-α, IL-6 (r = 0.58, 1.00 respectively, p < 0.05), and was negatively correlated with the level of IL-10 (r = -0.45, p < 0.05).. The high level of leptin and correlated inflammation were involved in the initiation and development of uremia; moreover, leptin was an important mediator. Topics: Adult; Aged; Body Mass Index; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Middle Aged; Neutrophils; Phagocytosis; Urea; Uremia; Young Adult | 2014 |
Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function.
Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH). Here, we show that microglia mediate this process and its functional impact. Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs), only the microglia undergo inflammatory activation, along with a buildup of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high. Topics: Animals; Astrocytes; Cells, Cultured; Dietary Fats; Eating; Energy Metabolism; Fatty Acids; Gliosis; Hypothalamus; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Neurons; Signal Transduction | 2014 |
Alterations in adipocytokines and cGMP homeostasis in morbid obesity patients reverse after bariatric surgery.
Obesity-associated nonalcoholic fatty liver disease (NAFLD), covering from simple steatosis to nonalcoholic steatohepatitis (NASH), is a common cause of chronic liver disease. Aberrant production of adipocytokines seems to play a main role in most obesity-associated disorders. Changes in adipocytokines in obesity could be mediated by alterations in cyclic GMP (cGMP) homeostasis. The aims of this work were: (1) to study the role of altered cGMP homeostasis in altered adipocytokines in morbid obesity, (2) to assess whether these alterations are different in simple steatosis or NASH, and (3) to assess whether these changes reverse in obese patients after bariatric surgery.. In 47 patients with morbid obesity and 45 control subjects, the levels in blood of adipocytokines, cGMP, nitric oxide (NO) metabolites, and atrial natriuretic peptide (ANP) were studied. Whether weight loss after a bariatric surgery reverses the changes in these parameters was evaluated.. NO metabolites and leptin increase (and adiponectin decreases) similarly in patients with steatosis or NASH, suggesting that these changes are due to morbid obesity and not to liver disease. Inflammation and cGMP homeostasis are affected both by morbid obesity and by liver disease. The increases in interleukin 6 (IL-6), interleukin 18 (IL-18), plasma cGMP, ANP, and the decrease in cGMP in lymphocytes are stronger in patients with NASH than with steatosis. All these changes reverse completely after bariatric surgery and weight loss, except IL-18.. Altered cGMP homeostasis seems to contribute more than inflammation to changes in leptin and adiponectin in morbid obesity. Topics: Adipokines; Adult; Bariatric Surgery; Body Mass Index; Case-Control Studies; Chronic Disease; Cyclic GMP; Fatty Liver; Female; Homeostasis; Humans; Inflammation; Interleukin-18; Interleukin-6; Leptin; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity, Morbid | 2013 |
Is the neck circumference an emergent predictor for inflammatory status in obese adults?
Plasminogen Activator Inhibitor 1 (PAI-1) is a prothrombotic adipokine involved in the coagulation cascade and fibrinolysis that associated with proinflammatory adipokines may increase the risk related to obesity. Anthropometric measures are commonly used in clinical practice and, currently, neck circumference (NC) has been used as a marker of cardiovascular risk that can favour inflammatory factors.. To verify the possible correlations between prothrombotic and pro/anti-inflammatory markers with anthropometric measurements in obese.. A total of 43 obese adults were enrolled. The variables include body mass, stature, body mass index (BMI), NC, chest circumference (CC), abdominal circumference (AC), hip circumference (HC), blood pressure and blood collection used to assess the level of adipokines.. The sample was stratified by BMI. PAI-1 levels were positively correlated with body mass (r=0.31, p=0.04), NC (r=0.43, p=0.004), CC (r=0.40, p=0.004), AC (r=0.37, p=0.01), diastolic blood pressure (r=0.35, p=0.03), leptin/adiponectin ratio (r=0.36, p=0.01) and negatively correlated with adiponectin (r=-0.34, p=0.02). In stepwise multiple linear regression analysis, NC showed to be an independent predictor to PAI-1 when adjusted for gender and BMI, according to the age (β=0.47, p=0.02 and β=0.42, p=0.02 respectively).. In conclusion, NC could be suggested as an independent predictor higher PAI-1. This association can be a new screening of persons at an enhanced cardiovascular risk and inflammation in this obese population, so useful in clinical practice. Topics: Adiponectin; Adult; Anthropometry; Blood Pressure; Body Mass Index; Female; Humans; Inflammation; Leptin; Male; Neck; Obesity; Plasminogen Activator Inhibitor 1 | 2013 |
Effect of glucose ingestion in plasma markers of inflammation and oxidative stress: analysis of 16 plasma markers from oral glucose tolerance test samples of normal and diabetic patients.
Sixteen plasma markers of inflammation and oxidative stress were measured during OGTT in 54 subjects. Leptin, RBP4, CRP, OPN, ANG, MDC, and MCSF concentrations significantly decreased during OGTT (P<0.05). IL6, IL8, and MCP3 concentrations significantly increased during OGTT (P<0.05). These results provide evidence that glucose ingestion affects systemic inflammation and oxidative stress. Topics: Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Chemokine CCL2; Chemokine CCL22; Diabetes Mellitus; Female; Glucose; Glucose Tolerance Test; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Osteopontin; Oxidative Stress; Retinol-Binding Proteins, Plasma; Ribonuclease, Pancreatic | 2013 |
Freeze-dried jaboticaba peel powder improves insulin sensitivity in high-fat-fed mice.
The peel of the native Brazilian fruit jaboticaba is rich in anthocyanins, which are known for their anti-obesity effects in animal models. The aim of the present study was to evaluate the effects of freeze-dried jaboticaba peel powder (FDJPP) on a number of metabolic parameters in a model of diet-induced obesity. Mice (n 8 per group) were initially fed on a high-fat diet (HFD, 35% w/w) for 4 weeks and then switched to a HFD supplemented with FDJPP (1, 2 or 4% w/w) for an additional 6 weeks. Energy intake, weight loss, glucose tolerance, insulin resistance and lipid profile were determined, and the results were evaluated using ANOVA and Tukey’s tests. The FDJPP exerted no protective effect on HFD-induced weight gain, hyperleptinaemia and glucose intolerance. However, the supplementation was effective to reduce insulin resistance, as evidenced in the insulin tolerance test, and subsequently confirmed by improved signal transduction through the insulin receptor/insulin receptor substrate-1/Akt/forkhead box protein pathway and by the attenuation of HFD-induced inflammation in the liver, verified by lower expressions of IL-1b and IL-6 and decreased phosphorylated IkB-a protein levels in all jaboticaba-treated mice. These results suggest that FDJPP may exert a protective role against obesity-associated insulin resistance. Topics: Analysis of Variance; Animals; Anthocyanins; Anti-Obesity Agents; Diet, High-Fat; Dietary Supplements; Fruit; Glucose Intolerance; Inflammation; Insulin; Insulin Resistance; Leptin; Liver; Male; Mice; Mice, Inbred Strains; Myrtaceae; Obesity; Phytotherapy; Plant Preparations; Powders; Receptor, Insulin; Signal Transduction; Weight Gain | 2013 |
Plasma concentration of soluble intercellular adhesion molecule-1 (sICAM-1) is elevated in type 2 diabetic patients, and sICAM-1 synthesis is associated with leptin-induced activation of the mitogen-activated protein kinase (MAPK) pathway.
The intercellular adhesion molecule-1 (ICAM-1) and leptin are important inflammatory biomarkers. We investigated whether plasma-soluble ICAM-1 levels were related to the diabetic nephropathy and systemic inflammation. One hundred forty-seven type 2 diabetic patients and 46 healthy control subjects were studied. Plasma sICAM-1 concentrations were significantly higher in the diabetic groups than controls and increased significantly as diabetic nephropathy advanced. Plasma sICAM-1 levels were positively correlated with body mass index, fasting and postprandial blood glucose, urinary albumin excretion, and negatively correlated with creatinine clearance. Multiple regression analysis showed that plasma leptin levels were associated with a significant increase in plasma sICAM-1 levels. In cultured HUVECs, leptin increased ICAM-1 production in a dose-dependent manner, and this stimulating effect of leptin on ICAM-1 expression was reversed by MEK inhibitor, PD98059. Overall, these findings suggest that activation of leptin synthesis in a diabetic environment promotes ICAM-1 activation via mitogen-activated protein kinase pathway in type 2 diabetic patients. Topics: Albuminuria; Blood Glucose; Body Mass Index; Cells, Cultured; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Enzyme Activation; Fasting; Female; Flavonoids; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Male; MAP Kinase Signaling System; Middle Aged; Mitogen-Activated Protein Kinases; Protein Kinase Inhibitors | 2013 |
Inflammatory markers and adipokines alter adipocyte-derived ASP production through direct and indirect immune interaction.
Obesity and related metabolic diseases are associated with chronic low-grade inflammation, characterized by increased pro-inflammatory proteins. Several studies have demonstrated increases in acylation stimulating protein (ASP) and its precursor protein C3 in obesity, diabetes and dyslipidemia. To evaluate the effects of acute inflammatory factors and adipokines on ASP production and potential mechanisms of action, 3T3-L1 adipocytes were treated for 24 h with adipokines, cytokines, macrophage-conditioned media and direct co-culture with J774 macrophages. ASP and C3 in the media were evaluated in relation to changes in adipocyte lipid metabolism (cellular triglyceride stores). Leptin, adiponectin, IL-10, LPS and TNF-α increased ASP production (151%, 153%, 190%, 318%, 134%, P<0.05, respectively,). C5a and RANTES (Regulated and normal T cell expressed and secreted) decreased ASP production ( - 34%, - 47%, P<0.05), which was also associated with a decrease in the precursor protein C3 ( - 39% to - 51%, P<0.01), while keratinocyte chemoattractant (KC; murine IL-8 ortholog) had no effect on ASP and C3 secretion. By contrast, apelin, omentin and visfatin also decreased ASP ( - 27%, - 49%, - 22%, P<0.05), but without changes in precursor protein C3 secretion. Macrophage-conditioned media alone had little effect on C3 or ASP, while co-culture of adipocytes with macrophages markedly increased ASP and C3 production (272%, 167%, P<0.05). These in vitro results suggest various metabolic hormones and inflammatory factors can affect ASP production through increased precursor C3 production and/or by changing the rate of C3 conversion to ASP. As an adipokine, ASP could constitute a new link between adipocytes and macrophages. Topics: 3T3-L1 Cells; Adipocytes; Adipokines; Adiponectin; Animals; Biomarkers; Cell Line; Chemokine CCL5; Coculture Techniques; Complement C3a; Complement C5a; Culture Media, Conditioned; Inflammation; Interleukin-10; Leptin; Lipid Metabolism; Lipopolysaccharides; Macrophages; Mice; Tumor Necrosis Factor-alpha | 2013 |
Leptin and its association with somatic depressive symptoms in patients with the metabolic syndrome.
This study aimed to determine the association between circulating leptin levels and total depressive symptoms as well as depressive symptom dimensions (cognitive and somatic) after controlling for important confounding factors.. The study sample was comprised of 135 participants with the metabolic syndrome. Depressive symptoms were measured using the Beck Depression Inventory-II. Leptin was measured using a leptin-specific enzyme immunoassay. Inflammation was assessed using C-reactive protein and interleukin-6 levels.. Leptin was significantly associated with somatic depressive symptoms (β = 0.33, P = 0.018), but not total depressive symptoms (β = 0.27, P = 0.067) or cognitive depressive symptoms (β = 0.21, P = 0.182), after controlling for age, gender, body mass index, and insulin resistance. Further adjustment for C-reactive protein and interleukin-6 levels did not alter the relationship (β = 0.32, P = 0.023) between circulating leptin levels and somatic depressive symptoms.. Leptin is independently associated with somatic depressive symptoms in patients with the metabolic syndrome. Topics: Adult; Body Mass Index; C-Reactive Protein; Depression; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Psychiatric Status Rating Scales; Risk Factors | 2013 |
Resveratrol has inhibitory effects on the hypoxia-induced inflammation and angiogenesis in human adipose tissue in vitro.
Hypoxia modulates the production of proteins involved in e.g. inflammation, angiogenesis and glucose utilization and hypoxia may therefore be an important factor underlying adipose tissue dysfunction in obesity. Resveratrol (RSV) is a natural polyphenolic compound and has been shown to have powerful anti-inflammatory effects and beneficial effects on several obesity-related complications. Thus, in the present study we investigated whether RSV has effects on hypoxic markers (GLUT-1, VEGF), hypoxia-induced key markers of inflammation (IL8, IL6), and leptin in human adipose tissue in vitro. Hypoxia was induced by incubating human adipose tissue fragments with 1% O2 for 24h as compared to 21% O2 The gene expressions were investigated by RT-PCR and protein release by Elisa. Hypoxia increases the expression of glucose transporter-1 (GLUT-1) (19-fold, p<0.001), vascular endothelial growth factor (VEGF) (10-fold, p<0.05), interleukin-8 (IL8) (8-fold, p<0.05), interleukin-6 (IL6) (5-fold, p<0.05) and leptin (9-fold). The protein levels of VEGF released to the medium was increased (8-fold, p<0.01) by hypoxia. RSV dose-dependently inhibited several of these hypoxia-induced expressions and at a concentration of 50 μM RSV almost completely inhibited the hypoxic responses at the above mentioned gene expression levels (p<0.05-p<0.001) and significantly attenuated the hypoxia-induced protein releases by 50-60%. These results demonstrate that hypoxia induces extensive changes in human adipose tissue in the expression and release of inflammation and angiogenesis-related adipokines. In addition the inhibition of hypoxia-mediated inflammation and angiogenesis might represent a novel mechanism of RSV in preventing obesity-related pathologies. Topics: Adipose Tissue; Adult; Angiogenesis Inhibitors; Anti-Inflammatory Agents; Female; Glucose Transporter Type 1; Humans; Hypoxia; In Vitro Techniques; Inflammation; Interleukin-6; Interleukin-8; Leptin; Neovascularization, Physiologic; Resveratrol; RNA, Messenger; Stilbenes; Vascular Endothelial Growth Factor A | 2013 |
Accelerometry-measured physical activity and inflammation after gestational diabetes.
Gestational diabetes mellitus (GDM) is associated with adverse metabolic outcomes after delivery. Physical activity practice improves the inflammatory profile; however, whether this association exists in women with prior GDM remains unknown. Our objective was to examine the cardiometabolic and inflammatory risk factors associated with accelerometer-based measures of physical activity in women with prior GDM.. Ninety-six women who had GDM between 2003 and 2010 were tested 2.9 ± 2.2 yr after delivery. The physical activity practice was measured with ActiGraph GT3X (ActiGraph™, Pensacola, FL) accelerometers worn ≥ 5 d, and the time spent weekly in moderate to vigorous physical activity (MVPA) was derived. The waist circumference was measured and the inflammatory marker or cytokine concentrations were measured in fasting plasma by the xMAP technology using the Bio-Plex 200 system. The lipid profile was also measured from fasting blood samples.. Only 31% of women accumulated at least 150 min of MVPA per week. No association was observed between the MVPA practice and any of the metabolic measurements in the whole group of women. The MVPA did not differ in groups stratified by waist circumference <88 or ≥ 88 cm. In women with waist circumference <88 cm, the MVPA was negatively correlated with circulating concentrations of C-reactive protein (r = -0.51, P = 0.006), leptin (r = -0.40, P = 0.008), plasminogen activator inhibitor-1 (r = -0.32, P = 0.04), and triglycerides (r = -0.44, P = 0.003). No association was seen with plasma interleukin-6; tumor necrosis factor-α; and total, LDL, or HDL cholesterol concentrations.. These analyses suggest that in the years after delivery, longer time spent in MVPA practice is associated with a lower cardiometabolic risk only in women with prior GDM who do not have abdominal obesity. Topics: Accelerometry; Adolescent; Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Cytokines; Diabetes, Gestational; Female; Humans; Inflammation; Leptin; Lipids; Metabolic Diseases; Motor Activity; Obesity, Abdominal; Plasminogen Activator Inhibitor 1; Pregnancy; Risk Factors; Young Adult | 2013 |
Hyperresistinemia is associated with postmenopausal breast cancer.
The constellation of obesity, insulin resistance, and serum adipocytokine levels is associated with the risk and prognosis of postmenopausal breast cancer (PBC). Altered secretion of resistin may underlie the association between overweight/obesity and PBC. We thus explored the association of serum resistin with PBC, taking into account established risk factors, including adipokines and anthropometric, metabolic, and inflammatory markers.. In a case-control study, we studied 102 postmenopausal women with pathologically confirmed, incident invasive breast cancer and 102 control participants matched on age and time of diagnosis between 2003 and 2010 at the Veterans' Administration General Hospital of Athens (NIMTS Hospital). Serum resistin, adiponectin, leptin, metabolic (homeostasis model assessment score of insulin resistance) and inflammatory (tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein) parameters, and tumor markers (carcinoembryonic antigen and CA 15-3) were determined.. The mean serum resistin level was significantly higher in case participants than in control participants (P < 0.001) in both univariate and multivariable analyses, adjusting for age, date of diagnosis, education, family history of cancer, use of exogenous hormones, alcohol consumption, smoking status, physical activity, reproductive markers, metabolic markers, anthropometric (body mass index and weight circumference) markers, inflammatory markers, and adipokines (odds ratio, 1.17; 95% CI, 1.03-1.34; P = 0.02). In case participants, resistin level correlated significantly with tumor markers and inflammatory parameters, but not with metabolic and anthropometric variables.. Further prospective, longitudinal, and mechanistic studies are needed to determine whether hyperresistinemia is involved in the development of PBC or reflects changes during PBC progression and therefore could be used as a biomarker for PBC. Targeting resistin inhibition could be an effective therapeutic strategy in breast cancer by down-regulating the inflammatory microenvironment in breast tissue. Topics: Adipokines; Aged; Aged, 80 and over; Biomarkers; Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; C-Reactive Protein; Case-Control Studies; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Middle Aged; Obesity; Postmenopause; Prognosis; Resistin; Risk Factors; Tumor Necrosis Factor-alpha | 2013 |
Fatty liver accompanies an increase in lactobacillus species in the hind gut of C57BL/6 mice fed a high-fat diet.
High-fat (HF) diets can produce obesity and have been linked to the development of nonalcoholic fatty liver disease and changes in the gut microbiome. To test the hypothesis that HF feeding increases certain predominant hind gut bacteria and development of steatohepatitis, C57BL/6 mice were fed an HF (45% energy) or low-fat (LF) (10% energy) diet for 10 wk. At the end of the feeding period, body weights in the HF group were 34% greater than those in the LF group (P < 0.05). These changes were associated with dramatic increases in lipid droplet number and size, inflammatory cell infiltration, and inducible nitric oxide (NO) synthase protein concentration in the livers of mice fed the HF diet. Consistent with the fatty liver phenotype, plasma leptin and tumor necrosis factor-α concentrations were also elevated in mice fed the HF diet, indicative of chronic inflammation. Eight of 12 pairs of polymerase chain reaction (PCR) primers for bacterial species that typically predominate hind gut microbial ecology generated specific PCR products from the fecal DNA samples. The amount of DNA from Lactobacillus gasseri and/or Lactobacillus taiwanensis in the HF group was 6900-fold greater than that in the LF group. Many of these bacteria are bile acid resistant and are capable of bile acid deconjugation. Because bile acids are regulators of hepatic lipid metabolism, the marked increase of gut L. gasseri and/or L. taiwanensis species bacteria with HF feeding may play a role in development of steatohepatitis in this model. Topics: Animals; Bile Acids and Salts; Body Weight; Diet, High-Fat; Dietary Fats; DNA, Bacterial; Energy Intake; Fatty Liver; Feces; Inflammation; Intestine, Large; Lactobacillus; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; Polymerase Chain Reaction; Tumor Necrosis Factor-alpha | 2013 |
Inflammatory "adiposopathy" in major amputation patients.
Much has been made of obesity's health impact, largely founded on data regarding patient weight and circulating adipose-derived mediator levels. Paradoxically, a "healthy obese" state exists, but substantial knowledge gaps also exist regarding human adipose-phenotype determinants. Surgical major amputation (AMP) patients are the "sickest-of-the-sick." Conversely, elective knee replacement (TKR) is reserved for patients who expect continued health and longevity. To delineate human adipose biology variability and clinical determinants, we studied fresh subcutaneous adipose from AMP patients, using TKR patients as controls. We hypothesized that AMP patients would display a pro-inflammatory adipokine signature, and that certain clinical conditions (diabetes, hypertension, hyperlipidemia, high BMI, uremia) would independently drive elevated adipose inflammation.. AMP (n = 29) and TKR (n = 20) adipose tissue samples and clinical data were collected prospectively, and protein was isolated and analyzed for 8 adipose-related mediators. Statistical analyses included Wilcoxon's rank sum test, Fisher's exact test, and multiple linear regression modeling of clinical parameter predictors of mediator expression.. Interleukin-(IL)-6, IL-8, leptin, resistin, and PAI-1 were differentially expressed (up to 200-fold) between AMP/TKR cohorts. Key clinical parameters that associated with protein levels of adipose phenotype included age, gender, hypertension, hyperlipidemia, congestive heart failure, cerebrovascular disease, renal disease, and warfarin, statin, and insulin use. BMI failed to be predictive.. AMP patients display adiposopathy with a pro-inflammatory adipose phenotypic signature compared with TKR controls. BMI fails to predict phenotype, yet other clinical conditions, such as age, hyperlipidemia, and renal insufficiency, do drive adipokine expression. Understanding human adipose phenotypic determinants stands as a fundamental priority when future studies dissect the interplay between adipose biology and surgical diseases/outcomes. Topics: Age Factors; Aged; Amputation, Surgical; Arthroplasty, Replacement, Knee; Cardiovascular Diseases; Case-Control Studies; Chronic Disease; Comorbidity; Cytokines; Diabetes Mellitus; Elective Surgical Procedures; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Leptin; Linear Models; Male; Middle Aged; Obesity; Peripheral Vascular Diseases; Phenotype; Plasminogen Activator Inhibitor 1; Polypharmacy; Prospective Studies; Resistin; Sex Factors; Subcutaneous Fat | 2013 |
Ghrelin-leptin network influences serum chitinase 3-like protein 1 (YKL-40) levels in obese prepubertal children.
This study aimed to investigate any possible interactions between hormonal regulators of weight gain and markers of subclinical inflammation in childhood obesity. Forty-one obese prepubertal children and 41 age- and gender-matched lean controls were included. Children were classified as obese or non-obese according to international age- and gender-specific body mass index (BMI) cutoff points defined by the International Obesity Task Force to define childhood obesity. Anthropometric measurements, serum insulin, chitinase 3-like protein (YKL-40), ghrelin and leptin levels as well as plasma glucose in the fasting state were determined.. Obese children as compared with controls had higher YKL-40 (50.7±15.2 vs 41.0±10.5 ng/ml, p=0.003), higher leptin (33.8±16.0 vs 9.7±7.5 ng/ml, p<0.001) and lower ghrelin serum levels (871.4±368.0 vs 1417.6±387.3 pg/ml, p<0.001). The obese children with ghrelin levels above median (43.8±10.2 ng/ml) as compared to those with ghrelin below median (57.2±16.6 ng/ml) presented lower serum YKL-40 levels (p=0.009), indicating more severe inflammation with lower levels of ghrelin. By contrast, although the obese children with leptin levels above median (49.7±16.3 ng/ml) presented lower serum YKL-40 levels as compared to those with leptin levels below median (51.6±14.6 ng/ml), this difference did not reach the level of statistical significance (p=0.726). Moreover, serum YKL-40 levels were significantly correlated with ghrelin (r=-0.359, p=0.014) but not with leptin levels (r=0.169, p=0.261). A significant negative correlation between ghrelin and leptin levels was also found (r=-0.276, p=0.041). These findings remained unchanged for obese, when analyses were done separately, whereas the significance of correlations was lost for non-obese subjects.. Ghrelin-leptin network had an impact on serum YKL-40 levels in obese prepubertal children; upregulation of YKL-40 secretion seems to be a consequence of reduced ghrelin rather than elevated leptin concentrations. Topics: Adipokines; Child; Child, Preschool; Chitinase-3-Like Protein 1; Ghrelin; Humans; Inflammation; Lectins; Leptin; Pediatric Obesity; Up-Regulation | 2013 |
Imbalanced network biomarkers for traditional Chinese medicine Syndrome in gastritis patients.
Cold Syndrome and Hot Syndrome are thousand-year-old key therapeutic concepts in traditional Chinese medicine (TCM), which depict the loss of body homeostasis. However, the scientific basis of TCM Syndrome remains unclear due to limitations of current reductionist approaches. Here, we established a network balance model to evaluate the imbalanced network underlying TCM Syndrome and find potential biomarkers. By implementing this approach and investigating a group of chronic superficial gastritis (CSG) and chronic atrophic gastritis (CAG) patients, we found that with leptin as a biomarker, Cold Syndrome patients experience low levels of energy metabolism, while the CCL2/MCP1 biomarker indicated that immune regulation is intensified in Hot Syndrome patients. Such a metabolism-immune imbalanced network is consistent during the course from CSG to CAG. This work provides a new way to understand TCM Syndrome scientifically, which in turn benefits the personalized medicine in terms of the ancient medicine and complex biological systems. Topics: Adult; Biomarkers; Chemokine CCL2; Chronic Disease; Cluster Analysis; Diagnosis, Differential; Energy Metabolism; Female; Gastric Mucosa; Gastritis; Gastritis, Atrophic; Gene Expression Profiling; Gene Regulatory Networks; Humans; Immunity; Immunohistochemistry; Inflammation; Leptin; Male; Medicine, Chinese Traditional; Middle Aged; Models, Genetic; Principal Component Analysis; Syndrome | 2013 |
Serum IL-12 is increased in Mexican obese subjects and associated with low-grade inflammation and obesity-related parameters.
Interleukin-(IL-) 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammation and obesity-related parameters. A total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese subjects participated in the study. Circulating levels of IL-12, tumor necrosis factor-alpha (TNF- α ), leptin, insulin, glucose, total cholesterol, and triglyceride were measured after overnight fasting in all of the study subjects. Waist circumference and body fat percentage were recorded for all the participants. Serum IL-12 was significantly higher in overweight and obese individuals than in normal weight controls. Besides being strongly related with body mass index (r = 0.5154), serum IL-12 exhibited a significant relationship with abdominal obesity (r = 0.4481), body fat percentage (r = 0.5625), serum glucose (r = 0.3158), triglyceride (r = 0.3714), and TNF- α (r = 0.4717). Thus, serum levels of IL-12 are increased in overweight and obese individuals and show a strong relationship with markers of low-grade inflammation and obesity in the Mexican adult population. Further research is needed to understand the role of IL-12 in developing obesity-associated alterations in humans. Topics: Adult; Female; Humans; Inflammation; Insulin; Interleukin-12; Leptin; Male; Obesity; Triglycerides; Tumor Necrosis Factor-alpha; Young Adult | 2013 |
Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure.
The molecular mechanisms involved in the development of obesity and related complications remain unclear. Here, we report that obese mice and human subjects have increased activity of neutrophil elastase (NE) and decreased serum levels of the NE inhibitor α1-antitrypsin (A1AT, SerpinA1). NE null (Ela2(-/-)) mice and A1AT transgenic mice were resistant to high-fat diet (HFD)-induced body weight gain, insulin resistance, inflammation, and fatty liver. NE inhibitor GW311616A reversed insulin resistance and body weight gain in HFD-fed mice. Ela2(-/-) mice also augmented circulating high molecular weight (HMW) adiponectin levels, phosphorylation of AMP-activated protein kinase (AMPK), and fatty acid oxidation (FAO) in the liver and brown adipose tissue (BAT) and uncoupling protein (UCP1) levels in the BAT. These data suggest that the A1AT-NE system regulates AMPK signaling, FAO, and energy expenditure. The imbalance between A1AT and NE contributes to the development of obesity and related inflammation, insulin resistance, and liver steatosis. Topics: Adiponectin; Adipose Tissue, Brown; alpha 1-Antitrypsin; AMP-Activated Protein Kinase Kinases; Animals; Diet, High-Fat; Energy Metabolism; Fatty Acids; Fatty Liver; Hep G2 Cells; Humans; Inflammation; Insulin Resistance; Ion Channels; Leptin; Leukocyte Elastase; Liver; Metabolome; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Mice, Transgenic; Mitochondrial Proteins; Obesity; Oxidation-Reduction; Phosphorylation; Piperidines; Protein Kinases; Uncoupling Protein 1; Weight Gain | 2013 |
Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology.
Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.. Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.. Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.. Our results support the role of cytokines in the pathophysiology of CFS. Topics: Adult; Algorithms; Biomarkers; Body Mass Index; Case-Control Studies; Cytokines; Fatigue; Fatigue Syndrome, Chronic; Female; Humans; Inflammation; Leptin; Longitudinal Studies; Middle Aged; Reproducibility of Results; Treatment Outcome | 2013 |
Dietary supplementation with Agaricus blazei murill extract prevents diet-induced obesity and insulin resistance in rats.
Dietary supplement may potentially help to fight obesity and other metabolic disorders such as insulin-resistance and low-grade inflammation. The present study aimed to test whether supplementation with Agaricus blazei murill (ABM) extract could have an effect on diet-induced obesity in rats.. Wistar rats were fed with control diet (CD) or high-fat diet (HF) and either with or without supplemented ABM for 20 weeks.. HF diet-induced body weight gain and increased fat mass compared to CD. In addition HF-fed rats developed hyperleptinemia and insulinemia as well as insulin resistance and glucose intolerance. In HF-fed rats, visceral adipose tissue also expressed biomarkers of inflammation. ABM supplementation in HF rats had a protective effect against body weight gain and all study related disorders. This was not due to decreased food intake which remained significantly higher in HF rats whether supplemented with ABM or not compared to control. There was also no change in gut microbiota composition in HF supplemented with ABM. Interestingly, ABM supplementation induced an increase in both energy expenditure and locomotor activity which could partially explain its protective effect against diet-induced obesity. In addition a decrease in pancreatic lipase activity is also observed in jejunum of ABM-treated rats suggesting a decrease in lipid absorption.. Taken together these data highlight a role for ABM to prevent body weight gain and related disorders in peripheral targets independently of effect in food intake in central nervous system. Topics: Agaricus; Animals; Biomarkers; Blood Glucose; Body Composition; Calorimetry, Indirect; Diet, High-Fat; Dietary Fats; Dietary Supplements; Energy Metabolism; Gastrointestinal Tract; Glucose Intolerance; Inflammation; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipase; Male; Microbiota; Obesity; Probiotics; Rats; Rats, Wistar; Subcutaneous Fat, Abdominal; Weight Gain | 2013 |
PPAR agonist-induced reduction of Mcp1 in atherosclerotic plaques of obese, insulin-resistant mice depends on adiponectin-induced Irak3 expression.
Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3) and decreased monocyte chemoattractant protein-1 (Mcp1) expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM), we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3(-/-) BMDM) resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3(-/-) BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists. Topics: Adipocytes; Adiponectin; Animals; Chemokine CCL2; Diet, High-Fat; Fenofibrate; Inflammation; Insulin; Insulin Resistance; Interleukin-1 Receptor-Associated Kinases; Leptin; Macrophages; Mice; Mice, Inbred C57BL; Obesity; Peroxisome Proliferator-Activated Receptors; Plaque, Atherosclerotic; PPAR alpha; PPAR gamma; Rosiglitazone; Thiazolidinediones | 2013 |
Lycopene supplementation modulates plasma concentrations and epididymal adipose tissue mRNA of leptin, resistin and IL-6 in diet-induced obese rats.
Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levels in vivo in obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C, n 6) ora hyperenergetic diet (DIO, n 12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n 6) and DIO supplemented with lycopene (DIO + L, n 6). The animals received maize oil (C and DIO) or lycopene (DIO + L, 10 mg/kg body weight(BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1(MCP-1), TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO + L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin and IL-6 gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression of MCP-1 in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity. Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Carotenoids; Dietary Supplements; Energy Intake; Epididymis; Inflammation; Interleukin-6; Leptin; Lycopene; Male; Obesity; Phytotherapy; Plant Extracts; Random Allocation; Rats; Rats, Wistar; Resistin; RNA, Messenger | 2013 |
Adipocytokines, inflammation, and breast cancer risk in postmenopausal women: a prospective study.
Obesity is a known risk factor for postmenopausal breast cancer; it has been postulated that adipocytokines may mediate this association. We explored the relationship between three markers altered by obesity: leptin, adiponectin, and soluble tumor necrosis factor receptor 2 (sTNF-R2), an inflammatory marker, with breast cancer risk in postmenopausal women. A nested case-control study of postmenopausal women was conducted within CLUE II, a prospective population-based cohort. Baseline plasma levels of leptin, adiponectin, and sTNF-R2 were assayed in 272 female breast cancer cases and 272 controls matched on age, date, and hour of blood draw. Conditional logistic regression was used to estimate matched odds ratios (OR) and 95% confidence intervals (CI). sTNF-R2 and leptin were independently positively associated with breast cancer risk in adjusted models. The OR for breast cancer comparing the highest to lowest tertile was 2.44 (95% CI: 1.30-4.58) for sTNF-R2 and 1.98 (95% CI: 1.20-3.29) for leptin. While higher levels of adiponectin were protective (OR for the lowest tertile = 1.63; 95% CI: 1.02-2.60), there was no dose response. A 20% reduction in the breast cancer risk associated with overweight/obesity was observed when sTNF-R2 alone was included in multivariable models. Including both sTNF-R2 and adiponectin in the models resulted in a 29% reduction in the OR. Adipocytokines and sTNF-R2 are important factors in the etiology of postmenopausal breast cancer due to adiposity. This study informs our understanding of the relationship between obesity, inflammation, and postmenopausal breast cancer and identifies potential biomarkers. Topics: Adipokines; Breast Neoplasms; Case-Control Studies; Cohort Studies; Female; Humans; Inflammation; Leptin; Middle Aged; Nitriles; Obesity; Postmenopause; Prospective Studies; Risk Factors | 2013 |
Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity.
The aim of this study was to investigate the effects of bariatric surgery on small artery function and the mechanisms underlying this.. In lean healthy humans, perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arteries, but this is lost in obesity-associated conditions such as the metabolic syndrome and type II diabetes where there is evidence of adipocyte inflammation and increased oxidative stress.. Segments of small subcutaneous artery and perivascular fat were harvested from severely obese individuals before (n = 20) and 6 months after bariatric surgery (n = 15). Small artery contractile function was examined in vitro with wire myography, and perivascular adipose tissue (PVAT) morphology was assessed with immunohistochemistry.. The anticontractile activity of PVAT was lost in obese patients before surgery when compared with healthy volunteers and was restored 6 months after bariatric surgery. In vitro protocols with superoxide dismutase and catalase rescued PVAT anticontractile function in tissue from obese individuals before surgery. The improvement in anticontractile function after surgery was accompanied by improvements in insulin sensitivity, serum glycemic indexes, inflammatory cytokines, adipokine profile, and systolic blood pressure together with increased PVAT adiponectin and nitric oxide bioavailability and reduced macrophage infiltration and inflammation. These changes were observed despite the patients remaining severely obese.. Bariatric surgery and its attendant improvements in weight, blood pressure, inflammation, and metabolism collectively reverse the obesity-induced alteration to PVAT anticontractile function. This reversal is attributable to reductions in local adipose inflammation and oxidative stress with improved adiponectin and nitric oxide bioavailability. Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Arteries; Bariatric Surgery; Blood Glucose; Blood Pressure; C-Reactive Protein; Case-Control Studies; Catalase; Cytokines; Free Radical Scavengers; Glycated Hemoglobin; Glycemic Index; Humans; Immunohistochemistry; Inflammation; Insulin; Insulin Resistance; Insulin-Secreting Cells; Leptin; Macrophages; Middle Aged; Nitric Oxide; Norepinephrine; Obesity; Resistin; Subcutaneous Tissue; Superoxide Dismutase; Vasoconstriction; Vasoconstrictor Agents | 2013 |
Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults.
Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population-based cohort of obese adults.. Among obese participants in the Dallas Heart Study, we examined the cross-sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation (n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography (n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index.. In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA-IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number (p < 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque (p < 0.001 for each). VAT independently associated with C-reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA-IR were significant in univariable analyses but attenuated after multivariable adjustment.. VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub-phenotypes with heterogeneous metabolic and atherosclerosis risk. Topics: Adiponectin; Adult; Atherosclerosis; Biomarkers; Body Fat Distribution; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Dyslipidemias; Female; Heart Diseases; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Obesity; Phenotype; Subcutaneous Fat | 2013 |
Zinc deficiency augments leptin production and exacerbates macrophage infiltration into adipose tissue in mice fed a high-fat diet.
Zinc (Zn) deficiency and obesity are global public health problems. Zn deficiency is associated with obesity and comorbid conditions that include insulin resistance and type 2 diabetes. However, the function of Zn in obesity remains unclear. Using a mouse model of combined high-fat and low-Zn intake (0.5-1.5 mg/kg), we investigated whether Zn deficiency exacerbates the extent of adiposity as well as perturbations in metabolic and immune function. C57BL/6 mice were randomly assigned to receive either a high-fat diet (HFD) or a control (C) diet for 6 wk, followed by further subdivision into 2 additional groups fed Zn-deficient diets (C-Zn, HFD-Zn), along with a C diet and an HFD, for 3 wk (n = 8-9 mice/group). The extent of visceral fat, insulin resistance, or systemic inflammation was unaffected by Zn deficiency. Strikingly, Zn deficiency significantly augmented circulating leptin concentrations (HFD-Zn vs. HFD: 3.15 ± 0.16 vs. 2.59 ± 0.12 μg/L, respectively) and leptin signaling in the liver of obese mice. Furthermore, gene expression of macrophage-specific markers ADAM8 (A disintegrin and metalloproteinase domain-containing protein 8) and CD68 (cluster of differentiation 68) was significantly greater in adipose tissue in the HFD-Zn group than in the HFD group, as confirmed by CD68 protein analysis, indicative of increased macrophage infiltration. Inspection of Zn content and mRNA profiles of all Zn transporters in the adipose tissue revealed alterations of Zn metabolism to obesity and Zn deficiency. Our results demonstrate that Zn deficiency increases leptin production and exacerbates macrophage infiltration into adipose tissue in obese mice, indicating the importance of Zn in metabolic and immune dysregulation in obesity. Topics: Adipokines; Adiposity; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Blotting, Western; Cytokines; Diabetes Mellitus, Type 2; Diet, High-Fat; Immunohistochemistry; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Leptin; Liver; Macrophages; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Mice, Obese; NF-kappa B; NIH 3T3 Cells; Obesity; PPAR gamma; Real-Time Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Transfection; Zinc | 2013 |
Leptin induces secretion of pro-inflammatory cytokines by human keratinocytes in vitro--a possible reason for increased severity of psoriasis in patients with a high body mass index.
Investigations about prevalence of obesity in psoriasis patients are increased nowadays. Higher serum levels of leptin in patients with psoriasis who are overweight or obese suggest that leptin may serve as a molecular link between psoriasis and metabolic comorbidities. However, the pathological functions of leptin in psoriasis are not clearly understood. We investigated the influence of being overweight or obese on the risk of psoriasis, and the relationship between serum leptin levels and the severity of psoriasis in Chinese Han patients. We also investigated biological effects of leptin on the proliferation and secretion of pro-inflammatory cytokines by human keratinocytes in vitro. Obesity was a significant risk factor for psoriasis in the Chinese Han population; however, we did not observe a significant correlation between Psoriasis Area and Severity Index (PASI) and body mass index (BMI). We observed a positive correlation between the serum leptin level and PASI in overweight and obese male patients with psoriasis. Strong leptin immunoreactivity was detected in the epidermis of psoriatic lesions, particularly in keratinocytes. Leptin significantly increased the proliferation and secretion of pro-inflammatory cytokines by keratinocytes in vitro. In conclusion, this study suggests leptin as a novel molecular link between psoriasis and obesity, which may help to explain the more server conditions of psoriasis in patients with obesity. Topics: Adolescent; Adult; Aged; Body Mass Index; Cell Cycle; Cell Proliferation; Cells, Cultured; China; Cytokines; Female; Gene Expression Regulation; Humans; Inflammation; Keratinocytes; Leptin; Male; Middle Aged; Obesity; Overweight; Psoriasis; Young Adult | 2013 |
NAG-1/GDF15 transgenic mouse has less white adipose tissue and a reduced inflammatory response.
NAG-1/GDF15 is a TGF- β superfamily member with poorly characterized biological activity proposed to inhibit inflammatory cytokine production. Transgenic mice expressing human NAG-1/GDF15 (NAG-1 (Tg/Lox) ) are leaner with lower body weight and are resistant to chemically or genetically induced intestinal tumors. Because of the link between obesity, inflammation, and cancer, we examined whether these mice exhibit a reduced response to inflammatory stimuli. The NAG-1 (Tg/Lox) mice had a reduced inflammatory response to LPS based on the serum levels of cytokines KC, IL-6, MCP-1, and TNF α . In contrast to literature reports and our in vivo results, NAG-1 did not inhibit LPS-induced cytokine expression in vitro in RAW264.7 cells, mouse peritoneal macrophages, or mouse liver Kupffer cells, suggesting that NAG-1/GDF15 does not directly inhibit LPS-induced inflammatory cytokine production. However, NAG-1 (Tg/Lox) mice have less white adipose tissue, the major source of inflammatory adipokines including leptin. Basal and LPS-treated serum leptin and mRNA levels in the adipose tissue of NAG-1 (Tg/Lox) mice were lower than those in WT mice. We propose that the reduced white adipose tissue and reduced leptin expression may be responsible, in part, for the reduced inflammatory response to LPS and the decrease in intestinal tumors observed in NAG-1 (Tg/Lox) mice. Topics: Adipose Tissue, White; Animals; Cytokines; Female; Growth Differentiation Factor 15; Humans; Inflammation; Leptin; Lipopolysaccharides; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic | 2013 |
Whole-body cryostimulation as an effective method of reducing low-grade inflammation in obese men.
This study was aimed to evaluate anti-inflammatory effect of the whole body cryostimulation in obese men. Fourteen subjects (BMI >30 kg m(-2)), divided into two subgroups according to cardiorespiratory fitness: higher (HCF) or lower (LCF), have been exposed to 10 sessions in a cryogenic chamber (-110 °C). Blood samples were collected before, 30 min and 24 h after the first, fifth and last cryostimulation. Coldness exposures affected blood cytokine profile; however, the response depended on subjects' fitness capacity. Concentrations of pro-inflammatory cytokines in the LCF decreased by 19, 6.8, and 7.4 % in IL-6, resistin, and visfatin, respectively. TNFα in the LCF dropped 4.3-fold compared to baseline, while in the HCF, changes were smaller, yet significant. Anti-inflammatory cytokine IL-10 increased in both groups. No changes in adiponectin and leptin were observed in either group. Obtained results suggest that whole body cryostimulation can be a supplementary method for obese in reducing systemic inflammation. Topics: Adiponectin; Adult; Cold Temperature; Humans; Inflammation; Interleukin-10; Interleukin-6; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Obesity; Tumor Necrosis Factor-alpha | 2013 |
Characterization of a novel proinflammatory effect mediated by BK and the kinin B₂ receptor in human preadipocytes.
Obesity and adipose tissue contribute to local and systemic inflammation. However the role of the inflammatory mediator bradykinin (BK) in this context is not known. We therefore evaluated the effect of BK on adipokines secretion in human preadipocytes during the course of differentiation and characterized the receptors involved. Results obtained from antibody array and ELISA experiments showed that several adipokines are released by human preadipocytes under basal conditions while BK specifically stimulated the production of interleukin(IL)-6 and IL-8. The effect of BK diminished with the progression of differentiation, being almost inactive on adipocytes. In preadipocytes, BK also induced a rapid and transient [Ca²⁺](i) mobilization, a rapid and sustained increase in ERK1/2 activation and enhanced forskolin-stimulated cAMP accumulation. BK was without effect on cell proliferation and viability as assessed by bromodeoxyuridine incorporation, WST-1 conversion, or lactate dehydrogenase leakage and was without effect on adipogenesis as measured by triglyceride accumulation, GPDH activity and leptin release. The B₁ receptor agonist, Lys-[des-Arg⁹]-BK, displayed poor activity or was without effect while overall BK effects were prevented by the selective B₂ receptor antagonist, fasitibant chloride, but not by the B₁ selective antagonist, Lys-[Leu⁸][des-Arg⁹]-BK. Immunoblot analysis and immunofluorescence studies showed that the kinin B₂ receptor was essentially expressed at the beginning of the differentiation program. In conclusion, human preadipocytes expressed kinin B₂ receptors linked to multiple signaling pathways, IL-6 and IL-8 production, and BK proinflammatory response in adipose tissue could be prevented by fasitibant chloride. Topics: Adipocytes; Adipokines; Bradykinin; Calcium; Cell Proliferation; Cell Survival; Cells, Cultured; Cyclic AMP; Cytokines; Glycerolphosphate Dehydrogenase; Humans; Inflammation; Interleukin-6; Interleukin-8; Leptin; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Receptor, Bradykinin B2; Signal Transduction; Stem Cells; Triglycerides | 2013 |
Quercetin suppresses inflammation by reducing ERK1/2 phosphorylation and NF kappa B activation in Leptin-induced Human Umbilical Vein Endothelial Cells (HUVECs).
High concentrations of plasma leptin and the release of pro-inflammatory cytokines in leptin-resistance in obesity have been reported to trigger endothelial dysfunction. The objective of this study was to elucidate the role of quercetin in modulating leptin-induced inflammation as assessed by the levels of Ob-Ra expression, ERK1/2 phosphorylation, NF-kappa B activation and TNF-alpha secretion in umbilical vein endothelial cells (HUVECs) in vitro.. HUVECs were exposed to either control levels (0 ng/ml) or 500 ng/mL leptin (L) for 48 hours, followed by control or 125 uM quercetin (Q) for another 6 h. The experimental groups were as follows: L0Q0, L0Q125, L500Q0, L500Q125. The presence of the short chain leptin receptor isoform Ob-Ra in HUVECs was determined by Western blot and immunocytochemistry analyses. Ob-Ra expression, ERK1/2 phosphorylation, NF-kappa B activation and TNF-alpha secretion were quantified by ELISA, and NF-kappa B activationby immunofluorescence staining. Our results showed that Ob-Ra expression, ERK1/2 phosphorylation and NF-kappa B activation increased significantly after 500 ng/mL leptin exposure (1.8x, 1.5x, 6.2x for Ob-Ra, ERK1/2 and NF-kappa B, respectively), but were reduced by addition of 125 uM quercetin (0.7x, 0.3x and 0.4x for Ob-Ra, ERK1/2 and NF-kappa B, respectively), and that quercetin could also partially suppress leptin-induced TNF-alpha secretion (3.8x) by 0.8x.. Exposure of HUVECs to leptin up-regulated Ob-Ra expression and elevated ERK1/2 phosphorylation and NFkB activation, and increased TNF-alpha secretion. These effects strongly suppressed by quercetin, with the exception of TNF-alpha which was partially suppressed. The findings might be of clinical significance, as endothelial dysfunction that could lead to cardiovascular disease is preventable, and quercetin is a natural compound found in various plants and fruits. Topics: Enzyme-Linked Immunosorbent Assay; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Leptin; MAP Kinase Signaling System; NF-kappa B; Phosphorylation; Quercetin | 2013 |
Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats.
Hypothalamic inflammation is associated with insulin and leptin resistance, hyperphagia, and obesity. In this scenario, hypothalamic protein tyrosine phosphatase 1B (PTP1B) has emerged as the key phosphatase induced by inflammation that is responsible for the central insulin and leptin resistance. Here, we demonstrated that acute exercise reduced inflammation and PTP1B protein level/activity in the hypothalamus of obese rodents. Exercise disrupted the interaction between PTP1B with proteins involved in the early steps of insulin (IRβ and IRS-1) and leptin (JAK2) signaling, increased the tyrosine phosphorylation of these molecules, and restored the anorexigenic effects of insulin and leptin in obese rats. Interestingly, the anti-inflammatory action and the reduction of PTP1B activity mediated by exercise occurred in an interleukin-6 (IL-6)-dependent manner because exercise failed to reduce inflammation and PTP1B protein level after the disruption of hypothalamic-specific IL-6 action in obese rats. Conversely, intracerebroventricular administration of recombinant IL-6 reproduced the effects of exercise, improving hypothalamic insulin and leptin action by reducing the inflammatory signaling and PTP1B activity in obese rats at rest. Taken together, our study reports that physical exercise restores insulin and leptin signaling, at least in part, by reducing hypothalamic PTP1B protein level through the central anti-inflammatory response. Topics: Animals; Blotting, Western; Corticosterone; Hypothalamus; Immunohistochemistry; Inflammation; Insulin; Interleukin-6; Leptin; Male; Mice; Mice, Obese; Obesity; Physical Conditioning, Animal; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Random Allocation; Rats; Rats, Wistar; Signal Transduction; Specific Pathogen-Free Organisms | 2013 |
Nutrition disorder and systemic inflammation in patients with chronic obstructive pulmonary disease.
To detect nutrition disorders (underweight and obesity) in patients with chronic obstructive disease (COPD) and presence of systemic inflammation by determination of inflammatory mediators serum values C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α) and leptin.. The examination involved 85 patients with COPD. Nutrition categories were defined by body mass index (BMI). Fat free mass (FFM) was evaluated by mid upper-arm circumference (MUAC) and fat mass (FM) by tricipital skin-fold thickness (TFS). Values of TNF-α and leptin were measured by standardized ELISA kits and, CRP by latex turbidimetry.. There were 14 (16.5%) underweight patients, 28 (32.9%) normal, 28 (32.9%) pre-obese and 15 (17.6%) obese. Values of MUAC and TSF were significantly different among the nutrition categories (p=0.000). The lowest MUAC and TSF values were in the underweight, and the highest in the obese. There was no significant difference of CRP and TNF-α among nutrition categories. Leptin of the underweight and normal nutrition was significantly different from leptin of the pre-obese and obese (p=0.000). The highest CRP and the lowest TNF-α and leptin were in the underweight patients. The obese had the lowest CRP (although increased as compared to normal values) and the highest leptin, while the pre-obese had the highest TNF-α.. Two basic nutrition disorders (underweight and obesity) were manifested in COPD patients. The inflammatory profile differs between underweight COPD patients and obese. Probably that happens due to systemic inflammation, and in part due to dysfunction of adipose tissue. Topics: Body Mass Index; C-Reactive Protein; Humans; Inflammation; Leptin; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha | 2013 |
Adipokines during early abstinence of crack cocaine in dependent women reporting childhood maltreatment.
Childhood maltreatment has been associated with addiction and immune dysregulation, although neurobiological substrates underlying this association remain largely unknown. The aim of the study was to compare plasma levels of adipokines during early abstinence in crack cocaine dependent women with (CM+) and without history of childhood maltreatment (CM-). One hundred four crack cocaine female users were followed for 20 days in a detoxification inpatient treatment unit. Plasma levels of adiponectin, resistin and leptin were assessed every 7 days during 3 weeks of follow-up. The Childhood Trauma Questionnaire (CTQ) retrospectively assessed childhood maltreatment history. A healthy control group was included to provide adipokines reference values (HC). All crack users increased leptin plasma levels during early abstinence despite concentrations remained lower in comparison with non-users group. Crack users reporting childhood maltreatment exhibited a significant reduction in plasma levels of adiponectin and resistin when compared to CM- group. In addition, only CM- participants increased plasma levels of adiponectin during detoxification. This is the first study evaluating adipokines during crack cocaine abstinence. Our results suggest a modulator effect of childhood maltreatment on inflammatory status in treatment-seeking crack cocaine dependents during early abstinence. Topics: Adipokines; Adult; Adult Survivors of Child Abuse; Biomarkers; Case-Control Studies; Cocaine-Related Disorders; Crack Cocaine; Female; Follow-Up Studies; Humans; Inflammation; Leptin; Male; Resistin; Retrospective Studies; Surveys and Questionnaires | 2013 |
Metabolic syndrome--from the neurotrophic hypothesis to a theory.
Metabolic syndrome (MetS) is a complex and heterogeneous disease characterized by central obesity, impaired glucose metabolism, dyslipidemia, arterial hypertension, insulin resistance and high-sensitivity C-reactive protein. In 2006, a neurotrophic hypothesis of the etiopathogenesis of MetS was launched. This hypothesis considered the neurotrophins a key factor in MetS development. Chronic inflammatory and/or psychoemotional distress provoke a series of neuroimmunoendocrine interactions such as increased tissue and plasma levels of proinflammatory cytokines and neurotrophins, vegetodystonia, disbalance of neurotransmitters, hormones and immunity markers, activation of the hypothalamo-pituitary-adrenal axis, insulin resistance, and atherosclerosis. An early and a late clinical stage in the course of MetS are defined. Meanwhile, evidence of supporting results from the world literature accumulates. This enables the transformation of the definition of the neurotrophic hypothesis into a neurotrophic theory of MetS. The important role of two neurotrophic factors, i.e. the nerve growth factor and brain-derived neurotrophic factor as well as of the proinflammatory cytokines, neurotransmitters, adipokines and, especially, of leptin for the development of MetS, obesity and type 2 diabetes mellitus is illustrated. There are reliable scientific arguments that the metabotrophic deficit due to reduced neurotrophins could be implicated in the pathogenesis of MetS, type 2 diabetes mellitus, and atherosclerosis as well. A special attention is paid to the activity of the hypothalamo-pituitary-adrenal axis after stress. The application of the neurotrophic theory of MetS could contribute to the etiological diagnosis and individualized management of MetS by eliminating the chronic distress, hyponeurotrophinemia and consequent pathology. It helps estimating the risk, defining the prognosis and implementing the effective prevention of this socially significant disease as evidenced by the dramatic recent growth of the world publication output on this interdisciplinary topic. Topics: Adipokines; Affective Symptoms; Brain-Derived Neurotrophic Factor; Cytokines; Humans; Hypothalamo-Hypophyseal System; Inflammation; Leptin; Metabolic Syndrome; Models, Biological; Nerve Growth Factor; Nerve Growth Factors; Neurotransmitter Agents; Pituitary-Adrenal System | 2013 |
Long-term exposure to a high-fat diet results in the development of glucose intolerance and insulin resistance in interleukin-1 receptor I-deficient mice.
Emerging evidence has demonstrated that saturated fatty acids prime pro-IL-1β production and inflammasome-mediated IL-1β activation is critical in obesity-associated insulin resistance (IR). Nonetheless, IL-1 receptor I-deficient (IL-1RI(-/-)) mice develop mature-onset obesity despite consuming a low-fat diet (LFD). With this apparent contradiction, the present study evaluated whether IL-1RI(-/-) mice were protected against long-term (6 mo) high-fat diet (HFD)-induced IR. Male wild-type and IL-1RI(-/-) mice were fed LFD or HFD for 3 or 6 mo, and glucose and insulin tolerance tests were performed. Adipose insulin sensitivity, cytokine profiles, and adipocyte morphology were assessed. The adipogenic potential of stromal vascular fraction was determined. Hepatic lipid accumulation and insulin sensitivity were characterized. IL-1RI(-/-) mice developed glucose intolerance and IR after 6 mo HFD compared with 3 mo HFD, coincident with enhanced weight gain, hyperinsulinemia, and hyperleptinemia. The aggravated IR phenotype was associated with loss of adipose functionality, switch from adipocyte hyperplasia to hypertrophy and hepatosteatosis. Induction of adipogenic genes was reduced in IL-1RI(-/-) preadipocytes after 6 mo HFD compared with 3 mo HFD. Obese LFD-IL-1RI(-/-) mice exhibited preserved metabolic health. IL-1RI(-/-) mice develop glucose intolerance and IR after 6 mo HFD intervention. While mature-onset obesity is evident in LFD-IL-1RI(-/-) mice, the additional metabolic insult of HFD was required to drive adipose inflammation and systemic IR. These findings indicate an important interaction between dietary fat and IL-1, relevant to optimal metabolic health. Topics: Adipose Tissue; Adiposity; Animals; Diet, High-Fat; Dietary Fats; Fatty Liver; Glucose Intolerance; Glucose Tolerance Test; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Mice; Mice, Knockout; Receptors, Interleukin-1 Type I | 2013 |
Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice.
This study investigated the effects of dietary methionine restriction (MR) on the progression of established hepatic steatosis in the leptin-deficient ob/ob mouse.. Ten-week-old ob/ob mice were fed diets containing 0.86% (control-fed; CF) or 0.12% methionine (MR) for 14 weeks. At 14 weeks, liver and fat were excised and blood was collected for analysis. In another study, blood was collected to determine in vivo triglyceride (TG) and very-low-density lipoprotein (VLDL) secretion rates. Liver histology was conducted to determine the severity of steatosis. Hepatic TG, free fatty acid levels, and fatty acid oxidation (FAO) were also measured. Gene expression was analyzed by quantitative PCR.. MR reversed the severity of steatosis in the ob/ob mouse. This was accompanied by reduced body weight despite similar weight-specific food intake. Compared with the CF group, hepatic TG levels were significantly reduced in response to MR, but adipose tissue weight was not decreased. MR reduced insulin and HOMA ratios but increased total and high-molecular-weight adiponectin levels. Scd1 gene expression was significantly downregulated, while Acadvl, Hadha, and Hadhb were upregulated in MR, corresponding with increased β-hydroxybutyrate levels and a trend toward increased FAO. The VLDL secretion rate was also significantly increased in the MR mice, as were the mRNA levels of ApoB and Mttp. The expression of inflammatory markers, such as Tnf-α and Ccr2, was also downregulated by MR.. Our data indicate that MR reverses steatosis in the ob/ob mouse liver by promoting FAO, increasing the export of lipids, and reducing obesity-related inflammatory responses. Topics: 3-Hydroxybutyric Acid; Animals; Biomarkers; Blood Glucose; Diet; Disease Progression; Fatty Acids; Fatty Liver; Gene Expression Regulation; Homeostasis; Inflammation; Insulin; Leptin; Lipid Metabolism; Lipoproteins, VLDL; Liver; Male; Methionine; Mice; Mice, Obese; Obesity; Oxidation-Reduction; Severity of Illness Index; Triglycerides | 2013 |
Sex and breed-dependent organ development and metabolic responses in foetuses from lean and obese/leptin resistant swine.
The present study aimed to determine the effects of breed and sex on growth patterns and metabolic features of advanced-pregnancy foetuses exposed to the same environmental conditions. Thus, at Day 62 of pregnancy, swine foetuses from an obese breed with leptin resistance (Iberian breed) were compared to lean crossbred foetuses (25% Large White ×25% Landrace ×50% Pietrain). There were differential developmental patterns in foetuses with leptin resistance, mainly a higher relative weight of the brain resembling "brain-sparing effect". Prioritization of brain growth may be protective for the adequate growth and postnatal survival of the Iberian individuals, an ancient breed reared in extensive semi-feral conditions for centuries. There were also clear sex-related differences in foetal development and metabolism in the Iberian breed. Female Iberian foetuses were similar in size and weight to male littermates but had a significantly higher relative liver to body weight ratio resembling "liver-sparing effect" and a trend for a higher relative intestine to body ratio. Moreover, the availability of triglycerides, cholesterol and IL-6 in female Iberian foetuses was similar to that of lean crossbred foetuses. Overall, these features may favour a better postnatal survival and development of females, the sex more critical for the species survival. These findings set the basis for future translational studies aimed at increasing the knowledge on the interaction between genetic and environmental factors in the early programming of the adult phenotype. Topics: Animals; Breeding; Endocrine System; Female; Fetal Development; Fetal Growth Retardation; Fetus; Glucose; Inflammation; Leptin; Lipid Metabolism; Male; Obesity; Organogenesis; Placenta; Pregnancy; Reproduction; Sex Characteristics; Swine; Thinness | 2013 |
Differential proinflammatory and oxidative stress response and vulnerability to metabolic syndrome in habitual high-fat young male consumers putatively predisposed by their genetic background.
The current nutritional habits and lifestyles of modern societies favor energy overloads and a diminished physical activity, which may produce serious clinical disturbances and excessive weight gain. In order to investigate the mechanisms by which the environmental factors interact with molecular mechanisms in obesity, a pathway analysis was performed to identify genes differentially expressed in subcutaneous abdominal adipose tissue (SCAAT) from obese compared to lean male (21-35 year-old) subjects living in similar obesogenic conditions: habitual high fat dietary intake and moderate physical activity. Genes involved in inflammation (ALCAM, CTSB, C1S, YKL-40, MIF, SAA2), extracellular matrix remodeling (MMP9, PALLD), angiogenesis (EGFL6, leptin) and oxidative stress (AKR1C3, UCHL1, HSPB7 and NQO1) were upregulated; whereas apoptosis, signal transcription (CITED 2 and NR3C1), cell control and cell cycle-related genes were downregulated. Interestingly, the expression of some of these genes (C1S, SAA2, ALCAM, CTSB, YKL-40 and tenomodulin) was found to be associated with some relevant metabolic syndrome features. The obese group showed a general upregulation in the expression of inflammatory, oxidative stress, extracellular remodeling and angiogenic genes compared to lean subjects, suggesting that a given genetic background in an obesogenic environment could underlie the resistance to gaining weight and obesity-associated manifestations. Topics: Adult; Calcium-Binding Proteins; Cell Adhesion Molecules; Humans; Inflammation; Leptin; Male; Matrix Metalloproteinase 9; Membrane Glycoproteins; Metabolic Syndrome; Obesity; Oxidative Stress; Receptors, Glucocorticoid; Subcutaneous Fat; Ubiquitin Thiolesterase; Young Adult | 2013 |
Impact of hematopoietic cyclooxygenase-1 deficiency on obesity-linked adipose tissue inflammation and metabolic disorders in mice.
Adipose tissue (AT)-specific inflammation is considered to mediate the pathological consequences of obesity and macrophages are known to activate inflammatory pathways in obese AT. Because cyclooxygenases play a central role in regulating the inflammatory processes, we sought to determine the role of hematopoietic cyclooxygenase-1 (COX-1) in modulating AT inflammation in obesity.. Bone marrow transplantation was performed to delete COX-1 in hematopoietic cells. Briefly, female wild type (wt) mice were lethally irradiated and injected with bone marrow (BM) cells collected from wild type (COX-1+/+) or COX-1 knock-out (COX-1-/-) donor mice. The mice were fed a high fat diet for 16 weeks.. The mice that received COX-1-/- bone marrow (BM-COX-1-/-) exhibited a significant increase in fasting glucose, total cholesterol and triglycerides in the circulation compared to control (BM-COX-1+/+) mice. Markers of AT-inflammation were increased and were associated with increased leptin and decreased adiponectin in plasma. Hepatic inflammation was reduced with a concomitant reduction in TXB2 levels. The hepatic mRNA expression of genes involved in lipogenesis and lipid transport was increased while expression of genes involved in regulating hepatic glucose output was reduced in BM-COX-1-/- mice. Finally, renal inflammation and markers of renal glucose release were increased in BM-COX-1-/- mice.. Hematopoietic COX-1 deletion results in impairments in metabolic homeostasis which may be partly due to increased AT inflammation and dysregulated adipokine profile. An increase in renal glucose release and hepatic lipogenesis/lipid transport may also play a role, at least in part, in mediating hyperglycemia and dyslipidemia, respectively. Topics: Adiponectin; Adipose Tissue; Animals; Biomarkers; Blotting, Western; Bone Marrow Cells; Bone Marrow Transplantation; Cyclooxygenase 1; Diet, High-Fat; Eating; Female; Fluorescent Antibody Technique; Inflammation; Kidney; Leptin; Liver; Macrophages; Mice; Mice, Knockout; Obesity; Real-Time Polymerase Chain Reaction; Weight Gain | 2013 |
Inflammation and hypertension in rheumatoid arthritis.
Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with HTN in RA.. We compared measures of inflammation [serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), homocysteine, and leptin concentrations] and insulin resistance [homeostasis model assessment index (HOMA)] in RA patients with (n = 90) and without HTN (n = 79). HTN was defined as blood pressure ≥ 140/90 mm Hg or treatment with antihypertensive therapy. The independent association of markers of interest with HTN was examined using multivariable logistic regression.. Patients with HTN were significantly older and had longer disease duration than those without HTN (both p < 0.001). Concentrations of homocysteine [11.1 (8.5-13.5) μmol/l vs 9.3 (7.8-11.0) μmol/l] were significantly higher in patients with HTN (p < 0.001). After adjustment for age, sex, race, smoking, body mass index, and corticosteroid and nonsteroidal antiinflammatory drugs (NSAID) use, increased concentrations of homocysteine (OR 2.9, 95% CI: 1.5-5.5, p = 0.001), and leptin (OR 2.0, 95% CI: 1.0-3.8, p = 0.046) were significantly associated with HTN, but the 28-joint Disease Activity Score, IL-6, CRP, TNF-α, and HOMA index were not (all p > 0.05).. HTN in patients with RA is not associated with generalized systemic inflammation or insulin resistance, but is associated with increasing concentrations of homocysteine and leptin. The pathogenesis of HTN in RA may involve pathways more regularly associated with fat and vascular homeostasis. Topics: Adult; Aged; Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Female; Humans; Hypertension; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Risk Factors; Tumor Necrosis Factor-alpha | 2013 |
Low serum concentration of obestatin as a predictor of mortality in maintenance hemodialysis patients.
Obestatin, a proposed anorexigenic gut hormone, has been shown to have a number of beneficial cardiotropic effects in experimental studies. We hypothesized that obestatin alteration in hemodialysis patients may link to clinical outcomes. This cross-sectional study with prospective followup for almost 4 years was performed on 94 prevalent hemodialysis patients. Obestatin, leptin, proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6, and various nutritional markers were measured. Patients with low obestatin levels, defined as a level less than median, had a worse all-cause mortality and cardiovascular mortality. The crude all-cause (HR 2.23, 95% CI 1.17 to 4.24) and cardiovascular mortality hazard ratios (HR 4.03, 95% CI 1.27 to 12.76) in these patients continued to be significant after adjustment for various confounders for all-cause mortality. Across the four obestatin-TNF-α categories, the group with low obestatin and high TNF-α (above median level) exhibited a worse outcome in both all-cause mortality and cardiovascular mortality. Clinical characteristics of patients in low obestatin high TNF-α group did not differ from other obestatin-TNF-α categorized groups. In summary, low serum obestatin concentration is an independent predictor of mortality in prevalent hemodialysis patients. Novel interactions were observed between obestatin and TNF-α, which were associated with mortality risk, especially those due to cardiovascular causes. Topics: Biomarkers; Cardiovascular Abnormalities; Female; Ghrelin; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Tumor Necrosis Factor-alpha | 2013 |
[Dynamics of serum visfatin level after abdominal surgery: a new proinflammatory marker in the early diagnosis?].
Visfatin is a newly recognized adipocytokine produced mainly in visceral fat tissue. Beside its effect on insulin receptor, it serves as proinflammatory cytokine and its level can be changed during inflammatory processes. The aim of the study was to analyze dynamics of serum visfatine level in early period after abdominal surgery and compare it with other proinflammatory markers.. In prospective cross-sectional study 20 patients after elective laparotomic abdominal surgery (partial colectomy) were enrolled and dynamics of visfatin, leptin, resistin, adiponectin, TNF-α , IL-6 and CRP in period +12, +24, +48 and + 72 hours was monitored. Serum visfatin was elevated already in +24 hrs period after surgery comparing the culmination of serum level of TNF-α and IL-6 12-24 hrs later and CRP even 48-72 hrs later.. Serum visfatin was elevated very early after abdominal surgery and thus its dynamic may be an early predictor of inflammatory processes namely in patients with visceral obesity. Topics: Adipokines; Adiponectin; Biomarkers; C-Reactive Protein; Colectomy; Cross-Sectional Studies; Cytokines; Early Diagnosis; Humans; Inflammation; Interleukin-6; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity, Abdominal; Postoperative Period; Prospective Studies; Resistin; Tumor Necrosis Factor-alpha | 2013 |
Dietary factors associated with subclinical inflammation among girls.
Dietary patterns and biomarkers of inflammation have been scarcely associated. The aim was to assess dietary factors associated with subclinical inflammation among girls.. Fasting blood samples were collected from 12- to 17-year old girls (n=219) to measure adiponectin, leptin, tumor necrosis factor-alpha, plasminogen activator inhibitor 1 (PAI-1), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels. Body mass index (BMI) and waist-to-height ratio (WHtR), and food intake were also measured. Western (WDP) and Mediterranean (MDP) dietary patterns were identified.. BMI and WHtR were associated with adiponectin, leptin and hs-CRP (the last, only associated with BMI). Intakes of β-carotene equivalents and vitamin C were associated with adiponectin; saturated fatty acids (SFA), vitamin A, manganese and selenium with leptin; linoleic acid with PAI-1; and oleic acid and vitamin E with IL-6. Selenium was inversely associated with adiponectin, whereas magnesium was positively associated with IL-6. MDP was associated with higher plasma concentrations of adiponectin (β=0.174, P<0.05); after adjustment for BMI, associations were not significant (β=0.144, P=0.076). WDP was negatively associated with adiponectin (β=-0.177, P<0.05) and positively with IL-6 (β=0.183, P<0.05).. Subclinical inflammation is detectable with increasing BMI and also WHtR. Measures of adiposity (BMI and WHtR) are significant predictors of adiponectin, leptin and hs-CRP. Dietary patterns per se have a small role in affecting inflammatory markers among adolescents. Topics: Adiponectin; Adolescent; Ascorbic Acid; beta Carotene; Biomarkers; Body Height; Body Mass Index; C-Reactive Protein; Child; Diet; Fatty Acids; Female; Humans; Inflammation; Interleukin-6; Leptin; Linoleic Acid; Manganese; Oleic Acid; Plasminogen Activator Inhibitor 1; Selenium; Tumor Necrosis Factor-alpha; Vitamin A; Vitamin E; Waist Circumference | 2013 |
Sedentary time and markers of chronic low-grade inflammation in a high risk population.
Sedentary behaviour has been identified as a distinct risk factor for several health outcomes. Nevertheless, little research has been conducted into the underlying mechanisms driving these observations. This study aimed to investigate the association of objectively measured sedentary time and breaks in sedentary time with markers of chronic low-grade inflammation and adiposity in a population at a high risk of type 2 diabetes mellitus.. This study reports data from an ongoing diabetes prevention programme conducted in Leicestershire, UK. High risk individuals were recruited from 10 primary care practices. Sedentary time (<25 counts per 15 s) was measured using Actigraph GT3X accelerometers (15 s epochs). A break was considered as any interruption in sedentary time (≥25 counts per 15 s). Biochemical outcomes included interleukin-6 (IL-6), C-reactive protein (CRP), leptin, adiponectin and leptin:adiponectin ratio (LAR). A sensitivity analysis investigated whether results were affected by removing participants with a CRP level >10 mg/L, as this can be indicative of acute inflammation.. 558 participants (age = 63.6±7.7 years; male = 64.7%) had complete adipokine and accelerometer data. Following adjustment for various confounders, sedentary time was detrimentally associated with CRP (β = 0.176±0.057, p = 0.002), IL-6 (β = 0.242±0.056, p = <0.001), leptin (β = 0.146±0.043, p = <0.001) and LAR (β = 0.208±0.052, p = <0.001). Associations were attenuated after further adjustment for moderate-to-vigorous physical activity (MVPA) with only IL-6 (β = 0.231±0.073, p = 0.002) remaining significant; this result was unaffected after further adjustment for body mass index and glycosylated haemoglobin (HbA1c). Similarly, breaks in sedentary time were significantly inversely associated with IL-6 (β = -0.094±0.047, p = 0.045) and leptin (β = -0.075±0.037, p = 0.039); however, these associations were attenuated after adjustment for accelerometer derived variables. Excluding individuals with a CRP level >10 mg/L consistently attenuated the significant associations across all markers of inflammation.. These novel findings from a high risk population recruited through primary care suggest that sedentary behaviour may influence markers associated with inflammation, independent of MVPA, glycaemia and adiposity. Topics: Adiponectin; Adiposity; Biomarkers; Body Mass Index; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Motor Activity; Risk Factors; Sedentary Behavior | 2013 |
Relation of leptin, ghrelin and inflammatory cytokines with body mass index in pulmonary tuberculosis patients with and without type 2 diabetes mellitus.
Pulmonary tuberculosis (TB) patients often suffer from anorexia and poor nutrition, causing weight loss. The peptide hormones leptin and its counterpart ghrelin, acting in the regulation of food intake and fat utilization, play an important role in nutritional balance. This study aimed to investigate the association of blood concentrations of leptin, ghrelin and inflammatory cytokines with body mass index (BMI) in TB patients with and without type 2 diabetes mellitus (T2DM).. BMI, biochemical parameters and plasma levels of leptin, ghrelin and inflammatory cytokines were measured before the start of treatment in 27 incident TB patients with T2DM, 21 TB patients and 23 healthy subjects enrolled in this study.. The levels of leptin were significantly higher in TB patients (35.2 ± 19.1 ng/ml) than TB+T2DM (12.6 ± 6.1 ng/ml) and control (16.1 ± 11.1 ng/ml) groups. The level of ghrelin was significantly lower in TB (119.9 ± 46.1 pg/ml) and non-significantly lower in TB+T2DM (127.7 ± 38.6 pg/ml) groups than control (191.6 ± 86.5 pg/ml) group. The levels of TNF-α were higher, while IFN-γ and IL-6 levels were lower in patients than in the control group. Leptin showed a negative correlation with BMI in TB (r=-0.622, p<0.05) and TB+T2DM (r= -0.654, p<0.05) groups, but a positive correlation with BMI in the control group (r=0.521, p<0.05). Contrary ghrelin showed a positive correlation with BMI in TB (r=0.695, p<0.05) and TB+T2DM (r= 0.199, p>0.05) groups, but negative correlation with BMI in the control (r=-0.693, p<0.05) group. Inflammatory cytokines were poorly correlated with BMI in this study. Only IFN-γ showed a significant negative correlation with BMI in the control group (r=-0.545, p<0.05).. This study may suggest that possible abnormalities in ghrelin and leptin regulation (high levels of leptin and low levels of ghrelin) may be associated with low BMI and may account for the poor nutrition associated with TB and TB+T2DM. Topics: Body Mass Index; Diabetes Mellitus, Type 2; Female; Ghrelin; Humans; Inflammation; Interferon-gamma; Interleukin-6; Leptin; Male; Middle Aged; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2013 |
Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case-control multicentre study.
Variants in the FTO gene have been associated with obesity in children, but this association has not been shown with other biomarkers. We assessed the association of 52 FTO polymorphisms, spanning the whole gene, with obesity and estimated the influence of these polymorphisms on anthropometric, clinical and metabolic parameters as well as inflammation and cardiovascular disease (CVD) risk biomarkers among Spanish children.. A multicentre case-control study was conducted in 534 children (292 obese and 242 with normal-BMI). Anthropometric, clinical, metabolic, inflammation and CVD risk markers were compared using the Student's t-test for unpaired samples. The genotype relative risk was assessed by comparing the obese and normal-BMI group, calculating the odds ratio. The association of each SNP with phenotypic parameters was analysed using either logistic or linear regression analysis.. All anthropometric, clinical and metabolic factors as well as inflammatory and CVD risk biomarkers were higher in the obese than in the normal-BMI group, except adiponectin and HDL-c that were lower, and glucose, LDL-c, and metalloproteinase-9 that did not show difference. Four polymorphisms (rs9935401, rs9939609, rs9928094 and rs9930333) were positively associated with obesity and in linkage disequilibrium between each other; the haplotype including the risk alleles of these polymorphisms showed a high risk for obesity. The rs8061518 was negatively associated with obesity and the haplotype including this SNP and rs3826169, rs17818902 and rs7190053 showed a decreased risk for obesity. Additionally, the rs8061518 was associated with weight, diastolic blood pressure, insulin, homeostatic model assessment of insulin resistance, leptin, and active plasminogen inhibitor activator-1 after sex and age adjustment; however, after an additional BMI adjustment, this polymorphism remained associated only with leptin.. We validated the previous reported association of genetic variability in intron 1 of the FTO gene with the risk of obesity and found no association with other related traits in this region of the gene. We have observed strong statistical evidence for an association of rs8061518 in intron 3 of the gene with decreased risk of obesity and low concentration of leptin. Topics: Adolescent; Alleles; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Child; Female; Genotype; Haplotypes; Humans; Inflammation; Introns; Leptin; Linkage Disequilibrium; Male; Obesity; Polymorphism, Single Nucleotide; Proteins; Risk Factors; Spain; White People | 2013 |
Obesity-related adipokines predict patient-reported shoulder pain.
Increasingly, an inflammatory modulating effect of adipokines within synovial joints is being recognized. To date, there has been no work examining a potential association between the presence of adipokines in the shoulder and patient-reported outcomes. This study undertakes an investigation assessing these potential links.. 50 osteoarthritis patients scheduled for shoulder surgery completed a pre-surgery questionnaire capturing demographic information including validated, patient-reported function (Disabilities of the Arm, Shoulder, and Hand questionnaire) and pain (Short Form McGill Pain Questionnaire) measures. Synovial fluid (SF) samples were analyzed for leptin, adiponectin, and resistin levels using Milliplex MAP assays. Linear regression modeling was used to assess the association between adipokine levels and patient-reported outcomes, adjusted for age, sex, BMI, and disease severity.. 54% of the cohort was female (n = 27). The mean age (SD) of the sample was 62.9 (9.9) years and the mean BMI (SD) was 28.1 (5.4) kg/m(2). From regression analyses, greater SF leptin and adiponectin levels, but not regarding resistin, were found to be associated with greater pain (p < 0.05). Adipokine levels were not associated with functional outcome scores.. The identified association between shoulder-derived SF leptin and adiponectin and shoulder pain is likely explained by the pro-inflammatory characteristics of the adipokines and represents potentially important therapeutic targets. Topics: Adiponectin; Aged; Body Mass Index; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Obesity; Osteoarthritis; Resistin; Shoulder Pain; Surveys and Questionnaires; Synovial Fluid | 2013 |
Bisphenol-A impairs insulin action and up-regulates inflammatory pathways in human subcutaneous adipocytes and 3T3-L1 cells.
Current evidence indicates that chemical pollutants may interfere with the homeostatic control of nutrient metabolism, thereby contributing to the increased prevalence of metabolic disorders. Bisphenol-A (BPA) is a lipophilic compound contained in plastic which is considered a candidate for impairing energy and glucose metabolism. We have investigated the impact of low doses of BPA on adipocyte metabolic functions. Human adipocytes derived from subcutaneous adipose tissue and differentiated 3T3-L1 cells were incubated with BPA, in order to evaluate the effect on glucose utilization, insulin sensitivity and cytokine secretion. Treatment with 1 nM BPA significantly inhibited insulin-stimulated glucose utilization, without grossly interfering with adipocyte differentiation. Accordingly, mRNA levels of the adipogenic markers PPARγ and GLUT4 were unchanged upon BPA exposure. BPA treatment also impaired insulin-activated receptor phosphorylation and signaling. Moreover, adipocyte incubation with BPA was accompanied by increased release of IL-6 and IFN-γ, as assessed by multiplex ELISA assays, and by activation of JNK, STAT3 and NFkB pathways. Treatment of the cells with the JNK inhibitor SP600125 almost fully reverted BPA effect on insulin signaling and glucose utilization. In conclusion, low doses of BPA interfere with inflammatory/insulin signaling pathways, leading to impairment of adipose cell function. Topics: 3T3-L1 Cells; Adipocytes; Animals; Benzhydryl Compounds; Cell Differentiation; Down-Regulation; Glucose; Humans; Inflammation; Insulin; JNK Mitogen-Activated Protein Kinases; Leptin; Mice; NF-kappa B; Phenols; Phosphorylation; Receptor, Insulin; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Subcutaneous Fat; Up-Regulation | 2013 |
Yerba mate extract (Ilex paraguariensis) attenuates both central and peripheral inflammatory effects of diet-induced obesity in rats.
To clarify the effects of natural dietary components on the metabolic consequences of obesity, we examined the effects of yerba mate extract Ilex paraguariensis on both central and peripheral inflammatory effects of diet-induced obesity and correlated the hypothalamic tumor necrosis factor (TNF)-α level with adipose depot weight. Wistar rats were divided into four groups: a control group (CTL) fed with chow diet, a second group fed with chow diet plus yerba mate extract (CTL+E), a third group fed with a high-fat diet rich in saturated fatty acids (HFD) and a fourth group fed with HFD plus yerba mate extract (HFD+E). Enzyme-linked immunosorbent assay, Western blotting, colorimetric method and treatment by gavage were utilized as materials and methods. The HFD groups showed a significant increase in food intake (kcal), body weight, adipose tissue and leptin level in comparison to CTL and CTL+E. HFD leads to increase of both central and peripheral inflammatory effects, and deregulation of insulin pathway. In addition, yerba mate extract intake blunted the proinflammatory effects of diet-induced obesity in rats by reducing the phosphorylation of hypothalamic IKK and NFκBp65 expression and increasing the phosphorylation of IκBα, the expression of adiponectin receptor-1 and consequently the amount of IRS-2. Moreover, the increase in interleukin (IL)-6 levels in the liver and muscle and of the IL-10/TNF-α ratio in groups that received yerba mate extract showed the anti-inflammatory effects of this natural substance. Taken together, our data suggest that the use of yerba mate extract may be useful for reducing low-grade obesity-associated inflammation. Topics: Adipose Tissue; Animals; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Diet, High-Fat; Energy Intake; Enzyme-Linked Immunosorbent Assay; fas Receptor; Fasting; Fatty Acids; Hypothalamus; I-kappa B Proteins; Ilex paraguariensis; Inflammation; Insulin; Insulin Receptor Substrate Proteins; Interleukin-10; Interleukin-6; Leptin; Liver; Male; Muscles; NF-kappa B; NF-KappaB Inhibitor alpha; Obesity; Phosphorylation; Plant Extracts; Rats; Rats, Wistar; Receptors, Adiponectin; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha | 2013 |
Low-molecular-weight adiponectin is more closely associated with episodes of asthma than high-molecular-weight adiponectin.
Adiponectin is divided into high-molecular-weight (HMW), middle-molecular-weight (MMW) and low-molecular-weight (LMW) types. While HMW adiponectin has been studied by many researchers, the roles of MMW and LMW adiponectin have not yet been sufficiently elucidated. In addition, there are conflicting findings regarding the role of adiponectin in chronic inflammatory diseases, especially asthma. Therefore, we compared patients who suffered episodes of asthma in the past (=asthmatics) with those who did not (=non-asthmatics) in order to investigate the relationship between asthma and HMW, MMW and LMW adiponectin. The subjects in this study included 76 university students. None of the subjects were smokers, on regular medications or seeing a doctor regularly at the time. Fourteen subjects reported past histories of asthma. We also measured and compared the levels of leptin and ghrelin to that of adiponectin, as these hormones are connected with inflammatory conditions. Although the physical data of the asthmatics were similar to those of the non-asthmatics, the levels of ghrelin and all fractions of adiponectin tended to be lower in the asthmatics than in the non-asthmatics. While the levels of MMW and LMW adiponectin in the asthmatics were found to be significantly low, the levels of ghrelin and HMW adiponectin were not clear. According to a multivariate regression analysis of the MMW and LMW adiponectin levels, asthma was found to be more significantly associated with the LMW adiponectin level than age, waist circumference or HDL-C. The results suggest that LMW adiponectin may be associated with episodes of asthma in males. Topics: Adiponectin; Adolescent; Adult; Asthma; Female; Ghrelin; Humans; Inflammation; Leptin; Male | 2013 |
Influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters.
We examined the effects of three high-fat diets (HFD), differing in the percentage of total calories from saturated fat (SF) (6%, 12%, and 24%) but identical in total fat (40%), on body composition, macrophage behavior, inflammation, and metabolic dysfunction in mice. Diets were administered for 16 weeks. Body composition and metabolism [glucose, insulin, triglycerides, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), total cholesterol (TC)] were examined monthly. Adipose tissue (AT) expression of marker genes for M1 and M2 macrophages and inflammatory mediators [Toll-like receptor (TLR)-2, TLR-4, MCP-1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, suppressor of cytokine signaling (SOCS)1, IFN-γ] was measured along with activation of nuclear factor kappa-B (NFκB), c-Jun N-terminal kinase (JNK), and p38- mitogen-activated protein kinase (MAPK). AT macrophage infiltration was examined using immunohistochemistry. Circulating MCP-1, IL-6, adiponectin, and leptin were also measured. SF content, independent of total fat, can profoundly affect adiposity, macrophage behavior, inflammation, and metabolic dysfunction. In general, the 12%-SF diet, most closely mimicking the standard American diet, led to the greatest adiposity, macrophage infiltration, and insulin resistance (IR), whereas the 6%-SF and 24%-SF diets produced lower levels of these variables, with the 24%-SF diet resulting in the least degree of IR and the highest TC/HDL-C ratio. Macrophage behavior, inflammation, and IR following HFD are heavily influenced by dietary SF content; however, these responses are not necessarily proportional to the SF percentage. Topics: Adipose Tissue; Adiposity; Animals; Body Weight; Diet, High-Fat; Dietary Fats; Energy Intake; Fatty Acids; Inflammation; Insulin Resistance; Leptin; Macrophages; Male; Mice | 2013 |
Leptin, adiponectin, and ghrelin levels in female patients with asthma during stable and exacerbation periods.
The mechanisms underlying the relationship between obesity and asthma have not been fully established. Data in the literature suggest that adipose tissue-derived hormones may be implicated. However, no definite conclusions regarding the role of leptin and adiponectin with asthma are available. No studies have examined the role of ghrelin in asthma.. We assessed the circulating concentrations of leptin, adiponectin, and ghrelin in 32 postmenopausal stable asthma patients, 37 female asthmatics during exacerbations and 8 weeks later, and 22 controls. We examined the relationship between the three peptides and indexes of pulmonary function, airway inflammation, and atopy.. Stable asthma patients exhibited higher leptin and lower ghrelin concentrations compared with controls. Patients with severe asthma had higher leptin and lower adiponectin levels versus patients with mild to moderate asthma. Both leptin concentrations and leptin/adiponectin ratio served as markers for discriminating asthma patients from controls on the one hand, and severe from mild to moderate asthmatics on the other. Leptin levels were inversely correlated with both FEV(1)/FVC and FEF(25-75) in patients with mild to moderate asthma. Atopic asthma patients had higher leptin concentrations than nonatopic asthma patients. There was a positive correlation between serum leptin and total IgE levels in atopic asthmatics. Finally, serum leptin levels and leptin/adiponectin ratio were significantly increased during asthma exacerbations, while adiponectin and ghrelin levels were significantly decreased.. Our findings suggest that leptin, adiponectin, and ghrelin may play a significant role in the pathogenesis of asthma during both stable state and asthma exacerbation, independent of obesity. Topics: Adiponectin; Area Under Curve; Asthma; Female; Forced Expiratory Volume; Ghrelin; Humans; Inflammation; Leptin; Middle Aged; Obesity; Postmenopause; ROC Curve | 2013 |
Non-hodgkin lymphoma and circulating markers of inflammation and adiposity in a nested case-control study: the multiethnic cohort.
Because immune dysfunction is thought to underlie the development of non-Hodgkin lymphoma (NHL), obesity and chronic inflammation may be involved in its etiology. We examined the association of prediagnostic inflammatory markers and adipokines with NHL risk.. We conducted a nested case-control analysis (272 cases and 541 matched controls) within the Multiethnic Cohort. Luminex technology was used to measure a 10-plex panel of cytokines, ELISA assays for adipokines, and an autoanalyzer for C-reactive protein (CRP). ORs and 95% confidence intervals (CI) for tertiles of analytes were estimated by conditional logistic regression.. After a median time of 2.7 years from phlebotomy to diagnosis, interleukin (IL)-10 was significantly related to NHL risk (ORT3 vs. T1 = 3.07; 95%CI, 2.02-4.66; Ptrend < 0.001). TNF-α and IL-8 showed borderline elevated risks, whereas IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, and CRP were not associated with NHL. Leptin but not adiponectin was related to NHL risk (ORT3 vs. T1 = 0.48; 95%CI, 0.30-0.76; Ptrend < 0.001). Adjustment for body mass index did not substantially affect the risk estimates. Stratification by subtype indicated significant associations with IL-10 and leptin for follicular but not for diffuse large B-cell lymphoma. Excluding cases diagnosed less than 1 year after phlebotomy attenuated all associations.. IL-10 was the only cytokine and leptin the only adipokine associated with NHL, but due to the short follow-up time, preclinical effects cannot be excluded.. Although markers of inflammation and adiposity may provide new insights into the etiology of NHL, they need to be assessed many years before clinical diagnosis. Topics: Adiposity; Aged; Biomarkers, Tumor; Case-Control Studies; Cytokines; Ethnicity; Female; Humans; Inflammation; Leptin; Lymphoma, Non-Hodgkin; Male; Middle Aged; Obesity; Prognosis; Prospective Studies; Risk Factors | 2013 |
Effects of leptin on lipopolysaccharide-induced remodeling in an in vitro model of human myometrial inflammation.
Reorganization of myometrial extracellular matrix (ECM) is essential for the uterus to achieve powerful synchronous contractions during labor. Remodeling of the ECM has been implicated in membrane rupture and cervical ripening. Because maternal obesity is associated with both delivery disorders and elevated circulating leptin levels, this study aimed to assess the ability of leptin to interfere with lipopolysaccharide (LPS)-induced myometrial ECM remodeling. Myometrial biopsy samples were obtained from women undergoing cesarean delivery before labor onset. Myometrial explants were incubated for 48 h with LPS and leptin. LPS challenge was associated with a marked decrease in collagen content and in heat shock protein (HSP) 47 expression, reflecting a disruption in collagen synthesis and an increase in matrix metalloproteinase (MMP) 2 and MMP9 activity and in MMP2, MMP9, and MMP13 expression. Leptin prevented an LPS-induced decrease in myometrial collagen content in a concentration-dependent manner. This effect was associated with an increase in HSP47 expression and a decrease in MMP2 and MMP9 activity and expression. These results show that leptin prevents LPS-induced myometrial remodeling through collagen synthesis stimulation and inhibition of MMP2 and MMP9. Our study strengthens the hypothesis that leptin plays a role in the development of obesity-related delivery disorders. Topics: Adult; Biopsy; Collagen; Dose-Response Relationship, Drug; Extracellular Matrix; Female; HSP47 Heat-Shock Proteins; Humans; In Vitro Techniques; Inflammation; Leptin; Lipopolysaccharides; Matrix Metalloproteinase 13; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myometrium; Obesity; Pregnancy; Pregnancy Complications | 2013 |
Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma.
Impaired lung function caused by decreased airway diameter (bronchoconstriction) is frequently observed whether body weight is abnormally high or low. That these opposite conditions affect the airways similarly suggests that the regulation of airway diameter and body weight are intertwined. We show here that, independently of its regulation of appetite, melanocortin pathway, or sympathetic tone, leptin is necessary and sufficient to increase airway diameter by signaling through its cognate receptor in cholinergic neurons. The latter decreases parasympathetic signaling through the M(3) muscarinic receptor in airway smooth muscle cells, thereby increasing airway diameter without affecting local inflammation. Accordingly, decreasing parasympathetic tone genetically or pharmacologically corrects bronchoconstriction and normalizes lung function in obese mice regardless of bronchial inflammation. This study reveals an adipocyte-dependent regulation of bronchial diameter whose disruption contributes to the impaired lung function caused by abnormal body weight. These findings may be of use in the management of obesity-associated asthma. Topics: Animals; Asthma; Body Weight; Bronchi; Bronchoconstriction; Cholinergic Antagonists; Cholinergic Neurons; Diet, High-Fat; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Myocytes, Smooth Muscle; Obesity; Parasympathetic Nervous System; Receptor, Muscarinic M3; Signal Transduction | 2013 |
Airway and systemic inflammation in obese children with asthma.
Obese asthma presents via altered airway and systemic inflammation in adults. This has not been comprehensively described in children. The aim of the present study was to compare airway and systemic inflammation in obese and nonobese asthmatic children and controls. In a cross-sectional study, children aged 8-17 years were assigned to one of four groups: obese asthma (OA, n=74); nonobese asthma (NOA, n=249); obese control (OC, n=9); nonobese control (NOC, n=29). Lung function, and both sputum and systemic inflammatory biomarkers were measured. Non-eosinophilic asthma was more prevalent among OA females (60.0%) versus OA males (30.8%). However, there were no differences in the percentage of eosinophils or neutrophils between OA and NOA. Leptin was higher in OC, but not OA, versus NOA and NOC, while adiponectin was reduced in OA versus NOC only. Expiratory reserve volume was reduced in OA, versus NOC. Residual volume (RV) and RV/total lung capacity were reduced in OC versus OA, and OC versus OA and NOA, respectively. Obesity was associated with significant lung restriction in children with and without asthma. Obesity was not associated with significantly altered airway or systemic inflammation in asthmatic children. However, the higher prevalence of non-eosinophilic asthma in female obese asthmatics, compared to males, warrants further investigation. Topics: Adiponectin; Adolescent; Asthma; Biomarkers; Child; Cohort Studies; Cross-Sectional Studies; Female; Humans; Inflammation; Leptin; Male; Nitric Oxide; Obesity; Quality of Life; Sex Factors; Sputum; Surveys and Questionnaires | 2013 |
Nuclear factor κB (NF-κB) suppresses food intake and energy expenditure in mice by directly activating the Pomc promoter.
While chronic low-grade inflammation is associated with obesity, acute inflammation reduces food intake and leads to negative energy balance. Although both types of inflammation activate nuclear factor κB (NF-κB) signalling, it remains unclear how NF-κB activation results in opposite physiological responses in the two types of inflammation. The goal of this study was to address this question, and to understand the link between inflammation and leptin signalling.. We studied the ability of NF-κB to modulate Pomc transcription, and how it impinges on signal transducer and activator of transcription 3 (STAT3)-mediated leptin signalling by using a combination of animal models, biochemical assays and molecular biology.. We report that suppression of food intake and physical movement with acute inflammation is not dependent on STAT3 activation in pro-opiomelanocortin (POMC) neurons. Under these conditions, activated NF-κB independently leads to increased Pomc transcription. Electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) experiments reveal that NF-κB v-rel reticuloendotheliosis viral oncogene homologue A (avian) (RELA [also known as p65]) binds to the Pomc promoter region between -138 and -88 bp, which also harbours the trans-acting transcription factor 1 (SP1) binding site. We found significant changes in the methylation pattern at this region and reduced Pomc activation under chronic inflammation induced by a high-fat diet. Furthermore, RELA is unable to bind and activate transcription when the Pomc promoter is methylated. Finally, RELA binds to STAT3 and inhibits STAT3-mediated promoter activity, suggesting that RELA, possibly together with forkhead box-containing protein 1 (FOXO1), may prevent STAT3-mediated leptin activation of the Pomc promoter.. Our study provides a mechanism for the involvement of RELA in the divergent regulation of energy homeostasis in acute and chronic inflammation. Topics: Animals; Base Sequence; Behavior, Animal; Eating; Feeding Behavior; Gene Expression Regulation; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; NF-kappa B; Pro-Opiomelanocortin; Promoter Regions, Genetic; Signal Transduction; STAT3 Transcription Factor | 2013 |
Adipose tissue-specific modulation of galectin expression in lean and obese mice: evidence for regulatory function.
Galectins (Gal) exert many activities, including regulation of inflammation and adipogenesis. We evaluated modulation of Gal-1, -3, -9 and -12 in visceral (VAT) and subcutaneous (SAT) adipose tissue in mice.. We used two mouse models of obesity, high-fat diet induced obesity (DIO) and ob/ob mice. We also evaluated the response of Gal-1 KO mice to DIO.. Both age and diet modulated expression of galectins, with DIO mice having higher serum Gal-1 and Gal-3 versus lean mice after 13-17 weeks of high-fat diet. In DIO mice there was a progressive increase in expression of Gal-1 and Gal-9 in SAT, whereas Gal-3 increased in both VAT and SAT. Expression of Gal-12 declined over time in VAT of DIO mice, similar to adiponectin. Obesity lead to increased production of Gal-1 in adipocytes, whereas the increased Gal-3 and Gal-9 of obesity mostly derived from the stromovascular fraction. Expression of Gal-12 was restricted to adipocytes. There was increased production of Gal-3 and Gal-9, but not Gal-1, in CD11c(-) and CD11c(+) macrophages from VAT of DIO versus lean mice. Expression of Gal-1, -3 and -12 in VAT and SAT of ob/ob mice followed a trend comparable to DIO mice. Rosiglitazone reduced serum Gal-1, but not Gal-3 and modulated expression of Gal-3 in VAT and Gal-9 and Gal-12 in SAT of DIO mice. High-fat feeding lead to increased adiposity in Gal-1 KO versus WT mice, with loss of correlation between leptin and adiposity and no alterations in glucose and insulin levels.. Obesity leads to differential modulation of Gal-1, 3, 9 and 12 in VAT and SAT, with Gal-1 acting as a modulator of adiposity. Topics: Adipocytes; Adiponectin; Adiposity; Animals; Diet, High-Fat; Galectins; Inflammation; Insulin; Intra-Abdominal Fat; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; Subcutaneous Fat | 2013 |
Adipocyte-macrophage interaction may mediate LPS-induced low-grade inflammation: potential link with metabolic complications.
Chronic low-grade infection has been suggested to be associated with metabolic disorder such as diabetes. However, the molecular mechanism underlying this important association is largely unknown. The only clue established so far is that many subjects exhibit elevated levels of C-reactive protein as measured by highly sensitive assay. Here, we hypothesized that adipocyte-macrophage interaction plays a key role in amplifying such low grade infection to the level of influencing metabolic disorders. The presence of macrophages in abdominal adipose tissues was investigated by immunohistochemistry. To see whether molecules associated with acute phase protein, LPS signaling, and persistent recruitment of monocytes, are produced at higher amounts in adipocytes co-cultured with macrophages stimulated with low concentration of LPS (1 ng/ml), we measured serum amyloid A (SAA), LPS binding protein (LBP), soluble CD14 (sCD14), and RANTES levels in culture supernatant of co-cultures. Lastly, we investigated in vivo effect of low-grade LPS infusion on the production of these molecules using obese model mice. The macrophages were certainly identified in abdominal adipose tissues. Investigated molecules, especially LBP, SAA, and RANTES were produced at higher amounts in co-cultures stimulated with LPS compared with the cells without LPS. The ob/ob, and high-fat diet-induced obesity mice produced higher amounts of LBP, SAA, and RANTES one day after LPS infusion (1 ng/ml/g body weight) compared with ob/- and normal-fat fed control mice. Thus, adipocytes and infiltrated macrophages, and their interaction with low endotoxin stimulation appear to play an important role in amplifying and maintaining LPS-induced low-grade inflammation. Topics: Abdominal Fat; Acute-Phase Proteins; Adipocytes; Animals; Carrier Proteins; Cell Communication; Cells, Cultured; Chemokine CCL5; Coculture Techniques; Diet, High-Fat; Disease Models, Animal; Gene Expression Regulation; Humans; Inflammation; Leptin; Lipid Metabolism Disorders; Lipopolysaccharide Receptors; Lipopolysaccharides; Macrophages; Membrane Glycoproteins; Mice; Mice, Knockout; Mice, Obese; Serum Amyloid A Protein | 2012 |
Angiotensin-converting enzyme inhibition reverses diet-induced obesity, insulin resistance and inflammation in C57BL/6J mice.
Angiotensin-converting enzyme (ACE) inhibition can reduce the body weight of mice maintained on a high-fat diet. The current study examined the effect of the ACE inhibitor, captopril (CAP), on the reversal of diet-induced obesity (DIO), insulin resistance and inflammation in mice.. DIO was produced in C57BL/6J male mice (n=30) by maintaining animals on a high-fat diet (w/w 21% fat) for 12 weeks. During the subsequent 12-week treatment period, the animals were allowed access to the high-fat diet and either water containing CAP (0.05 mg ml(-1)) or plain tap water (CON, control).. From the first week of treatment, food intake and body weight decreased in CAP-treated mice compared with CON mice. Both peripheral insulin sensitivity and hepatic insulin sensitivity were improved in CAP-treated mice compared with CON mice. CAP-treated mice had decreased absolute and relative liver and epididymal fat weights compared with CON mice. CAP-treated mice had higher plasma adiponectin and lower plasma leptin levels than CON mice. Relative to CON mice, CAP-treated mice had reduced adipose and skeletal muscle monocyte chemoattractant protein 1 (MCP-1), adipose interleukin-6 (IL-6), toll-like receptor 4 (TLR4) and uncoupling protein 2 (UCP2) mRNA expressions. Furthermore, CAP-treated mice had increased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), long chain acyl-CoA dehydrogenase (LCAD), hormone sensitive lipase (HSL) and decreased lipoprotein lipase (LPL) mRNA expressions in the liver.. The results of the current study indicate that in mice with DIO, CAP treatment reduced food intake and body weight, improved insulin sensitivity and decreased the mRNA expression of markers of inflammation. Thus, CAP may be a viable treatment for obesity, insulin resistance and inflammation. Topics: Acyl-CoA Dehydrogenase, Long-Chain; Adiponectin; Adipose Tissue; Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Body Weight; Captopril; Chemokine CCL2; Diet, High-Fat; Gene Expression Regulation; Glucose Tolerance Test; Inflammation; Insulin Resistance; Interleukin-6; Ion Channels; Leptin; Lipid Metabolism; Lipoprotein Lipase; Male; Mice; Mice, Inbred C57BL; Mitochondrial Proteins; Muscle, Skeletal; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Sterol Esterase; Toll-Like Receptor 4; Trans-Activators; Transcription Factors; Uncoupling Protein 2 | 2012 |
Hyperleptinemia is associated with hypertension, systemic inflammation and insulin resistance in overweight but not in normal weight men.
High leptin (LPT) is associated with high blood pressure (BP), insulin resistance and systemic inflammation but also excess body weight and adiposity. To disentangle these multiple relations, we analyzed BP, HOMA and circulating C-reactive protein concentration (hs-CRP) in white male adults with different LPT levels but similar age, body mass index (BMI) and body fat distribution. The novel aspect is the different statistical approach used to investigate the relation between LPT and the other alterations present in obesity.. 972 Olivetti Heart Study participants were stratified according to the median LPT distribution (2.97 ng/ml) into low LPT (l-LPT) and high LPT (h-LPT). The two groups were then carefully matched for age and BMI. We identified two groups of 207 h-LPT and 207 l-LPT individuals with overlapping age, BMI and waist/hip ratio. The two groups had different BP (132.9 ± 16.2/85.7 ± 9.0 vs 128.7 ± 18.2/82.8 ± 9.8 mmHg, p = 0.014 for SBP and p = 0.002 for DBP) and prevalence of hypertension (57% vs 43%, p = 0.027). Upon separate evaluation of untreated individuals with BMI < 25 or BMI ≥ 25, within the latter subgroup h-LPT compared with l-LPT participants (n = 133 each group) had higher BP (p = 0.0001), HOMA index (p = 0.013), hs-CRP (p = 0.002) and heart rate (p = 0.008) despite similar age and BMI. By contrast, within the normal weight subgroup, h-LPT individuals did not differ from l-LPT (n = 37 each) for any of these variables.. High LPT is associated with higher BP, HR, hs-CRP and HOMA index independently of BMI and fat distribution but only among overweight individuals. Topics: Adiposity; Adult; Aged; Analysis of Variance; Biomarkers; Blood Pressure; Body Mass Index; C-Reactive Protein; Case-Control Studies; Humans; Hypertension; Inflammation; Inflammation Mediators; Insulin Resistance; Italy; Leptin; Linear Models; Logistic Models; Male; Middle Aged; Odds Ratio; Overweight; Risk Assessment; Risk Factors; Sex Factors; Up-Regulation | 2012 |
Induction of osteoarthritis and metabolic inflammation by a very high-fat diet in mice: effects of short-term exercise.
To test the hypotheses that obesity due to a very high-fat diet induces knee osteoarthritis (OA), and that short-term wheel-running exercise protects against obesity-induced knee OA by reducing systemic inflammation and metabolic dysregulation.. Male C57BL/6J mice were fed either a control diet (13.5% kcal from fat) or a very high-fat diet (60% kcal from fat) from age 12 weeks to age 24 weeks. From 20 to 24 weeks of age, half of the mice were housed with running wheels. The severity of knee OA was determined by assessing histopathologic features, and serum cytokines were measured using a multiplex bead immunoassay and enzyme-linked immunosorbent assays. Body composition was quantified by dual-energy x-ray absorptiometry, and insulin resistance was assessed by glucose tolerance testing.. Feeding mice with a very high-fat diet increased knee OA scores and levels of serum leptin, adiponectin, KC (mouse analog of interleukin-8 [IL-8]), monokine induced by interferon-γ (CXCL9), and IL-1 receptor antagonist to an extent in proportion to the gain in body fat (3-fold increase in percent body fat compared to controls). Wheel-running exercise reduced progression of OA in the medial femur of obese mice. In addition, exercise disrupted the clustering of cytokine expression and improved glucose tolerance, without reducing body fat or cytokine levels.. Obesity induced by a very high-fat diet in mice causes OA and systemic inflammation in proportion to body fat. Increased joint loading is not sufficient to explain the increased incidence of knee OA with obesity, as wheel running is protective rather than damaging. Exercise improves glucose tolerance and disrupts the coexpression of proinflammatory cytokines, suggesting that increased aerobic exercise may act independently of weight loss in promoting joint health. Topics: Adiponectin; Animals; Body Composition; Chemokine CXCL1; Chemokine CXCL9; Diet, High-Fat; Inflammation; Interleukin 1 Receptor Antagonist Protein; Leptin; Male; Mice; Obesity; Osteoarthritis, Knee; Physical Conditioning, Animal | 2012 |
Inflammatory markers and their relationships with leptin and insulin from acute mania to full remission in bipolar disorder.
Weight gain and increased production of leptin may be associated with immuno-modulation and insulin resistance in bipolar disorder. The links among inflammatory markers, leptin, and insulin of bipolar patients from acute mania to full remission remain unclear.. Thirty-three healthy, bipolar I patients under 45 years of age were enrolled. We measured the circulating levels of high-sensitivity C-reactive protein (hs-CRP), anti-inflammatory mediators (interleukin-1 receptor antagonist [IL-1Ra] and soluble tumor necrosis factor receptor 1 [sTNF-R1]), leptin, and insulin during acute mania and subsequent partial and full remission. The results were compared with 33 age- and gender-matched healthy subjects.. The levels of IL-1Ra and hs-CRP of bipolar patients in both acute mania and partial remission were significantly higher than their levels of control subjects. The hs-CRP level of bipolar patients was also elevated in full remission. The elevation of IL-1Ra and hs-CRP levels in acute mania was independent of each other. They were also independent of the body mass index (BMI) and levels of leptin and insulin measurements. The levels of leptin were all positively associated with insulin levels in the normal subjects and bipolar patients in three phases. However, a significant relationship between leptin and immunoparameter was only seen in full remission with sTNF-R1 (r=0.51). Furthermore, IL-1Ra was inversely correlated with sTNF-R1 (r=-0.37, p<0.05) during partly remission, and while levels of IL-1Ra tended to normalize when patients remitted, levels of hs-CRP and sTNF-R1 showed the opposite trend.. Activated inflammation was found in acute mania, as evidenced by high levels of IL-1Ra, hs-CRP, and sTNF-R1. The production of leptin may be more tightly linked to insulin than the immunomodulators. Chronic inflammation may exist in bipolar patients and is reflected by elevations of IL-1Ra and hs-CRP levels in acute mania and persistent higher hs-CRP in full remission. Topics: Adult; Biomarkers; Bipolar Disorder; Body Mass Index; C-Reactive Protein; Female; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin 1 Receptor Antagonist Protein; Leptin; Male; Receptors, Tumor Necrosis Factor, Type I; Remission Induction; Young Adult | 2012 |
IL-6 regulates exercise and training-induced adaptations in subcutaneous adipose tissue in mice.
The aim of this study was to test the hypothesis that IL-6 regulates exercise-induced gene responses in subcutaneous adipose tissue in mice.. Four-month-old male IL-6 whole body knockout (KO) mice and C57B wild-type (WT) mice performed 1 h of treadmill exercise, where subcutaneous adipose tissue (AT) was removed either immediately after, 4 h or 10 h after exercise as well as from mice not running acutely. Moreover, AT was sampled at resting conditions after 5 weeks of exercise training.. AT leptin mRNA decreased immediately after a single running exercise bout in both genotypes and returned to baseline within 10 h of recovery in IL-6 KO mice, but not WT mice. Leptin mRNA content decreased in WT and increased in IL-6 KO mice with training, but without significant alterations in leptin protein. Acute exercise induced a decrease in the AT TNFα mRNA content in WT, but not in IL-6-KO mice, while training lowered resting levels of TNFα mRNA in both genotypes. In addition, an exercise-induced decline in AT PPARγ mRNA content was absent in IL-6 KO mice and in line training increased PPARγ mRNA only in IL-6 KO mice.. The present findings indicate a role of IL-6 in regulating exercise- and training-induced leptin and PPARγ expression in adipose tissue. In addition, while IL-6 is required for TNF-α mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue. Topics: Adaptation, Physiological; Animals; Inflammation; Interleukin-6; Leptin; Male; Mice; Mice, Knockout; Physical Conditioning, Animal; Subcutaneous Fat; Tumor Necrosis Factor-alpha | 2012 |
Comparison of markers of appetite and inflammation between hemodialysis patients with and without failed renal transplants.
The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aim to compare the markers of appetite and malnutrition, and their relation with inflammation in HD patients with and without previous kidney transplantation.. Fifty-six patients with failed renal allografts at least 3 months on dialysis (31 men, 25 women; mean age, 46 ± 9 years) and 77 HD patients who never underwent a transplant (43 men, 34 women; mean age, 50 ± 15 years) were included in the study. The appetite and diet assessment tool (ADAT) was used to determine the self reported appetite of patients. Serum concentrations of ghrelin, leptin, insulin like growth factor 1 (IGF-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were measured. Associations among these variables were analyzed.. There were no significant differences considering age, gender or duration of renal replacement therapy between the 2 groups. The scores from Appetite and Diet Assessment Tool were significantly higher in the failed-transplant group. Serum ghrelin levels were significantly higher and serum albumin levels were significantly lower in the failed-transplant group. Serum leptin levels were similar between 2 groups. In addition, hs-CRP, IL-6, and TNF-α levels, which were used as inflammatory parameters, were significantly higher in the failed-transplant group.. Elevated serum ghrelin levels and inflammation may cause diminished appetite and malnutrition in patients with failed renal allografts, and higher levels of this hormone seem to be associated with inflammation caused by retained failed allografts. Topics: Adult; Appetite; Biomarkers; C-Reactive Protein; Female; Ghrelin; Humans; Inflammation; Insulin-Like Growth Factor I; Interleukin-6; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Malnutrition; Middle Aged; Nutritional Status; Renal Dialysis; Transplantation, Homologous; Treatment Failure; Tumor Necrosis Factor-alpha | 2012 |
Effects of high-fat diet on plasma lipids, adiposity, and inflammatory markers in ovariectomized C57BL/6 mice.
We hypothesized that a high-fat (HF) diet aggravates ovariectomy-related complications. To test this hypothesis, ovariectomized (OVX) mice were fed a HF diet, and we investigated the lipid metabolism, adipose tissue remodeling, adipokines, and inflammatory cytokines.. To investigate the situation in a mouse model of ovariectomy, OVX and SHAM C57BL/6 mice fed a HF diet (60% fat) or standard chow (SC, 10% fat) were monitored for 18 wk. We evaluated daily food intake and weekly body weight. Mice were killed at 30 wk of age. Blood samples and adipose tissue were collected for biochemical, histologic, and molecular analysis.. OVX groups showed atrophied uterus compared to the SHAM groups, ensuring the success of surgically induced menopause. Despite lower food intake, OVX-HF mice gained about 52% more weight and had heavier total body fats, especially in relation to ovarian fat pad (372%)-a visceral fat which is associated with increased pathogenicity in obesity, and showed larger adipocytes (30%) when compared to OVX-SC mice. Biochemical analysis showed that the OVX-HF mice had increased levels of serum total cholesterol (51%), greater serum triglycerides (158%), lower serum adiponectin (40%), and higher plasma leptin (323%) than OVX-SC mice. The obese group (OVX-HF) also had higher IL-6 levels than both SHAM-HF (241%) and OVX-SC mice (870%).. OVX C57BL/6 mice fed HF diet had greater adipose fat pad, larger adipocytes, and increased inflammatory markers, reinforcing the idea that a HF diet aggravates the complications of ovariectomy-associated inflammation. Topics: Adipokines; Adiponectin; Adipose Tissue; Adiposity; Animals; Biomarkers; Body Weight; Cholesterol; Diet, High-Fat; Dietary Fats; Female; Inflammation; Interleukin-6; Leptin; Lipid Metabolism; Mice; Mice, Inbred C57BL; Obesity; Ovariectomy; Triglycerides | 2012 |
Effects of the insulin sensitizing drug, pioglitazone, and lipopolysaccharide administration on markers of systemic inflammation and clinical parameters in horses.
Equine metabolic syndrome (EMS) is a condition of obese horses characterized by insulin resistance, systemic inflammation, and an increased risk of laminitis. The pathogenesis of EMS is thought, in part, to be due to inflammatory proteins produced by adipose tissue. Reducing inflammation may decrease the incidence of laminitis in horses with EMS. Pioglitazone hydrochloride, a thiazolidinedione, has efficacy to reduce obesity associated inflammation in humans. Eight normal, adult, horses were administered 1mg/kg pioglitazone for 14 days, and eight horses served as controls. Physical examination and hematologic variables, transcript abundance of pro-inflammatory cytokines in skeletal muscle and adipose tissue, and circulating concentrations of the acute phase protein, serum amyloid A and pro-inflammatory cytokine, TNF-α were assessed prior to, and following, an LPS infusion (35 ng/kg). The objective was to determine if pre-treatment with pioglitazone would mitigate the development of inflammation and associated clinical markers of inflammation following LPS administration. Lipopolysaccharide administration induced systemic inflammation, as assessed by clinical and hematological aberrations, increased TNF-α, SAA and adipose tissue IL-6 mRNA abundance, however no mitigating effects of pioglitazone were detected. A longer treatment period or higher dose might be indicated for future experiments. Topics: Adipose Tissue; Animals; Biomarkers; Chemokine CCL2; Chemokine CCL8; Female; Horse Diseases; Horses; Hypoglycemic Agents; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Leptin; Lipopolysaccharides; Muscle, Skeletal; Pioglitazone; Plasminogen Activator Inhibitor 1; Thiazolidinediones; Tumor Necrosis Factor-alpha | 2012 |
Cardiac autonomic imbalance in newly diagnosed and established diabetes is associated with markers of adipose tissue inflammation.
Diabetics die from cardiovascular disease at a much greater rate than nondiabetics. Cardiac autonomic imbalance predicts increased cardiovascular risk and mortality. We studied the relationship between cardiac autonomic imbalance and adipose tissue-derived inflammation in newly diagnosed and established type 2 diabetes.. Non-diabetics, newly diagnosed diabetics, and established diabetics were included. Anthropomorphic and biochemical measurements were obtained, and insulin resistance was approximated. Cardiac autonomic function was assessed using conventional measures and with power spectral analysis of heart rate.. Heart rate variability was reduced in all diabetics. Interleukin-6 was higher in diabetics, as was the high molecular weight adiponectin-to-leptin ratio. Interleukin-6 correlated negatively with measures of autonomic balance. Ratios of adiponectin to leptin correlated positively with measures of autonomic balance. Cardiac autonomic imbalance and inflammation occur early in diabetes and are interrelated.. Cardiac autonomic imbalance correlates with the adipose tissue-derived inflammation seen early in type 2 diabetes. Topics: Adiponectin; Adipose Tissue; Autonomic Nervous System Diseases; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Heart; Heart Rate; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin | 2012 |
Leptin and interleukin-6 alter the function of mesolimbic dopamine neurons in a rodent model of prenatal inflammation.
Maternal inflammation during critical stages of gestation is thought to underlie the link between prenatal infection and several neurodevelopmental psychiatric disorders in the offspring, including schizophrenia. Increased activity of mesolimbic dopamine (DA) neurons, a hallmark of psychosis, is found in offspring of rodents exposed to a prenatal inflammatory challenge but it is unclear how this effect is elicited. Using an experimental model of localized aseptic inflammation with turpentine oil (TURP) we sought to establish whether circulating interleukin-6 (IL-6) and leptin play a role in the effects of prenatal inflammation on DA neurons. Both mediators are involved in the systemic inflammatory response to immunogens, with IL-6 mediating the early phase, followed by leptin in the late phase of the response. Maternal treatment with TURP at gestational day (GD) 15 enhanced the locomotor response to the DA indirect agonist, amphetamine (AMPH), increased the expression of tyrosine hydroxylase (TH), an enzyme involved in DA synthesis, DA levels and the expression of the post-synaptic protein spinophilin in the nucleus accumbens (NAcc) in the adult offspring. All of these alterations were totally abolished by co-treating the pregnant dams with a neutralizing IL-6 antiserum. Neutralization of maternal leptin prevented the enhanced behavioral sensitization and elevation of DA and spinophilin in the NAcc but spared other changes regulated by IL-6, such as increased NAcc TH levels and acute locomotor response to AMPH. Our results provide novel evidence to suggest that prenatal surges in both maternal circulating IL-6 and leptin contribute to the appearance of sensitized DA function in the adult offspring. Topics: Animals; Antibodies; Dopaminergic Neurons; Female; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Limbic System; Models, Animal; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Rodentia; Turpentine | 2012 |
Serum leptin level mediates the association of body composition and serum C-reactive protein in HIV-infected persons on antiretroviral therapy.
Higher body mass index (BMI) is associated with increased serum C-reactive protein (CRP) levels in HIV-infected individuals on antiretroviral therapy (ART), but the relationship of adipose tissue mass to systemic inflammation is not well described in this population. We hypothesized that serum adipokine levels (i.e., hormones produced by adipocytes) are a superior predictor of CRP compared to anthropometric or radiographic measures of body composition in patients on effective, stable ART. We evaluated the relationship of serum leptin, adiponectin, and resistin, BMI, and dual energy x-ray absorptiometry (DEXA) measurements with serum highly sensitive CRP (hsCRP) in a cross-sectional cohort of 106 predominantly virologically suppressed, HIV-infected adults on ART for ≥24 weeks using multivariable linear regression and formal criteria to assess statistical mediation. Median BMI, hsCRP, and leptin values were 25.2 kg/m(2), 3.0 mg/liter, and 3.8 ng/ml, respectively. BMI and DEXA limb fat, body fat, and trunk fat measurements were significantly associated with both serum leptin and hsCRP levels (all p≤0.02). Leptin was also associated with hsCRP (p<0.01). The regression coefficient for the effect of BMI or DEXA measurements on hsCRP was reduced, and the relationship was no longer statistically significant, after adjusting for leptin, indicating leptin functioned as a mediating variable within these relationships. Adiponectin and resistin levels did not demonstrate similar effects. Serum leptin was a superior predictor of hsCRP compared to BMI and DEXA body fat measurements, which may reflect alterations in body composition in treated HIV infection and the important contribution of adipose tissue to inflammation in this population. Topics: Absorptiometry, Photon; Acquired Immunodeficiency Syndrome; Adiponectin; Adipose Tissue; Adult; Anti-HIV Agents; Body Composition; Body Mass Index; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Predictive Value of Tests | 2012 |
Sedentary behavior and adiposity-associated inflammation: the Multi-Ethnic Study of Atherosclerosis.
Sedentary behavior is associated with adiposity and cardiometabolic risk.. To determine the associations between sedentary behavior and measures of adiposity-associated inflammation.. Between 2002 and 2005, a total of 1543 Multi-Ethnic Study of Atherosclerosis participants completed detailed health history questionnaires, underwent physical measurements, and had blood assayed for adiponectin, leptin, tumor necrosis factor-alpha (TNF-α) and resistin. Analyses included linear regression completed in 2010. The mean age was 64.3 years and nearly 50% were female. Forty-one percent were non-Hispanic white, 24% Hispanic-American, 20% African-American, and 14% Chinese-American.. In linear regression analyses and with adjustment for age, gender, ethnicity, education, BMI, smoking, alcohol consumption, hypertension, diabetes mellitus, dyslipidemia, hormone therapy and waist circumference, sedentary behavior was associated with higher natural log ("ln") of leptin and ln TNF-α but a lower ln adiponectin-to-leptin ratio (β=0.07, β=0.03 and -0.07, p<0.05 for all). Compared to the first tertile, and after the same adjustment, the second and third tertiles of sedentary behavior were associated with higher levels of ln leptin (β=0.11 and β=0.12, respectively; p<0.05 for both) but lower levels of the adiponectin-to-leptin ratio (β=-0.09 and -0.11, respectively; p<0.05 for both).. Sedentary behavior is associated with unfavorable levels of adiposity-associated inflammation. Topics: Adiponectin; Adiposity; Aged; Aged, 80 and over; Atherosclerosis; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Ethnicity; Female; Humans; Inflammation; Leptin; Linear Models; Longitudinal Studies; Male; Metabolic Diseases; Middle Aged; Sedentary Behavior; Tumor Necrosis Factor-alpha | 2012 |
Differential insulin receptor substrate-1 (IRS1)-related modulation of neuropeptide Y and proopiomelanocortin expression in nondiabetic and diabetic IRS2-/- mice.
Insulin resistance and type 2 diabetes correlate with impaired leptin and insulin signaling. Insulin receptor substrate-2 deficient (IRS2(-/-)) mice are an accepted model for the exploration of alterations in these signaling pathways and their relationship with diabetes; however, disturbances in hypothalamic signaling and the effect on neuropeptides controlling food intake remain unclear. Our aim was to analyze how leptin and insulin signaling may differentially affect the expression of hypothalamic neuropeptides regulating food intake and hypothalamic inflammation in diabetic (D) and nondiabetic (ND) IRS2(-/-) mice. We analyzed the activation of leptin and insulin targets by Western blotting and their association by immunoprecipitation, as well as the mRNA levels of neuropeptide Y (NPY), proopiomelanocortin, and inflammatory markers by real-time PCR and colocalization of forkhead box protein O1 (FOXO1) and NPY by double immunohistochemistry in the hypothalamus. Serum leptin and insulin levels and hypothalamic Janus kinase 2 and signal transducer and activator of transcription factor 3 activation were increased in ND IRS2(-/-) mice. IRS1 levels and its association with Janus kinase 2 and p85 and protein kinase B activation were increased in ND IRS2(-/-). Increased FOXO1 positively correlated with NPY mRNA levels in D IRS2(-/-) mice, with FOXO1 showing mainly nuclear localization in D IRS2(-/-) and cytoplasmic in ND IRS2(-/-) mice. D IRS2(-/-) mice exhibited higher hypothalamic inflammation markers than ND IRS2(-/-) mice. In conclusion, differential activation of these pathways and changes in the expression of NPY and inflammation may exert a protective effect against hypothalamic deregulation of appetite, suggesting that manipulation of these targets could be of interest in the treatment of insulin resistance and type 2 diabetes. Topics: Animals; Blood Glucose; Diabetes Mellitus; Gene Expression Regulation; Hypothalamus; Immunohistochemistry; Inflammation; Insulin Receptor Substrate Proteins; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Biological; Neuropeptide Y; Pro-Opiomelanocortin | 2012 |
Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation.
The mechanisms underlying the pathogenesis of obesity-related atherosclerosis remain to be clarified. To investigate the preclinical phase, interleukin-6 (IL-6) plasma levels were analyzed together with clinical, anthropometric, inflammatory, and metabolic variables in a well-defined cohort of 677 young and middle-aged overweight/obese and normal-weight subjects. In the juvenile and adult overweight/obese study group, IL-6 levels were increased significantly compared with normal-weight, age-matched controls (P < 0.001). In both juveniles and adults, higher levels of IL-6 were observed in obese compared with overweight participants. Subjects with metabolic syndrome (MS) had significantly higher IL-6 levels than those without MS. In juveniles, leptin, and in adults, the waist-to-height ratio, turned out to be the best predictor of IL-6 plasma levels in a multiple stepwise regression model. Taken together, in every age group, interleukin-6 is associated positively with the grade of overweight. Interestingly, leptin, which is the best known adipokine, is associated predictively with interleukin-6 plasma levels only in juveniles, which may indicate an important role of this molecule in the initiation of obesity-related inflammation. Topics: Adolescent; Adult; Age Factors; Atherosclerosis; Biomarkers; Body Height; Body Mass Index; Child; Cohort Studies; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Regression Analysis; Waist Circumference | 2012 |
Early postnatal hyperalimentation impairs renal function via SOCS-3 mediated renal postreceptor leptin resistance.
Early postnatal hyperalimentation has long-term implications for obesity and developing renal disease. Suppressor of cytokine signaling (SOCS) 3 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and ERK1/2 and thereby plays a pivotal role in mediating leptin resistance. In addition, SOCS-3 is induced by both leptin and inflammatory cytokines. However, little is known about the intrinsic-renal leptin synthesis and function. Therefore, this study aimed to elucidate the implications of early postnatal hyperalimentation on renal function and on the intrinsic-renal leptin signaling. Early postnatal hyperalimentation in Wistar rats during lactation was induced by litter size reduction at birth (LSR) either to LSR10 or LSR6, compared with home cage control male rats. Assessment of renal function at postnatal day 70 revealed decreased glomerular filtration rate and proteinuria after LSR6. In line with this impairment of renal function, renal inflammation and expression as well as deposition of extracellular matrix molecules, such as collagen I, were increased. Furthermore, renal expression of leptin and IL-6 was up-regulated subsequent to LSR6. Interestingly, the phosphorylation of Stat3 and ERK1/2 in the kidney, however, was decreased after LSR6, indicating postreceptor leptin resistance. In accordance, neuropeptide Y (NPY) gene expression was down-regulated; moreover, SOCS-3 protein expression, a mediator of postreceptor leptin resistance, was strongly elevated and colocalized with NPY. Thus, our findings not only demonstrate impaired renal function and profibrotic processes but also provide compelling evidence of a SOCS-3-mediated intrinsic renal leptin resistance and concomitant up-regulated NPY expression as an underlying mechanism. Topics: Animal Feed; Animals; Cytokines; Feeding Behavior; Gene Expression Regulation; Inflammation; Kidney; Leptin; Male; MAP Kinase Signaling System; Mice; Neuropeptide Y; PC12 Cells; Rats; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins | 2012 |
The role of leptin and its short-form receptor in inflammation in db/db mice infused with peritoneal dialysis fluid.
In peritoneal dialysis (PD), the peritoneal membrane exhibits structural and functional changes following continuous exposure to the non-physiological peritoneal dialysis fluid (PDF). In this study, we examined the effect of PDF on peritoneal adipose tissue in a diabetic milieu.. Six-week-old db/db mice and their non-diabetic littermates (db/m) were subjected to uninephrectomy. All animals then received intra-abdominal infusion of lactated Ringer's solution (Ringer) or 1.5% glucose-containing PDF (Dianeal) twice daily. Mice were sacrificed 4 weeks later. Parietal and visceral adipose tissues were harvested for examining gene and protein expression of adiponectin, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, tumor necrosis factor alpha (TNF-α), transforming growth factor beta and interleukin 6 (IL-6). Expression of TNF-α and F4/80+ macrophage accumulation in adipose tissues was assessed by immunohistochemical staining. Modulation of leptin synthesis and leptin receptors expression and the relevant signaling pathways were also determined by quantitative reverse transcription-polymerase chain reaction, immunoblotting or enzyme-linked immunosorbent assay.. Compared to Ringer infusion, Dianeal infusion significantly increased serum leptin but decreased adiponectin in db/db mice. Increased expression of leptin, TNF-α and IL-6 was observed in visceral but not in parietal adipose tissue. Dianeal infusion also increased F4/80+ macrophage accumulation and enhanced the expression of pro-inflammatory cytokines including IL-6 and TNF-α in the visceral adipose tissue. Compared to db/m mice, infusion with Dianeal exhibited a more deleterious effect on db/db mice, characterized by an upregulation of short-form leptin receptor ObRa and activation of the mitogen-activated protein kinase signaling pathway.. In conclusion, PD-induced hyperleptinemia amplifies the inflammatory response of adipose tissue through short-form leptin receptor when the long-form isotype is defective. Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Base Sequence; Diabetes Mellitus; Dialysis Solutions; DNA Primers; Inflammation; Interleukin-6; Leptin; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Peritoneal Dialysis, Continuous Ambulatory; Receptors, Leptin; RNA, Messenger; Tumor Necrosis Factor-alpha | 2012 |
Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure.
Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. Topics: Acute-Phase Reaction; Adiponectin; Animals; Asbestos, Amphibole; Biomarkers; Inflammation; Leptin; Lipocalin-2; Lipocalins; Macroglobulins; Male; Metabolic Syndrome; Orosomucoid; Osteopontin; Proteomics; Rats; Rats, Inbred F344; Rats, Inbred SHR; Rats, Inbred WKY; Retrospective Studies | 2012 |
Adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure: correction after ventricular assist device implantation.
Heart failure (HF) is characterized by inflammation, insulin resistance, and progressive catabolism. We hypothesized that patients with advanced HF also develop adipose tissue inflammation associated with impaired adipokine signaling and that hemodynamic correction through implantation of ventricular assist devices (VADs) would reverse adipocyte activation and correct adipokine signaling in advanced HF.. Circulating insulin, adiponectin, leptin, and resistin levels were measured in 36 patients with advanced HF before and after VAD implantation and 10 healthy control subjects. Serum adiponectin was higher in HF patients before VAD implantation compared with control subjects (13.3±4.9 versus 6.4±2.1 μg/mL, P=0.02). VAD implantation (mean, 129±99 days) reduced serum adiponectin (7.4±3.4 μg/mL, P<0.05) and improved insulin resistance (Homeostasis Assessment Model of insulin resistance: 7.6±7.7-4.5±3.6; P=0.012). [corrected] Adiponectin expression in adipose tissue decreased after VAD implantation (-65%; P<0.03). Adiponectin receptor expression was suppressed in the failing myocardium compared with control subjects and increased after mechanical unloading. Histomorphometric analysis of adipose tissue specimens revealed reduced adipocyte size in patients with advanced HF compared with control subjects (2105±585 μm(2) [corrected] versus 5583±142 μm(2) in control subjects; P<0.05), which increased after VAD placement. Of note, macrophage infiltration in adipose tissue was higher in advanced HF patients compared with control subjects (+25%; P<0.01), which normalized after VAD implantation.. Adipose tissue inflammation and adiponectin resistance develop in advanced HF. Mechanical unloading of the failing myocardium reverses adipose tissue macrophage infiltration, inflammation, and adiponectin resistance in patients with advanced HF. Topics: Adiponectin; Adipose Tissue; Adult; Aged; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Heart Failure; Heart-Assist Devices; Hemodynamics; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Macrophages; Male; Middle Aged; Resistin; Retrospective Studies; Severity of Illness Index; Signal Transduction | 2012 |
Is a body mass index of 23 kg/m² a reliable marker of protein-energy wasting in hemodialysis patients?
To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m² for the body mass index (BMI).. Forty-seven patients (30 men, 11 diabetics, 53.8 ± 12.2 y of age, 58.2 ± 50.9 mo on HD) were studied. Anthropometric data and handgrip strength were evaluated. C-reactive protein, tumor necrosis factor-α, leptin, and interleukin-6 were measured. Mortality was assessed after 24 mo of follow-up.. Nineteen patients (40.4%) presented BMI values lower than 23 kg/m² and leptin levels, midarm muscle area, and free-fat mass were significantly lower in these patients. The prevalence of functional muscle loss according to handgrip strength was not different between the BMI groups. The sum of skinfold thicknesses, the percentage of body fat, fat mass, the fat mass/free-fat mass ratio, and waist circumference were significantly lower in patients with a BMI lower than 23 kg/m², but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m² presented a higher prevalence of inflammation and higher waist circumference and body fat values. The adiposity parameters were correlated with C-reactive protein and leptin. A Cox multivariate regression analysis demonstrated that C-reactive protein, tumor necrosis factor-α, and interleukin-6 predict cardiovascular mortality.. Patients on HD with a BMI lower than 23 kg/m² did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m² had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m² does not seem to be a reliable marker of protein-energy wasting in patients on HD. Topics: Adult; Aged; Biomarkers; Body Composition; Body Fluid Compartments; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Diabetes Complications; Female; Humans; Inflammation; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Muscle, Skeletal; Obesity; Proportional Hazards Models; Protein-Energy Malnutrition; Reference Values; Renal Dialysis; Reproducibility of Results; Wasting Syndrome | 2012 |
Allergen-induced bone marrow eosinophilopoiesis and airways eosinophilic inflammation in leptin-deficient ob/ob mice.
Asthma and obesity are growing epidemics in the world. It is well established that obesity worsens the asthma outcomes. High-fat diet-induced obesity in mice exacerbates the pulmonary eosinophilic inflammation. We have used wild-type (WT) and ob/ob mice to further explore the mechanisms by which obesity aggravates the pulmonary eosinophilic inflammation. The eosinophil (EO) number in bronchoalveolar lavage (BAL) fluid, lung tissue, blood, and bone marrow were evaluated at 24, 48, and 72 h after ovalbumin (OVA) challenge in sensitized mice. The basal EO number (phosphate-buffered saline (PBS)-instilled mice) in lung tissue was about 3.5-fold greater in ob/ob compared with WT mice. OVA challenge in ob/ob mice promoted an EO accumulation into the lung that was accompanied by a lower emigration to airways lumen (BAL fluid) in comparison with WT mice. OVA challenge also markedly elevated the number of mature and immature EO in bone marrow of ob/ob mice at 24 h compared with WT group. Blood EO at 48 h was markedly greater in ob/ob mice. Tumor necrosis factor (TNF)-α and interleukin (IL)-10 levels in BAL fluid were significantly higher in ob/ob mice, whereas no changes for IL-5 and eotaxin were found. The IL-6 levels were significantly lower in ob/ob mice. In conclusion, OVA challenge in ob/ob obese mice potentiates eosinophilopoiesis and promotes an accumulation of EO into the lung tissue, delaying their transit to airways lumen. The longer EO remain into the lung tissue is likely to contribute, at least in part, to the asthma worsened by obesity. Topics: Allergens; Animals; Bone Marrow; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Eosinophils; Female; Inflammation; Interleukin-6; Leptin; Leukocyte Count; Lung; Male; Mice; Mice, Obese; Obesity; Ovalbumin; Respiratory Hypersensitivity | 2012 |
Inhibition of hypothalamic inflammation reverses diet-induced insulin resistance in the liver.
Defective liver gluconeogenesis is the main mechanism leading to fasting hyperglycemia in type 2 diabetes, and, in concert with steatosis, it is the hallmark of hepatic insulin resistance. Experimental obesity results, at least in part, from hypothalamic inflammation, which leads to leptin resistance and defective regulation of energy homeostasis. Pharmacological or genetic disruption of hypothalamic inflammation restores leptin sensitivity and reduces adiposity. Here, we evaluate the effect of a hypothalamic anti-inflammatory approach to regulating hepatic responsiveness to insulin. Obese rodents were treated by intracerebroventricular injections, with immunoneutralizing antibodies against Toll-like receptor (TLR)4 or tumor necrosis factor (TNF)α, and insulin signal transduction, hepatic steatosis, and gluconeogenesis were evaluated. The inhibition of either TLR4 or TNFα reduced hypothalamic inflammation, which was accompanied by the reduction of hypothalamic resistance to leptin and improved insulin signal transduction in the liver. This was accompanied by reduced liver steatosis and reduced hepatic expression of markers of steatosis. Furthermore, the inhibition of hypothalamic inflammation restored defective liver glucose production. All these beneficial effects were abrogated by vagotomy. Thus, the inhibition of hypothalamic inflammation in obesity results in improved hepatic insulin signal transduction, leading to reduced steatosis and reduced gluconeogenesis. All these effects are mediated by parasympathetic signals delivered by the vagus nerve. Topics: Animals; Antibodies, Neutralizing; Fatty Liver; Gluconeogenesis; Homeostasis; Hypothalamus; Inflammation; Insulin; Insulin Resistance; Leptin; Liver; Male; Mice; Obesity; Rats; Rats, Wistar; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha | 2012 |
Acute leptin treatment enhances functional recovery after spinal cord injury.
Spinal cord injury is a major cause of long-term disability and has no current clinically accepted treatment. Leptin, an adipocyte-derived hormone, is best known as a regulator of food intake and energy expenditure. Interestingly, several studies have demonstrated that leptin has significant effects on proliferation and cell survival in different neuropathologies. Here, we sought to evaluate the role of leptin after spinal cord injury.. Based on its proposed neuroprotective role, we have evaluated the effects of a single, acute intraparenchymal injection of leptin in a clinically relevant animal model of spinal cord injury. As determined by quantitative Real Time-PCR, endogenous leptin and the long isoform of the leptin receptor genes show time-dependent variations in their expression in the healthy and injured adult spinal cord. Immunohistochemical analysis of post-injury tissue showed the long isoform of the leptin receptor expression in oligodendrocytes and, to a lesser extent, in astrocytes, microglia/macrophages and neurons. Moreover, leptin administered after spinal cord injury increased the expression of neuroprotective genes, reduced caspase-3 activity and decreased the expression of pro-inflammatory molecules. In addition, histological analysis performed at the completion of the study showed that leptin treatment reduced microglial reactivity and increased caudal myelin preservation, but it did not modulate astroglial reactivity. Consequently, leptin improved the recovery of sensory and locomotor functioning.. Our data suggest that leptin has a prominent neuroprotective and anti-inflammatory role in spinal cord damage and highlights leptin as a promising therapeutic agent. Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Gene Expression Profiling; Inflammation; Leptin; Locomotion; Macrophages; Male; Microglia; Neuralgia; Neurons; Neuroprotective Agents; Oligodendroglia; Peroxisome Proliferator-Activated Receptors; Rats; Rats, Wistar; Receptors, Leptin; Spinal Cord; Spinal Cord Injuries; Transcription, Genetic; Treatment Outcome; Up-Regulation | 2012 |
Evaluation of serum adipokines in peripheral arterial occlusive disease.
Out study aimed to assess the serum levels of adipokines in patients with peripheral arterial occlusive disease (PAOD) caused by atherosclerosis.. Serum samples were obtained from 221 patients. One hundred and forty patients, (26 females and 114 males) met the inclusion criteria and were assigned into the case group. Eighty one patients (17 females and 64 males), were included in the control group. Circulating plasma levels of adiponectin, leptin, resistin, and TNF-α were measured using the enzyme-linked immunosorbent assay (ELISA) method.. Significant lower levels of adiponectin were present (P = 0.0061) in PAOD patients (2380.23 ± 1634.42 pg/mL) compared to the control group (3065.06 ± 1901.2 pg/mL). The mean value of leptin (2844.42 ± 3301.08 pg/mL) and resistin (2047.81±3301.08 pg/mL) patients included in the PAOD group was higher, as compared to the control group. Statistically significant difference was found between the two groups for leptin (P = 0.0332) and for resistin (P = 0.0352). No statistically significant difference for TNF-α was found between the two groups (P > 0.05).. The markers of inflammation secreted by the adipose tissue (adiponectin, leptin, resistin) showed significant differences in patients from the case group (with PAOD) compared to the control group. Topics: Adipokines; Adiponectin; Adipose Tissue; Adipose Tissue, White; Aged; Arterial Occlusive Diseases; Atherosclerosis; Body Mass Index; C-Reactive Protein; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Models, Biological; Models, Statistical; Resistin; Tumor Necrosis Factor-alpha | 2012 |
Resistance to obesity by repression of VEGF gene expression through induction of brown-like adipocyte differentiation.
Adipose tissues are classified into white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is responsible for energy storage, and malfunction is associated with obesity. BAT, on the contrary, consumes fat to generate heat through uncoupling mitochondrial respiration and is important in body weight control. Vascular endothelial growth factor (VEGF)-A is the founding member of the VEGF family and has been found highly expressed in adipose tissue. A genetic mouse model of an inducible VEGF (VEGF-A) repression system was used to study VEGF-regulated energy metabolism in WAT. VEGF-repressed mice demonstrated lower food efficiency, lower body weight, and resistance to high-fat diet-induced obesity. Repression of VEGF expression caused morphological and molecular changes in adipose tissues. VEGF repression induced brown-like adipocyte development in WAT, up-regulation of BAT-specific genes including PRDM16, GATA-1, BMP-7, CIDEA, and UCP-1 and down-regulation of leptin, a WAT-specific gene. VEGF repression up-regulated expression of VEGF-B and its downstream fatty acid transport proteins. Relative levels of VEGF/VEGF-B may be important switches in energy metabolism and of pharmaceutical significances. Topics: Adipocytes; Adipogenesis; Adipose Tissue; Adipose Tissue, Brown; Animals; Body Weight; Cell Differentiation; Female; Gene Expression Profiling; Gene Expression Regulation; Inflammation; Leptin; Male; Mice; Mice, Transgenic; Microscopy, Fluorescence; Models, Genetic; Obesity; Phenotype; Vascular Endothelial Growth Factor A | 2012 |
Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation.
The metabolic actions of the ghrelin gene-derived peptide obestatin are still unclear. We investigated obestatin effects in vitro, on adipocyte function, and in vivo, on insulin resistance and inflammation in mice fed a high-fat diet (HFD). Obestatin effects on apoptosis, differentiation, lipolysis, and glucose uptake were determined in vitro in mouse 3T3-L1 and in human subcutaneous (hSC) and omental (hOM) adipocytes. In vivo, the influence of obestatin on glucose metabolism was assessed in mice fed an HFD for 8 wk. 3T3-L1, hSC, and hOM preadipocytes and adipocytes secreted obestatin and showed specific binding for the hormone. Obestatin prevented apoptosis in 3T3-L1 preadipocytes by increasing phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK)1/2 signaling. In both mice and human adipocytes, obestatin inhibited isoproterenol-induced lipolysis, promoted AMP-activated protein kinase phosphorylation, induced adiponectin, and reduced leptin secretion. Obestatin also enhanced glucose uptake in either the absence or presence of insulin, promoted GLUT4 translocation, and increased Akt phosphorylation and sirtuin 1 (SIRT1) protein expression. Inhibition of SIRT1 by small interfering RNA reduced obestatin-induced glucose uptake. In HFD-fed mice, obestatin reduced insulin resistance, increased insulin secretion from pancreatic islets, and reduced adipocyte apoptosis and inflammation in metabolic tissues. These results provide evidence of a novel role for obestatin in adipocyte function and glucose metabolism and suggest potential therapeutic perspectives in insulin resistance and metabolic dysfunctions. Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Animals; Apoptosis; Diet, High-Fat; Extracellular Signal-Regulated MAP Kinases; Ghrelin; Glucose; Glucose Transporter Type 4; Humans; Inflammation; Insulin Resistance; Islets of Langerhans; Leptin; Lipolysis; Mice; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction | 2012 |
Insulin resistance in the defense against obesity.
In the face of the current obesity epidemic, the nature of the relationship between overnutrition and type 2 diabetes is of great importance. Obesity can be considered a state of excessive insulin action that elicits a series of cellular homeostatic responses, producing systemic insulin resistance. These responses occur in four steps: homologous desensitization to insulin action, leptin secretion, inflammation, and, finally, a counter-inflammatory phase that serves to conserve energy storage. The molecular mechanisms underlying these steps are discussed in the context of potential new therapeutic approaches. Topics: Animals; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Obesity | 2012 |
Circulating levels of adiponectin, leptin, fetuin-A and retinol-binding protein in patients with tuberculosis: markers of metabolism and inflammation.
Wasting is known as a prominent feature of tuberculosis (TB). To monitor the disease state, markers of metabolism and inflammation are potentially useful. We thus analyzed two major adipokines, adiponectin and leptin, and two other metabolic markers, fetuin-A and retinol-binding protein 4 (RBP4).. The plasma levels of these markers were measured using enzyme-linked immunosorbent assays in 84 apparently healthy individuals (=no-symptom group) and 46 patients with active pulmonary TB around the time of treatment, including at the midpoint evaluation (=active-disease group) and compared them with body mass index (BMI), C-reactive protein (CRP), chest radiographs and TB-antigen specific response by interferon-γ release assay (IGRA).. In the no-symptom group, adiponectin and leptin showed negative and positive correlation with BMI respectively. In the active-disease group, at the time of diagnosis, leptin, fetuin-A and RBP4 levels were lower than in the no-symptom group [adjusted means 2.01 versus 4.50 ng/ml, P<0.0001; 185.58 versus 252.27 µg/ml, P<0.0001; 23.88 versus 43.79 µg/ml, P<0.0001, respectively]. High adiponectin and low leptin levels were associated with large infiltrates on chest radiographs even after adjustment for BMI and other covariates (P=0.0033 and P=0.0020). During treatment, adiponectin levels increased further and then decreased. Leptin levels remained low. Initial low levels of fetuin-A and RBP4 almost returned to the normal reference range in concert with reduced CRP.. Our data and recent literature suggest that low fat store and underlying inflammation may regulate these metabolic markers in TB in a different way. Decreased leptin, increased adiponectin, or this ratio may be a promising marker for severity of the disease independent of BMI. We should further investigate pathological roles of the balance between these adipokines. Topics: Adiponectin; Adult; alpha-2-HS-Glycoprotein; Analysis of Variance; Biomarkers; Body Mass Index; C-Reactive Protein; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Retinol-Binding Proteins, Plasma; Tuberculosis, Pulmonary | 2012 |
High leptin and resistin expression in chronic heart failure: adverse outcome in patients with dilated and inflammatory cardiomyopathy.
The expression of leptin and resistin is known to be positively correlated with the incidence of chronic heart failure (CHF). Both adipokines have been implicated in immunomodulation and cardiac remodelling. Therefore, we performed for the first time a clinical study to elucidate the effects of leptin and resistin on progression of CHF in patients with non-ischaemic dilated (DCM) and inflammatory (DCMi) cardiomyopathy.. For the clinical study 120 patients were divided into a control (n = 16), DCM (n = 52), and DCMi (n = 52) group to determine the effect of leptin and resistin on CHF progression. Nuclear factor-κB (NF-κB) activation, reactive oxygen species generation, and tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression following adipokine exposition were determined in vitro in cardiomyocytes. Leptin and resistin systemic plasma levels and not cardiac expression were significantly elevated in patients with DCM (leptin, 13.12 ± 17.2 ng/mL, P < 0.05; resistin, 6.87 ± 2.25 ng/mL, P < 0.05) and DCMi (leptin, 13.63 ± 16 ng/mL, P < 0.05; resistin, 7.27 ± 2.2 ng/mL, P < 0.05) compared with the control group (leptin, 7.34 ± 5.7 ng/mL; resistin, 4.4 ± 1.18 ng/mL). A multivariate linear regression model revealed low leptin and resistin plasma levels as contributors for favourable cardiac functional parameters at 6-month follow-up independent of inflammatory conditions. Cell culture experiments in vitro showed leptin and resistin to be potent regulators of TNF-α and IL-6 expression in cardiomyocytes, leading to significantly increased redox stress in cardiac cells.. High leptin and resistin expression in patients with DCM and DCMi is associated with CHF progression, i.e. severe cardiac dysfunction, independent of immune responses. Topics: Adult; Biomarkers; Cardiomyopathies; Disease Progression; Female; Health Status Indicators; Heart Failure; Hemodynamics; Humans; Inflammation; Leptin; Male; Middle Aged; Multivariate Analysis; Prognosis; Resistin; ROC Curve; Statistics as Topic; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left | 2012 |
Analysis of adipose tissues and stromal vascular cells in a murine arthritis model.
Changes in body composition in rheumatoid arthritis (RA), including a reduction in skeletal muscle mass and the accumulation of visceral fat, have been identified, and the interaction between immune abnormality and metabolic disorders has received much attention. The effect of a high-fat (HF) diet and the role of adipose tissue in an arthritis model were investigated.. The effect of an HF diet on the histopathology of joints in murine type II collagen-induced arthritis (CIA) was evaluated. The morphology and adipokine production of adipose tissues were analyzed, and macrophages in the stromal vascular fraction (SVF) were counted by flow cytometry. Serum adipokine levels were measured by ELISA.. Significant exacerbation of joint destruction and aggravated pathological conditions were observed in CIA mice that were fed an HF diet. However, the boundary length of adipose tissue tended to decrease and the levels of adipokines (leptin and adiponectin) were lowered by the induction of arthritis. In HF/CIA mice, nevertheless, the production of MCP-1 in adipose tissues and the accumulation of macrophages in the SVF were significantly higher than CON/CIA group. The serum leptin/adiponectin (L/A) ratio was positively correlated with the number of macrophages in the SVF and MCP-1 production by adipose tissue, particularly in the CIA group.. Functional alterations of adipose tissues could be originated from HF diet during developing arthritis. An abnormal activation of macrophages and an increased production of MCP-1 in adipose tissues might be both involved in joint destruction and inflammation. Topics: Adiponectin; Animals; Arthritis, Experimental; Blood Vessels; Body Weight; Collagen Type II; Diet, High-Fat; Edema; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Inflammation; Intra-Abdominal Fat; Joints; Leptin; Male; Mice; Mice, Inbred DBA; Severity of Illness Index; Spleen; Stromal Cells | 2012 |
Systemic inflammation in childhood obesity: circulating inflammatory mediators and activated CD14++ monocytes.
In adults, circulating inflammatory mediators and activated CD14(++) monocytes link obesity to its metabolic and cardiovascular complications. However, it is largely unknown whether these inflammatory changes already occur in childhood obesity. To survey inflammatory changes during the early stages of obesity, we performed a comprehensive analysis of circulating inflammatory mediators, monocyte populations and their function in childhood obesity.. In lean and obese children aged 6 to 16 years (n = 96), 35 circulating inflammatory mediators including adipokines were measured. Hierarchical cluster analysis of the inflammatory mediator profiles was performed to investigate associations between inflammatory mediator clusters and clinical variables. Whole-blood monocyte phenotyping and functional testing with the toll-like receptor 4 ligand, lipopolysaccharide, were also executed.. First, next to leptin, the circulating mediators chemerin, tissue inhibitor of metalloproteinase 1, EGF and TNF receptor 2 were identified as novel inflammatory mediators that are increased in childhood obesity. Second, cluster analysis of the circulating mediators distinguished two obesity clusters, two leanness clusters and one mixed cluster. All clusters showed distinct inflammatory mediator profiles, together with differences in insulin sensitivity and other clinical variables. Third, childhood obesity was associated with increased CD14(++) monocyte numbers and an activated phenotype of the CD14(++) monocyte subsets.. Inflammatory mediator clusters were associated with insulin resistance in obese and lean children. The activation of CD14(++) monocyte subsets, which is associated with increased development of atherosclerosis in obese adults, was also readily detected in obese children. Our results indicate that inflammatory mechanisms linking obesity to its metabolic and cardiovascular complications are already activated in childhood obesity. Topics: Adolescent; Case-Control Studies; Cell Count; Chemokines; Child; Cluster Analysis; Comorbidity; Epidermal Growth Factor; Female; Humans; Inflammation; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Leptin; Lipopolysaccharide Receptors; Male; Monocytes; Obesity; Receptors, Tumor Necrosis Factor, Type II; Regression Analysis; Tissue Inhibitor of Metalloproteinase-1; Vascular Endothelial Growth Factor A | 2012 |
Alterations in mouse hypothalamic adipokine gene expression and leptin signaling following chronic spinal cord injury and with advanced age.
Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein response (UPR) as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions. Topics: Adipokines; Aging; Angiopoietin-Like Protein 4; Angiopoietins; Animals; eIF-2 Kinase; Eukaryotic Initiation Factor-2; Female; Gene Expression Regulation; Hypothalamus; Inflammation; Leptin; Membrane Proteins; Mice; Mice, Inbred C57BL; Protein Serine-Threonine Kinases; Receptors, Leptin; Resistin; Signal Transduction; Spinal Cord Injuries; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins | 2012 |
C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation.
Acute phase C-reactive protein (CRP), elevated in obesity and inflammation, is a major binding protein for leptin. It is thought that CRP contributes to leptin resistance by preventing leptin from crossing the blood-brain barrier (BBB). Here we determined how CRP interacts with the BBB and whether it deters leptin from reaching CNS targets.. BBB permeability, compartmental distribution, tracer stability, and expression of tight junction protein and inflammatory marker were determined.. CRP was stable in blood, but did not permeate the BBB in trace amounts. However, it increased paracellular permeability at a higher dose. Agouti viable (A(vy)) mice with adult-onset obesity show higher CRP entry into the brain. CRP did not permeate hCMEC/D3 cells nor change zona occludin-1 or cyclooxygenase-2 expression. An intermediate dose of CRP had no effect on leptin transport across the BBB after co-treatment. Thus, acute interactions between CRP and leptin at the BBB level were negligible and did not explain the leptin resistance seen in obesity.. The interactions of CRP and the BBB are a two-phase process, with increased paracellular permeability at a high dose that enables its entry into the CNS and serves to induce reactive gliosis and impair CNS function. Topics: Animals; Blood-Brain Barrier; C-Reactive Protein; Capillary Permeability; Central Nervous System; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Obesity | 2012 |
Metabolic and inflammatory links to depression in youth with diabetes.
Youth with diabetes are at increased risk for depression. The objectives of this study were to provide preliminary evidence that this at-risk status for depression is associated with metabolic and inflammatory markers and to inform future, more stringent examinations of the directionality of these associations.. Data from SEARCH for Diabetes in Youth (SEARCH), an observational study of U.S. children diagnosed with diabetes at <20 years of age, were used for these analyses. SEARCH participants were drawn from four geographically defined populations in Ohio, Washington, South Carolina, and Colorado; health plan enrollees in Hawaii and California; and Indian Health Service beneficiaries from four Native American populations. Participants were 2,359 youth with diabetes from the 2001 prevalent and 2002-2004 incident SEARCH cohorts. Depression was measured with the Center for Epidemiologic Studies Depression scale. Eight metabolic and inflammatory markers were measured: adiponectin, leptin, C-reactive protein, serum amyloid A, apolipoprotein B (apoB), lipoprotein A, interleukin-6, and LDL.. Six of eight markers were significantly (P < 0.006) associated with depression in youth with diabetes in bivariate analyses. In general, higher levels of depression were associated with indicators of worse metabolic or inflammatory functioning. In regression models stratified by diabetes type and accounting for demographic and clinical characteristics, only higher levels of apoB remained associated with higher levels of depression in youth with type 1 diabetes.. These data suggest that depression reported by youth with diabetes is partially associated with metabolic abnormalities and systemic inflammation. Topics: Adiponectin; Adolescent; Apolipoproteins B; C-Reactive Protein; Child; Depression; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interleukin-6; Leptin; Male | 2012 |
Regulation of insulin and leptin signaling by muscle suppressor of cytokine signaling 3 (SOCS3).
Skeletal muscle resistance to the key metabolic hormones, leptin and insulin, is an early defect in obesity. Suppressor of cytokine signaling 3 (SOCS3) is a major negative regulator of both leptin and insulin signaling, thereby implicating SOCS3 in the pathogenesis of obesity and associated metabolic abnormalities. Here, we demonstrate that SOCS3 mRNA expression is increased in murine skeletal muscle in the setting of diet-induced and genetic obesity, inflammation, and hyperlipidemia. To further evaluate the contribution of muscle SOCS3 to leptin and insulin resistance in obesity, we generated transgenic mice with muscle-specific overexpression of SOCS3 (MCK/SOCS3 mice). Despite similar body weight, MCK/SOCS3 mice develop impaired systemic and muscle-specific glucose homeostasis and insulin action based on glucose and insulin tolerance tests, hyperinsulinemic-euglycemic clamps, and insulin signaling studies. With regards to leptin action, MCK/SOCS3 mice exhibit suppressed basal and leptin-stimulated activity and phosphorylation of alpha2 AMP-activated protein kinase (α2AMPK) and its downstream target, acetyl-CoA carboxylase (ACC). Muscle SOCS3 overexpression also suppresses leptin-regulated genes involved in fatty acid oxidation and mitochondrial function. These studies demonstrate that SOC3 within skeletal muscle is a critical regulator of leptin and insulin action and that increased SOCS may mediate insulin and leptin resistance in obesity. Topics: Adenylate Kinase; Animals; Homeostasis; Hyperlipidemias; Inflammation; Insulin; Leptin; Mice; Mice, Transgenic; Muscle, Skeletal; Obesity; RNA, Messenger; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins | 2012 |
Peroxisome deficient aP2-Pex5 knockout mice display impaired white adipocyte and muscle function concomitant with reduced adrenergic tone.
Peroxisomes are essential for intermediary lipid metabolism, but the role of these organelles has been primarily studied in the liver. We recently generated aP2-Pex5 conditional knockout mice that due to the nonselectivity of the aP2 promoter, not only had dysfunctional peroxisomes in the adipose tissue but also in the central and peripheral nervous system, besides some other tissues. Peroxisomes were however intact in the liver, heart, pancreas and muscle. Surprisingly, these mice not only showed dysfunctional white adipose tissue with increased fat mass and reduced lipolysis but also the skeletal muscle was affected including impaired shivering thermogenesis, reduced motor performance and increased insulin resistance. Non-shivering thermogenesis by brown adipose tissue was not altered. Strongly reduced levels of plasma adrenaline and to a lesser extent noradrenaline, impaired expression of catecholamine synthesizing enzymes in the adrenal medulla and reversal of all pathologies after administration of the β-agonist isoproterenol indicated that β-adrenergic signaling was reduced. Based on normal white adipose and muscle function in Nestin-Pex5 and Wnt-Pex5 knockout mice respectively, it is unlikely that peroxisome absence from the central and peripheral nervous system caused the phenotype. We conclude that peroxisomal metabolism is necessary to maintain the adrenergic tone in mice, which in turn determines metabolic homeostasis. Topics: Adipocytes, White; Adipose Tissue, White; Animals; Body Weight; Fatty Acid-Binding Proteins; Inflammation; Insulin; Leptin; Mice; Mice, Knockout; Muscle, Skeletal; Muscles; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Phenotype; Receptors, Cytoplasmic and Nuclear; Shivering; Signal Transduction; Sympathetic Nervous System; Thermogenesis | 2012 |
Changed adipocytokine concentrations in colorectal tumor patients and morbidly obese patients compared to healthy controls.
Obesity has been associated with increased incidence of colorectal cancer. Adipose tissue dysfunction accompanied with alterations in the release of adipocytokines has been proposed to contribute to cancer pathogenesis and progression. The aim of this study was to analyze plasma concentrations of several adipose tissue expressed hormones in colorectal cancer patients (CRC) and morbidly obese (MO) patients and to compare these concentrations to clinicopathological parameters.. Plasma concentrations of adiponectin, resistin, leptin, active plasminogen activator inhibitor (PAI)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1 alpha, and tumor necrosis factor (TNF)-alpha were determined in 67 patients operated on for CRC (31 rectal cancers, 36 colon cancers), 37 patients operated on for morbid obesity and 60 healthy blood donors (BD).. Compared to BD, leptin concentrations were lowered in CRC patients whereas those of MO patients were elevated. Adiponectin concentrations were only lowered in MO patients. Concentrations of MCP-1, PAI-1, and IL-1 alpha were elevated in both CRC and MO patients, while resistin and TNF-alpha were similarly expressed in MO and CRC patients compared to BD. Resistin concentrations positively correlated with tumor staging (p<0.002) and grading (p=0.015) of rectal tumor patients.. The results suggest that both MO and CRC have low-grade inflammation as part of their etiology. Topics: Adipokines; Adiponectin; Adipose Tissue; Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Transformation, Neoplastic; Chemokine CCL2; Colorectal Neoplasms; Female; Humans; Inflammation; Interleukin-1alpha; Leptin; Male; Middle Aged; Obesity, Morbid; Plasminogen Activator Inhibitor 1; Resistin; Tumor Necrosis Factor-alpha; Young Adult | 2012 |
Fat-free mass depletion and inflammation in patients with bronchiectasis.
Fat-free mass depletion has been related to increased inflammatory activity and to increased morbidity and mortality in chronic respiratory diseases. The aims of our study were to determine the nutritional status and serum levels of adipocytokines and inflammatory cytokines in patients with bronchiectasis of any etiology and their relation with respiratory parameters. A cross-sectional study was designed that included patients aged >14 years with diagnostic criteria for bronchiectasis. Anthropometric parameters; a diet questionnaire; hand grip dynamometry; levels of leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-α, and ultrasensitive C-reactive protein; as well as respiratory parameters (ie, clinical, radiologic, and spirometric values) were assessed. Ninety-three clinically stable patients were recruited, 43 with cystic fibrosis, 31 with noncystic fibrosis bronchiectasis, and 19 with cystic fibrosis transmembrane conductance regulator-related bronchiectasis. Fat-free mass depletion was present in 31% of patients, with no differences according to the etiology of the bronchiectasis. Correlations were found between inflammatory cytokines (ie, IL-6) and exacerbations, bronchorrea, forced expiratory volume in 1 second, and Bhalla score. Patients with worse respiratory disease severity, malnutrition, and diabetes had significantly higher levels of IL-6. Adiponectin correlated significantly and positively with fat mass and fat mass index and negatively with fat-free mass, fat-free mass index, and hand dynamometry. Leptin correlated positively with body mass index, fat mass and fat mass index, and negatively with fat-free mass, fat-free mass index, and dynamometry. Patients with bronchiectasis present a high percentage of fat-free mass depletion, independent of the etiology of the disease. The levels of inflammatory cytokines (especially IL-6) may be useful markers of disease severity. Adiponectin levels were higher in patients with fat-free mass depletion. Topics: Adipokines; Adult; Biomarkers; Body Composition; Body Mass Index; Bronchiectasis; C-Reactive Protein; Cross-Sectional Studies; Cystic Fibrosis; Cytokines; Diet; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Male; Muscle Strength Dynamometer; Muscle, Skeletal; Nutrition Assessment; Nutritional Status; Tumor Necrosis Factor-alpha | 2012 |
Effects of enriched environment on COX-2, leptin and eicosanoids in a mouse model of breast cancer.
Cyclooxygenase-2 (COX-2) and adipokines have been implicated in breast cancer. This study investigated a possible link between COX-2 and adipokines in the development of mammary tumors. A model of environmental enrichment (EE), known to reduce tumor growth was used for a syngeneic murine model of mammary carcinoma. 3-week-old, female C57BL/6 mice were housed in standard environment (SE) or EE cages for 9 weeks and transplanted orthotopically with syngeneic EO771 adenocarcinoma cells into the right inguinal mammary fat pad. EE housing influenced mammary gland development with a decrease in COX-2 expressing cells and enhanced side-branching and advanced development of alveolar structures of the mammary gland. Tumor volume and weight were decreased in EE housed mice and were associated with a reduction in COX-2 and Ki67 levels, and an increase in caspase-3 levels. In tumors of SE mice, high COX-2 expression correlated with enhanced leptin detection. Non-tumor-bearing EE mice showed a significant increase in adiponectin levels but no change in those of leptin, F(2)-isoprostanes, PGF(2α), IL-6, TNF-α, PAI-1, and MCP-1 levels. Both tumor-bearing groups (SE and EE housing) had increased resistin, IL-6, TNF-α, PAI-1 and MCP-1 levels irrespective of the different housing environment demonstrating higher inflammatory response due to the presence of the tumor. This study demonstrates that EE housing influenced normal mammary gland development and inhibited mammary tumor growth resulting in a marked decrease in intratumoral COX-2 activity and an increase in the plasma ratio of adiponectin/leptin levels. Topics: Adipokines; Adiponectin; Animals; Body Composition; Body Weight; Caspase 3; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Eicosanoids; Environment; Female; Humans; Immunohistochemistry; Inflammation; Ki-67 Antigen; Leptin; Mammary Neoplasms, Animal; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Time Factors | 2012 |
Serum levels of the adipokine zinc-α2-glycoprotein are increased in chronic hemodialysis.
Zinc-α2-glycoprotein (ZAG) has recently been proposed as a new adipokine involved in body weight control. In the current study, we investigated renal elimination of this adipokine by comparing circulating ZAG levels in patients on chronic hemodialysis (CD) with controls. Sixty CD patients and 60 controls with a glomerular filtration rate greater than 50 mL/min were included. Serum concentrations of ZAG were determined by enzyme-linked immunosorbent assay; and its relationship with renal function, glucose and lipid metabolism, as well as inflammation was studied in both groups. Median ZAG serum levels were almost 2-fold higher in CD patients (94.4 ± 29.4 mg/L) as compared with controls (48.3 ± 23.5 mg/L) (P < .001). Furthermore, circulating ZAG was negatively correlated with fasting insulin, homeostasis model assessment of insulin resistance, and leptin in controls in univariate analysis. Moreover, CD independently predicted ZAG concentrations in multiple regression analysis. Renal filtration appears to be an important route of ZAG elimination, and markers of renal function should be included in studies on ZAG physiology. Topics: Aged; Aged, 80 and over; Chronic Disease; Fasting; Female; Glomerular Filtration Rate; Glucose; Humans; Inflammation; Insulin; Insulin Resistance; Kidney; Leptin; Lipid Metabolism; Male; Middle Aged; Renal Dialysis; Seminal Plasma Proteins; Zn-Alpha-2-Glycoprotein | 2011 |
Body mass index is associated with leukotriene inflammation in asthmatics.
Obesity and asthma are characterized by the presence of inflammation. Leptin and adiponectin are circulating hormones produced by adipose tissue that regulate several metabolic and inflammatory functions. We aimed to determine whether obesity influences asthmatic inflammation as well as the contribution of leptin or/and adiponectin to a possible linkage between asthmatic and obesity-related inflammation.. One hundred patients with asthma and 60 healthy controls were studied. Subjects who had a comorbid illness that could interfere with the proposed tests were excluded. All subjects were divided into three groups (normal range, pre-obese, obese) according to the criteria of the current WHO international classification for body mass index (BMI). Possible associations between variables expressing airway inflammation, bronchial hyper-responsiveness, systemic inflammation and obesity, as assessed by BMI, were evaluated. Leptin and adiponectin were also measured and were associated with asthma airway and systemic inflammatory variables to elucidate possible associations.. Obese patients had significant higher values of LTE(4) /creatinine in urine compared with pre-obese and normal range ones. In a linear regression model, the only significant associations were those between BMI and LTE(4) /creatinine in urine. Using the same model, log leptin and log adiponectin presented positive and negative associations, respectively with LTE(4) /creatinine in urine. No other significant associations were observed in both patients and healthy subjects.. In a selected cohort of asthmatic patients, obesity is significantly associated with increased urinary leukotriene levels. Alterations of leptin/adiponectin balance may be related to the presence of leukotriene inflammation in obese asthmatic patients. Topics: Adiponectin; Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Body Mass Index; Case-Control Studies; Female; Humans; Inflammation; Leptin; Leukotrienes; Male; Middle Aged; Obesity; Young Adult | 2011 |
Early inflammatory and metabolic changes in association with AGTR1 polymorphisms in prehypertensive subjects.
The Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in 2003 created a prehypertension category for persons with blood pressures ranging from systolic blood pressure (SBP) of 120-139 mm Hg or diastolic blood pressure (DBP) from 80 to 89 mm Hg, due to increased risk of cardiovascular disease.. Our study utilized the University of California-San Diego (UCSD) Twin Hypertension Cohort. We measured comprehensive plasma cholesterol levels and metabolic (glucose, insulin, leptin) and inflammatory markers (interleukin-6 (IL-6), C-reactive protein (CRP), free fatty acids) to determine the differences between normotensive and prehypertensive subjects. Additionally, we determined whether angiotensin II receptor type-1 (AGTR1) polymorphisms, previously associated with hypertension, could predict prehypertension.. A total of 455 white subjects were included in the study (mean age 37.1 years). Prehypertensive subjects were older with greater body mass index (BMI) than the normotensives, and after adjusting for sex and age, had greater plasma glucose, insulin, and IL-6. The common AGTR1 A1166C (rs5186) polymorphism in the 3'-UTR region, particularly the presence of the 1166C allele, which fails to downregulate gene expression, predicted greater likelihood of being in the prehypertension group and higher SBP. A lesser-studied polymorphism in intron-2 of AGTR1 (A/G; rs2276736) was associated with plasma high-density lipoprotein (HDL) and apolipoprotein A-1. In a subgroup analysis of nonobese subjects (N = 405), similar associations were noted.. Prehypertensive subjects already exhibit early pathophysiologic changes putting them at risk of future cardiovascular disease, and AGTR1 may also contribute to this increased risk. Further investigation is needed to confirm these findings and the precise molecular mechanisms of action. Topics: Adult; Biomarkers; Blood Glucose; Blood Pressure; C-Reactive Protein; California; Cholesterol; Fatty Acids, Nonesterified; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Inflammation; Inflammation Mediators; Insulin; Interleukin-6; Least-Squares Analysis; Leptin; Male; Middle Aged; Phenotype; Polymorphism, Genetic; Prehypertension; Receptor, Angiotensin, Type 1; Risk Assessment; Risk Factors; Young Adult | 2011 |
The portal theory supported by venous drainage-selective fat transplantation.
The "portal hypothesis" proposes that the liver is directly exposed to free fatty acids and cytokines increasingly released from visceral fat tissue into the portal vein of obese subjects, thus rendering visceral fat accumulation particularly hazardous for the development of hepatic insulin resistance and type 2 diabetes. In the present study, we used a fat transplantation paradigm to (artificially) increase intra-abdominal fat mass to test the hypothesis that venous drainage of fat tissue determines its impact on glucose homeostasis.. Epididymal fat pads of C57Bl6/J donor mice were transplanted into littermates, either to the parietal peritoneum (caval/systemic venous drainage) or, by using a novel approach, to the mesenterium, which confers portal venous drainage.. Only mice receiving the portal drained fat transplant developed impaired glucose tolerance and hepatic insulin resistance. mRNA expression of proinflammatory cytokines was increased in both portally and systemically transplanted fat pads. However, portal vein (but not systemic) plasma levels of interleukin (IL)-6 were elevated only in mice receiving a portal fat transplant. Intriguingly, mice receiving portal drained transplants from IL-6 knockout mice showed normal glucose tolerance.. These results demonstrate that the metabolic fate of intra-abdominal fat tissue transplantation is determined by the delivery of inflammatory cytokines to the liver specifically via the portal system, providing direct evidence in support of the portal hypothesis. Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Cytokines; DNA Primers; Epididymis; Fatty Acids, Nonesterified; Glucose Clamp Technique; Glucose Intolerance; Hyperinsulinism; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Leptin; Male; Mesentery; Mice; Mice, Inbred C57BL; Mice, Knockout; Peritoneum; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger | 2011 |
High-carbohydrate high-fat diet–induced metabolic syndrome and cardiovascular remodeling in rats.
The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome. Topics: Abdominal Fat; Animals; Body Weight; Diabetes Mellitus, Experimental; Dietary Carbohydrates; Dietary Fats; Energy Intake; Fructose; Glucose Intolerance; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Liver; Male; Metabolic Syndrome; Obesity; Random Allocation; Rats; Rats, Wistar; Ventricular Remodeling | 2011 |
Protein-energy wasting modifies the association of ghrelin with inflammation, leptin, and mortality in hemodialysis patients.
Ghrelin abnormalities contribute to anorexia, inflammation, and cardiovascular risk in hemodialysis patients, leading to worse outcome. However, ghrelin levels are influenced by the nutritional status of the individual. We hypothesized that the consequences of ghrelin alterations in hemodialysis patients are context sensitive and dependent on the presence of protein-energy wasting (PEW). In this cross-sectional study of 217 prevalent hemodialysis patients followed for 31 months, we measured ghrelin, leptin, PEW (subjective global assessment), and C-reactive protein (an index of inflammation). Compared to patients in the middle and upper tertile of ghrelin levels, those in the lowest tertile were older, had higher leptin levels and body mass index, and presented an increased mortality risk that persisted after adjustment for age, gender, and dialysis vintage. This risk was lost after correction for comorbidities. Patients with PEW and low ghrelin values had abnormally high C-reactive protein and leptin by multivariate analysis of variance, and the highest mortality risk compared to non-PEW with high ghrelin from all-cause and cardiovascular-related mortality (adjusted hazard ratios of 3.34 and 3.54, respectively). Low ghrelin values in protein-energy wasted hemodialysis patients were linked to a markedly increased cardiovascular mortality risk. Thus, since these patients were more anorectic, our results provide a clinical scenario where ghrelin therapies may be particularly useful. Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Cross-Sectional Studies; Female; Ghrelin; Humans; Inflammation; Kaplan-Meier Estimate; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proportional Hazards Models; Protein-Energy Malnutrition; Renal Dialysis; Risk Assessment; Risk Factors; Sweden; Time Factors | 2011 |
Appetite-regulating hormones in chronic kidney disease patients.
Inflammation and loss of appetite is the most common problem in patients with chronic kidney disease (CKD). This comparative cross-sectional study aimed to characterize the changes in circulating levels of ghrelin, obestatin, leptin, all of which have an effect on food intake, and proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) in patients with CKD who were undergoing different treatments.. Study participants included 36 patients who had undergone hemodialysis (body mass index [BMI]: 22.3 ± 4.17 kg/m(2)); 41 who had undergone peritoneal dialysis (BMI: 23.5 ± 3.10 kg/m(2)), 30 with early stage CKD (BMI: 24.4 ± 3.32 kg/m(2)), and 31 healthy subjects (24.3 ± 2.14 kg/m(2)). The patients with CKD were kept under a standard diet with restricted salt, potassium, and protein intake.. Levels of leptin, acylated ghrelin, obestatin, TNF-α, and IL-6 were measured by commercially available enzyme-linked immunosorbent assay kits. Total nitrite/nitrate was analyzed using colorimetric assay kit.. Significantly high leptin levels, accompanied by low acylated ghrelin levels, were observed in patients with CKD. Maintenance dialysis did not affect these levels. TNF-α and IL-6 levels were significantly higher in CKD patients than in healthy subjects, the highest being in dialysis patients. Obestatin levels were relatively low in patients who had undergone hemodialysis.. Low acyl-ghrelin levels, accompanied with high levels of TNF-α and IL-6 may be involved in the loss of appetite and poor nutritional status in CKD patients. Topics: Adolescent; Adult; Aged; Appetite; Body Mass Index; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Feeding and Eating Disorders; Female; Ghrelin; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nitrates; Nitrites; Nutritional Status; Renal Dialysis; Tumor Necrosis Factor-alpha; Young Adult | 2011 |
Plasma leptin levels and digital pulse volume in obese patients without metabolic syndrome--a pilot study.
The mechanism of obesity leading to endothelial function is complex, and involves many adipokines and inflammatory cytokines. The data is especially lacking in obese patients without metabolic syndrome. We assessed the relationship among endothelial dysfunction, anthropometric indices, adipokines and inflammatory cytokines in this population.. Obese patients without metabolic syndrome were included in this study. The plasma resistin, leptin, retinol-binding-protein 4 and inflammatory cytokines were examined. Endothelial function was assessed by a fingertip peripheral arterial tonometry (PAT) device. Data are expressed as the natural logarithm (ln) of the PAT ratio. Endothelial dysfunction was defined by a ln (PAT ratio) <0.30.. A total of 35 patients were enrolled, 11 of whom were with endothelial dysfunction. There was a significant difference of ln leptin (p=0.007), ln [leptin/visceral fat thickness] (p=0.004) and ln [leptin/subcutaneous fat thickness] (p<0.001) between patients with and without endothelial dysfunction. Multivariate linear regression analyses showed that ln [leptin/subcutaneous fat thickness] was significantly related to the ln (PAT ratio) (p=0.002). Using ln [leptin/subcutaneous fat thickness] to detect endothelial dysfunction, the area of receiver operating characteristic curves was 0.843 (p=0.002). Using 6.10 as a cutoff point, the sensitivity and specificity to determine endothelial dysfunction were 91% and 78%, respectively.. Abnormal digital vascular function occurs in obese patients without metabolic syndrome. Low plasma leptin/subcutaneous fat ratio is associated with endothelial dysfunction in this population. Topics: Adipose Tissue; Adult; Age Factors; Arteries; Body Mass Index; Cytokines; Endothelium, Vascular; Female; Humans; Inflammation; Leptin; Male; Manometry; Metabolic Syndrome; Obesity; Pilot Projects; Sex Factors | 2011 |
Association of visceral and subcutaneous fat with glucose intolerance, insulin resistance, adipocytokines and inflammatory markers in Asian Indians (CURES-113).
The aim of the study was to assess the association between visceral and subcutaneous fat with glucose intolerance, adipocytokines, inflammatory markers and carotid IMT in Asian Indians.. Subjects with NGT (n=85), IGT (n=49) and T2DM (n=93) were randomly selected from CURES. Total abdominal, visceral and subcutaneous fat were measured using Helical CT scan. Adiponectin, hs-CRP, TNF-alpha, oxidized LDL, visfatin and leptin and IMT and insulin resistance were assessed.. Total abdominal fat (p=0.041) and the visceral fat (p=0.039) but not subcutaneous fat progressively increased from NGT, IGT and T2DM subjects. With increasing quartiles of visceral fat, there was a significant increase in insulin resistance (p=0.040); significant decrease in adiponectin (p=0.043) and increase in TNF-alpha (p=0.028), hs-CRP (p=0.043), OX-LDL (p=0.034) and visfatin (p=0.040), and carotid IMT (p=0.047) was observed.. Visceral fat levels increased with increasing glucose intolerance and are associated with decreased levels of adiponectin and increased levels of hs-CRP, TNF-alpha, oxidized LDL, visfatin, HOMA-IR and IMT. Topics: Abdominal Fat; Adipokines; Adiponectin; Adiposity; Adult; Asian People; Biomarkers; Blood Glucose; C-Reactive Protein; Causality; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; India; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipoproteins, LDL; Male; Nicotinamide Phosphoribosyltransferase; Subcutaneous Fat; Tumor Necrosis Factor-alpha | 2011 |
Leptin activates human B cells to secrete TNF-α, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway.
Leptin, one of the adipokines, functions as a hormone and a cytokine. In this investigation, we show for the first time that leptin, in a concentration-dependent manner, activates human peripheral blood B cells to induce secretion of IL-6, IL-10, and TNF-α. Leptin increased B cells expressing CD25 and HLA-DR. Leptin induces phosphorylation of Janus activation kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), p38 mitogen-activated protein kinase (p38MAPK), and extracellular signal-regulated kinase (ERK1/2). Furthermore, leptin-induced cytokine secretion by B cells was blocked by inhibitors of JAK2, STAT3, p38MAPK, and ERK1/2. These data demonstrate that leptin activates human B cells to secrete cytokines via activation of JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathways, which may contribute to its inflammatory and immunoregulatory properties. Topics: Autoimmunity; B-Lymphocytes; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation; Interleukin-10; Interleukin-6; Janus Kinase 2; Leptin; Lymphocyte Activation; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase 6; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Receptors, Leptin; Signal Transduction; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha | 2011 |
FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women.
The adipocyte/macrophage fatty acid-binding protein 4 (FABP4) has been described as a biomarker for adiposity and metabolic syndrome (MS). The aims of this study were to assess the relationship between FABP4 and inflammatory cytokines related to obesity, and to evaluate FABP4 mRNA expression in visceral and subcutaneous adipose tissue in non-diabetic morbidly obese women versus healthy lean women.. We analyzed circulating levels of FABP4 in 81 Spanish women: 38 lean (body mass index (BMI)<25 kg/m(2)) and 43 morbidly obese (BMI>40 kg/m(2)). We took 30 follow-up blood samples at 6 and 12 months after bariatric surgery. We assessed FABP4 gene expression in samples of subcutaneous abdominal and visceral adipose tissue. Adipose tissue mRNA expression was determined by real-time RT-PCR.. In morbidly obese women, plasma FABP4 levels were significantly higher than in non-obese patients. These levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin levels. Post-operative FABP4 levels decreased by a maximum of 30% after 12 months. We also found an inverse association between FABP4 and adiponectin levels, and positive correlations between FABP4 and circulating leptin, tumor necrosis factor (TNF) receptors, C-reactive protein (CRP) and interleukin 6 levels. Linear regression analysis revealed that FABP4 was more closely related to HOMA2-IR than adiponectin, CRP, TNF-RI, or leptin. Furthermore, high circulating FABP4 levels were associated with the presence of MS. FABP4 mRNA expression in visceral adipose tissue was related to its circulating levels in morbidly obese women.. Our results indicate that serum FABP4 is associated with inflammatory factors related to obesity and MS in non-diabetic morbidly obese women. Topics: Adiponectin; Adult; C-Reactive Protein; Cytokines; Enzyme-Linked Immunosorbent Assay; Fatty Acid-Binding Proteins; Female; Humans; In Vitro Techniques; Inflammation; Leptin; Metabolic Syndrome; Obesity, Morbid; Receptors, Tumor Necrosis Factor, Type I | 2011 |
Airway and plasma leptin and adiponectin in lean and obese asthmatics and controls.
Obesity-mediated changes in plasma adipokines have been associated with increased systemic inflammation and oxidative stress. However, it is unknown whether obesity induces similar changes in airway levels of these adipokines and whether these changes are associated with increased airway biomarkers of inflammation and oxidative stress.. Lean and obese asthmatics and controls underwent bronchoscopy with bronchoalveolar lavage (BAL), spirometry, and provided fasting plasma leptin and adiponectin. Biomarkers of oxidation and inflammation in the BAL included exhaled nitric oxide (NO), 8-isoprostanes, pH, and nitrogen oxide products (NOx).. Out of a total of 48 subjects, 44% had asthma and 56% were healthy controls. Among subjects with asthma, 66% were obese, 10% overweight, and 24% lean; in the controls these proportions were 63%, 11%, and 26%, respectively. After adjusting for age, sex, smoking history, ethnicity, and prebronchodilator forced exhalation in 1 second (FEV(1)), obesity was associated with higher BAL and plasma leptin levels in asthmatics and controls. Increasing BMI was associated with increased BAL leptin and was marginally and inversely associated with BAL adiponectin. Significant associations between BAL and plasma levels were only observed for leptin. No significant associations were observed between BAL and plasma adipokines with the airway biomarkers of oxidation and inflammation.. Increasing BMI is associated with changes in the concentrations of airway adipokines in asthmatics and healthy controls; however, these associations are not related with biomarkers of airway oxidation or inflammation. Topics: Adiponectin; Adolescent; Adult; Asthma; Biomarkers; Body Mass Index; Bronchoalveolar Lavage Fluid; Case-Control Studies; Female; Humans; Inflammation; Leptin; Lung; Male; Middle Aged; Obesity; Oxidative Stress; Thinness; Young Adult | 2011 |
Leptin resistance and desensitization of hypophagia during prolonged inflammatory challenge.
Acute exposure to bacterial lipopolysaccharide (LPS) is a potent inducer of immune response as well as hypophagia. Nevertheless, desensitization of responses to LPS occurs during long-term exposure to endotoxin. We induced endotoxin tolerance, injecting repeated (6LPS) LPS doses compared with single (1LPS) treatment. 1LPS, but not 6LPS group, showed decreased food intake and body weight, which was associated with an increased plasma leptin and higher mRNA expression of OB-Rb, MC4R, and SOCS3 in the hypothalamus. Hypophagia induced by 1LPS was associated with lower levels of 2-arachidonoylglycerol (2-AG), increased number of p-STAT3 neurons, and decreased AMP-activated protein kinase (AMPK) activity. Desensitization of hypophagia in the 6LPS group was related to high 2-AG, with no changes in p-STAT3 or increased p-AMPK. Leptin decreased food intake, body weight, 2-AG levels, and AMPK activity and enhanced p-STAT3 in control rats. However, leptin had no effects on 2-AG, p-STAT3, or p-AMPK in the 1LPS and 6LPS groups. Rats treated with HFD to induce leptin resistance showed neither hypophagia nor changes in p-STAT3 after 1LPS, suggesting that leptin and LPS recruit a common signaling pathway in the hypothalamus to modulate food intake reduction. Desensitization of hypophagia in response to repeated exposure to endotoxin is related to an inability of leptin to inhibit AMPK phosphorylation and 2-AG production and activate STAT3. SOCS3 is unlikely to underlie this resistance to leptin signaling in the endotoxin tolerance. The present model of prolonged inflammatory challenge may contribute to further investigations on mechanisms of leptin resistance. Topics: Animals; Arachidonic Acids; Body Weight; Cyclic AMP-Dependent Protein Kinases; Diet; Dietary Fats; Eating; Endocannabinoids; Endotoxins; Gas Chromatography-Mass Spectrometry; Glycerides; Immunohistochemistry; Inflammation; Interleukin-10; Leptin; Lipopolysaccharides; Male; Phosphorylation; Rats; Rats, Wistar; Receptor, Melanocortin, Type 4; Receptors, Interleukin-10; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins | 2011 |
Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease.
The role of fat-bone interactions in the pathogenesis of osteoporosis in chronic obstructive pulmonary disease (COPD) is poorly understood. Our aim was to investigate expressions of leptin and osteoprotegerin (OPG) in the adipose tissue, and their relationships to osteoporosis in patients with COPD.. In 39 patients with stable COPD, bone mineral density (BMD) and body composition was assessed by Dual Energy X-Ray Absorptiometry. Serum leptin was determined by the enzyme-linked immunosorbent assay, and bone turnover markers osteocalcin and β-crosslaps by the electrochemiluminiscence immunoassays. Subcutaneous adipose tissue samples were analyzed using real-time PCR.. Twenty-one patients without, and 18 with osteoporosis were enrolled (35 men; age 62.2 ± 7.3years). Compared to patients without osteoporosis, those with the disease had significantly lower serum levels and adipose tissue expressions of leptin, in association with increased serum β-crosslaps (p=0.028, p=0.034, p=0.022, respectively). Log adipose tissue leptin was inversely related to serum β-crosslaps (p=0.015), and directly to serum leptin (p<0.001) and to the total, femoral, and lumbar BMD and T-score (p<0.02 for all relationships). Adipose tissue OPG expression was related to all variables of bone density except for lumbar BMD and T-score (p<0.05 for all relationships). Log adipose tissue leptin and OPG expressions predicted femoral T-score independently of age, gender and pulmonary function (p<0.001, adjusted R(2)=0.383; p=0.008, adjusted R(2)=0.301, respectively). Introducing body mass (or fat mass) index into these models eliminated independent predictive value of leptin and OPG expressions.. Our results suggest that adipose tissue leptin and OPG expressions are related to osteoporosis in patients with COPD, and appear to act as mediators between fat mass and BMD. Topics: Adipose Tissue; Biomarkers; Bone Density; Bone Remodeling; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Osteoporosis; Osteoprotegerin; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests | 2011 |
Is ghrelin a biomarker for mortality in end-stage renal disease?
Ghrelin is involved in the pathogenesis of protein-energy wasting (PEW), inflammation, and cardiovascular complications in end-stage renal disease (ESRD). Plasma ghrelin may prove to be a powerful biomarker of mortality in ESRD but should be considered in the context of assay specificity, other weight-regulating hormones, nutritional status, systemic inflammation, and cardiovascular risk factors. ESRD patients with PEW, systemic inflammation, and low ghrelin and high leptin concentrations have the highest mortality risk and may benefit the most from ghrelin therapy. Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Protein-Energy Malnutrition; Renal Dialysis; Risk Assessment; Risk Factors; Time Factors | 2011 |
Resistin is linked to inflammation, and leptin to metabolic syndrome, in women with inflammatory arthritis.
To investigate how inflammation and metabolic syndrome (MetS) are associated with adipokine levels in patients with inflammatory arthritis.. Fifty-four female patients with arthritis were enrolled in the study. Twenty (37%) of these patients had MetS, which was diagnosed according to the definition of the International Diabetes Federation (IDF). Interleukin (IL)-6 and four adipokines (resistin, leptin, adiponectin, and adipsin) were determined by immunoassay. Healthy women with body mass index (BMI) between 22 and 25 kg/m(2) served as controls.. The patients with arthritis had higher levels of resistin than the healthy controls. This difference was clear in patients without MetS (17.4 in patients vs. 10.8 ng/mL in controls, p < 0.001), and even higher resistin levels were found in the patients with MetS (20.7 ng/mL; p < 0.001 vs. healthy controls; and p = 0.095 vs. patients without MetS). In the patients with arthritis and MetS, resistin correlated positively with IL-6 (Pearson's r = 0.5, p = 0.03). Leptin levels were increased in arthritis patients with MetS as compared to healthy controls, but not in patients without MetS. The statistically significant difference between patients with MetS and controls remained when leptin was adjusted with BMI. Accordingly, adiponectin levels were lower in patients with MetS than in healthy controls (p < 0.05). Leptin, adiponectin, and adipsin did not correlate with the inflammatory cytokine IL-6 or with C-reactive protein (CRP).. The results show that high resistin levels are associated with arthritis independently of MetS, whereas leptin is increased only in arthritis patients with MetS. Topics: Adiponectin; Adult; Arthritis; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; Comorbidity; Complement Factor D; Female; Humans; Inflammation; Leptin; Metabolic Syndrome; Middle Aged; Resistin | 2011 |
Leptin up-regulates pro-inflammatory cytokines in discrete cells within mouse colon.
Dysregulation of leptin associated with obesity is implicated in obesity-related colon cancer, but mechanisms are elusive. Increased adiposity and elevated plasma leptin are associated with perturbed metabolism in colon and leptin receptors are expressed on colon epithelium. We hypothesise that obesity increases the sensitivity of the colon to cancer by disrupting leptin-regulated gene targets within colon tissues. PCR arrays were used to firstly identify leptin responsive genes and secondly to identify responses to leptin challenge in wild-type mice, or those lacking leptin (ob/ob). Leptin-regulated genes were localised in the colon using in situ hybridisation. IL6, IL1β and CXCL1 were up-regulated by leptin and localised to discrete cells in gut epithelium, lamina propria, muscularis and at the peritoneal serosal surface. Leptin regulates pro-inflammatory genes such as IL6, IL1β and CXCL1, and might increase the risk of colon cancer among obese individuals. Topics: Animals; Chemokine CXCL1; Colon; Cytokines; Gene Expression; Inflammation; Interleukin-1beta; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Up-Regulation | 2011 |
Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias.
Calorie restriction (CR) has been demonstrated to alter cytokine levels; however, its potential to modify sickness behavior (fever, anorexia, cachexia) has not. The effect of CR on sickness behavior was examined in male C57BL/6J mice fed ad libitum or restricted 25% (CR25%) or restricted 50% (CR50%) in food intake for 28 days and injected with 50 μg/kg of LPS on day 29. Changes in body temperature, locomotor activity, body weight, and food intake were determined. A separate cohort of mice were fed ad libitum or CR50% for 28 days, and hypothalamic mRNA expression of inhibitory factor κB-α (IκB-α), cyclooxygenase-2 (COX-2), prostaglandin E(2) (PGE(2)), suppressor of cytokine signaling 3 (SOCS3), IL-10, neuropeptide Y (NPY), leptin, proopiomelanocortin (POMC), and corticotrophin-releasing hormone (CRH) were determined at 0, 2, and 4 h post-LPS. CR50% mice did not develop fevers, whereas the CR25% mice displayed a fever shorter in duration but with the same peak as the controls. Both CR25% and CR50% mice showed no sign of anorexia and reduced cachexia after LPS administration. Hypothalamic mRNA expression of NPY and CRH were both increased by severalfold in CR50% animals preinjection compared with controls. The CR50% mice did not demonstrate the expected rise in hypothalamic mRNA expression of COX-2, microsomal prostaglandin E synthase-1, POMC, or CRH 2 h post-LPS, and leptin expression was decreased at this time point. Increases in SOCS3, IL-10, and IκB-α expression in CR50% animals were enhanced compared with ad libitum-fed controls at 4 h post-LPS. CR results in a suppression of sickness behavior in a dose-dependent manner, which may be due to CR attenuating proinflammatory pathways and enhancing anti-inflammatory pathways. Topics: Animals; Body Temperature; Body Weight; Caloric Restriction; Cyclooxygenase 2; Disease Models, Animal; Eating; Hypothalamus; Illness Behavior; Inflammation; Intramolecular Oxidoreductases; Leptin; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Motor Activity; Pro-Opiomelanocortin; Prostaglandin-E Synthases; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins | 2011 |
Differences in diet between the 19th and 21st centuries: could they lead to insulin and leptin resistance and inflammation?
Topics: Diet; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Inflammation; Insulin Resistance; Leptin | 2011 |
Hemodynamics and metabolism at low versus moderate altitudes.
Despite the higher prevalence of diabetes and hypertension in populations residing at moderate altitudes, mortality in these populations is lower than in populations residing at low altitudes. To examine whether metabolic and hemodynamic differences can explain this apparent paradox, we performed a cross-sectional study of a general population sample recruited in the Canary Islands, Spain (n=6729). We recorded altitude of residence, age, heart rate, blood pressure, body mass index, social class, physical activity, energy intake, alcohol intake, smoking habit, prevalence of type 2 diabetes mellitus and hypertension. In a subsample (n=903), we recorded serum concentration of cholesterol, triglycerides, glucose, C peptide, leptin, soluble leptin receptor (sObR), C-reactive protein, resistin, soluble CD40 ligand (sCD40L), and paraoxonase activity (PON), and we estimated insulin resistance and free leptin index. We found an inverse association between altitude and heart rate (p<0.001), leptin (p<0.001), free leptin index (p<0.001), resistin (p<0.001), and sCD40L (p<0.05) and a direct association between altitude and hypertension (odds ratio=1.29 for altitude >600 m; 95% confidence interval=1.03-1.62), glycemia (p<0.05), C peptide (p<0.001), insulin resistance (p<0.001), sObR (p<0.05), and PON (p<0.05). When social class was included in the multivariate model, the association with PON was no longer significant. In conclusion, individuals residing at moderate altitudes have a lower heart rate and lower serum concentration of total leptin, free leptin, and sCD40L. These differences may partially explain the lower mortality in these populations. Topics: Adolescent; Adult; Aged; Altitude; Blood Pressure; CD40 Ligand; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Energy Metabolism; Female; Heart Rate; Hemodynamics; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Male; Middle Aged; Young Adult | 2011 |
Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes.
Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) during sleep. Both obesity and OSA are associated with insulin resistance and systemic inflammation, which may be attributable to tissue hypoxia. We hypothesized that a pattern of hypoxic exposure determines both oxygen profiles in peripheral tissues and systemic metabolic outcomes, and that obesity has a modifying effect. Lean and obese C57BL6 mice were exposed to 12 h of intermittent hypoxia 60 times/h (IH60) [inspired O₂ fraction (Fi(O₂)) 21-5%, 60/h], IH 12 times/h (Fi(O₂) 5% for 15 s, 12/h), sustained hypoxia (SH; Fi(O₂) 10%), or normoxia while fasting. Tissue oxygen partial pressure (Pti(O₂)) in liver, skeletal muscle and epididymal fat, plasma leptin, adiponectin, insulin, blood glucose, and adipose tumor necrosis factor-α (TNF-α) were measured. In lean mice, IH60 caused oxygen swings in the liver, whereas fluctuations of Pti(O₂) were attenuated in muscle and abolished in fat. In obese mice, baseline liver Pti(O₂) was lower than in lean mice, whereas muscle and fat Pti(O₂) did not differ. During IH, Pti(O₂) was similar in obese and lean mice. All hypoxic regimens caused insulin resistance. In lean mice, hypoxia significantly increased leptin, especially during SH (44-fold); IH60, but not SH, induced a 2.5- to 3-fold increase in TNF-α secretion by fat. Obesity was associated with striking increases in leptin and TNF-α, which overwhelmed effects of hypoxia. In conclusion, IH60 led to oxygen fluctuations in liver and muscle and steady hypoxia in fat. IH and SH induced insulin resistance, but inflammation was increased only by IH60 in lean mice. Obesity caused severe inflammation, which was not augmented by acute hypoxic regimens. Topics: Acute Disease; Adiponectin; Adipose Tissue; Animals; Blood Glucose; Disease Models, Animal; Hypoxia; Inflammation; Inflammation Mediators; Insulin; Insulin Resistance; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Obesity; Oxygen; Time Factors; Tumor Necrosis Factor-alpha | 2011 |
Anti-obesity and antioxidative effects of purple sweet potato extract in 3T3-L1 adipocytes in vitro.
The purpose of the current study was to determine the anti-obesity and anti-inflammatory effects of an extract of purple sweet potatoes (PSPs) on 3T3-L1 adipocytes. For this purpose, differentiated 3T3-L1 adipocytes were treated with a PSP extract at concentrations of 1,000, 2,000, and 3,000 μg/mL for 24 hours. Then, we measured the changes in the sizes of the adipocytes, the secretion of leptin, and the mRNA/protein expression of lipogenic, inflammatory, and lipolytic factors after the treatment with the PSP extract. The PSP extract diminished leptin secretion, indicating that growth of fat droplets was suppressed. The extract also suppressed the expression of mRNAs of lipogenic and inflammatory factors and promoted lipolytic action. The antioxidative activity of the PSP extract was also measured using three different in vitro methods: 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity, ferric reducing ability potential assay, and chelating activity of transition metal ions. Taken together, our study shows that PSP extract has antilipogenic, anti-inflammatory, and lipolytic effects on adipocytes and has radical scavenging and reducing activity. Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Anthocyanins; Anti-Inflammatory Agents; Anti-Obesity Agents; Antioxidants; Biphenyl Compounds; Blotting, Western; Cell Differentiation; Inflammation; Ipomoea batatas; Leptin; Lipolysis; Mice; Picrates; Plant Extracts; Real-Time Polymerase Chain Reaction | 2011 |
Elimination of the NLRP3-ASC inflammasome protects against chronic obesity-induced pancreatic damage.
Clinical evidence that the blockade of IL-1β in type-2 diabetic patients improves glycemia is indicative of an autoinflammatory mechanism that may trigger adiposity-driven pancreatic damage. IL-1β is a key contributor to the obesity-induced inflammation and subsequent insulin resistance, pancreatic β-cell dysfunction, and the onset of type 2 diabetes. Our previous studies demonstrated that the ceramides activate the Nod-like receptor family, pyrin domain containing 3 (Nlrp3) inflammasome to cause the generation of mature IL-1β and ablation of the Nlrp3 inflammasome in diet-induced obesity improves insulin signaling. However, it remains unclear whether the posttranslational processing of active IL-1β in pancreas is regulated by the NLRP3 inflammasome or whether the alternate mechanisms play a dominant role in chronic obesity-induced pancreatic β-cell exhaustion. Here we show that loss of ASC, a critical adaptor required for the assembly of the NLRP3 and absent in melanoma 2 inflammasome substantially improves the insulin action. Surprisingly, despite lower insulin resistance in the chronically obese NLRP3 and ASC knockout mice, the insulin levels were substantially higher when the inflammasome pathway was eliminated. The obesity-induced increase in maturation of pancreatic IL-1β and pancreatic islet fibrosis was dependent on the NLRP3 inflammasome activation. Furthermore, elimination of NLRP3 inflammasome protected the pancreatic β-cells from cell death caused by long-term high-fat feeding during obesity with significant increase in the size of the islets of Langerhans. Collectively, this study provides direct in vivo evidence that activation of the NLRP3 inflammasome in diet-induced obesity is a critical trigger in causing pancreatic damage and is an important mechanism of progression toward type 2 diabetes. Topics: Animals; Apoptosis Regulatory Proteins; CARD Signaling Adaptor Proteins; Carrier Proteins; Cytoskeletal Proteins; Fibrosis; Inflammasomes; Inflammation; Insulin; Insulin Resistance; Interleukin-1beta; Leptin; Mice; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Obesity; Pancreas | 2011 |
Role of nitric oxide (NO) metabolism and inflammatory mediators in childhood obesity.
The role of NO and adipocytokines in childhood obesity was studied, supposing that obesity provokes inflammation. Children were admitted to the pediatric clinic for a regular check up because of obesity.. Obese (n = 79) and healthy (n = 12) children were selected and divided into subgroups according to their age, gender, glucose tolerance and nitric oxide synthase (NOS II) positivity.. Urine and blood nitrite plus nitrate, the expression of NOS II in white blood cells, serum adipocytokines and clinical characteristics were analyzed in each group. Significance was tested by unpaired two-tailed t test and by ANOVA.. NOS II was only detected in the white blood cells of a subgroup (17/79) of obese children. Serum leptin and resistin concentrations were significantly higher, adiponectin was lower compared to healthy children. Significant correlations were observed between serum adiponectin and resistin levels (reciprocal, R (2) = 0.4), and between body mass index and serum leptin levels.. NOS II expression in white blood cells was observed in a minority of patients. Low-grade inflammation in obese children was suggested by the increased resistin levels, particularly in NOS II-positive patients. Correlation between different adipocytokines was restricted for a few subgroups. Topics: Adipocytes; Adipokines; Adiponectin; Adolescent; Body Mass Index; C-Reactive Protein; Child; Child, Preschool; Female; Gene Expression Regulation, Enzymologic; Humans; Inflammation; Interleukin-6; Leptin; Leukocytes; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Obesity; Resistin | 2011 |
Serotonin receptor type 3 antagonists improve obesity-associated fatty liver disease in mice.
Obesity is a major cause for nonalcoholic fatty liver disease (NAFLD). Previous studies suggested that alterations in intestinal motility and permeability contribute to the development of NAFLD. Serotonin and serotonin receptor type 3 (5-HT(3)R) are key factors in the regulation of intestinal motility and permeability. Therefore, we studied the effect of the 5-HT(3)R antagonists tropisetron and palonosetron on the development of NAFLD in leptin-deficient obese mice. Four-week-old ob/ob mice and lean controls were treated for 6 weeks orally with tropisetron or palonosetron at 0.2 mg/kg per day. We determined markers of liver damage and inflammation, portal endotoxin levels, and duodenal concentrations of serotonin, serotonin-reuptake transporter (SERT), occludin, and claudin-1. Tropisetron treatment significantly reduced liver fat content (-29%), liver inflammation (-56%), and liver cell necrosis (-59%) in ob/ob mice. The beneficial effects of tropisetron were accompanied by a decrease in plasma alanine aminotransferase and portal vein plasma endotoxin levels, an attenuation of enhanced MyD88 and tumor necrosis factor-α mRNA expression in the liver, and an increase of tight junction proteins in the duodenum. Tropisetron treatment also caused a reduction of elevated serotonin levels and an increase of SERT in the duodenum of ob/ob mice. Palonosetron had similar effects as tropisetron with regard to the reduction of liver fat and other parameters. Tropisetron and palonosetron are effective in attenuating NAFLD in a genetic mouse model of obesity. The effect involves the intestinal nervous system, resulting in a reduction of endotoxin influx into the liver and subsequently of liver inflammation and fat accumulation. Topics: Actins; Animals; Azo Compounds; Drug Evaluation, Preclinical; Duodenum; Endotoxins; Fatty Liver; Indoles; Inflammation; Isoquinolines; Leptin; Liver; Mice; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Palonosetron; Proteins; Quinuclidines; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Tropisetron; Tumor Necrosis Factor-alpha | 2011 |
Effects of alfacalcidol on circulating cytokines and growth factors in rat skeletal muscle.
Supra-physiological levels of vitamin D induce skeletal muscle atrophy, which may be particularly detrimental in already sarcopaenic elderly. Neither the cause nor whether the atrophy is fibre type specific are known. To obtain supraphysiological levels of circulating vitamin D (1,25(OH)(2)D(3)) 27.5-month-old female Fischer(344) × Brown Norway F1 rats were orally treated for 6 weeks with vehicle or the vitamin D analogue alfacalcidol. Alfacalcidol treatment induced a 22% decrease in body mass and 17% muscle atrophy. Fibre atrophy was restricted to type IIb fibres in the low-oxidative part of the gastrocnemius medialis only (-22%; P < 0.05). There was a concomitant 1.6-fold increase in mRNA expression of the ubiquitin ligase MuRF-1 (P < 0.001), whereas those of insulin-like growth factor 1 and myostatin were not affected. Circulating IL-6 was unaltered, but leptin and adiponectin were decreased (-39%) and increased (64%), respectively. The treated rats also exhibited a reduced food intake. In conclusion, supraphysiological levels of circulating 1,25(OH)(2)D(3) cause preferential atrophy of type IIb fibres, which is associated with an increased expression of MuRF-1 without evidence of systemic inflammation. The atrophy and loss of body mass in the presence of supra-physiological levels of vitamin D are primarily due to a reduced food intake. Topics: Adiponectin; Animals; Body Mass Index; Dietary Supplements; Eating; Female; Hydroxycholecalciferols; Inflammation; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Muscle Fibers, Skeletal; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Myostatin; Organ Size; Rats; RNA, Messenger; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Vitamin D | 2011 |
Like total ghrelin, acylated ghrelin is also lower in HD patients with cardiovascular disease.
Topics: Cardiovascular Diseases; Female; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Protein-Energy Malnutrition; Renal Dialysis | 2011 |
Association with Helicobacter pylori infection and ghrelin level in hemodialysis patients.
Topics: Cardiovascular Diseases; Female; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Protein-Energy Malnutrition; Renal Dialysis | 2011 |
Dysglycemia induces abnormal circadian blood pressure variability.
Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).. Systemic inflammation and glycemia influence circadian blood pressure variability.. Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP) and heart rate (HR) were recorded by telemetry every 5 minutes during both sleep (day) and active (night) periods. Pulse pressure (PP) was calculated (PP = SBP-DBP).. [mean(SEM)]: The AD fed group displayed significant increase in body weight (after 90 days; p < 0.01). Fasting glucose, adipokine (leptin and adiponectin) concentrations significantly increased (at 90 and 172 days; all p < 0.05), along with a trend for increased concentrations of systemic pro-inflammatory cytokines (MCP-1 and TNF-α) on day 90. The AD fed group, with significantly higher FG, also exhibited significantly elevated circadian (24-hour) overall mean SBP, DBP, PP and HR (all p < 0.05).. These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system) which generate abnormal CBPV. Topics: Adiponectin; Animals; Biomarkers; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Chemokine CCL2; Circadian Rhythm; Diet, High-Fat; Disease Models, Animal; Heart Rate; Inflammation; Inflammation Mediators; Leptin; Prediabetic State; Rats; Rats, Inbred Dahl; Telemetry; Time Factors; Tumor Necrosis Factor-alpha; Weight Gain | 2011 |
Diet-induced obesity leads to decreased hepatic iron storage in mice.
An increased risk of iron deficiency has been reported in obese individuals. We investigated hepatic iron status and serum levels of both adipokines and inflammatory markers in obese mice to test the hypothesis that high-fat-diet (HFD)-induced obesity leads to reduced iron storage associated with inflammation. Four-week-old C57BL mice were fed a HFD containing 60% energy from fat for 16 weeks and were compared with mice on a control diet with 10% energy from fat. The HFD group had significantly higher levels of leptin (43.7 ng/mL in control, n = 16 vs 104.3 ng/mL in HFD, n = 17; P < .001) and significantly lower amounts of high-molecular-weight adiponectin (4.80 μg/mL in control, n = 16 vs 3.67 μg/mL in HFD, n = 18; P = .002) compared with the control group. Higher serum amyloid A levels in the HFD group (60.4 μg/mL in control, n = 17 vs 117.9 μg/mL in HFD, n = 18; P < .001) suggest inflammation in the HFD-induced obese animals. The HFD group had lower hepatic nonheme iron (3.12 μg/mg protein in control, n = 17 vs 0.869 μg/mg protein in HFD, n = 16; P < .001). Expression of hepcidin messenger RNA (mRNA) was only 54% of the control levels in HFD mice (P = .016). However, the ratio of hepcidin mRNA expression to nonheme iron was 2.5-fold higher in the HFD compared with the control animals. Hepcidin is a homeostatic regulator of iron metabolism that restricts intestinal iron absorption and is also known as a mediator of inflammation. Increased serum amyloid A levels and a higher ratio of hepatic hepcidin mRNA expression to nonheme iron suggest that lower hepatic iron status in obese animals might be associated with inflammation. Topics: Adiponectin; Anemia, Iron-Deficiency; Animals; Antimicrobial Cationic Peptides; Diet; Dietary Fats; Heme; Hepcidins; Inflammation; Iron; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; RNA, Messenger; Serum Amyloid A Protein | 2011 |
Metabolic characterization of a mouse deficient in all known leptin receptor isoforms.
We have characterized a newly generated mouse model of obesity, a mouse strain deficient in all five previously described leptin receptor isoforms. These transgenic mice, named the db (333)/db (333) mice, were identified from an ENU mutagenesis screen and carry a point mutation in the seventh exon of the db gene encoding the leptin receptor, resulting in a premature stop codon (Y(333)Stop) and gene product that lacks STAT signaling domains. db (333)/db (333) mice have a morbidly obese phenotype, with body weights diverging from wild type as early as 4 weeks of age (P < 0.05). To determine the contribution of the short isoforms of the leptin receptor in this metabolic phenotype, we performed an extensive metabolic characterization of the db (333)/db (333) mouse in relation to the well-characterized db/db mouse lacking only the long form of the leptin receptor. db (333)/db (333) mice have similar endocrine and metabolic parameters as previously described in other leptin receptor transgenic mice including db/db mice that lack only the long isoform of the leptin receptor. However, db (333)/db (333) mice show a subtle trend toward higher body weight and insulin levels, lower oxygen, carbon dioxide production, respiratory exchange ratio (RER), and temperature than db/db mice suggesting the short isoforms may play an additional role in energy homeostasis. Topics: Animals; Base Sequence; Body Temperature; Body Weight; Carbon Dioxide; Codon, Nonsense; DNA Mutational Analysis; Endocrine Glands; Glucose Tolerance Test; Hyperphagia; Inflammation; Insulin; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Molecular Sequence Data; Motor Activity; Obesity; Oxygen Consumption; Phenotype; Protein Isoforms; Receptors, Leptin; Respiration | 2010 |
Enhanced production of IL-17A during zymosan-induced peritonitis in obese mice.
IL-17A is a proinflammatory cytokine critical for host defense and involved in the pathogenesis of autoimmune disorders. Obesity is associated with chronic low-grade inflammation but also with a heightened acute inflammatory response. We investigated the effect of obesity on IL-17A production using the model of ZY-induced peritonitis. Compared with lean controls, administration of ZY induced a significantly exacerbated inflammatory response in obese leptin-deficient ob/ob mice and in mice with diet-induced obesity (DIO). Levels of IL-17A in the peritoneal fluid in response to ZY were elevated significantly in ob/ob and DIO mice compared with lean animals. Reconstitution of ob/ob mice with exogenous leptin did not alter production of IL-17A significantly in response to ZY. Peritoneal cells and adipose tissue obtained from ZY-injected obese mice expressed significantly higher levels of IL-17A mRNA compared with lean mice. Approximately 2% of peritoneal Ly6G(+) neutrophils from ZY-injected obese mice expressed IL-17A protein, compared with 0.2% of cells obtained from lean mice. Neutralization of IL-17 in ob/ob mice inhibited neutrophil recruitment and production of neutrophil-attracting CXC chemokines and IL-6, without affecting macrophage infiltration or levels of IL-10 and the chemokine CCL2. In contrast, neutralization of IL-6 did not affect production of IL-17A or chemokines while reducing production of the acute-phase protein serum amyloid A significantly. These data demonstrate that neutrophil-derived IL-17A is increased in obese mice during acute inflammation and contributes to exacerbation of inflammatory responses. Topics: Acute Disease; Animals; Ascitic Fluid; Chemokines, CXC; Dietary Fats; Female; Gene Expression Regulation; Inflammation; Interleukin-17; Interleukin-6; Intra-Abdominal Fat; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Neutrophils; Obesity; Peritonitis; T-Lymphocyte Subsets; Thinness; Zymosan | 2010 |
Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet.
Obesity-induced inflammation contributes to the development of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether dietary capsaicin can reduce obesity-induced inflammation and metabolic disorders such as insulin resistance and hepatic steatosis. Male C57BL/6 obese mice fed a high-fat diet for 10 weeks received a supplement of 0.015% capsaicin for a further 10 weeks and were compared with unsupplemented controls. Glucose intolerance was estimated by glucose tolerance tests. Transcripts of adipocytokine genes and the corresponding proteins were measured by reverse transcription-PCR and enzyme-linked immunosorbent assay, and macrophage numbers were determined by flow cytometric analysis. Transient receptor potential vanilloid type-1 (TRPV-1), peroxisome proliferator-activated receptor (PPAR)-alpha, and PPARgamma coactivator-1alpha (PGC-1alpha) mRNAs were also measured by RT-PCR, and PPARalpha luciferase assays were performed. Dietary capsaicin lowered fasting glucose, insulin, leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Levels of tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-6 mRNAs and proteins in adipose tissue and liver decreased markedly, as did macrophage infiltration, hepatic triglycerides, and TRPV-1 expression in adipose tissue. At the same time, the mRNA/protein of adiponectin in the adipose tissue and PPARalpha/PGC-1alpha mRNA in the liver increased. Moreover, luciferase assays revealed that capsaicin is capable of binding PPARalpha. Our data suggest that dietary capsaicin may reduce obesity-induced glucose intolerance by not only suppressing inflammatory responses but also enhancing fatty acid oxidation in adipose tissue and/or liver, both of which are important peripheral tissues affecting insulin resistance. The effects of capsaicin in adipose tissue and liver are related to its dual action on PPARalpha and TRPV-1 expression/activation. Topics: Adiponectin; Adipose Tissue; Animals; Anti-Inflammatory Agents; Blood Glucose; Capsaicin; Dietary Fats; Dietary Supplements; Disease Models, Animal; Fatty Liver; Flow Cytometry; Gene Expression; Glucose Intolerance; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; PPAR alpha; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Triglycerides; TRPV Cation Channels | 2010 |
Inflammatory biomarkers in patients with posttraumatic stress disorder caused by myocardial infarction and the role of depressive symptoms.
Inflammation might link posttraumatic stress disorder (PTSD) with an increased risk of cardiovascular events. We explored the association between PTSD and inflammatory biomarkers related to cardiovascular morbidity and the role of co-morbid depressive symptoms in this relationship.. We investigated 15 patients with interviewer-rated PTSD caused by myocardial infarction (MI) and 29 post-MI patients with no PTSD. All patients completed the depression subscale of the Hospital Anxiety and Depression Scale and had blood collected to determine inflammatory markers of increased cardiovascular risk.. Controlling for demographic and medical covariates, patients with PTSD had higher leptin levels than patients with no PTSD (p = 0.038, explained variance 10.4%); this difference became nonsignificant when controlling for depressive symptoms. After controlling for depressive symptoms, PTSD patients had higher interleukin-6 (p = 0.041; explained variance 10%), lower C-reactive protein (p = 0.022, explained variance 12.1%), and lower soluble CD40 ligand (p = 0.016, explained variance 13.4%) than patients without PTSD. After controlling for PTSD status, depressive symptoms correlated with soluble CD40 ligand (r = 0.45, p = 0.002) and with C-reactive protein (r = 0.29, p < 0.07).. The findings provide further evidence for altered inflammation in PTSD. Comorbid depressive symptoms ought to be considered to disentangle the unique associations of PTSD caused by MI and systemic inflammation. Topics: Aged; Biomarkers; CD40 Ligand; Comorbidity; Depressive Disorder; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Male; Middle Aged; Myocardial Infarction; Neuropsychological Tests; Stress Disorders, Post-Traumatic; Surveys and Questionnaires | 2010 |
Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats.
Postmenopausal women (PMW) are at greater risk for salt-sensitive hypertension and insulin resistance than premenopausal women. Peroxisome-proliferator-activated receptor-gamma (PPARgamma) agonists reduce blood pressure (BP) and insulin resistance in humans. As in PMW, ovariectomy (OVX) increases salt sensitivity of BP and body weight in Dahl salt-sensitive (DS) rats. This study addressed whether rosiglitazone (ROSI), a PPARgamma agonist, attenuates salt-sensitive hypertension in intact (INT) and OVX DS rats, and if so, whether insulin resistance, nitric oxide (NO), oxidative stress, and/or renal inflammation were contributing mediators. Telemetric BP was similar in OVX and INT on low salt diet (0.3% NaCl), but was higher in OVX than INT on high salt (8% NaCl). ROSI reduced BP in OVX and INT on both low and high salt diet, but only attenuated salt sensitivity of BP in OVX. Nitrate/nitrite excretion (NO(x); index of NO) was similar in INT and OVX on low salt diet, and ROSI increased NO(x) in both groups. High salt diet increased NO(x) in all groups but ROSI only increased NO(x) in OVX rats. OVX females exhibited insulin resistance, increases in body weight, plasma leptin, cholesterol, numbers of renal cortical macrophages, and renal MCP-1 and osteopontin mRNA expression compared to INT. ROSI reduced cholesterol and macrophage infiltration in OVX, but not INT. In summary, PPARgamma activation reduces BP in INT and OVX females, but attenuates the salt sensitivity of BP in OVX only, likely due to increases in NO and in part to reductions in renal resident macrophages and inflammation. Topics: Albuminuria; Animals; Biomarkers; Blood Glucose; Blood Pressure; Body Weight; Chemokine CCL2; Cholesterol; Estradiol; Feeding Behavior; Female; Gene Expression Regulation; Immunohistochemistry; Inflammation; Insulin; Kidney; Leptin; Nitrates; Nitrites; Osteopontin; Ovariectomy; Rats; Rats, Inbred Dahl; RNA, Messenger; Rosiglitazone; Thiazolidinediones | 2010 |
Human IL6 enhances leptin action in mice.
Interleukin-6 is an inflammatory cytokine with pleiotropic effects upon nutrient homeostasis. Many reports show that circulating IL6 correlates with obesity and contributes to insulin resistance; however, IL6 can promote energy expenditure that improves glucose homeostasis.. We investigated nutrient homeostasis in C57BL/6J mice with sustained circulating human IL6 (hIL6) secreted predominantly from brain and lung (hIL6(tg) mice).. The hIL6(tg) mice displayed no features of systemic inflammation and were more insulin-sensitive than wild-type mice. On a high-fat diet, hIL6(tg) mice were lean, had low leptin concentrations, consumed less food and expended more energy than wild-type mice. Like ob/ob mice, the ob/ob (IL6) mice (generated by intercrossing ob/ob and hIL6(tg) mice) were obese and glucose-intolerant. However, low-dose leptin injections increased physical activity and reduced both body weight and food intake in ob/ob (IL6) mice, but was ineffective in ob/ob mice. Leptin increased hypothalamic signal transducer and activator of transcription-3 phosphorylation in ob/ob (IL6) mice, whereas ob/ob mice barely responded.. Human IL6 enhanced central leptin action in mice, promoting nutrient homeostasis and preventing diet-induced obesity. Topics: Animal Feed; Animals; Crosses, Genetic; Glucose; Homeostasis; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Mice, Transgenic; Obesity | 2010 |
Leptin modulates cell morphology and cytokine release in microglia.
The appetite suppressing hormone, leptin is now established as an important component of the immune response to pathogens partly via the induction of brain IL-1beta. We have previously demonstrated that this hormone acts on microglia to induce the release of IL-1beta through actions on its functional receptors. In the present study, we extended these findings by demonstrating that leptin's action on microglia is that of a modulator rather than a direct trigger of inflammation. Using primary microglia cultures prepared from rat brain we show that pre-incubation of these cells with leptin for 24h prior to treatment with LPS increased the IL-1beta output 2-fold. This effect was not limited to IL-1beta but was also true for another cytokine, TNF-alpha and chemokines such as CINC-1 and MIP-2. The role of leptin in potentiating the microglial response to LPS appeared to be linked to morphological changes rendering the microglia more reactive. These results suggest that leptin has an important role in microglial function in inflammation and given that its circulating levels fluctuate across a number of conditions, these findings can have important implications for an individual's ability to mount an efficient and complete response to invading pathogens. Topics: Animals; Brain; Brain Chemistry; Cells, Cultured; Chemokines; Cytokines; Dose-Response Relationship, Drug; Immunoassay; Immunohistochemistry; Inflammation; Interleukin-1beta; Leptin; Lipopolysaccharides; Microglia; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha | 2010 |
Editorial: acute inflammation in obesity: IL-17A in the middle of the battle.
Topics: Acute Disease; Adipose Tissue; Animals; CD4-Positive T-Lymphocytes; Diet; Female; Humans; Immunity, Innate; Inflammation; Interleukin-17; Leptin; Mice; Mice, Obese; Neutrophils; Obesity; Peritonitis; Zymosan | 2010 |
Adipokines and nutritional status for patients on maintenance hemodialysis.
The aim of this study was to investigate the serum concentration of adipokines, such as leptin, adiponectin, and resistin, and assess its relation to nutritional and inflammatory parameters in both overweight and normal weight patients on maintenance hemodialysis.. A total of 36 hemodialysis patients (27 M, 9 F; mean age 55.3 +/- 12 yr.) were examined and 23 additional healthy volunteers were recruited as the control group. The concentrations of leptin, leptin receptor, adiponectin, resistin, IL-6, TNFa and CRP were measured by ELISA. Assessment of nutritional status was determined by the levels of albumin, BMI, percentage of body fat (%F), lean body mass (LBM), and Subjective Global Assessment Score (SGA).. According to the SGA 7-points score and the albumin level, 20 patients were of good nutritional status (6-7 points), while 16 patients were mildly malnourished (4-5 points). The concentrations of CRP, resistin, adiponectin, and TNFa were statistically higher in hemodialysis patients than in the control group (p pound 0.05). The adiponectin level was inversely correlated with %F (R Spearman=-0.3; p pound 0.05). The level of leptin was positively correlated with %F as well as with BMI and SGA scores (R Spearman=0.4; p pound 0.05). Although there was no significant difference in the nutritional status between the nonoverweight (BMI 18.5-24.99) and overweight (BMI (3)25.0) groups of patients, in the nonoverweight group there were 12 patients (54.5%) with signs of mild malnutrition compared to 4 malnourished patients (28.5%) in the overweight group. Nonoverweight patients presented significantly lower leptin concentration (12.7 vs 27.8 ug/l) and higher adiponectin level (38.9 vs 32.5 ng/ml) when compared to overweight patients. The levels of IL-6 and TNFa were higher in the nonoverweight group of patients. Overweight patients also had shorter durations of stay in the hemodialysis program (30.5 vs. 87.6 months).. The results of our study indicate that lean hemodialysis patients are more prone to malnutrition and inflammation. The increased levels of leptin and decreased levels of adiponectin in the overweight hemodialysis patients support the idea of a reverse epidemiology phenomenon in this group of patients. Topics: Adipokines; Adiponectin; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Malnutrition; Middle Aged; Nutritional Status; Overweight; Renal Dialysis; Resistin | 2010 |
Macronutrient composition and increased physical activity modulate plasma adipokines and appetite hormones during a weight loss intervention.
We have shown previously that in overweight premenopausal women, changes in macronutrient composition and increasing the number of steps walked per day favorably affect body composition and plasma lipid profiles. As a follow-up, we evaluated the effect of moderate carbohydrate intake and increased physical activity on inflammation and regulation of appetite.. Seventy premenopausal women with a body mass index (BMI) between 25 and 37 kg/m(2) participated in a 10-week weight loss intervention program consisting of the following macronutrient energy distribution: 40% carbohydrate, 30% fat, and 30% protein, in addition to a progressive increase in the number of steps taken per day. Plasma adiponectin, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), leptin, and ghrelin levels were assessed at baseline and after 10 weeks.. Subjects reduced body weight by 4.5%, waist circumference (WC) by 6.4%, and trunk fat by 4.6%. Plasma insulin and insulin resistance assessed by homeostasis model assessment (HOMA) were reduced after 10 weeks (p < 0.01). Plasma adiponectin was increased by 11% (p < 0.05), and ICAM-1 levels were decreased (p < 0.05) after 10 weeks. A negative correlation was found between changes in insulin and changes in adiponectin between baseline and 10 weeks (r = -0.397, p < 0.01), indicating a role of adiponectin in increasing insulin sensitivity. In addition, plasma ghrelin levels were increased by 17% (p < 0.001), indicating a signal for increased appetite associated with weight loss.. These studies indicate that weight loss interventions involving moderate changes in dietary carbohydrate and increases in physical activity favorably affect insulin sensitivity and decrease inflammation. Topics: Adipokines; Adult; Appetite Regulation; Body Composition; Body Mass Index; Carnitine; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Double-Blind Method; Exercise; Female; Ghrelin; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Middle Aged; Premenopause; Vascular Cell Adhesion Molecule-1; Weight Loss | 2010 |
Effects of body weight and alcohol consumption on insulin sensitivity.
Obesity is a risk factor for the development of insulin resistance, which can eventually lead to type-2 diabetes. Alcohol consumption is a protective factor against insulin resistance, and thus protects against the development of type-2 diabetes. The mechanism by which alcohol protects against the development of type-2 diabetes is not well known. To determine the mechanism by which alcohol improves insulin sensitivity, we fed water or alcohol to lean, control, and obese mice. The aim of this study was to determine whether alcohol consumption and body weights affect overlapping metabolic pathways and to identify specific target genes that are regulated in these pathways.. Adipose tissue dysfunction has been associated with the development of type-2 diabetes. We assessed possible gene expression alterations in epididymal white adipose tissue (WAT). We obtained WAT from mice fed a calorie restricted (CR), low fat (LF Control) or high fat (HF) diets and either water or 20% ethanol in the drinking water. We screened the expression of genes related to the regulation of energy homeostasis and insulin regulation using a gene array composed of 384 genes.. Obesity induced insulin resistance and calorie restriction and alcohol improved insulin sensitivity. The insulin resistance in obese mice was associated with the increased expression of inflammatory markers Cd68, Il-6 and Il-1alpha; in contrast, most of these genes were down-regulated in CR mice. Anti-inflammatory factors such as Il-10 and adrenergic beta receptor kinase 1 (Adrbk1) were decreased in obese mice and increased by CR and alcohol. Also, we report a direct correlation between body weight and the expression of the following genes: Kcnj11 (potassium inwardly-rectifying channel, subfamily J, member 11), Lpin2 (lipin2), and Dusp9 (dual-specificity MAP kinase phosphatase 9).. We show that alcohol consumption increased insulin sensitivity. Additionally, alterations in insulin sensitivity related with obesity were coupled with alterations in inflammatory genes. We provide evidence that alcohol may improve insulin sensitivity by up-regulating anti-inflammatory genes. Moreover, we have indentified potential gene targets in energy metabolic pathways and signal transducers that may contribute to obesity-related insulin resistance as well as calorie restriction and alcohol-induced insulin sensitivity. Topics: Adipose Tissue; Alcohol Drinking; Animals; Body Weight; Cytokines; Diet; Dietary Fats; Energy Intake; Energy Metabolism; Ethanol; Gene Expression Profiling; Gene Expression Regulation; Glucose Tolerance Test; Inflammation; Insulin; Insulin Resistance; Intramolecular Oxidoreductases; Leptin; Lipocalins; Male; Mice; Mice, Inbred C57BL; Obesity; Phosphatidate Phosphatase; Potassium Channels, Inwardly Rectifying; RNA, Messenger; Signal Transduction | 2010 |
Adipocytokines in nonalcoholic fatty liver disease: key players regulating steatosis, inflammation and fibrosis.
Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of the metabolic syndrome and covers a large spectrum of liver diseases ranging from benign steatosis to steatohepatitis, cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is currently believed to involve various hits including lipotoxicity, gut-derived signals, inflammatory attacks directed by proinflammatory cytokines, oxidative stress and others. All these factors finally lead to the development of necroinflammation and fibrosis in a substantial proportion of patients. There is increasing evidence that mediators released from the adipose tissue in obese subjects, such as adipocytokines and classical cytokines, are key players in NAFLD. The prototypic adipocytokines adiponectin and leptin are able to regulate many features of NAFLD such as accumulation of liver fat, insulin resistance, inflammatory processes and development of fibrosis. Therefore, this heterogenous and rapidly growing family of mediators elegantly explains many aspects of NAFLD as demonstrated by numerous experimental and clinical studies. Topics: Adipokines; Adiponectin; Animals; Cytokines; Fatty Liver; Humans; Inflammation; Leptin; Liver Cirrhosis; Obesity; Oxidative Stress | 2010 |
Inflammatory markers are increased in youth with type 1 diabetes: the SEARCH Case-Control study.
Increased inflammation may contribute to type 1 diabetes (T1D) complications.. The objective of the study was to investigate the association of inflammation with obesity, hyperglycemia and dyslipidemia in youth with T1D.. This was a cross-sectional study of youth with and without T1D.. The study was conducted in Colorado and South Carolina.. SEARCH Case-Control participants with T1D [n = 553, mean age 15 yr (range 10-22), median duration 2.7 yr] and without diabetes [n = 215, mean age 15 yr (range 10-22)].. This was an observational study.. IL-6, high-sensitivity C-reactive protein (hsCRP), fibrinogen, and leptin were measured.. Inflammatory markers were evaluated by diabetes status, quartiles of glycated hemoglobin, and obesity using multiple linear regression analyses, adjusted for age, sex, study site, race/ethnicity, T1D duration, body mass index, and pubertal status. Compared with controls, youth with T1D had higher IL-6 and fibrinogen levels at all levels of glycemia and obesity, and hsCRP levels were significantly higher in youth with T1D in the top three quartiles of glycated hemoglobin (> or = 7.2%) and among normal-weight subjects. Leptin was lower in youth with poor glycemic control. Higher hsCRP and fibrinogen were correlated with higher total and LDL cholesterol, and apolipoprotein B in youth with T1D, whereas higher fibrinogen was correlated with higher LDL and apolipoprotein B in controls.. T1D is characterized by excess inflammation, independent of adiposity and glycemic control. Even T1D youth in good glycemic control had higher levels of IL-6 and fibrinogen than controls. Elevated inflammatory markers were associated with an atherogenic lipid profile, which may contribute to accelerated atherosclerosis in youth with T1D. Topics: Adolescent; Anthropometry; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; Child; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus, Type 1; Dyslipidemias; Ethnicity; Female; Fibrinogen; Glycated Hemoglobin; Humans; Hyperglycemia; Inflammation; Interleukin-6; Leptin; Male; Obesity; Puberty; Young Adult | 2010 |
Central administration of interleukin-4 exacerbates hypothalamic inflammation and weight gain during high-fat feeding.
In peripheral tissues, the link between obesity and insulin resistance involves low-grade inflammation induced by macrophage activation and proinflammatory cytokine signaling. Since proinflammatory cytokines are also induced in the hypothalamus of animals placed on a high-fat (HF) diet and can inhibit neuronal signal transduction pathways required for normal energy homeostasis, hypothalamic inflammation is hypothesized to contribute to the pathogenesis of diet-induced obesity (DIO). We addressed this hypothesis by perturbing the inflammatory milieu of the hypothalamus in adult male Wistar rats using intracerebroventricular (icv) administration of interleukin-4 (IL-4), a Th2 cytokine that promotes alternative activation (M2) of macrophages and microglia. During HF feeding, icv IL-4 administration increased hypothalamic proinflammatory cytokine gene expression and caused excess weight gain. Intracerebroventricular pretreatment with PS1145, an inhibitor of IKKbeta (a key intracellular mediator of inflammatory signaling), blocked both IL-4 effects, suggesting a causal relationship between IL-4-induced weight gain and hypothalamic inflammation. These observations add to growing evidence linking hypothalamic inflammation to obesity pathogenesis. Topics: Animals; Blood Glucose; Body Weight; Dietary Fats; Energy Metabolism; Heterocyclic Compounds, 3-Ring; Hypothalamus; I-kappa B Kinase; Inflammation; Insulin; Interleukin-4; Leptin; Macrophage Activation; Male; Obesity; Pyridines; Rats; Rats, Wistar; Specific Pathogen-Free Organisms | 2010 |
Adiponectin, resistin and leptin response to dietary intervention in diabetic nephropathy.
Adipokines play an important role in metabolic regulations. Obesity, diabetes, and renal disturbances affect adipokine profile by influencing their complex effects on metabolism. Our objective was to assess the effect of low-energy diet intervention on serum adiponectin, leptin, and resistin levels in diabetic nephropathy.. Seventeen subjects with diabetes type 2 and nephropathy participated in the study. After estimation of individual resting metabolic rates by indirect calorimetry, diets introducing 20% energy deficit were applied. At baseline and after 2 months of dieting, the following parameters were measured: body composition by dual x-ray spectrometry and serum adiponectin (Adp), leptin (Lep), resistin (Res), insulin, urea, creatinine, glucose, glycosylated hemoglobin, C-reactive protein, and tumor necrosis factor-alpha concentrations. Homeostatic model assessment (HOMA) was used to quantify insulin resistance.. Total energy, protein, and fat intakes diminished significantly with intentional dieting. Significant decreases in total body fat mass (FM) and its percentage in body mass (FM%) and trunk and gynoid fat mass, as well as in serum resistin and tumor necrosis factor-alpha levels, were also observed. Responses of adipokines to dietary treatment varied individually. Generally, they were affected by FM. Alterations in Lep concentrations correlated negatively with baseline FM, FM%, and android and gynoid fat mass and positively with changes in intake of protein, carbohydrates, and total energy of the consumed diet. Changes in Adp were inversely related to FM after therapy. Alterations in Res concentrations correlated positively with android fat mass before therapy and initial Lep levels. Adiponectin was inversely related to HOMA index before and after treatment.. Low-energy diet applied in diabetic nephropathy may decrease serum resistin levels and inflammation. In addition, responses of all adipokines to dieting appear to be affected by body fat mass, especially android fat mass. Topics: Adiponectin; Adipose Tissue; Aged; Blood Glucose; Body Composition; C-Reactive Protein; Calorimetry, Indirect; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Energy Intake; Female; Humans; Inflammation; Leptin; Male; Resistin | 2010 |
Circulating leptin and inflammatory response in esophageal cancer, esophageal cancer-related cachexia-anorexia syndrome (CAS) and non-malignant CAS of the alimentary tract.
We investigated the association between esophageal cancer and cachexia-anorexia syndrome (CAS) of the alimentary tract and leptin, an adipocytokine crucial for body weight regulation, a modulator of inflammatory/immune response, implication of which in cancer and CAS development remains debatable. Circulating leptin was measured in 135 esophageal cancer patients (51 non-cachectic and 84 cachectic) and 83 controls (63 non-cachectic and 20 cachectic) and referred to cancer stage, CAS, and inflammatory and nutritional indices. Leptin was down-regulated in cancer patients and cachectic controls as compared to non-cachectic controls, with more pronounced hypoleptinemia in advanced cancers. Leptin correlated directly with BMI, TNF-alpha, albumin, and hemoglobin and indirectly with IL-6, IL-8, and hsCRP. The correlations, except for hsCRP, were more pronounced in females. BMI alone (females) and BMI and hsCRP (males) were independent predictors of leptin explaining over 60% of its variability. Following adjustment for BMI and gender, cancer-related CAS but not cancer itself negatively affected leptin. Leptin and BMI were independently associated with cancer-related and non-malignant CAS with diagnostic accuracy of 93% in identifying subjects with CAS. Pro-inflammatory, angiogenic and mitogenic properties of leptin do not seem to be important for esophageal cancer development but hypoleptinemia, independently from co-occurring reduction of adiposity, appears to be strongly associated with esophageal cancer-related CAS and non-malignant CAS of the alimentary tract. Topics: Adenocarcinoma; Anorexia; Body Mass Index; C-Reactive Protein; Cachexia; Carcinoma, Squamous Cell; Down-Regulation; Esophageal Neoplasms; Female; Gastrointestinal Tract; Hemoglobins; Humans; Inflammation; Interleukin-6; Interleukin-8; Leptin; Male; Serum Albumin; Syndrome; Tumor Necrosis Factor-alpha | 2010 |
Identification of the nasal mucosa as a new target for leptin action.
The aim of this study was to examine systemic and local nasal leptin and leptin receptor expression in patients with nasal polyposis and healthy controls.. Serum leptin and soluble leptin receptor levels were examined by enzyme-linked immunosorbent assay (ELISA). The presence of leptin and leptin receptor mRNA was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), and tissue leptin and leptin receptor protein expression was analysed by immunohistochemistry and ELISA. Serum levels of biologically active leptin were significantly elevated in patients with nasal polyps compared with control subjects. These serum leptin levels were strongly correlated with the levels found in tissue in both study groups, although leptin was not significantly elevated in nasal polyp tissue. Using RT-PCR, we showed that both leptin and its receptors were produced in nasal mucosa. Finally, immunohistochemistry showed that leptin and leptin receptor protein were expressed in several cells of the normal and inflamed nasal mucosa.. Leptin receptors and their biological ligand leptin are expressed in the nasal mucosa, suggesting a possible role in upper airway immunology. Topics: Adult; Aged; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Nasal Mucosa; Nasal Polyps; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Young Adult | 2010 |
Olanzapine-induced accumulation of adipose tissue is associated with an inflammatory state.
Second-generation antipsychotics are widely used in the treatment of all forms of psychoses, but they often produce undesirable side effects, among which are weight gain and other elements of metabolic syndrome. The mechanisms of these adverse effects are not known. The liver and adipose tissue are the principal candidate organs implicated in the development of antipsychotic-induced metabolic adverse effects. The present study investigated in the rat the effects on liver and white adipose tissue of a chronic treatment (46 days) with olanzapine 2 mg/kg or haloperidol 1 mg/kg, as compared with a control solution. In the liver, the expression of key genes involved in glucose transport and lipid metabolism and of regulatory transcription factors, as well as the TNFalpha gene, was not altered in response to either antipsychotic. Similarly, key genes involved in glucose transport and lipid metabolism were not changed in adipose tissue. However, the white adipose tissue was inflammatory in olanzapine-treated rats, with extensive macrophage infiltration and a significant increase in TNFalpha expression. In the plasma, TNFalpha and IL-1beta concentrations were slightly elevated. Chronic olanzapine treatment therefore produces a low-grade inflammatory state, likely initiated in the adipose tissue. Such an inflammatory state is known to be associated with an increased risk of insulin-resistance and cardiovascular diseases. This antipsychotic-induced inflammatory syndrome may participate in the inflammatory syndrome often observed in patients with schizophrenia. The strong and rather selective effect of olanzapine on TNFalpha expression may open new therapeutic opportunities for the prevention of olanzapine-induced metabolic abnormalities. Topics: Adipose Tissue; Analysis of Variance; Animals; Antipsychotic Agents; Benzodiazepines; Cytokines; Glucose; Haloperidol; Immunoassay; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Liver; Male; Olanzapine; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction | 2010 |
Molecular mechanism underlying the inflammatory complication of leptin in macrophages.
Leptin, a key adipokine involved in regulating food intake and body weight, has been recently implicated in the exacerbation of inflammation. Elevated leptin levels in blood circulation are correlated with increased inflammation in obese individuals with cardiovascular complications. However, the underlying molecular mechanism is poorly understood. In this report, we demonstrated that leptin alone failed to induce the expression of inflammatory cytokines such as IL-6 in murine macrophages and human monocytic cells. Instead, leptin significantly augment the effect of LPS in inducing the expression of IL-6. The key inflammatory signaling molecule, Interleukin-Receptor Associate Kinase 1 (IRAK-1), is partially involved in mediating the effects of both LPS and leptin. IRAK-1 deficient macrophages exhibit significantly lower expression of IL-6 following LPS or LPS plus leptin stimulation. Mechanistically, we observed that leptin increases the expression of IRAK-1 in both human monocytes and murine macrophages. Taken together, our data reveal that leptin primarily serves as a helper, instead of an initiator of inflammation during the pathogenesis of obesity-related inflammation. Topics: Animals; Cell Line, Tumor; Gene Expression Regulation; Humans; Inflammation; Interleukin-1 Receptor-Associated Kinases; Leptin; Lipopolysaccharides; Macrophages; Mice; Monocytes; Obesity; Polymerase Chain Reaction | 2010 |
Adipokines, endothelial dysfunction and nutritional status in peritoneal dialysis patients.
Adipokines such as leptin and adiponectin are adipocyte-specific secretory proteins that play important roles in the metabolic regulation of body weight, insulin resistance and cardiovascular complications. The relationship between the malnutrition-inflammation complex syndrome and high levels of some adipokines in peritoneal dialysis (PD) patients is still unclear. An association between high body mass index (BMI) and improved survival in PD patients has also been proposed. The purpose of this study was to investigate the levels of plasma adipokines and inflammation and oxidative stress markers in overweight and normal weight PD patients.. Thirty PD patients (12 M, 18 F; mean age 57.3 ± 16.6 years) were examined and 23 healthy volunteers were included as a control group. The levels of high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, leptin, the leptin receptor, adiponectin, malondialdehyde/4-hydroxynonenal, oxidized low-density lipoprotein, carbonyl groups and asymmetric dimethylarginine (ADMA) were measured in both groups. The nutritional status of each patient was determined by albumin levels, BMI, percentage of body fat (%F), lean body mass (LBM) and the Subjective Global Assessment (SGA) score. The adequacy of dialysis was estimated by weekly Kt/V measurements.. According to the seven-point SGA scores and the albumin levels, the nutrition status of 15 patients was good (6-7 points), while 15 patients were mildly malnourished (3-5 points). The concentrations of hsCRP, leptin and adiponectin were statistically higher in the PD group than in the control group (p < 0.05). Markers of oxidative stress and inflammation were also higher in the PD group. The adiponectin level was inversely correlated with %F and BMI (Spearman's R = -0.3, p ≤ 0.05) and positively correlated with hsCRP level (R = -0.4). The level of leptin was positively correlated with %F, BMI and LBM (R = 0.4, p ≤ 0.05). Patients with normal BMI values had lower leptin concentrations (50.2 vs 242.8 μg/l) and higher adiponectin levels (30.0 vs 20.3 μg/ml) than overweight patients. The statistical analysis indicated that there were no differences in oxidative stress, inflammation and ADMA concentration between the lean and overweight PD patients.. The nutritional status of lean and overweight patients was comparable. Signs of malnutrition were detected in both groups. The severity of chronic inflammation and oxidative stress were not related to BMI in PD patients. Topics: Adiponectin; Adult; Aged; Aldehydes; Arginine; Biomarkers; Body Mass Index; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Endothelium; Female; Humans; Inflammation; Interleukin-6; Leptin; Lipoproteins, LDL; Male; Malnutrition; Malondialdehyde; Middle Aged; Nutritional Status; Oxidative Stress; Peritoneal Dialysis; Risk Factors; Tumor Necrosis Factor-alpha | 2010 |
Association between adiposity and inflammatory markers in maternal and fetal blood in a group of Mexican pregnant women.
In the present pilot study, we evaluated the effect of maternal adiposity on the plasma concentration of adipocytokines in pregnant women and their newborns. Twenty patients with term gestations without labour were initially selected by pregestational BMI and then classified into two study groups (n 10 each), according to their median value of adiposity (total body fat). Concentrations of TNF-α, IL-1β, IL-6, leptin and adiponectin in plasma of maternal peripheral blood and fetal cord blood were measured and correlated to maternal adiposity. Maternal adiposity showed a significant negative correlation with fetal adiponectin (r - 0·587, P = 0·01) and IL-6 (r - 0·466, P = 0·05), a significant positive correlation with maternal leptin (r 0·527, P = 0·02) and no correlation with TNF-α or IL-1β. Adiponectin was higher in fetal plasma than in maternal plasma (P = 0·043), but significantly lower in newborns from women with high adiposity than in newborns from women with low adiposity (P = 0·040). Our results suggest that fetuses from obese women may be less able to control inflammation, due to lower circulating anti-inflammatory adipocytokines, which could limit their optimal development or even increase the risk of abortion or preterm labour. Topics: Adipokines; Adiponectin; Adiposity; Adult; Biomarkers; Birth Weight; Cytokines; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Inflammation; Leptin; Male; Maternal Age; Mexico; Pilot Projects; Pregnancy; Young Adult | 2010 |
Leptin administration downregulates the increased expression levels of genes related to oxidative stress and inflammation in the skeletal muscle of ob/ob mice.
Obese leptin-deficient ob/ob mice exhibit a low-grade chronic inflammation together with a low muscle mass. Our aim was to analyze the changes in muscle expression levels of genes related to oxidative stress and inflammatory responses in leptin deficiency and to identify the effect of in vivo leptin administration. Ob/ob mice were divided in three groups as follows: control ob/ob, leptin-treated ob/ob (1 mg/kg/d) and leptin pair-fed ob/ob mice. Gastrocnemius weight was lower in control ob/ob than in wild type mice (P < .01) exhibiting an increase after leptin treatment compared to control and pair-fed (P < .01) ob/ob animals. Thiobarbituric acid reactive substances, markers of oxidative stress, were higher in serum (P < .01) and gastrocnemius (P = .05) of control ob/ob than in wild type mice and were significantly decreased (P < .01) by leptin treatment. Leptin deficiency altered the expression of 1,546 genes, while leptin treatment modified the regulation of 1,127 genes with 86 of them being involved in oxidative stress, immune defense and inflammatory response. Leptin administration decreased the high expression of Crybb1, Hspb3, Hspb7, Mt4, Cat, Rbm9, Serpinc1 and Serpinb1a observed in control ob/ob mice, indicating that it improves inflammation and muscle loss. Topics: Animals; Down-Regulation; Gene Expression Regulation; Inflammation; Leptin; Male; Mice; Mice, Obese; Microarray Analysis; Molecular Sequence Data; Muscle, Skeletal; Oxidative Stress; Thiobarbituric Acid Reactive Substances | 2010 |
Adipocytokine: a new family of inflammatory and immunologic markers of invasiveness in major urologic surgery.
Laparoscopic surgery has been proposed to reduce surgical trauma and diminish patients' stress response.. To investigate the role of the adipocytokine, in combination with changes in other known inflammatory markers, in patients undergoing radical prostatectomy.. A total of 580 patients were enrolled in this prospective study. Laparoscopic extraperitoneal radical prostatectomy (LRP) was performed in 286 patients, and open retropubic radical prostatectomy (RRP) in 294 patients.. Blood samples were collected preoperatively and up to 5 d postoperatively.. Serum concentrations of acute phase markers, interleukins (IL), and the adipocytokine leptin were measured at each time point by means of enzyme-linked immunosorbent assay. Clinical data were collected and analysed.. Patients undergoing LRP had significantly lower IL-6 and adipocytokine levels at all measurement time points. However, biphasic kinetics of adipocytokine serum levels were observed during the postoperative course in all patients. LRP was associated with less adipocytokine and IL-6 release, indicating a smaller degree of surgical insult and the minimal invasive nature of this procedure. The limitation of this study was its nonrandomised design.. Adipocytokines might serve as additional immunologic markers of invasiveness in major urologic surgery. Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Humans; Inflammation; Interleukin-10; Interleukin-6; Leptin; Male; Middle Aged; Minimally Invasive Surgical Procedures; Postoperative Complications; Prostatectomy; Prostatic Neoplasms; Serum Amyloid A Protein | 2010 |
Postdiagnosis diet quality is inversely related to a biomarker of inflammation among breast cancer survivors.
Inflammation and immune response have potential prognostic implications for breast cancer survivors. We examined how postdiagnosis diet quality is cross-sectionally related to biomarkers of inflammation and adipose-derived hormones among breast cancer survivors and determined whether physical activity or body size modified any observed associations.. Participants included 746 women diagnosed with stage 0 to IIIA breast cancer. Thirty months after diagnosis, the women completed food frequency questionnaires. We scored diet quality with the Healthy Eating Index (HEI)-2005. Serum concentrations of C-reactive protein (CRP), serum amyloid A, leptin, and adiponectin were measured in fasting 30 mL blood samples. Log biomarker values were regressed on quartiles of HEI-2005 scores in multivariate models, and beta scores were exponentiated and expressed as geometric means within quartiles of HEI-2005 scores.. Women with better versus poor quality postdiagnosis diets, as defined by higher HEI-2005 scores (Q4 versus Q1), had lower concentrations of CRP (1.6 mg/L versus 2.5 mg/L), but no significant difference in concentrations of serum amyloid A, leptin, or adiponectin. Among women not engaging in recreational physical activity after diagnosis, better diet quality was associated with lower CRP concentrations (2.5 mg/L versus 5.0 mg/L), but no association was observed among women engaging in any recreational physical activity (1.4 mg/L versus 1.6 mg/L; P heterogeneity = 0.03).. Among breast cancer survivors, a better-quality diet seems to be associated with lower levels of chronic inflammation.. Lower levels of chronic inflammation have been associated with improved survival after breast cancer. Topics: Adiponectin; Biomarkers, Tumor; Breast Neoplasms; C-Reactive Protein; Cohort Studies; Diet; Female; Humans; Inflammation; Leptin; Middle Aged; Motor Activity; Prognosis; Prospective Studies; Quality of Life; Serum Amyloid A Protein; Surveys and Questionnaires; Survivors | 2010 |
Deletion of Nhlh2 results in a defective torpor response and reduced Beta adrenergic receptor expression in adipose tissue.
Mice with a targeted deletion of the basic helix-loop-helix transcription factor, Nescient Helix-Loop-Helix 2 (Nhlh2), display adult-onset obesity with significant increases in their fat depots, abnormal responses to cold exposure, and reduced spontaneous physical activity levels. These phenotypes, accompanied by the hypothalamic expression of Nhlh2, make the Nhlh2 knockout (N2KO) mouse a useful model to study the role of central nervous system (CNS) control on peripheral tissue such as adipose tissue.. Differences in body temperature and serum analysis of leptin were performed in fasted and ad lib fed wild-type (WT) and N2KO mice. Histological analysis of white (WAT) and brown adipose tissue (BAT) was performed. Gene and protein level expression of inflammatory and metabolic markers were compared between the two genotypes.. We report significant differences in serum leptin levels and body temperature in N2KO mice compared with WT mice exposed to a 24-hour fast, suggestive of a defect in both white (WAT) and brown adipose tissue (BAT) function. As compared to WT mice, N2KO mice showed increased serum IL-6 protein and WAT IL-6 mRNA levels. This was accompanied by slight elevations of mRNA for several macrophage markers, including expression of macrophage specific protein F4/80 in adipose, suggestive of macrophage infiltration of WAT in the mutant animals. The mRNAs for beta3-adrenergic receptors (beta3-AR), beta2-AR and uncoupling proteins were significantly reduced in WAT and BAT from N2KO mice compared with WT mice.. These studies implicate Nhlh2 in the central control of WAT and BAT function, with lack of Nhlh2 leading to adipose inflammation and altered gene expression, impaired leptin response to fasting, all suggestive of a deficient torpor response in mutant animals. Topics: Adipocytes, Brown; Adipocytes, White; Adipose Tissue; Animals; Antigens, Differentiation; Basic Helix-Loop-Helix Transcription Factors; Biomarkers; Body Temperature; Energy Metabolism; Fasting; Gene Deletion; Gene Expression Profiling; Gene Expression Regulation; Gene Knockout Techniques; Inflammation; Leptin; Macrophages; Male; Mice; Receptors, Adrenergic, beta | 2010 |
Hepatic gene expression profiling reveals key pathways involved in leptin-mediated weight loss in ob/ob mice.
Leptin, a cytokine-like protein, plays an important role in the regulation of body weight through inhibition of food intake and stimulation of energy expenditure. Leptin circulates in blood and acts on the brain, which sends downstream signals to regulate body weight. Leptin therapy has been successful in treating leptin deficient obese patients. However, high levels of leptin have been observed in more common forms of obesity indicating a state of leptin resistance which limits the application of leptin in the treatment of obesity. If the central effect of leptin could be by-passed and genes which respond to leptin treatment could be regulated directly, new therapeutic targets for the treatment of obesity may be possible. The purpose of this study was to identify genes and subsequent pathways correlated with leptin-mediated weight loss.. WE UTILIZED MICROARRAY TECHNOLOGY TO COMPARE HEPATIC GENE EXPRESSION CHANGES AFTER TWO TYPES OF LEPTIN ADMINISTRATION: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We identified 214 genes that correlate with leptin mediated weight loss. Several biological processes such as mitochondrial metabolic pathways, lipid metabolic and catabolic processes, lipid biosynthetic processes, carboxylic acid metabolic processes, iron ion binding and glutathione S-transferases were downregulated after leptin administration. In contrast, genes involved in the immune system inflammatory response and lysosomal activity were found to be upregulated. Among the cellular compartments mitochondrion (32 genes), endoplasmic reticulum (22 genes) and vacuole (8 genes) were significantly over represented.. In this study we have identified key molecular pathways and downstream genes which respond to leptin treatment and are involved in leptin-mediated weight loss. Many of these genes have previously been shown to be associated with obesity; however, we have also identified a number of other novel target genes. Further investigation will be required to assess the possible use of these genes and their associated protein products as therapeutic targets for the treatment of obesity. Topics: Adipocytes; Animals; Body Weight; Carboxylic Acids; Cell Differentiation; Cell Proliferation; Cluster Analysis; Down-Regulation; Drug Administration Routes; Eating; Female; Gene Expression Profiling; Glutathione Transferase; Hypothalamus; Inflammation; Insulin; Iron; Leptin; Lipid Metabolism; Liver; Lysosomes; Mice; Mitochondria; Obesity; Oligonucleotide Array Sequence Analysis; Weight Loss | 2010 |
High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease.
In earlier studies we found that a high-fat, high-energy diet (HFED) attenuates proteinuria, azotemia and lipid accumulation in the remnant kidney of rats subjected to 5/6 nephrectomy. This study was conducted to explore the mechanism of the salutary effect of HFED in association with moderate protein restriction in this model.. The 5/6 nephrectomized male rats were randomized to receive regular rat chow (CRF group, n = 6) or HFED diet (CRF + HFED, n = 7) for 12 weeks. Sham-operated rats served as controls (n = 6).. The CRF group exhibited azotemia, hypertension, proteinuria, diminished body weight, oxidative stress, glomerulosclerosis, tubulo-interstitial inflammation and upregulation of pro-oxidant [NAD(P)H oxidase], pro-inflammatory (NF-κB activation, increased MCP-1, lipoxygenase, ICAM-1, VCAM-1), pro-fibrotic (TGF-β, CTGF) and pro-apoptotic pathways (Bax, caspase-3) in the remnant kidney. Consumption of the HFED resulted in a 66% increment in lipid intake, 8% increment in carbohydrate intake and a 24% reduction in protein intake. The CRF + HFED group gained weight normally, had increments in leptin and adiponectin levels, and despite increments in plasma cholesterol and fatty acids, showed significant attenuation of oxidative stress, proteinuria and inflammation, and partial reversal of the remnant kidney upregulation of pro-oxidant, pro-inflammatory, pro-fibrotic and pro-apoptotic pathways.. Consumption of high-energy diet in association with mild protein restriction results in suppression of upregulated pathways that drive progression of renal injury in the remnant kidney model. These findings may have relevance in the management of chronic kidney disease in humans. Topics: Adiponectin; Animals; bcl-2-Associated X Protein; Cachexia; Caspase 3; Creatinine; Diet, Protein-Restricted; Dietary Fats; Energy Intake; Inflammation; Leptin; Male; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Oxidative Stress; Proteinuria; Rats; Thiobarbituric Acid Reactive Substances | 2010 |
Inflammation, a link between obesity and cardiovascular disease.
Obesity, the most common nutritional disorder in industrialized countries, is associated with an increased mortality and morbidity of cardiovascular disease (CVD). Obesity is primarily considered to be a disorder of energy balance, and it has recently been suggested that some forms of obesity are associated with chronic low-grade inflammation. The present paper focuses on the current status of our knowledge regarding chronic inflammation, a link between obesity and CVDs, including heart diseases, vascular disease and atherosclerosis. The paper discusses the methods of body fat evaluation in humans, the endocrinology and distribution of adipose tissue in the genders, the pathophysiology of obesity, the relationship among obesity, inflammation, and CVD, and the adipose tissue-derived cytokines known to affect inflammation. Due to space limitations, this paper focuses on C-reactive protein, serum amyloid A, leptin, adiponectin, resistin, visfatin, chemerin, omentin, vaspin, apelin, and retinol binding protein 4 as adipokines. Topics: Adiponectin; Animals; Cardiovascular Diseases; Humans; Inflammation; Leptin; Obesity; Resistin; Serum Amyloid A Protein | 2010 |
Relevance of serum leptin and leptin-receptor concentrations in critically ill patients.
The adipocyte-derived cytokine leptin was implicated to link inflammation and metabolic alterations. We investigated the potential role of leptin components in critically ill patients, because systemic inflammation, insulin resistance, and hyperglycemia are common features of critical illness. Upon admission to Medical Intensive Care Unit (ICU), free leptin and soluble leptin-receptor serum concentrations were determined in 137 critically ill patients (95 with sepsis, 42 without sepsis) and 26 healthy controls. Serum leptin or leptin-receptor did not differ between patients or controls and were independent of sepsis. However, serum leptin was closely associated with obesity and diabetes and clearly correlated with markers of metabolism and liver function. Leptin-receptor was an unfavourable prognostic indicator, associated with mortality during three years follow-up. Our study indicates a functional role of leptin in the pathogenesis of severe illness and emphasizes the impact of complex metabolic alterations on the clinical outcome of critically ill patients. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Critical Illness; Diabetes Mellitus; Diagnosis, Differential; Female; Glucose; Humans; Inflammation; Intensive Care Units; Kaplan-Meier Estimate; Leptin; Lipid Metabolism; Male; Middle Aged; Obesity; Prognosis; Receptors, Leptin; Sepsis; Young Adult | 2010 |
Effect of feeding status on adjuvant arthritis severity, cachexia, and insulin sensitivity in male Lewis rats.
We studied the effect of food restriction, overfeeding, and normofeeding on cachexia, inflammatory and metabolic parameters, and insulin sensitivity in chronic adjuvant arthritis (AA) in rats. Food restriction during AA increased circulating ghrelin, corticosterone, decreased leptin, and ameliorated arthrogram score and systemic inflammation compared to normofeeding. Overfeeding worsened arthrogram score and systemic inflammation, and led to lipid accumulation in the liver, but not to alterations of adipokine and ghrelin plasma levels relative to normofeeding. Independently of feeding status, AA induced cachexia, in which modulation of mRNA expressions for appetite-regulating neuropeptides (NPY, AgRP, POMC, CART) in the arcuate nucleus (ARC) does not play a primary role. The overexpression of IL-1β mRNA in the ARC suggests its role in the mechanisms of impaired energy balance during AA under all feeding conditions. Normal HOMA index in all arthritic groups does not indicate the development of insulin resistance by feeding interventions in these rats. Topics: Adipokines; Adrenal Cortex Hormones; Animal Feed; Animals; Arcuate Nucleus of Hypothalamus; Arthritis; Cachexia; Chemotherapy, Adjuvant; Ghrelin; Inflammation; Insulin; Leptin; Male; Neuropeptides; Rats; Rats, Inbred Lew | 2010 |
Diet-induced obesity, exogenous leptin-, and MADB106 tumor cell challenge affect tissue leukocyte distribution and serum levels of cytokines in F344 rats.
The adipocyte-derived catabolic protein leptin alters cell-mediated immunity and cytokine crosstalk. This may provide new insights into the altered immune response, seen in obese individuals. Therefore, we determined the tissue distribution of immune cells in diet-induced obese (dio) and normal weight F344 rats challenged with MADB106 tumor cells or leptin. Immune cell distribution in blood (by FACS analysis) and tissues (NK cells in spleen and liver, immunohistologically) as well as pro-inflammatory cytokines (IL-6, TNF-α; by flow cytometry) were investigated in 28 normal weight and 28 dio rats (n = 4-6/group). Pro-inflammatory cytokines were increased 3-fold for IL-6 and 7-fold for TNF-α in obese animals. Higher numbers of blood monocytes and NK cells were found in obese as compared to normal weight animals. In dio rats challenged with leptin and MADB106 tumor cells, monocyte numbers were decreased as compared to the obese control animals. Immunohistochemistry revealed an altered NK cell distribution in a compartment-, treatment-, and bodyweight-specific manner. In conclusion, our data reveal a distinct distribution pattern of monocytes and NK cells in dio rats as compared to normal weight littermates and an additional modulatory effect of a leptin- and MADB106 tumor cell challenge. Topics: Adenocarcinoma; Animals; Body Weight; Female; Flow Cytometry; Inflammation; Interleukin-6; Killer Cells, Natural; Leptin; Male; Mammary Neoplasms, Animal; Monocytes; Neoplasm Transplantation; Obesity, Abdominal; Rats; Rats, Inbred F344; Recombinant Proteins; Tumor Microenvironment; Tumor Necrosis Factor-alpha | 2010 |
Effects of exercise combined with caloric restriction on inflammatory cytokines.
Chronic inflammation has been implicated in the pathogenesis of several chronic diseases, such as atherosclerosis and diabetes, as well as certain types of cancers. It has been suggested that circulating biomarkers for inflammation may be modified by exercise; however, few laboratory-based studies have been conducted in nonobese premenopausal women. The purpose of this investigation was to determine the impact of a 4-month exercise training and caloric-restriction intervention with the goal of weight loss on circulating biomarkers of inflammation in sedentary premenopausal women aged 25- 40 years (weight, 57 ± 2 kg). Subjects were studied for 6 consecutive menstrual cycles: 1 Screening, 1 Baseline, then 4 interventions (Interventions 1-4). Supervised aerobic training, consisting primarily of treadmill running and elliptical machine exercise, was performed 4 times per week for 40-90 min at 79% ± 0.7% of maximal heart rate. Subjects also consumed 30% fewer calories vs. baseline (1863 ± 58 to 1428 ± 53 kcalday(-1) (1 kcal = 4.186 kJ), p < 0.0001). Circulating inflammatory biomarkers, including adiponectin, high-sensitivity (hs) C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interferon-gamma (IFN-γ), and leptin, as well as body composition, aerobic capacity, and energy balance, were measured before and after the intervention. Maximal aerobic capacity increased by 8.5 ± 1.7 mL kg(-1)min-1 (p < 0.001) and body mass declined by an average of 3.7 ± 0.5 kg (p < 0.001). Significant reductions in IL-6 (0.39 ± 0.04 to 0.30 ± 0.03 pgmL(-1), p = 0.025), IFN-γ (0.58 ± 0.83 to 0.42 ± 0.64 pgmL-1, p = 0.030), and leptin (13.18 ± 1.28 to 6.28 ± 0.71 pgmL(-1), p < 0.001) were detected in response to the intervention. No significant changes in adiponectin, hs-CRP, or TNF-α were found. Weight loss in response to exercise training and caloric restriction is effective in reducing inflammatory markers, specifically IL-6 and leptin. Topics: Adiponectin; Adult; Biomarkers; Body Composition; C-Reactive Protein; Caloric Restriction; Energy Metabolism; Exercise; Female; Humans; Inflammation; Interferon-gamma; Interleukin-6; Leptin; Patient Dropouts; Physical Fitness; Premenopause; Tumor Necrosis Factor-alpha | 2010 |
Sleep deprivation affects inflammatory marker expression in adipose tissue.
Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation.. The study consisted of two groups: a control (C) group and a paradoxical sleep deprivation by 96 h (PSD) group. Ten rats were randomly assigned to either the control group (C) or the PSD. Mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL)-6, interleukin (IL)-10 and tumour necrosis factor (TNF)-α were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum.. IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-α levels decreased in MEAT. Glucose, triglycerides (TG), VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased.. PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-α protein concentrations in MEAT and increased levels of corticosterone in serum. Topics: Adipokines; Adipose Tissue; Animals; Corticosterone; Inflammation; Interleukin-10; Interleukin-6; Leptin; Male; Rats; Rats, Wistar; Sleep Deprivation; Tumor Necrosis Factor-alpha | 2010 |
Serum adipocytokine and vascular inflammation marker levels in Beta-thalassaemia major patients.
The adipocytokines leptin and adiponectin represent a critical link between metabolism, immunity and chronic inflammation. A chronic vascular inflammatory state plays an important role in the pathophysiology of thalassaemia. We aimed to analyze the levels of these adipocytokines and determine any possible correlations with disease severity or vascular inflammation markers in beta-thalassaemia.. Serum leptin, adiponectin, high-sensitivity C-reactive protein, endothelins, vascular adhesion molecule-1, intracellular adhesion molecule-1 and L- and E-selectin were measured in 28 beta-thalassaemia patients and compared with levels in healthy controls.. Leptin was significantly lower in patients compared to controls (2.23 ± 1.8 vs. 10.24 ± 5.78 μg/l; p = 0.0018), whereas adiponectin was elevated (11.75 ± 5.67 vs. 6.83 ± 2.75 μg/l; p = 0.009). For both adipocytokines, no correlations were found with characteristics such as age, gender, type of chelation, body mass index z score or haemoglobin. Leptin, but not adiponectin, was negatively correlated with ferritin (p = 0.032, r = -0.61). No correlations were found between leptin and the inflammation markers. However, adiponectin was positively correlated with endothelin-1 (p = 0.022, r = 0.63).. Serum leptin is low in beta-thalassaemia, perhaps due to the toxic effect of iron overload on adipose tissue. Paradoxically, adiponectin levels are high and positively correlated with endothelin-1, raising questions about the pro- or anti-inflammatory role of this adipocytokine in beta-thalassaemia. Topics: Adipokines; Adiponectin; Adolescent; Adult; Aging; beta-Thalassemia; Biomarkers; Blood Transfusion; Body Mass Index; C-Reactive Protein; Chelating Agents; Child; Endothelin-1; Endothelin-3; Female; Ferritins; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Male; Middle Aged; Vascular Cell Adhesion Molecule-1 | 2010 |
Pilot study: alterations of intestinal microbiota in obese humans are not associated with colonic inflammation or disturbances of barrier function.
Obesity is associated with low-grade inflammation contributing to insulin-resistance. Gut barrier alterations, described in animal models of obesity, probably favour inflammation. This has not been hitherto described in obese humans.. To evaluate gut permeability in asymptomatic obese and its association with plasma (C-reactive protein (CRP), arachidonate/eicosapentaenoate ratio) and faecal (calprotectin and leptin) markers of inflammation and microbiota alterations.. A total of 13 obese (age: 33.9 ± 11.5 years; BMI: 35.9 ± 5.0 kg/m²) and 11 control subjects (age: 30.3 ± 8.1 years; BMI: 23.5 ± 2.4 kg/m²) were recruited. Gut permeability was assessed by the lactulose-mannitol-sucralose test, plasma fatty acids by gas chromatography, faecal calprotectin and leptin by Elisa and faecal microbiota by G+C profiling.. C-reactive protein was increased in the obese subjects (P = 0.01), but neither the plasma arachidonate/eicosapentaenoate ratio, the faecal levels of calprotectin and leptin, nor the gut permeability were altered. The faecal microbiota was altered in the obese (P = 0.0002), with predominance of bacterial populations having a lower G+C content and decreased concentrations of high G+C populations.. Asymptomatic obese individuals with systemic low-grade inflammation do not have evidence of colonic inflammation or gut barrier alteration; however, the biodiversity of their intestinal microbiota is affected. Topics: Adult; Biomarkers; C-Reactive Protein; Case-Control Studies; Colon; Feces; Female; Humans; Inflammation; Intestinal Absorption; Leptin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Obesity; Permeability; Pilot Projects; Statistics as Topic; Young Adult | 2010 |
Leptin modulates the survival of autoreactive CD4+ T cells through the nutrient/energy-sensing mammalian target of rapamycin signaling pathway.
Chronic inflammation can associate with autoreactive immune responses, including CD4(+) T cell responses to self-Ags. In this paper, we show that the adipocyte-derived proinflammatory hormone leptin can affect the survival and proliferation of autoreactive CD4(+) T cells in experimental autoimmune encephalomyelitis, an animal model of human multiple sclerosis. We found that myelin olygodendrocyte glycoprotein peptide 35-55 (MOG(35-55))-specific CD4(+) T cells from C57BL/6J wild-type mice could not transfer experimental autoimmune encephalomyelitis into leptin-deficient ob/ob mice. Such a finding was associated with a reduced proliferation of the transferred MOG(35-55)-reactive CD4(+) T cells, which had a reduced degradation of the cyclin-dependent kinase inhibitor p27(kip1) and ERK1/2 phosphorylation. The transferred cells displayed reduced Th1/Th17 responses and reduced delayed-type hypersensitivity. Moreover, MOG(35-55)-reactive CD4(+) T cells in ob/ob mice underwent apoptosis that associated with a downmodulation of Bcl-2. Similar results were observed in transgenic AND-TCR- mice carrying a TCR specific for the pigeon cytochrome c 88-104 peptide. These molecular events reveal a reduced activity of the nutrient/energy-sensing AKT/mammalian target of rapamycin pathway, which can be restored in vivo by exogenous leptin replacement. These results may help to explain a link between chronic inflammation and autoimmune T cell reactivity. Topics: Animals; Apoptosis; Cell Proliferation; Chronic Disease; Cyclin-Dependent Kinase Inhibitor p27; Encephalomyelitis, Autoimmune, Experimental; Energy Metabolism; Female; Glycoproteins; Humans; Inflammation; Leptin; Mice; Mice, Obese; Mice, Transgenic; Mitogen-Activated Protein Kinase 3; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Species Specificity; Th1 Cells; Th17 Cells; TOR Serine-Threonine Kinases | 2010 |
Leptin and inflammation in patients with chronic heart failure.
There is an increasing interest in the role of leptin in cardiovascular pathophysiology, including proinflammatory effects. Many studies have reported elevated leptin levels in non-cachectic patients with chronic heart failure (CHF), however, the role of leptin in CHF remains unclear.. To assess the relationship between leptin levels in patients with CHF and left ventricular (LV) systolic dysfunction in relation to ventilatory response to exercise and hsCRP levels.. The study group consisted of 41 patients (mean age 50.2 ± 9.3 years) with stable CHF and LV ejection fraction < 45% and eight healthy controls (mean age 43.6 ± 14.7 years). Sixteen (39%) patients had coronary artery disease. All subjects underwent anthropometric measurements (weight, height, and waist circumference), standard echocardiography, and maximal cardiopulmonary exercise treadmill test. Biochemical analysis included the assessment of leptin and hsCRP levels as well as white blood count (WBC) and erythrocyte sedimention rate.. Leptin levels, including body mass index (BMI)-adjusted leptin levels, were significantly higher in the CHF patients than in the controls (9.2 ± 7.5 vs 2.9 ± 1.25 ng/mL; p = 0.005). We found significantly higher WBC, neutrophil count, lymphocyte percentage and BNP levels in the CHF group vs controls. There were significant correlations in the CHF group between leptin levels and BMI (r = 0.55; p < 0.05), waist circumference (r = 0.49; p < 0.05), leukocyte count (r = 0.41; p < 0.05), hsCRP levels (r = 0.34; p < 0.05), and peak VO₂ (r = -0.34; p < 0.05). Multivariate step forward regression analysis showed that peak VO₂ was significantly related with leptin levels. After adding VE/VCO₂ slope to the multivariate regression analysis model, only VE/VCO₂ slope was independently associated with leptin levels.. There is a significant relationship between serum leptin levels and peak VO₂, VE/VCO₂ slope and levels of inflammatory markers in patients with CHF. Topics: Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; Female; Heart Failure; Humans; Inflammation; Leptin; Male; Middle Aged; Ventricular Dysfunction, Left | 2010 |
Adipocytokines in subjects with and without ischemic cerebrovascular disease.
To investigate adipocytokines in patients with ischemic cerebrovascular disease and to develop an association between them.. In this study plasma adiponectin, leptin and Interleukin 6 (IL 6) concentration were measured by ELISA. Blood glucose and lipid profile was done by standard kit methods.. A total of 80 subjects with and without CVD were studied. The mean plasma level of IL6 of the forty patients with ischemic CVD was significantly higher than that of the forty subjects without CVD (41.64 + 2.50 versus 22.76 + 0.76 pg/mL; P < 0.001). The mean plasma level of adiponectin was significantly lower in patients with ischemic CVD than that of subjects without CVD (4.36 +/- 0.21 microg/mL versus 6.9 +/-0.241microg/mL; P < 0.001). Serum leptin concentrations were significantly higher (p < 0.001) in stroke patients (51.61 + 1.39) as compared with controls (37.76 + 1.207). Leptin levels were significantly negatively correlated with adiponectin (P < 0.01) and significantly positively correlated (P < 0.01) with interleukin 6 in stroke patients.. Present report provides additional support to the evidence of involvement of cytokines in inflammatory immune response of patients with cerebrovascular disease. Topics: Adiponectin; Aged; Brain Ischemia; Cerebrovascular Disorders; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Stroke | 2010 |
Interleukin-6 and leptin as markers of energy metabolic changes in advanced ovarian cancer patients.
The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint. Topics: Adult; Aged; Aged, 80 and over; Energy Metabolism; Female; Gene Expression Regulation, Neoplastic; Glutathione Peroxidase; Humans; Inflammation; Interleukin-6; Leptin; Middle Aged; Ovarian Neoplasms; Reactive Oxygen Species; Treatment Outcome | 2009 |
The effect of pheochromocytoma treatment on subclinical inflammation and endocrine function of adipose tissue.
The aim of our study was to evaluate the influence of surgical removal of pheochromocytoma on the endocrine function of adipose tissue and subclinical inflammation as measured by circulating C-reactive protein (CRP) levels. Eighteen patients with newly diagnosed pheochromocytoma were included into study. Anthropometric measures, biochemical parameters, serum CRP, leptin, adiponectin and resistin levels were measured at the time of diagnosis and six months after surgical removal of pheochromocytoma. Surgical removal of pheochromocytoma significantly increased body weight, decreased both systolic and diastolic blood pressure, fasting blood glucose and glycated hemoglobin levels. Serum CRP levels were decreased by 50 % six months after surgical removal of pheochromocytoma (0.49+/-0.12 vs. 0.23+/-0.05 mg/l, p<0.05) despite a significant increase in body weight. Serum leptin, adiponectin and resistin levels were not affected by the surgery. We conclude that increased body weight in patients after surgical removal of pheochromocytoma is accompanied by an attenuation of subclinical inflammation probably due to catecholamine normalization. We failed to demonstrate an involvement of the changes in circulating leptin, adiponectin or resistin levels in this process. Topics: Adiponectin; Adipose Tissue; Adrenal Gland Neoplasms; Adrenalectomy; Adult; Biomarkers; Blood Pressure; C-Reactive Protein; Down-Regulation; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Pheochromocytoma; Resistin; Treatment Outcome; Weight Gain | 2009 |
Sepsis-induced intestinal microvascular and inflammatory responses in obese mice.
Although clinical obesity is associated with increases in the morbidity and mortality of sepsis, little is known about the mechanisms that underlie the influence of obesity on sepsis. The objective of this study was to determine (a) whether obesity is associated with exaggerated inflammatory and thrombogenic responses in the intestinal microvasculature of septic mice and (b) whether these microvascular alterations are related to changes in the serum levels of cytokines that are produced by adipose tissue. Intravital microscopy was used to quantify leukocyte and platelet adhesion in intestinal postcapillary venules of lean wild-type (WT) mice, and two murine models of obesity, that is, ob/ob and db/db mice. Sepsis was induced by cecal ligation and perforation (CLP). Serum cytokine levels were measured using a cytometric bead assay, whereas adipokines were quantified using enzyme-linked immunosorbent assay. Cecal ligation and perforation elicited significant increases in the adhesion of leukocytes and platelets in venules of lean WT mice. These CLP-induced adhesive interactions were much more pronounced in the microvasculature of both ob/ob and db/db mice. Cecal ligation and perforation was associated with significant increases in serum cytokines in both WT and ob/ob mice, but such changes were not detected in db/db mice. However, db/db (but not WT or ob/ob) mice did exhibit significant increases in serum leptin and adiponectin levels after CLP. Sepsis promotes more intense inflammatory and thrombogenic responses in the gut microcirculation of obese mice than in their lean counterparts. The obesity-enhanced microvascular dysfunction in septic mice shows no consistent correlation with serum cytokines or adipokines. Topics: Adiponectin; Animals; Blood Platelets; Capillaries; Cell Adhesion; Cytokines; Humans; Inflammation; Intestinal Mucosa; Intestines; Leptin; Mice; Mice, Obese; Microcirculation; Obesity; Platelet Adhesiveness; Sepsis; Venules | 2009 |
ICV vs. VMH injection of leptin: comparative effects on hypothalamic gene expression.
Leptin regulates feeding behavior and body weight by binding to its receptors localized in specific areas of the hypothalamus. Leptin injected twice daily for 4 days either into the right ventromedial hypothalamus (VMH) or into the right lateral cerebral ventricle (ICV) and using Real-Time Taqman RT-PCR, mRNA expression levels of selected genes in the arcuate nucleus-median eminence (ARC-ME) complex were quantitatively measured. Expression of selected genes from the ipsi- vs. contralateral VMH areas in rats injected with leptin into the VMH was also compared. VMH injections of leptin increased ARC-ME mRNAs of proopiomelanocortin (POMC), 27.3% (p<0.05); gamma-aminobutyric acid A receptor (GABRD), 89.3% (p<0.01); and thyrotropin-releasing hormone (TRH), 57.7% (p<0.01); and decreased janus kinase 2 (JAK2), 44.4% (p<0.001); suppressor of cytokine signaling 3 (SOCS3), 86.6% (p<0.001); signal transducer and activator of transcription 3 (STAT3), 46.8% (p<0.01); tyrosine hydroxylase (TH), 51.1% (p<0.001); prostaglandin E synthase (PTGES), 96.5% (p<0.001); tumor necrosis factor-alpha (TNF-alpha), 47% (p<0.01); and secretin, 55.4% (p<0.001). Only GABRD, 76.6% (p<0.01) and SCT, 64.9% (p<0.01) were up-regulated in the hypothalamic ARC-ME of rats with ICV leptin injections. VMH injections of leptin induced identical reductions in expression levels of CART, SOCS3, PTGES, and TNF-alpha in both VMH areas; except TH mRNA, whose expression was lowered ipsilaterally. Food intake, body and fat pad weights and serum insulin and leptin were also decreased in rats given leptin through VMH. This study suggests that leptin either unilateral exposure through VMH or bilateral exposure through ICV injections induces divergent ARC-ME gene profiles. Topics: Animals; Arcuate Nucleus of Hypothalamus; Body Weight; Cachexia; Eating; Gene Expression; Hypothalamus; Inflammation; Injections; Injections, Intraventricular; Leptin; Male; Median Eminence; Organ Size; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Ventromedial Hypothalamic Nucleus | 2009 |
Proinflammatory markers, insulin sensitivity, and cardiometabolic risk factors in treated HIV infection.
Treated HIV infection and HIV-lipoatrophy increases risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Circulating inflammatory molecules may, in part, explain this increased risk. This study examined circulating inflammatory molecules in treated HIV infection in relation to insulin sensitivity, lipids total body, and intramyocellular fat, compared to insulin-resistant obesity (an index group at high risk of diabetes). Detailed metabolic phenotypes were measured in 20 treated HIV-infected men (with and without subcutaneous lipoatrophy) vs. 26 insulin-resistant obese men (IR-O, n = 26), including inflammatory molecules, insulin sensitivity, total body fat (TBF), visceral fat (visceral adipose tissue (VAT)), and intramyocellular lipid (IMCL). C-reactive protein (CRP) levels in treated HIV were similar to those in IR-O, despite lower TBF and greater insulin sensitivity in treated HIV. In HIV-lipoatrophy, CRP was higher than that found in IR-O. Adiponectin was similar between treated HIV and IR-O, but significantly lower in those with HIV-lipoatrophy. In treated HIV, subjects with higher CRP had significantly higher total cholesterol, VAT, and IMCL. In treated HIV, subjects with lower adiponectin had significantly lower HDL and higher triglycerides, glucose, VAT, and IMCL. In conclusion, a proinflammatory milieu equivalent to that of insulin-resistant obesity characterizes lean men with treated HIV infection, worse in those with subcutaneous lipoatrophy. These factors may contribute to the accelerated diabetogenesis and cardiac risk observed in treated HIV infection. Topics: Adiponectin; Adult; Antiretroviral Therapy, Highly Active; Biomarkers; Body Composition; C-Reactive Protein; Heart Diseases; HIV Infections; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Diseases; Risk Factors; Tumor Necrosis Factor-alpha | 2009 |
Peroxisome proliferator-activated receptor-alpha modulates insulin gene transcription factors and inflammation in adipose tissues in mice.
We have recently reported that PPAR alpha deficiency leads to hypoglycaemia and hypoinsulinemia in mice (Yessoufou et al. Endocrinology 147:4410-4418, 2006). Besides, these mice exhibited high adiposity with an inflammatory state. We, therefore, assessed, in this study, the effects of PPAR alpha deficiency on the expression of mRNA encoding for the insulin gene transcription factors in pancreatic beta-cells along with those implicated in inflammation in adipose tissues. On fasting, the adult PPAR alpha-null mice were hypoglycemic. Serum insulin concentrations and its pancreatic mRNA transcripts were downregulated in PPAR alpha-null mice, suggesting that PPAR alpha gene deletion contributes to low insulin gene transcription. The PPAR alpha gene deletion downregulates the mRNA expression of insulin gene transcription factors, i.e., Pdx-1, Nkx6.1, and MafA. Besides, the pancreatic function was diminished by PPAR alpha deficiency as PPAR alpha-null mice expressed low pancreatic Glut2 and glucokinase mRNA. PPAR alpha-null mice also expressed high adiponectin and leptin mRNA levels compared to wild type animals. Adipose tissues of PPAR alpha-null mice exhibited upregulation of CD14 and CD68 mRNA, generally expressed by macrophages. PPAR alpha gene deletion downregulates the adipocyte mRNA of certain pro-inflammatory agents, like MCP-1, TNF-alpha, IL-1 beta, IL-6, and RANTES, though pro-inflammatory TLR-2 and TLR-4 mRNAs were upregulated in the adipose tissues. Our results suggest that PPAR alpha deficiency, in mice, is implicated in the modulation of insulin gene transcription and inflammatory status in adipose tissues. Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Body Weight; Fatty Acids; Gene Expression Regulation; Inflammation; Insulin; Insulin-Secreting Cells; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; PPAR alpha; RNA, Messenger; Toll-Like Receptor 2; Toll-Like Receptor 4; Transcription Factors; Triglycerides; Tumor Necrosis Factor-alpha | 2009 |
Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue.
Progranulin is an important molecule in inflammatory response. Chronic inflammation is frequently associated with central obesity and associated disturbances; however, the role of circulating progranulin in human obesity, type 2 diabetes, and dyslipidemia is unknown.. For the measurement of progranulin serum concentrations, we developed an enzyme-linked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating progranulin in a cross-sectional study of 209 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal (NGT) or impaired (IGT) glucose tolerance or type 2 diabetes before and after a 4-week physical training program. Progranulin mRNA and protein expression was measured in paired samples of omental and subcutaneous adipose tissue (adipocytes and cells of the stromal vascular fraction) from 55 lean or obese individuals. Measurement of Erk activation and chemotactic activity induced by progranulin in vitro was performed using THP-1-based cell migration assays.. Progranulin serum concentrations were significantly higher in individuals with type 2 diabetes compared with NGT and in obese subjects with predominant visceral fat accumulation. Circulating progranulin significantly correlates with BMI, macrophage infiltration in omental adipose tissue, C-reactive protein (CRP) serum concentrations, A1C values, and total cholesterol. Multivariable linear regression analyses revealed CRP levels as the strongest independent predictor of circulating progranulin. The extent of in vitro progranulin-mediated chemotaxis is similar to that of monocyte chemoattractant protein-1 but independent of Galpha. Moreover, in type 2 diabetes, but not in IGT and NGT individuals, physical training for 4 weeks resulted in significantly decreased circulating progranulin levels.. Elevated progranulin serum concentrations are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. We identified progranulin as a novel marker of chronic inflammation in obesity and type 2 diabetes that closely reflects omental adipose tissue macrophage infiltration. Physical training significantly reduces elevated circulating progranulin in patients with type 2 diabetes. Topics: Adiponectin; Adipose Tissue; Adult; Cohort Studies; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose Intolerance; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Lipids; Macrophages; Male; Middle Aged; Obesity; Omentum; Progranulins; Reference Values; RNA, Messenger | 2009 |
Adipokines, inflammation, and visceral adiposity across the menopausal transition: a prospective study.
Postmenopausal women have greater visceral adiposity compared with premenopausal women. Adipokines are associated with increased adiposity, insulin resistance, and atherosclerosis.. The objective of the study was to assess changes in adipokines and inflammatory markers through the menopausal transition and correlate them with changes in visceral adiposity.. This was a prospective cohort study of women through the menopausal transition conducted at the University of Washington.. Sixty-nine healthy women were followed up longitudinally from premenopausal (aged 45-55 yr) to postmenopausal status (aged 49-60 yr).. On premenopausal and postmenopausal visits, fasting blood was drawn for adiponectin, leptin, serum amyloid A (SAA), C-reactive protein (CRP), monocyte-chemotactic protein-1, tissue plasminogen activator antigen (tPA), IL-6, and TNF-alpha. Body composition measures were assessed by body mass index, whole-body dual x-ray absorptiometry scan, and computed tomography scan of the abdomen at the lumbar 4-5 level.. Women had a statistically significant increase in SAA, tPA, monocyte-chemotactic protein-1, and adiponectin between the two measurement occasions (P = 0.04, P = 0.02, P = 0.001, and P < 0.001, respectively). The increase in intraabdominal fat was correlated positively with the change in SAA (r = 0.31, P = 0.02), CRP (r = 0.56, P < 0.001), tPA (r = 0.40, P = 0.002), and leptin (r = 0.41, P = 0.002) and negatively correlated with the change in adiponectin (r = -0.37, P = 0.005). After adjustment for change in sc abdominal fat, the correlation between change in CRP, tPA, leptin, and adiponectin remained significantly associated with change in intraabdominal fat.. Women going through the menopausal transition have deleterious changes in inflammatory markers and adipokines that correlate with increased visceral adiposity. Topics: Abdomen; Adipokines; Adiponectin; Adipose Tissue; Adult; Body Composition; C-Reactive Protein; Cohort Studies; Female; Humans; Inflammation; Leptin; Menopause; Middle Aged; Postmenopause; Premenopause; Prospective Studies; Viscera | 2009 |
Impact of increased adipose tissue mass on inflammation, insulin resistance, and dyslipidemia.
Obesity is associated with increased prevalence of metabolic disorders, such as inflammation, insulin resistance, and dyslipidemia, which can predispose an individual to develop diabetes and cardiovascular disease. Adipose tissue (AT) is now recognized as a metabolically active organ that controls plasma free fatty acid levels and contributes to systemic metabolic homeostasis by secreting adipokines. In obesity, the recruitment of immune cells, such as T cells and macrophages, to AT causes inflammation, which is thought to contribute to local insulin resistance. This loss of insulin sensitivity within AT can lead to uncontrolled release of fatty acids, secretion of inflammatory cytokines, and alterations in the balance of adipokines, which ultimately impact lipoprotein metabolism and insulin sensitivity systemically. Thus, AT itself plays an important role in the increased risk of diabetes and cardiovascular disease that is associated with obesity. Topics: Adipocytes; Adipose Tissue; Apoptosis; Cell Differentiation; Chemokines; Dyslipidemias; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Obesity; Signal Transduction; T-Lymphocytes | 2009 |
Therapeutic effect of puerarin on non-alcoholic rat fatty liver by improving leptin signal transduction through JAK2/STAT3 pathways.
In order to investigate the mechanism of the therapeutic effect of puerarin on non-alcoholic fatty liver disease, a non-alcoholic fatty disease male rat model was induced by a high fat diet, all rats were randomly divided into a blank group, model group, simavastatin group and puerarin group. After 4 weeks of drug treatment, the liver was slided to investigate pathological morphology. Elisa was used to measure the total cholesterol (TC), triglyeride (TG) in liver, and leptin content in serum. RT-PCR and Western blotting were employed to detect liver leptin mRNA receptor expression and P-JAK2, P-STAT3 expression levels in the liver respectively. The results showed that puerarin significantly decreased the TG, TC content in liver of the non-alcoholic fatty disease rats, ameliorated steatosis in liver, lowered liver inflammatory reaction, decreased leptin level in serum, and enhanced the expression of leptin receptor mRNA and P-JAK2/P-STAT3 level. All the results demonstrated that puerarin can exhibit therapeutic effect on non-alcoholic fatty liver disease by improving leptin signal transduction through JAK2/STAT3 pathways. Topics: Animals; Cholesterol; Dietary Fats; Disease Models, Animal; Dose-Response Relationship, Drug; Fatty Liver; Inflammation; Isoflavones; Janus Kinase 2; Leptin; Lipid Metabolism; Liver; Male; Phytotherapy; Plant Extracts; Pueraria; Rats; Rats, Wistar; Receptors, Leptin; RNA, Messenger; Signal Transduction; Simvastatin; STAT3 Transcription Factor; Triglycerides | 2009 |
Leptin attenuates cardiac apoptosis after chronic ischaemic injury.
We have previously shown that activation of leptin signalling in the heart reduces cardiac morbidity and mortality after myocardial infarction (MI). In the present study, we tested the hypothesis that leptin signalling limits cardiac apoptosis after MI through activation of signal transducer and activator of transcription (STAT)-3 responsive anti-apoptotic genes, including B-cell lymphoma (bcl)-2 and survivin, that serve to downregulate the activity of caspase-3.. Hearts from C57BL/6J and three groups of leptin-deficient Ob/Ob mice (food-restricted, ad libitum, and leptin-repleted) were examined 4 weeks after permanent left coronary artery ligation or sham operation. Inflammatory and apoptotic cell number was determined in cardiac sections by immunostaining. Expression of cardiac bcl-2, survivin, and pro and active caspase-3 was determined and correlated with in vitro caspase-3 activity. In the absence of MI, both lean and obese leptin-deficient mice exhibited increased cardiac apoptosis compared with wild-type mice. After MI, the highest rates of apoptosis were seen in the infarcted tissue of lean and obese Ob/Ob mice. Further, leptin-deficient hearts, as well as hearts from wild-type mice treated with the STAT-3 inhibitor WP1066, exhibited blunted anti-apoptotic bcl-2 and survivin gene expression, and increased caspase-3 protein expression and activity. The increased caspase-3 activity and apoptosis in hearts of leptin-deficient mice after MI was significantly attenuated in Ob/Ob mice replete with leptin, reducing apoptosis to levels comparable to that observed in wild-type mice after MI.. These results demonstrate that intact leptin signalling post-MI acts through STAT-3 to increase anti-apoptotic bcl-2 and survivin gene expression and reduces caspase-3 activity, consistent with a cardioprotective role of leptin in the setting of chronic ischaemic injury. Topics: Animals; Apoptosis; bcl-Associated Death Protein; Caspase 3; Chronic Disease; Coronary Vessels; Disease Models, Animal; Inflammation; Inhibitor of Apoptosis Proteins; Leptin; Ligation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microtubule-Associated Proteins; Myocardial Infarction; Myocardium; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Pyridines; Repressor Proteins; Signal Transduction; STAT3 Transcription Factor; Survivin; Tyrphostins | 2009 |
Nutritional and inflammatory status of hemodialysis patients in relation to their body mass index.
The study tested whether obese hemodialysis (HD) patients have a better nutritional and inflammatory state than those with overweight or normal body mass index (BMI).. This was a single-center, cross-sectional study.. Ninety-six stable HD patients from a local HD unit were divided into 3 groups according to BMI (normal, overweight, and obese).. Anthropometry, body composition by multifrequency bioelectrical impedance analysis, biochemical nutritional markers, as well as interleukins (IL-1, IL-6, and IL-10), tumor necrosis factor, leptin, and soluble leptin receptor (sOB-R) were measured.. Serum creatinine was significantly elevated in the highest BMI category. Albumin and transferrin were significantly elevated in higher BMI groups after adjustment for age, sex, and diabetes status. The higher BMI group had greater lean body mass (P = .001) and fat mass (P = .0001), higher phase angle (PA), and lower extracellular mass-to-body-cell-mass ratio (ECM/BCM) (P < .05). Inflammatory cytokine levels were not different in the 3 BMI groups. In parallel with increasing BMI, a gradual increase in serum leptin and a trend for decreasing sOB-R were detected (P = .0001 and P = .055, respectively). Both PA (r = 0.295, P = .008) and ECM/BCM (r = -0.345, P = .002) significantly correlated with serum leptin concentration. According to a multiple linear regression analysis, with PA as the dependent variable, age (beta = 0.274, P = .008), creatinine (beta = 0.355, P = .001), and log sOB-R/leptin ratio (beta = -0.465, P = .008) were significant independent predictors of PA.. HD patients with elevated BMI demonstrate better nutritional status compared to normal BMI or overweight patients, whereas the severity of inflammation is not related to BMI in HD patients. Topics: Aged; Albumins; Biomarkers; Body Composition; Body Mass Index; Creatinine; Cross-Sectional Studies; Cytokines; Electric Impedance; Female; Health Status; Humans; Inflammation; Interleukins; Israel; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Renal Dialysis; Transferrin; Tumor Necrosis Factor-alpha | 2009 |
A nutrigenomic inflammation-related PBMC-based approach to predict the weight-loss regain in obese subjects.
Long-term maintenance of a dietary-induced weight loss continues to be a major health problem and warrants research on innovative approaches to understand weight stability. We investigated the role of the proinflammatory status on weight changes in obese subjects receiving a low-calorie diet (LCD) and during the subsequent 6-month weight maintenance period.. Eighty-four subjects (age: 34.2 +/- 0.53 years; body mass index, BMI: 30.4 +/- 1.8 kg/m(2)) followed an 8-week LCD intervention and were contacted again 6 months later. Body composition, circulating proinflammatory markers [tumor necrosis factor (TNF)alpha, interleukin-6, C-reactive protein and leptin] and mRNA levels of inflammation-related genes [TNFalpha and nuclear factor (NF) kappaB transcription subunits] in peripheral blood mononuclear cells (PBMC) were evaluated.. The 6-month weight regain was predicted by high concentrations of TNFalpha at LCD completion (OR = 4.21, p = 0.036) along with the baseline amount of fat mass (OR = 7.23, p = 0.029). In addition, baseline leptin concentrations (p = 0.028) as well as mRNA levels of TNFalpha and NFkappaB subunits were higher at the end of the dietary intervention (p < 0.05) in PBMC of subjects who regained >or=10% of the dietary-induced weight loss.. These findings demonstrate a role for the proinflammatory state and body adiposity in the prediction of weight-loss regain. This relationship could contribute to the design of more personalized nutritional treatments in obese patients and favor the weight maintenance process. Topics: Adult; C-Reactive Protein; Female; Gene Expression Profiling; Humans; Inflammation; Interleukin-6; Leptin; Leukocytes, Mononuclear; Male; NF-kappa B; Nutrigenomics; Obesity; Predictive Value of Tests; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Gain; Weight Loss; Young Adult | 2009 |
Diet-induced obese mice are leptin insufficient after weight reduction.
Behavioral therapies aimed at reducing excess body fat result in limited fat loss after dieting. To understand the causes for maintenance of adiposity, high-fat (HF) diet-induced obese (DIO) mice were switched to a low-fat chow diet, and the effects of chow on histological and molecular alterations of adipose tissue and metabolic parameters were examined. DIO mice reduced and stabilized their body weights after being switched to chow (HF-chow), but retained a greater amount of adiposity than chow-fed mice. Reduction in adipocyte volume, not number, caused a decrease in fat mass. HF-chow mice showed normalized circulating insulin and leptin levels, improved glucose tolerance, and reduced inflammatory status in white adipose tissue (WAT). Circulating leptin levels corrected for fat mass were lower in HF-chow mice. Leptin administration was used to test whether reduced leptin level of HF-chow mice inhibited further fat loss. Leptin treatment led to an additional reduction in adiposity. Finally, HF-HF mice had lower mRNA levels of beta(3) adrenergic receptor (beta(3)-AR) in epididymal WAT (EWAT) compared to chow-fed mice, and diet change led to an increase in the WAT beta(3)-AR mRNA levels that were similar to the levels of chow-fed mice, suggesting an elevation in sympathetic activation of WAT during diet switch relative to HF-HF mice leading to the reduced leptin level and proinflammatory cytokine content. In summary, HF-chow mice were resistant to further fat loss due to leptin insufficiency. Diet alteration from HF to low fat improved metabolic state of DIO mice, although their adiposity was defended at a higher level. Topics: Adipose Tissue, Brown; Adipose Tissue, White; Adiposity; Animals; Blood Glucose; Cell Size; Diet, Fat-Restricted; Dietary Fats; Disease Models, Animal; Eating; Fatty Liver; Feeding Behavior; Inflammation; Insulin; Leptin; Macrophages; Male; Mice; Mice, Inbred C57BL; Obesity; Receptors, Adrenergic, beta-3; RNA, Messenger; Time Factors; Weight Loss | 2009 |
[Nonrespiratory sleep disorders in obese and diabetic patients].
Pneumologists frequently see obese and diabetic patients because of the high prevalence of these pathologies associated with sleep apneas. Nevertheless, the search for a sleep apnea syndrome is sometimes negative and the pneumologist is faced with unexplained complaints of sleepiness and sleep disorders. Pneumologists have to be familiar with and explore other nonrespiratory disorders in order to improve patient care. Inflammatory mechanisms have been suspected in several recent studies on daytime sleepiness. Sleep duration, obesity and diabetes are supposed to be linked because of hormonal modifications induced by sleep deprivation. Moreover, a relationship between diabetes and restless legs syndrome is not excluded. Topics: Cytokines; Diabetes Mellitus, Type 2; Ghrelin; Humans; Inflammation; Leptin; Obesity; Restless Legs Syndrome; Sleep Wake Disorders | 2009 |
A new mouse model of metabolic syndrome and associated complications.
Metabolic syndrome (MS) encompasses a clustering of risk factors for cardiovascular disease, including obesity, insulin resistance, and dyslipidemia. We characterized a new mouse model carrying a dominant mutation, C57BL/6J-Nmf15/+ (B6-Nmf15/+), which develops additional complications of MS such as adipose tissue inflammation and cardiomyopathy. A backcross was used to genetically map the Nmf15 locus. Mice were examined in the comprehensive laboratory animal monitoring system, and dual energy X-ray absorptiometry and blood chemistry analyses were performed. Hypothalamic LEPR, SOCS1, and STAT3 phosphorylation were examined. Cardiac function was assessed by echo- and electrocardiography. Adipose tissue inflammation was characterized by in situ hybridization and measurement of Jun kinase activity. The Nmf15 locus mapped to distal mouse chromosome 5 with an LOD (logarithm of odds) score of 13.8. Nmf15 mice developed obesity by 12 weeks of age. Plasma leptin levels were significantly elevated in pre-obese Nmf15 mice at 8 weeks of age and an attenuated STAT3 phosphorylation in the hypothalamus suggests a primary leptin resistance. Adipose tissue from Nmf15 mice showed a remarkable degree of inflammation and macrophage infiltration as indicated by expression of the F4/80 marker and increased phosphorylation of JUN N-terminal kinase 1/2. Lipidosis was observed in tubular epithelial cells and glomeruli of the kidney. Nmf15 mice demonstrate both histological and pathophysiological evidence of cardiomyopathy. The Nmf15 mouse model provides a new entry point into pathways mediating leptin resistance and obesity. It is one of few models that combine many aspects of MS and can be useful for testing new therapeutic approaches for combating obesity complications, particularly cardiomyopathy. Topics: Adipose Tissue; Animals; Blood Glucose; Cardiomyopathies; Chromosome Mapping; Disease Models, Animal; Female; Hypothalamus; Inflammation; Leptin; Lipidoses; Male; Metabolic Syndrome; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Oxygen Consumption; Quantitative Trait Loci | 2009 |
Patterns and prognostic value of troponin, interleukin-6, and leptin after pediatric open-heart surgery.
Leptin and interleukin-6 (IL-6) are inversely correlated and associated with decreased survival in critically ill patients. We investigated changes in leptin, IL-6, and troponin in children undergoing open-heart surgery, hypothesizing that IL-6 and troponin will increase after cardiopulmonary bypass (CPB) and will be negatively correlated with leptin.. Serial blood samples were collected from 21 patients 24 hours before and up to 48 hours after surgery.. Leptin levels decreased by 50% during CPB (P < .001), then gradually increased, reaching baseline levels 12 hours after surgery. The IL-6 levels increased (P < .001) during CPB, peaking 2 hours after surgery and remaining slightly elevated at 24 hours after surgery (P < .001). Leptin and IL-6 were negatively correlated (R = -0.448, P < .001). Troponin levels increased during CPB (P < .001). Postoperative leptin and troponin were inversely correlated (r = -0.535, P < .001). Patients with modest elevations in troponin levels (<20 microg/L) had a shorter aortic clamp and CPB time (P < .01), lower IL-6 peak levels (P = .03), and shorter duration of ventilation and inotropic support compared with patients with peak troponin levels greater than 20 microg/L.. Lower leptin and higher IL-6 levels correlated with troponin, a marker of myocardial injury. Because leptin may have cardioprotective effects, the postoperative drop in its levels may further contribute to myocardial dysfunction. Topics: Biomarkers; Cardiopulmonary Bypass; Critical Illness; Female; Heart Defects, Congenital; Hospital Mortality; Humans; Infant; Inflammation; Interleukin-6; Leptin; Male; Myocardial Ischemia; Postoperative Complications; Prognosis; Survival Analysis; Time Factors; Troponin | 2009 |
Visfatin: the link between inflammation and childhood obesity.
Topics: Adolescent; Child; Gene Expression Regulation, Enzymologic; Humans; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Tumor Necrosis Factor-alpha | 2009 |
The effects of PACAP and related peptides on leptin, soluble leptin receptor and resistin in normal condition and LPS-induced inflammation.
Leptin and resistin are adipokines considered as pro-inflammatory factors related to metabolic syndrome, inflammatory and/or autoimmune conditions. Pituitary adenylate cyclase activating peptide (PACAP) is a pleiotropic neuropeptide with anti-inflammatory properties. We investigated the influence of PACAP on the serum level of leptin, soluble leptin receptor (SLR) and resistin in ordinary and LPS-induced inflammatory conditions using PACAP38 and a series of selective agonist for each PACAP receptor types. It was found that PACAP exerted opposite effects on the leptin:SLR ratio and the serum resistin level. In ordinary condition, PACAP acted as a pro-inflammatory factor by increasing the leptin:SLR ratio and serum resistin level. But in LPS-induced acute inflammatory condition, PACAP not only antagonized the effects of LPS, but also even reversed the effects of LPS. In mice treated with LPS, co-treatment with PACAP decreased the serum leptin and resistin levels and increased the serum soluble leptin receptor level significantly. It was also found that, in ordinary condition, treatment with PAC1 agonist maxadilan induced marked increase in serum leptin, leptin:SLR ratios and resistin levels; while in LPS-induced inflammation, VPAC1 mediated much more anti-inflammatory and reversing-LPS effects of PACAP on leptin and resistin than PAC1 and VPAC2. It is concluded that different receptors mediates different effects of PACAP on leptin, SLR and resistin in non-inflammatory and LPS-induced inflammatory conditions. Topics: Animals; Enzyme-Linked Immunosorbent Assay; Growth Substances; Inflammation; Insect Proteins; Leptin; Lipopolysaccharides; Male; Mice; Pituitary Adenylate Cyclase-Activating Polypeptide; Random Allocation; Receptors, Leptin; Resistin | 2009 |
Antibody blockade of c-fms suppresses the progression of inflammation and injury in early diabetic nephropathy in obese db/db mice.
Macrophage-mediated renal injury plays an important role in the development of diabetic nephropathy. Colony-stimulating factor (CSF)-1 is a cytokine that is produced in diabetic kidneys and promotes macrophage accumulation, activation and survival. CSF-1 acts exclusively through the c-fms receptor, which is only expressed on cells of the monocyte-macrophage lineage. Therefore, we used c-fms blockade as a strategy to selectively target macrophage-mediated injury during the progression of diabetic nephropathy.. Obese, type 2 diabetic db/db BL/KS mice with established albuminuria were treated with a neutralising anti-c-fms monoclonal antibody (AFS98) or isotype matched control IgG from 12 to 18 weeks of age and examined for renal injury.. Treatment with AFS98 did not affect obesity, hyperglycaemia, circulating monocyte levels or established albuminuria in db/db mice. However, AFS98 did prevent glomerular hyperfiltration and suppressed variables of inflammation in the diabetic kidney, including kidney macrophages (accumulation, activation and proliferation), chemokine CC motif ligand 2 levels (mRNA and urine protein), kidney activation of proinflammatory pathways (c-Jun amino-terminal kinase and activating transcription factor 2) and Tnf-alpha (also known as Tnf) mRNA levels. In addition, AFS98 decreased the tissue damage caused by macrophages including tubular injury (apoptosis and hypertrophy), interstitial damage (cell proliferation and myofibroblast accrual) and renal fibrosis (Tgf-beta1 [also known as Tgfb1] and Col4a1 mRNA).. Blockade of c-fms can suppress the progression of established diabetic nephropathy in db/db mice by targeting macrophage-mediated injury. Topics: Animals; Antibodies, Monoclonal; Cell Division; Diabetic Nephropathies; Genotype; Inflammation; Kidney Tubules; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Polymerase Chain Reaction; Receptor, Macrophage Colony-Stimulating Factor | 2009 |
Environmental tobacco smoke and cardiometabolic risk in young children: results from a survey in south-west Germany.
We explored the association between exposure to environmental tobacco smoke (ETS) and various cardiometabolic biomarkers in 10-year-old children.. A population-based cross-sectional study was carried out. Data on ETS exposure and potential confounders were collected by parental questionnaire. Adiponectin, leptin, markers of inflammation, apolipoproteins (apo) AI and B, and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) were measured. Linear and logistic regression models were applied using the 90th percentile as a cut-off point except for adiponectin and apoAI (10th percentile). In linear models, ETS exposure was significantly associated with increasing plasma concentrations of leptin, C-reactive protein, fibrinogen, interleukin (IL)-6, and Lp-PLA(2). When compared with none, ETS exposure of more than 10 cigarettes per day was associated with elevated concentrations of leptin (OR 6.40; 95% CI, 2.67-15.39), C-reactive protein (OR 3.17; 95% CI, 1.31-7.68), Lp-PLA(2) (OR 2.97 95% CI, 1.32-6.68), low adiponectin (OR 2.69; 95% CI, 1.10-6.57), and low apoAI (OR 4.48; 95% CI, 2.16-10.85). Increasing dose of ETS exposure was related to an increasing number of abnormal cardiometabolic markers.. Among children, ETS exposure was associated with a low-grade inflammatory response and altered markers of lipid metabolism, which may initiate atherosclerosis in early life. However, longitudinal studies are necessary to determine the potential causal relevance of these associations. Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Biomarkers; C-Reactive Protein; Child; Cross-Sectional Studies; Female; Germany, West; Humans; Inflammation; Leptin; Lipid Metabolism; Logistic Models; Male; Parents; Risk Factors; Surveys and Questionnaires; Tobacco Smoke Pollution | 2009 |
Degree of weight loss required to improve adipokine concentrations and decrease fat cell size in severely obese women.
Adipose tissue physiology plays an important role in mediating disease risk. Weight loss in obese individuals improves indicators of adipocyte physiology. However, the minimum degree of weight loss required to elicit improvements remains unknown. The objective of the present study was to determine the minimum weight loss required to improve adipokine profile and decrease fat cell size in severely obese women. Thirteen severely obese women (body mass index, 50 +/- 3 kg/m(2); age, 35 +/- 1 years) consumed a low-calorie diet for 3 weeks with the goal of losing 5% of their initial weight. Subjects were divided into 2 weight loss groups posttreatment: less than 5% weight loss and 5% to 10% weight loss. Body weight was reduced (P < .05) in both groups (-1.4 +/- 1.0 and -6.8 +/- 0.6 kg, respectively). Adiponectin concentrations increased (P < .05) by 20% in the 5% to 10% weight loss group only. Likewise, leptin and resistin decreased (P < .05) by 37% and 27%, respectively, in the group that lost more weight. Visceral and subcutaneous fat cell size was 41% and 37% smaller (P < .01), respectively, in the 5% to 10% weight loss group. Smaller visceral adipocyte size was related to lower insulin (r = 0.82, P = .01) and glucose (r = 0.58, P = .04) concentrations posttreatment. These findings suggest that a minimum weight loss of 5% is required to improve adipokine profile and decrease fat cell size in severely obese women. These changes in adipocyte physiology may be linked to reductions in metabolic disease risk in this population. Topics: Adipocytes; Adipokines; Adiponectin; Adult; Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Caloric Restriction; Female; Humans; Inflammation; Insulin; Intra-Abdominal Fat; Leptin; Middle Aged; Obesity; Resistin; Subcutaneous Fat; Weight Loss | 2009 |
Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis.
Chemerin is a recently discovered adipokine that regulates adipocyte differentiation and modulates chemotaxis and activation of dendritic cells and macrophages. Given the convergence of adipocyte and macrophage function, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis in humans. We sought to examine the relationship of i) chemerin and markers of inflammation, ii) chemerin and components of the metabolic syndrome, and iii) chemerin and coronary atherosclerotic plaque burden and morphology.. Serum chemerin levels were determined in 303 patients with stable typical or atypical chest pain who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed, or non-calcified.. Chemerin levels were highly correlated with high sensitivity C-reactive protein (r=0.44, P<0.0001), interleukin-6 (r=0.18, P=0.002), tumor necrosis factor-alpha (r=0.24, P<0.0001), resistin (r=0.28, P<0.0001), and leptin (r=0.36, P<0.0001) concentrations. Furthermore, chemerin was associated with components of the metabolic syndrome including body mass index (r=0.23, P=0.0002), triglycerides (r=0.29, P<0.0001), HDL-cholesterol (r=-0.18, P=0.003), and hypertension (P<0.0001). In bivariate analysis, chemerin levels were weakly correlated with coronary plaque burden (r=0.16, P=0.006) and the number of non-calcified plaques (r=0.14, P=0.02). These associations, however, were lost after adjusting for established cardiovascular risk factors (odds ratio, OR 1.17, 95% confidence interval (CI) 0.97-1.41, P=0.11 for coronary plaque burden; OR 1.06, 95% CI 0.96-1.17, P=0.22 for non-calcified plaques).. Chemerin is strongly associated with markers of inflammation and components of the metabolic syndrome. However, chemerin does not predict coronary atherosclerosis. Topics: Aged; C-Reactive Protein; Chemokines; Cholesterol; Cohort Studies; Coronary Artery Disease; Female; Humans; Hypertension; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Regression Analysis; Resistin; Triglycerides; Tumor Necrosis Factor-alpha | 2009 |
Maternal obesity and markers of inflammation in pregnancy.
To evaluate whether obesity is associated with changes in pro-inflammatory and immunomodulatory cytokines in pregnancy.. We performed a cross-sectional study using maternal serum from the early second trimester to examine biomarkers associated with inflammation in relation to maternal body mass index (n=80 total).. Leptin and high sensitivity C-reactive protein were significantly different between groups and increased with increasing body mass index. MCP-1 was significantly increased in the morbidly obese mothers. Interleukin-2 exhibited a U-shaped relationship with body mass index; transforming growth factor-beta1 demonstrated a nonsignificant negative trend with body mass index; and the levels of hepatocyte growth factor and tumor necrosis factor-alpha did not differ appreciably between groups.. Maternal obesity in pregnancy is associated with changes in cytokines, protein hormones and acute phase proteins in the second trimester, with an increase in MCP-1 in the morbid obesity category, and an increase in Leptin and hsCRP with increasing BMI category. Topics: Acute-Phase Proteins; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Chemokine CCL2; Cytokines; Female; Hepatocyte Growth Factor; Humans; Inflammation; Interleukin-2; Leptin; Obesity; Obesity, Morbid; Peptide Hormones; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Young Adult | 2009 |
Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis.
Obesity-associated inflammation is of critical importance in the development of insulin resistance and non-alcoholic fatty liver disease. Since the cannabinoid receptor CB2 regulates innate immunity, the aim of the present study was to investigate its role in obesity-induced inflammation, insulin resistance and fatty liver.. Murine obesity models included genetically leptin-deficient ob/ob mice and wild type (WT) mice fed a high fat diet (HFD), that were compared to their lean counterparts. Animals were treated with pharmacological modulators of CB2 receptors. Experiments were also performed in mice knock-out for CB2 receptors (Cnr2 -/-).. In both HFD-fed WT mice and ob/ob mice, Cnr2 expression underwent a marked induction in the stromal vascular fraction of epididymal adipose tissue that correlated with increased fat inflammation. Treatment with the CB2 agonist JWH-133 potentiated adipose tissue inflammation in HFD-fed WT mice. Moreover, cultured fat pads isolated from ob/ob mice displayed increased Tnf and Ccl2 expression upon exposure to JWH-133. In keeping, genetic or pharmacological inactivation of CB2 receptors decreased adipose tissue macrophage infiltration associated with obesity, and reduced inductions of Tnf and Ccl2 expressions. In the liver of obese mice, Cnr2 mRNA was only weakly induced, and CB2 receptors moderately contributed to liver inflammation. HFD-induced insulin resistance increased in response to JWH-133 and reduced in Cnr2 -/- mice. Finally, HFD-induced hepatic steatosis was enhanced in WT mice treated with JWH-133 and blunted in Cnr2 -/- mice.. These data unravel a previously unrecognized contribution of CB2 receptors to obesity-associated inflammation, insulin resistance and non-alcoholic fatty liver disease, and suggest that CB2 receptor antagonists may open a new therapeutic approach for the management of obesity-associated metabolic disorders. Topics: Adipocytes; Adipose Tissue; Animals; Fatty Liver; Inflammation; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Obesity; Triglycerides | 2009 |
Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis.
We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin and visfatin were measured in 109 patients with SLE and 78 control subjects. Coronary calcification was measured using electron beam-computed tomography, and insulin resistance was defined by the homeostasis model assessment index. Concentrations of adiponectin (28.7 +/- 17.9 vs 22.0 +/- 15.3 microg/mL, P = 0.003), leptin (41.1 +/- 49.9 vs 19.8 +/- 24.6 ng/mL, P < 0.001) and visfatin (7.5 +/- 10.5 vs 4.5 +/- 2.8 ng/mL, P < 0.001) were higher in patients with SLE than in controls. These differences remained significant after adjustment for age, race, sex and body mass index (BMI; all P values < 0.02). Concentrations of resistin (10.7 +/- 7.6 vs 9.1 +/- 5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (rho = 0.80, P < 0.001), insulin resistance (rho = 0.46, P < 0.001) and C-reactive protein (CRP) (rho = 0.30, P = 0.002), whereas adiponectin was negatively associated with the same factors (rho = -0.40, P < 0.001; rho = -0.38, P < 0.001; rho = -0.22, P = 0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE. Topics: Adipokines; Adiponectin; Adult; Body Mass Index; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Insulin Resistance; Leptin; Lupus Erythematosus, Systemic; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Resistin; Risk Factors | 2009 |
Is chronic inflammation a possible cause of obesity-related depression?
Adult obesity has been associated with depression, especially in women. Whether depression leads to obesity or obesity causes depression is unclear. Chronic inflammation is observed in obesity and depression. In 63 obese women without additional diseases depression level was assessed with the Beck's questionnaire. After evaluation of depression level study group was divided into groups according to the mood status (A--without depression, B-mild depression, and C--severe depression), and serum concentration of TNF-alpha, sTNFs, leptin, and IL-6 were measured by ELISA. No differences in age, body mass, BMI, and body composition were observed in study groups. We did not observe differences of serum concentrations of TNF-alpha, sTNFRs, leptin, and IL-6 between subgroup A and subgroups B and C. It seems that circulating adipokines did not exert influence on depression levels in obese women. Topics: Age Factors; Body Mass Index; Depression; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Interleukin-6; Leptin; Middle Aged; Obesity; Receptors, Tumor Necrosis Factor; Sex Factors; Tumor Necrosis Factor-alpha | 2009 |
Relationship between adiposity and cardiovascular risk factors in prevalent hemodialysis patients.
Increased body mass index (BMI) is associated with reduced all-cause and cardiovascular (CV) mortality in hemodialysis (HD) patients, whereas CV risk increases with BMI in the general population. In the general population, obesity is associated with inflammation, decreased high-density lipoprotein (HDL) cholesterol, increased low-density lipoprotein (LDL) cholesterol, and triglycerides (TGs), all risk factors for CV disease. Low-density lipoprotein cholesterol does not predict CV risk in HD, whereas increased C-reactive protein and interleukin-6 (IL-6), low HDL and apolipoprotein (apo) AI, and increased fasting TGs do predict risk. Renal failure is associated with dyslipidemia and inflammation in normal-weight patients. We hypothesized that the effects of obesity may be obscured by renal failure in HD.. We explored the relationship between adipose tissue pools and distribution, i.e., subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) (measured by magnetic resonance imaging) and measures of inflammation (C-reactive protein, IL-6, ceruloplasmin, and alpha1 acid glycoprotein), HDL and LDL cholesterol, total TGs, apo AI, apo B, apo CII (an activator of lipoprotein lipase), apo CIII (an inhibitor of lipoprotein lipase), and the adipokines, leptin and adiponectin, in 48 patients with prevalent HD.. Total TG concentrations were positively correlated with VAT controlled for age, sex, and weight. Both apo CII and apo CIII were correlated only with VAT. Adiponectin was inversely correlated with VAT, and leptin was positively associated with SAT. C-reactive protein and alpha1 acid glycoprotein were weakly associated with SAT, whereas ceruloplasmin was strongly associated with VAT according to multiple regression analysis. In contrast, apo B, LDL, apo AI, HDL, and IL-6 were not correlated with any measure of body composition, potentially mitigating the effects of obesity in HD. Topics: Adiponectin; Adiposity; Adult; Aged; Aged, 80 and over; Apolipoprotein A-I; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Ceruloplasmin; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Inflammation; Interleukin-6; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity; Renal Dialysis; Risk Factors; Subcutaneous Fat; Triglycerides | 2009 |
Inflammatory state and stress condition in weight-lowering Lys109Arg LEPR gene polymorphism carriers.
Carrying variants on the leptin receptor gene (LEPR) may have an impact on inflammatory and stress markers. Thus, the aim of the study was to analyze the role of the Lys109Arg LEPR gene polymorphism on inflammatory (leptin and IL-6) and stress (cortisol) markers in obese subjects who followed a hypocaloric diet designed to lose weight.. One hundred and seventy (80 females/90 males) Caucasian subjects (body mass index: 30.8 +/- 2.4 kg/m(2)), were genotyped for the Lys109Arg polymorphism by a PCR/RFLP procedure. Anthropometric measurements were assessed and blood samples were drawn in all the volunteers before and after an 8-week energy-restricted diet (-30% E). Plasma levels of leptin as well as interleukin-6 (IL-6) as proinflammatory markers and circulating cortisol concentrations as a stress hormone were measured.. Weight loss (-6.1 +/- 2.7%; p <0.001) induced significant changes in anthropometric and biochemical determinations. The AA genotype group showed a higher fat mass loss as well as greater total cholesterol decrease compared with the minor allele carriers. Moreover, the G allele carriers were associated with a higher basal risk of inflammation (OR = 2.5; p = 0.042) and stress (OR = 3.3; p = 0.011), which were reduced after weight lowering (p >0.05).. The Arg allele carriers of the Lys109Arg LEPR gene polymorphism were associated with an increased proinflammatory state and stress condition at baseline. These obesity-related markers were importantly decreased after following a hypocaloric diet. Topics: Adult; Alleles; Body Mass Index; Caloric Restriction; Female; Genotype; Humans; Hydrocortisone; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Polymorphism, Genetic; Receptors, Leptin; Stress, Physiological; Weight Loss | 2009 |
Which components of malnutrition-inflammation-atherosclerosis syndrome are more common in haemodialysis patients with diabetic nephropathy?
Malnutrition-inflammation-atherosclerosis syndrome (MIA) in haemodialysis (HD) patients is a common clinical condition characterized by increased mortality rate. The aim of this study was to analyze the frequency of MIA components in a selected population of HD patients with and without diabetic nephropathy.. The frequency of MIA components was analysed in 49 patients with an over 10-year history of diabetes before initiation of HD (DM group) and 49 non-diabetic HD patients (non-DM group).. The chance for occurrence of atherosclerosis (odds ratio = 3.26) was markedly higher in DM than non-DM subjects. The most frequent MIA component in DM and non-DM subjects was atherosclerosis (67.3% and 40.8%, respectively). Atherosclerosis frequently coexisted with inflammation in both groups (51.5% in DM and 20.0% in non-DM) and less frequently with malnutrition. The frequency of inflammation was only slightly higher in DM, while of malnutrition was similar. Patients with atherosclerosis in the DM group had significantly higher serum concentrations of interleukin-6 than the ones in the non-DM group: 11 (6-24) versus 5 (2-9) pg/mL, respectively (P = 0.002).. We can conclude that: (i) atherosclerosis is more common in HD patients with diabetic nephropathy; and (ii) this fact may explain the poor outcome of these patients and indicates the challenge in diagnostic and therapeutic management. Topics: Aged; Atherosclerosis; Diabetic Nephropathies; Female; Humans; Inflammation; Leptin; Male; Malnutrition; Middle Aged; Renal Dialysis; Serum Albumin | 2009 |
Obesity, insulin resistance, and cancer prognosis: implications for practice for providing care among cancer survivors.
Topics: Adipokines; Adiponectin; Cytokines; Dietetics; Disease Progression; Health Behavior; Humans; Inflammation; Insulin Resistance; Leptin; Life Style; Neoplasms; Obesity; Prevalence; Prognosis; Risk Factors; Survival Rate; United States | 2009 |
Feto-placental adaptations to maternal obesity in the baboon.
Maternal obesity is present in 20-34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes in the placenta. The major findings of this study were: 1) decreased placental syncytiotrophoblast amplification factor, intact syncytiotrophoblast endoplasmic reticulum structure and decreased system A placental amino acid transport in obese animals; 2) fetal serum amino acid composition and mononuclear cells (PBMC) transcriptome were different in fetuses from obese compared with non-obese animals; and 3) maternal obesity in humans and baboons is similar in regard to increased placental and adipose tissue macrophage infiltration, increased CD14 expression in maternal PBMC and maternal hyperleptinemia. In summary, these data demonstrate that in obese baboons in the absence of increased fetal weight, placental and fetal phenotype are consistent with those described for large-for-gestational age human fetuses. Topics: Adaptation, Physiological; Amino Acid Transport System A; Amino Acids; Animals; Body Weight; Chorionic Villi; Crown-Rump Length; Disease Models, Animal; Female; Fetal Blood; Inflammation; Kidney; Leptin; Leukocytes, Mononuclear; Lipopolysaccharide Receptors; Macrophages; Matched-Pair Analysis; Maternal-Fetal Exchange; Obesity; Organ Size; Papio; Placenta; Pregnancy; Pregnancy Complications; Trophoblasts | 2009 |
Different modulation by dietary restriction of adipokine expression in white adipose tissue sites in the rat.
White adipose tissue (WAT) is a disperse organ acting as energy storage depot and endocrine/paracrine controlling factor in the management of energy availability and inflammation. WAT sites response under energy-related stress is not uniform. In the present study we have analyzed how different WAT sites respond to limited food restriction as a way to better understand the role of WAT in the pathogenesis of the metabolic syndrome.. Overweight male rats had their food intake reduced a 40% compared with free-feeding controls. On day ten, the rats were killed; circulating glucose, insulin, leptin, adiponectin, triacylglycerols and other parameters were measured. The main WAT sites were dissected: mesenteric, retroperitoneal, epididymal and subcutaneous inguinal, which were weighed and frozen. Later all subcutaneous WAT was also dissected and weighed. Samples were used for DNA (cellularity) analysis and mRNA extraction and semiquantitarive RT-PCR analysis of specific cytokine gene expressions.. There was a good correlation between serum leptin and cumulative WAT leptin gene mRNA, but not for adiponectin. Food restriction reduced WAT size, but not its DNA content (except for epididymal WAT). Most cytokines were correlated to WAT site weight, but not to DNA. There was WAT site specialization in the differential expression (and probably secretion) of adipokines: subcutaneous WAT showed the highest concentration for leptin, CD68 and MCP-1, mesenteric WAT for TNFalpha (and both tissues for the interleukins 1beta and 6); resistin was highly expressed in subcutaneous and retroperitoneal WAT.. Food restriction induced different patterns for mesenteric and the other WAT sites, which may be directly related to both the response to intestine-derived energy availability, and an inflammatory-related response. However, retroperitoneal WAT, and to a lower extent, subcutaneous and epididymal, reacted decreasing the expression of inflammatory markers and the signaling of decreased energy availability in their stores. The varying cytokine expression patterns highlight the fact that WAT sites show different inflammatory and signaling responses to energy availability; they are too much different to simply extend to the whole-body WAT the findings of one or even a couple of sites. Topics: Adipokines; Adiponectin; Adipose Tissue, White; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Blood Glucose; Carrier Proteins; Cytokines; Food Deprivation; Gene Expression Regulation; Inflammation; Insulin; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Organ Specificity; Overweight; Perilipin-1; Phosphoproteins; Random Allocation; Rats; Resistin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Triglycerides | 2009 |
Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage--mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production.
Obesity is an important risk factor for osteoarthritis (OA) in weight-bearing joints, but also in hand joints, pointing to an obesity-related metabolic factor that influences on the pathogenesis of OA. Leptin is an adipokine regulating energy balance, and it has recently been related also to arthritis and inflammation as a proinflammatory factor. In the present paper, the effects of leptin on human OA cartilage were studied. Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE(2), IL-6, and IL-8. The results suggest that the effects of leptin are mediated through activation of transcription factor nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathway c-Jun NH(2)-terminal kinase (JNK). Interestingly, inhibition of leptin-induced NO production with a selective iNOS inhibitor 1400 W inhibited also the production of IL-6, IL-8, and PGE(2), and this was reversed by exogenously added NO-donor SNAP, suggesting that the effects of leptin on IL-6, IL-8, and PGE(2) production are dependent on NO. These findings support the idea of leptin as a factor enhancing the production of proinflammatory factors in OA cartilage and as an agent contributing to the obesity-associated increased risk for osteoarthritis. Topics: Aged; Aged, 80 and over; Cartilage; Dinoprostone; Humans; Inflammation; Interleukin-6; Interleukin-8; JNK Mitogen-Activated Protein Kinases; Leptin; MAP Kinase Signaling System; Middle Aged; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis | 2009 |
EGFR tyrosine kinase inhibitor (PD153035) improves glucose tolerance and insulin action in high-fat diet-fed mice.
In obesity, an increased macrophage infiltration in adipose tissue occurs, contributing to low-grade inflammation and insulin resistance. Epidermal growth factor receptor (EGFR) mediates both chemotaxis and proliferation in monocytes and macrophages. However, the role of EGFR inhibitors in this subclinical inflammation has not yet been investigated. We investigated, herein, in vivo efficacy and associated molecular mechanisms by which PD153035, an EGFR tyrosine kinase inhibitor, improved diabetes control and insulin action.. The effect of PD153035 was investigated on insulin sensitivity, insulin signaling, and c-Jun NH(2)-terminal kinase (JNK) and nuclear factor (NF)-kappaB activity in tissues of high-fat diet (HFD)-fed mice and also on infiltration and the activation state of adipose tissue macrophages (ATMs) in these mice.. PD153035 treatment for 1 day decreased the protein expression of inducible nitric oxide synthase, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 in the stroma vascular fraction, suggesting that this drug reduces the M1 proinflammatory state in ATMs, as an initial effect, in turn reducing the circulating levels of TNF-alpha and IL-6, and initiating an improvement in insulin signaling and sensitivity. After 14 days of drug administration, there was a marked improvement in glucose tolerance; a reduction in insulin resistance; a reduction in macrophage infiltration in adipose tissue and in TNF-alpha, IL-6, and free fatty acids; accompanied by an improvement in insulin signaling in liver, muscle, and adipose tissue; and also a decrease in insulin receptor substrate-1 Ser(307) phosphorylation in JNK and inhibitor of NF-kappaB kinase (IKKbeta) activation in these tissues.. Treatment with PD153035 improves glucose tolerance, insulin sensitivity, and signaling and reduces subclinical inflammation in HFD-fed mice. Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Dietary Fats; Enzyme Inhibitors; ErbB Receptors; Gene Expression Regulation, Enzymologic; Glucose Tolerance Test; Hypoglycemic Agents; Immunoblotting; Immunoprecipitation; Inflammation; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Leptin; Liver; Macrophages; Male; Mice; Muscle, Skeletal; NF-kappa B p50 Subunit; Nitric Oxide Synthase Type II; Phosphorylation; Protein-Tyrosine Kinases; Quinazolines; Signal Transduction; Tumor Necrosis Factor-alpha | 2009 |
1,2-vinyldithiin from garlic inhibits differentiation and inflammation of human preadipocytes.
Obesity is a state of chronic low-grade inflammation. Limiting white adipose tissue (WAT) expansion and therefore reducing inflammation could be effective in preventing the progression of obesity and the development of associated complications. We investigated the effects of 1,2-vinyldithiin (1,2-DT), a garlic-derived organosulfur, on the differentiation and inflammatory state of human preadipocytes. Preadipocytes were prepared from subcutaneous adipose tissue of nonobese young women and differentiated in the presence of 1,2-DT. Inflammatory preadipocytes were obtained following treatment with human macrophage-secreted factors. 1,2-DT (100 micromol/L) significantly reduced gene expression of PPARgamma2 (-40%), CCAAT/enhancer binding protein-alpha (-25%), lipoprotein lipase (-22%), leptin (-30%), and adiponectin (-15%). Lipid accumulation was also significantly diminished in preadipocytes differentiated in the presence of 100 micromol/L 1,2-DT (-37%) compared with controls. Furthermore, 100 micromol/L 1,2-DT treatment for 10 d significantly reduced PPARgamma activity (-27%). The protein expression of perilipin and the secretion levels for 2 adipokines, leptin and adiponectin, were significantly diminished in 1,2-DT-cultured preadipocytes (-37, -51, and -43%, respectively). Moreover, the secretion of inflammatory molecules (interleukin-6 and monocyte chemoattractant protein-1) induced by macrophage-secreted factors was partially abolished in 100 micromol/L 1,2-DT-treated preadipocytes (-28 and -25%, respectively). In conclusion, we demonstrated that 1,2-DT, a garlic-derived organosulfur, has antiadipogenic and antiinflammatory actions on human preadipocytes and may be a novel, antiobesity nutraceutical. Topics: Adipocytes; Adiponectin; Anti-Inflammatory Agents; Anti-Obesity Agents; Carrier Proteins; Cell Differentiation; Female; Garlic; Humans; Inflammation; Leptin; Perilipin-1; Phosphoproteins; Plant Extracts; PPAR gamma; Young Adult | 2009 |
Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis.
To test the hypothesis that obesity resulting from deletion of the leptin gene or the leptin receptor gene results in increased knee osteoarthritis (OA), systemic inflammation, and altered subchondral bone morphology.. Leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) female mice compared with wild-type mice were studied, to document knee OA via histopathology. The levels of serum proinflammatory and antiinflammatory cytokines were measured using a multiplex bead immunoassay. Cortical and trabecular subchondral bone changes were documented by microfocal computed tomography, and body composition was quantified by dual x-ray absorptiometry.. Adiposity was increased by approximately 10-fold in ob/ob and db/db mice compared with controls, but it was not associated with an increased incidence of knee OA. Serum cytokine levels were unchanged in ob/ob and db/db mice relative to controls, except for the level of cytokine-induced neutrophil chemoattractant (keratinocyte chemoattractant; murine analog of interleukin-8), which was elevated. Leptin impairment was associated with reduced subchondral bone thickness and increased relative trabecular bone volume in the tibial epiphysis.. Extreme obesity due to impaired leptin signaling induced alterations in subchondral bone morphology without increasing the incidence of knee OA. Systemic inflammatory cytokine levels remained largely unchanged in ob/ob and db/db mice. These findings suggest that body fat, in and of itself, may not be a risk factor for joint degeneration, because adiposity in the absence of leptin signaling is insufficient to induce systemic inflammation and knee OA in female C57BL/6J mice. These results imply a pleiotropic role of leptin in the development of OA by regulating both the skeletal and immune systems. Topics: Adiposity; Animals; Biomechanical Phenomena; Body Composition; Bone and Bones; Bone Density; Cytokines; Disease Models, Animal; Female; Inflammation; Joints; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity, Morbid; Osteoarthritis; Receptors, Leptin; Risk Factors; Signal Transduction | 2009 |
Adipokine expression in adipose tissue and in peripheral blood mononuclear cells in children Correlation with BMI and fatty acid content.
Adipose tissue contributes in energy, lipid homeostasis and inflammation, through the adipokines it releases. Our aim was to study the associations between adipose tissue (AT) fatty acid content, adipokines' expression in AT and PBMCs and BMI in children.. Thirty-one (17 male) healthy children aged 10.9+/-1.8years and of BMI 19.3+/-3.5kg/m(2) were enrolled. Adipokines (TNF-alpha, IL-6, leptin and visfatin) expression was quantified by real-time quantitative PCR in AT and PBMCs. Serum levels were measured by ELISA and fatty acids (FA) from AT by gas chromatography.. BMI was correlated with monounsaturated fatty acids (MUFAs) (beta=0.339, p=0.043), arachidonic (AA) (beta=0.576, p< or =0.001) and eicosapentaenoic acids (EPA) (beta=0.404, p=0.004) and negatively with stearic acid (beta=-0.577, p< or =0.001). TNF-alpha and visfatin expression from PBMCs were positively correlated with MUFAs (beta=0.271, p=0.027 and beta=0.214, p=0.020, respectively), n-9 fatty acids (beta=0.313, p=0.010 and beta=0.269 and p=0.024, respectively) and with docosahexaenoic acid (DHA) (beta=0.429, p=0.004 and beta=0.484, p< or =0.001, respectively), while negatively with the ratio n-6/n-3 (beta=-0.490, p=0.007 and beta=-0.374, p=0.044).. A series of FA molecules were correlated with children's BMI and with TNF-alpha and visfatin expression from PBMCs indicating that AT fatty acid content, might have a role, as a potential regulator of PBMCs inflammatory gene expression. Topics: Adipokines; Adipose Tissue; Blood Cells; Body Composition; Body Mass Index; Child; Fatty Acids; Female; Humans; Inflammation; Interleukin-6; Leptin; Leukocytes, Mononuclear; Male; Nicotinamide Phosphoribosyltransferase; Tumor Necrosis Factor-alpha | 2009 |
Atypical protein kinase C activity in the hypothalamus is required for lipopolysaccharide-mediated sickness responses.
By activating the Toll-like receptor 4-nuclear factor-kappaB signal transduction pathway, the bacterial endotoxin lipopolysaccharide (LPS) induces anorexia, weight loss, fever, and other components of the sickness response. By comparison, the hormones leptin and insulin cause anorexia without sickness via a central mechanism involving the phosphatidylinositol-3 kinase signaling pathway. In the current study, we investigated whether a common Toll-like receptor 4 and phosphatidylinositol-3 kinase signaling intermediate, atypical protein kinase Czeta/lambda (aPKC), contributes to changes of energy balance induced by these stimuli. Immunohistochemistry analysis revealed that aPKC is expressed in the arcuate and paraventricular nuclei of the hypothalamus, key sites of leptin, insulin, and LPS action. Although administration of LPS, insulin, and leptin each acutely increased hypothalamic aPKC activity at doses that also reduce food intake, LPS treatment caused over 10-fold greater activation of hypothalamic a PKC signaling than that induced by leptin or insulin. Intracerebroventricular pretreatment with an aPKC inhibitor blocked anorexia induced by LPS but not insulin or leptin. Similarly, LPS-induced hypothalamic inflammation (as judged by induction of proinflammatory cytokine gene expression) and neuronal activation in the paraventricular nucleus (as judged by c-fos induction) were reduced by central aPKC inhibition. Although intracerebroventricular aPKC inhibitor administration also abolished LPS-induced fever, it had no effect on sickness-related hypoactivity or weight loss. We conclude that although hypothalamic aPKC signaling is not required for food intake inhibition by insulin or leptin, it plays a key role in inflammatory anorexia and fever induced by LPS. Topics: Animals; Anorexia; Cell Line; Cytokines; Eating; Fever; Gene Expression; Humans; Hypothalamus; Immunohistochemistry; Inflammation; Insulin; Isoenzymes; Leptin; Lipopolysaccharides; Male; Neurons; Paraventricular Hypothalamic Nucleus; Protein Kinase C; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction | 2009 |
Deletion of tumor necrosis factor-alpha receptor 1 (TNFR1) protects against diet-induced obesity by means of increased thermogenesis.
In diet-induced obesity, hypothalamic and systemic inflammatory factors trigger intracellular mechanisms that lead to resistance to the main adipostatic hormones, leptin and insulin. Tumor necrosis factor-alpha (TNF-alpha) is one of the main inflammatory factors produced during this process and its mechanistic role as an inducer of leptin and insulin resistance has been widely investigated. Most of TNF-alpha inflammatory signals are delivered by TNF receptor 1 (R1); however, the role played by this receptor in the context of obesity-associated inflammation is not completely known. Here, we show that TNFR1 knock-out (TNFR1 KO) mice are protected from diet-induced obesity due to increased thermogenesis. Under standard rodent chow or a high-fat diet, TNFR1 KO gain significantly less body mass despite increased caloric intake. Visceral adiposity and mean adipocyte diameter are reduced and blood concentrations of insulin and leptin are lower. Protection from hypothalamic leptin resistance is evidenced by increased leptin-induced suppression of food intake and preserved activation of leptin signal transduction through JAK2, STAT3, and FOXO1. Under the high-fat diet, TNFR1 KO mice present a significantly increased expression of the thermogenesis-related neurotransmitter, TRH. Further evidence of increased thermogenesis includes increased O(2) consumption in respirometry measurements, increased expressions of UCP1 and UCP3 in brown adipose tissue and skeletal muscle, respectively, and increased O(2) consumption by isolated skeletal muscle fiber mitochondria. This demonstrates that TNF-alpha signaling through TNFR1 is an important mechanism involved in obesity-associated defective thermogenesis. Topics: Abdominal Fat; Adipose Tissue, Brown; Animals; Diet; Dietary Fats; Forkhead Box Protein O1; Forkhead Transcription Factors; Inflammation; Insulin; Ion Channels; Janus Kinase 2; Leptin; Mice; Mice, Knockout; Mitochondrial Proteins; Muscle, Skeletal; Nerve Tissue Proteins; Obesity; Oxygen Consumption; Rats; Receptors, Tumor Necrosis Factor, Type I; STAT3 Transcription Factor; Thermogenesis; Tumor Necrosis Factor-alpha; Uncoupling Protein 1; Uncoupling Protein 3 | 2009 |
Leptin induces an inflammatory phenotype in lean Wistar rats.
The present study addressed the hypothesis that leptin promotes leukocyte trafficking into adipose tissue. Accordingly, male Wistar rats were treated with saline or recombinant rat leptin (1 mg/kg) via the tail vein. Leukocyte trafficking in mesenteric venules was quantified by intravital microscopy. Treatment with leptin resulted in a 3- and 5-fold increases in rolling and firm adhesion, respectively. Compared to vehicle controls, leptin enhanced mRNA levels of IL-6 (8-fold) and MCP-1 (5-fold) in mesenteric adipose tissue (MAT). Similar increases in these markers were observed in mesenteric venules and in liver. Finally, the direct effect of leptin was assessed in C3A hepatocytes treated with leptin for 24 hours (7.8 ng/mL-125 ng/mL). Consistent with observations in vivo, production of ICAM-1, MCP-1, and IL-6 by hepatocytes was increased significantly. These findings support the hypothesis that leptin directly initiates inflammation in the local environment of mesenteric adipose tissue as well as systemically. Topics: Adipose Tissue; Animals; Chemokine CCL2; Hepatocytes; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Male; Models, Biological; Phenotype; Rats; Rats, Wistar; Time Factors | 2009 |
Differential adipokine response in genetically predisposed lean and obese rats during inflammation: a role in modulating experimental colitis?
The relationship between a predisposition to obesity and the development of colitis is not well understood. Our aim was to characterize the adipokine response and the extent of colitis in diet-induced obese (DIO) rats. DIO and control, diet-resistant (DR) animals were administered either saline or trinitrobenzene sulfonic acid (TNBS) to induce colitis. Macroscopic damage scores and myeloperoxidase (MPO) activity were measured to determine the extent of inflammation. Trunk blood was collected for the analysis of plasminogen activator inhibitor-1 (PAI-1) as well as leptin, ghrelin, and adiponectin. Colonic epithelial physiology was assessed using Ussing chambers. DIO rats had a modestly increased circulating PAI-1 before TNBS treatment; however, during colitis, DR animals had more than a fourfold increase in circulating PAI-1 compared with DIO rats. Circulating leptin was higher in DIO rats compared with DR animals, in the inflamed and noninflamed states. These changes in TNBS-induced adipokine profile were accompanied by decreased macroscopic tissue damage score in DIO animals compared with DR tissues. Furthermore, TNBS-treated DR animals lost significantly more weight than DIO rats during active inflammation. Colonic epithelial physiology was comparable between groups, as was MPO activity. The factors contributing to the decreased colonic damage are almost certainly multifold, driven by both genetic and environmental factors, of which adipokines are likely to play a part given the increasing body of evidence for their role in modulating intestinal inflammation. Topics: Adipokines; Adiponectin; Animals; Body Weight; Colitis, Ulcerative; Colon; Eating; Electric Impedance; Electrophysiological Phenomena; Genetic Predisposition to Disease; Ghrelin; Inflammation; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Peroxidase; Plasminogen Activator Inhibitor 1; Rats; Rats, Inbred Strains; Serpin E2; Serpins; Thinness; Trinitrobenzenesulfonic Acid | 2009 |
Adipocytokines leptin and adiponectin, and measures of malnutrition-inflammation in chronic renal failure: is there a relationship?
Serum levels of adipocytokines such as leptin and adiponectin are significantly elevated in patients with chronic renal failure (CRF). The effect of such adipocytokines on malnutrition in the CRF population has been of substantial interest. We sought to determine the relationship between plasma leptin and adiponectin levels and malnutrition-inflammation status in end-stage renal disease patients.. Thirty patients (15 women and 15 men; mean [+/-SD] age, 50 +/- 14 years) on hemodialysis, and 30 patients (12 women and 18 men; mean [+/-SD] age, 47 +/- 16) on continuous ambulatory peritoneal dialysis, were enrolled in this study. Adipocytokine levels were measured by enzyme-linked immunosorbent assay. Inflammatory markers, such as high-sensitivity serum C-reactive protein (hs-CRP), ferritin, and a nutritional inflammatory scoring system known as the malnutrition-inflammation score (MIS), were also measured in all patients.. Serum leptin had negative correlations with ferritin (r = -0.33, P = .016) and MIS (r = -0.39, P = .003). Adiponectin had a weak positive correlation with MIS (r = 0.26, P = .050), indicating that an increased level of serum adiponectin was associated with a worse nutritional status. Levels of hs-CRP, serum albumin, cholesterol, and triglycerides did not correlate with nutritional status.. Serum leptin concentration seems to be a marker of good nutritional status, rather than an appetite-suppressing uremic toxin, in patients with CRF. However, the positive correlation between serum adiponectin and worse nutritional-inflammatory status suggests that elevated adiponectin levels may contribute to the pathogenesis of malnutrition in such patients. Topics: Adipokines; Adiponectin; Biomarkers; C-Reactive Protein; Female; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Peritoneal Dialysis, Continuous Ambulatory; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin | 2008 |
Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice.
Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity correlates with increased production of inflammatory cytokines, which in turn, contributes to systemic insulin resistance. To test the hypothesis that exercise mitigates this inflammatory response, thereby improving insulin sensitivity, we developed a model of voluntary exercise in mice made obese by feeding of a high fat/high sucrose diet (HFD). Over four wk, mice fed chow gained 2.3 +/- 0.3 g, while HFD mice gained 6.8 +/- 0.5 g. After 4 wk, mice were subdivided into four groups: chow-no exercise, chow-exercise, HFD-no exercise, HFD-exercise and monitored for an additional 6 wk. Chow-no exercise and HFD-no exercise mice gained an additional 1.2 +/- 0.3 g and 3.3 +/- 0.5 g respectively. Exercising mice had higher food consumption, but did not gain additional weight. As expected, GTT and ITT showed impaired glucose tolerance and insulin resistance in HFD-no exercise mice. However, glucose tolerance improved significantly and insulin sensitivity was completely normalized in HFD-exercise animals. Furthermore, expression of TNF-alpha, MCP-1, PAI-1 and IKKbeta was increased in adipose tissue from HFD mice compared with chow mice, whereas exercise reversed the increased expression of these inflammatory cytokines. In contrast, expression of these cytokines in liver was unchanged among the four groups. These results suggest that exercise partially reduces adiposity, reverses insulin resistance and decreases adipose tissue inflammation in diet-induced obese mice, despite continued consumption of HFD. Topics: Adiponectin; Adipose Tissue; Animals; Body Composition; Body Weight; Cytokines; Diet; Dietary Fats; Glucose Tolerance Test; Hepatitis; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Motor Activity; Obesity; Physical Conditioning, Animal; Retinol-Binding Proteins, Plasma; Reverse Transcriptase Polymerase Chain Reaction | 2008 |
Resistin is closely related to systemic inflammation in obstructive sleep apnea.
Obstructive sleep apnea (OSA) is closely related to systemic inflammation. Resistin is an adipocyte-derived cytokine (adipokine) that may link obesity with inflammation.. We aimed to investigate whether incremental changes in OSA severity, from normal to severe, primarily affect the levels of resistin and other adipokines.. Serum levels of resistin, interleukin-6 (IL-6) and leptin were examined in 31 men with OSA and 10 men without OSA, matched for age, body mass index (BMI) and several metabolic profiles. In 11 of the 31 men with OSA, these mediators were reexamined after 3 months of nasal continuous airway pressure (nCPAP) therapy.. Levels of resistin and IL-6 were simultaneously elevated in men with OSA compared with those in men without OSA (p < 0.05), while levels of leptin did not differ. The resistin and IL-6 levels tended to increase with increasing disease severity (p < 0.05), which was based on the apnea-hypopnea index (AHI). The average oxyhemoglobin saturation during sleep (p < 0.01) and IL-6 (p < 0.05) emerged as significant determinants of resistin, even after adjustments for age, BMI, leptin levels and metabolic risk factors. After nCPAP therapy, the elevated levels of resistin and IL-6 decreased, reaching almost baseline levels of controls. Before treatment, AHI correlated positively with the reduction rate in resistin (p < 0.05).. In OSA patients, resistin production can be enhanced by hypoxic stress during sleep, possibly mediating systemic inflammatory processes. nCPAP therapy may play a beneficial role in the control of resistin production. Topics: Adult; Continuous Positive Airway Pressure; Cross-Sectional Studies; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Polysomnography; Resistin; Sleep Apnea, Obstructive | 2008 |
Adiponectin, but not leptin or high-sensitivity C-reactive protein, is associated with blood pressure independently of general and abdominal adiposity.
The role of adiponectin, a marker of the metabolic syndrome, on the pathogenesis of hypertension in comparison with markers of adipose tissue mass (leptin) and inflammation (high-sensitivity C-reactive protein [hs-CRP]) remains to be clarified. The eligible study population consisted of 2,045 residents aged > or =40 years who had participated in a community-based survey and had complete data for serum adiponectin, leptin, and hs-CRP, and for whom homeostasis model assessment of insulin resistance (HOMA-IR) had been calculated from insulin and plasma glucose. Among all eligible participants, as well as in the subgroup of nondiabetic normotensives (blood pressure <140/90 mmHg and without antihypertensive medication), all three markers were significantly correlated with systolic blood pressure (negative correlation for adiponectin and positive correlations for leptin and hs-CRP). Among all participants, systolic blood pressure and the presence of hypertension were determined mainly by age, sex, body mass index, and waist circumference. None of the markers further contributed to the multivariate linear regression or logistic regression models. In contrast, adiponectin, but not leptin, hs-CRP, or HOMA-IR, was significantly associated with systolic blood pressure and the presence of pre-hypertension (blood pressure within 120-139/80-89 mmHg) after adjustment for age, sex, body mass index, and waist circumference in the nondiabetic normotensive subgroup. Similarly, adiponectin was independently associated with diastolic blood pressure in the nondiabetic normotensive subgroup but not in the whole population. In conclusion, adiponectin, but not leptin or hs-CRP, was independently associated with blood pressure in a nondiabetic normotensive subgroup. Topics: Abdominal Fat; Adiponectin; Adult; Aged; Biomarkers; Blood Pressure; C-Reactive Protein; Cross-Sectional Studies; Female; Health Surveys; Humans; Hypertension; Inflammation; Leptin; Linear Models; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Obesity | 2008 |
Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity.
Adipose tissue (AT) can accumulate macrophages and secrete several inflammatory mediators. Despite its pivotal role in the progression of chronic inflammatory processes such as atherosclerosis, the adaptive role of immunity in obesity remains poorly explored. Visceral AT of diet-induced obese C57BL/6 mice had higher numbers of both CD4(+) and CD8(+) T cells than lean controls, monitored by flow cytometry. When stimulated in vitro, T cells from obese AT produced more interferon (IFN)gamma than those from controls. AT from obese animals also had more cells expressing I-A(b), a mouse class II histocompatibility marker implicated in antigen presentation, as determined by immunostaining. Differentiated 3T3-L1 cells stimulated with recombinant IFNgamma or T-helper 1-derived supernatant produced several chemokines and their mRNAs. Obese IFNgamma-deficient animals had significantly reduced AT expression of mRNA-encoding inflammatory genes such as tumor necrosis factor-alpha and monocyte chemoattractant protein-1, decreased AT inflammatory cell accumulation, and better glucose tolerance than control animals consuming the same diet. Obese mice doubly deficient for IFNgamma receptor and apolipoprotein (Apo)E on a mixed 129SvEv/C57BL/6 (129/B6) genetic background, despite exhibiting similar AT mRNA levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 as 129/B6-ApoE(-/-) controls, had decreased expression of important T cell-related genes, such as IFNgamma-inducible protein-10 and I-A(b), and lower plasma triglycerides and glucose. These results indicate a role for T cells and IFNgamma, a prototypical T-helper 1 cytokine, in regulation of the inflammatory response that accompanies obesity. Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue, White; Animal Feed; Animals; Apolipoproteins E; Blood Glucose; Cholesterol; Gene Expression; Inflammation; Insulin Resistance; Interferon gamma Receptor; Interferon-gamma; Intra-Abdominal Fat; Leptin; Leukocyte Count; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Organ Culture Techniques; Receptors, Interferon; Th1 Cells | 2008 |
Selective contribution of interleukin-6 and leptin to brain inflammatory signals induced by systemic LPS injection in mice.
This study aimed to address the relative contributions of the proinflammatory cytokine interleukin-6 (IL-6) and the cytokine-like hormone leptin to the genomic activation of brain cells during lipopolysaccharide (LPS)-induced systemic inflammation. Wildtype and IL-6KO mice were injected with LPS (50 microg/kg, intraperitoneally) and the brains analyzed by immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR). LPS induced a pronounced nuclear translocation of the signal transducer and activator of transcription (STAT3) throughout the brains of wildtype mice, an effect that was significantly diminished, but not abolished, in the IL-6KOs. The remnant STAT3-activation, although still observed within some of the same areas activated by IL-6, was most intense in ependymal and meningial cells and along distinct blood vessels throughout the brain. This expression was almost totally abolished in the presence of an anti-leptin antiserum. Interestingly, the induction of cyclooxygenase 2 and microsomal prostaglandin E synthase (mPGES), the rate-limiting enzymes for synthesis of PGE2 by LPS, was diminished to a degree that correlated with the absence of IL-6 but not entirely with leptin. These results demonstrate that the induction of the inflammatory pathway in the brain is mediated by both IL-6 and leptin, which appear to work in tandem. Unlike IL-6, however, the contribution of leptin to this response was limited to distinct cell types/brain areas and STAT3-responsive target genes implicated in the brain-controlled sickness-type response. The physiological significance of leptin's action on meningeal and endothelial cells remains to be clarified but might reflect a role in LPS-induced immune cell infiltration into the brain. Topics: Animals; Brain; Cyclooxygenase 2; I-kappa B Proteins; Inflammation; Interleukin-1beta; Interleukin-6; Leptin; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-KappaB Inhibitor alpha; Prostaglandin-Endoperoxide Synthases; Receptors, Leptin; STAT3 Transcription Factor; von Willebrand Factor | 2008 |
Why is obesity associated with osteoarthritis? Insights from mouse models of obesity.
Obesity is one of the most significant, and potentially most preventable, risk factors for the development of osteoarthritis, and numerous studies have shown a strong association between body mass index and osteoarthritis of the hip, knee, foot and hand. However, the mechanism(s) by which obesity contributes to the onset and progression of osteoarthritis are not fully understood. The strong association between body mass index, altered limb alignment, and osteoarthritis of the knee--and the protective effects of weight loss--support the classic hypothesis that the effects of obesity on the joint are due to increased biomechanical loading and associated alterations in gait. However, obesity is now considered to be a low-grade systemic inflammatory disease, and recent studies suggest that metabolic factors associated with obesity alter systemic levels of pro-inflammatory cytokines that are also associated with osteoarthritis. Thus, the ultimate influence of obesity on osteoarthritis may involve a complex interaction of genetic, metabolic, and biomechanical factors. In this respect, mouse models of obesity can provide excellent systems in which to examine causal relationships among these factors. In recent years, there have been surprisingly few reports examining the effects of obesity on osteoarthritis using mouse models. In this paper, we review studies on mice and other animal models that provide both direct and indirect evidence on the role of obesity and altered diet in the development of osteoarthritis. We also examine the use of different body mass indices for characterizing "obesity" in mice by comparing these indices to typical adiposity levels observed in obese humans. Taken together, evidence from studies using mice suggest that a complex interaction of environmental and genetic factors associated with obesity contribute to the incidence and severity of osteoarthritis. The ability to control these factors, together with the development of methods to conduct more intricate measures of local biomechanical factors, make mouse models an excellent system to study obesity and osteoarthritis. Topics: Adipokines; Adiposity; Animals; Body Composition; Body Mass Index; Disease Models, Animal; Guinea Pigs; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Obesity; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Risk Factors | 2008 |
Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest.
Physical inactivity is often associated with positive energy balance and fat gain.. We aimed to assess whether energy intake in excess of requirement activates systemic inflammation and antioxidant defenses and accelerates muscle atrophy induced by inactivity.. Nineteen healthy male volunteers were studied before and at the end of 5 wk of bed rest. Subjects were allowed to spontaneously adapt to decreased energy requirement (study A, n = 10) or were provided with an activity-matched diet (study B, n = 9). Groups with higher (HEB) or lower (LEB) energy balance were identified according to median values of inactivity-induced changes in fat mass (DeltaFM, assessed by bioelectrical impedance analysis).. In pooled subjects (n = 19; median DeltaFM: 1.4 kg), bed rest-mediated decreases in fat-free mass (bioelectrical impedance analysis) and vastus lateralis thickness (ultrasound imaging) were significantly greater (P < 0.03) in HEB(AB) (-3.8 +/- 0.4 kg and -0.32 +/- 0.04 cm, respectively) than in LEB(AB) (-2.3 +/- 0.5 kg and -0.09 +/- 0.04 cm, respectively) subjects. In study A (median DeltaFM: 1.8 kg), bed rest-mediated increases in plasma leptin, C-reactive protein, and myeloperoxidase were greater (P < 0.04) in HEB(A) than in LEB(A) subjects. Bed rest-mediated changes of glutathione synthesis rate in eythrocytes (l-[3,3-(2)H(2)]cysteine incorporation) were greater (P = 0.03) in HEB(A) (from 70 +/- 19 to 164 +/- 29%/d) than in LEB(A) (from 103 +/- 23 to 84 +/- 27%/d) subjects.. Positive energy balance during inactivity is associated with greater muscle atrophy and with activation of systemic inflammation and of antioxidant defenses. Optimizing caloric intake may be a useful strategy for mitigating muscle loss during period of chronic inactivity. Topics: Adipose Tissue; Adult; Bed Rest; Biomarkers; Body Composition; C-Reactive Protein; Electric Impedance; Energy Intake; Energy Metabolism; Erythrocytes; Glutathione; Humans; Inflammation; Leptin; Lipid Metabolism; Male; Muscular Atrophy; Nutritional Requirements; Oxidation-Reduction; Oxidative Stress; Risk Factors; Weight Gain | 2008 |
Serum concentrations of cortisol, interleukin 6, leptin and adiponectin predict stress induced insulin resistance in acute inflammatory reactions.
Inflammatory stimuli are causative for insulin resistance in obesity as well as in acute inflammatory reactions. Ongoing research has identified a variety of secreted proteins that are released from immune cells and adipocytes as mediators of insulin resistance; however, knowledge about their relevance for acute inflammatory insulin resistance remains limited. In this study we aimed for a clarification of the relevance of different insulin resistance mediating factors in an acute inflammatory situation.. Insulin resistance was measured in a cohort of 37 non-diabetic patients undergoing cardiac surgery by assessment of insulin requirement to maintain euglycaemia and repeated measurements of an insulin glycaemic index. The kinetics of cortisol, interleukin 6 (IL6), tumour necrosis factor alpha (TNFalpha), resistin, leptin and adiponectin were assessed by repeated measurements in a period of 48 h.. Insulin resistance increased during the observation period and peaked 22 h after the beginning of the operation. IL6 and TNFalpha displayed an early increase with peak concentrations at the 4-h time point. Serum levels of cortisol, resistin and leptin increased more slowly and peaked at the 22-h time point, while adiponectin declined, reaching a base at the 22-h time point. Model assessment identified cortisol as the best predictor of insulin resistance, followed by IL6, leptin and adiponectin. No additional information was gained by modelling for TNFalpha, resistin, catecholamine infusion rate, sex, age, body mass index (BMI), operation time or medication.. Serum cortisol levels are the best predictor for inflammatory insulin resistance followed by IL6, leptin and adiponectin. TNFalpha, and resistin have minor relevance as predictors of stress dependent insulin resistance. Topics: Adiponectin; Aged; Biomarkers; Cardiac Surgical Procedures; Female; Germany; Glycemic Index; Humans; Hydrocortisone; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Prospective Studies | 2008 |
[Effect of acute intra-peritoneal infection on leptin expression levels in peripheral blood and vital organs of rats].
To explore the effect of acute intra-peritoneal infection on leptin expression levels in peripheral blood and vital organs, and find out the role leptin plays in acute inflammation.. A cecal ligation and perforation model of rats was established, setting groups of sham-operation, intralipid injection, injury, estradiol injection and insulin injection. A rat leptin radioimmunoassay was used to check serum leptin concentrations at 12 h after the injury, and RT-PCR was also used to detect leptin mRNA expressions in adipose tissue, lung and liver.. Compared with serum leptin level of sham-operation group after injury, that of all the other four groups showed no significant difference, while the level of intralipid group was significantly higher than that of injury group and estradiol group. Compared with leptin mRNA expression level of sham-operation group after injury, that of the other four groups had different changes. Leptin mRNA expression of intralipid group was significantly increased in adipose tissue but decreased in lung and liver.. Leptin expression levels may be affected by the changes of energy metabolism and neuroendocrine function after injury, which suggests a possible protective role for leptin in the recovery of body homeostasis. Topics: Animals; Female; Inflammation; Intestinal Perforation; Leptin; Ligation; Male; Peritonitis; Rabbits; Rats; Rats, Sprague-Dawley; RNA, Messenger | 2008 |
Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism.
Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Lipid bodies (lipid droplets) are emerging as dynamic organelles with roles in lipid metabolism and inflammation. Here we investigated the roles of leptin in signaling pathways involved in cytoplasmic lipid body biogenesis and leukotriene B(4) synthesis in macrophages. Our results demonstrated that leptin directly activated macrophages and induced the formation of adipose differentiation-related protein-enriched lipid bodies. Newly formed lipid bodies were sites of 5-lipoxygenase localization and correlated with an enhanced capacity of leukotriene B(4) production. We demonstrated that leptin-induced macrophage activation was dependent on phosphatidylinositol 3-kinase (PI3K) activity, since the lipid body formation was inhibited by LY294002 and was absent in the PI3K knock-out mice. Leptin induces phosphorylation of p70(S6K) and 4EBP1 key downstream signaling intermediates of the mammalian target of rapamycin (mTOR) pathway in a rapamycin-sensitive mechanism. The mTOR inhibitor, rapamycin, inhibited leptin-induced lipid body formation, both in vivo and in vitro. In addition, rapamycin inhibited leptin-induced adipose differentiation-related protein accumulation in macrophages and lipid body-dependent leukotriene synthesis, demonstrating a key role for mTOR in lipid body biogenesis and function. Our results establish PI3K/mTOR as an important signaling pathway for leptin-induced cytoplasmic lipid body biogenesis and adipose differentiation-related protein accumulation. Furthermore, we demonstrate a previously unrecognized link between intracellular (mTOR) and systemic (leptin) nutrient sensors in macrophage lipid metabolism. Leptin-induced increased formation of cytoplasmic lipid bodies and enhanced inflammatory mediator production in macrophages may have implications for obesity-related cardiovascular diseases. Topics: Adipocytes; Animals; Cell Differentiation; Cells, Cultured; Chromones; Enzyme Inhibitors; Inflammation; Leptin; Leukotriene B4; Lipid Metabolism; Macrophage Activation; Macrophages, Peritoneal; Male; Membrane Proteins; Mice; Mice, Knockout; Morpholines; Organelles; Perilipin-2; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Kinases; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; TOR Serine-Threonine Kinases | 2008 |
Prevalence and cluster of cardiometabolic biomarkers in overweight and obese schoolchildren: results from a large survey in southwest Germany.
Obesity is associated with substantial metabolic changes and subclinical inflammation. We explored associations between body mass index (BMI) and cardiometabolic biomarkers and their clustering in overweight and obese schoolchildren.. In this population-based, cross-sectional study among 450 children 10 years old, we measured adiponectin, leptin, inflammatory markers, apolipoprotein (apo) AI and B, and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)). Except for adiponectin and apoAI (10th percentile) the 90th percentile was used as cutoff point. Body weight was categorized in age- and sex-specific BMI percentiles and overweight and obesity according to International Obesity Task Force definitions.. In linear regression models, all cardiometabolic markers except apoB were statistically significantly associated with overweight. In logistic regression models, compared with the reference category (25th-75th percentile of BMI), overweight was associated with increased concentrations of leptin [odds ratio (OR) 59.80; 95% CI 16.68-214.39], C-reactive protein (6.30; 2.95-13.45), fibrinogen (2.82; 1.33-6.01), and low apoAI (2.62; 1.19-5.75). Overweight was positively associated with interleukin-6, Lp-PLA(2), and apoB concentrations and inversely with adiponectin concentrations. Most importantly, in obese children 35% showed one, 20% two, 10% three, and 15% four or more abnormal cardiometabolic biomarkers. The number of abnormal cardiometabolic markers increased in overweight (p(trend) <0.001) and obese (p(trend) <0.001) children.. Overweight and obesity in children are associated with complex metabolic changes and a low-grade inflammatory response, and thus might not only accelerate cardiovascular disease later on, but may also be associated with the initiation of atherosclerosis in early life. Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adiponectin; Apolipoprotein A-I; Apolipoproteins B; Body Mass Index; C-Reactive Protein; Child; Cross-Sectional Studies; Fibrinogen; Germany; Humans; Inflammation; Interleukin-6; Leptin; Linear Models; Logistic Models; Obesity; Overweight | 2008 |
Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet.
Obesity and hypertension have been identified as cardiovascular risk factors that contribute to the progression of end-stage renal disease. To examine the mechanisms by which a high-fat diet and hypertension contribute to endothelial dysfunction and renal injury, 8-week-old male spontaneously hypertensive rats and Wistar rats were fed a high-fat (36% fat) or a normal-fat (7% fat) diet for 10 weeks. The high-fat diet increased body weight in Wistar and hypertensive rats by 25 and 31 g, respectively. Systolic blood pressure was higher in the hypertensive rats compared with Wistar rats; however, blood pressure was unaltered by the high-fat diet. Afferent arteriole response to acetylcholine was impaired in the high-fat groups after just 3 weeks. Renal macrophage infiltration was increased in the hypertensive high-fat group compared with others, and monocyte chemoattractant protein-1 excretion was increased in both of the high-fat-fed groups. Renal PCR arrays displayed significant increases in 2 inflammatory genes in hypertensive rats fed a normal diet, 1 gene was increased in high-fat-fed Wistar rats, whereas 12 genes were increased in high-fat-fed hypertensive rats. Urinary albumin excretion was increased in the hypertensive rats compared with the Wistar rats, which was further exacerbated by the high-fat diet. Glomerular nephrin expression was reduced and desmin was increased by the high-fat diet in the hypertensive rats. Our results indicate that endothelial dysfunction precedes renal injury in normotensive and spontaneously hypertensive rats fed a high-fat diet, and hypertension with obesity induces a powerful inflammatory response and disruption of the renal filtration barrier. Topics: Albuminuria; Animals; Arterioles; Biomarkers; Blood Glucose; Blood Pressure; Body Weight; Chemokine CCL2; Cholesterol; Cytokines; Dietary Fats; Dose-Response Relationship, Drug; Endothelium, Vascular; Gene Expression Profiling; Inflammation; Inflammation Mediators; Insulin Resistance; Kidney; Kidney Cortex; Leptin; Macrophages; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, CCR1; RNA, Messenger | 2008 |
Nutrition, inflammation, and leptin levels in aging and frailty.
To examine nutritional indices and levels of leptin and inflammatory markers across age and frailty.. Observational study.. Continuing care wards and a day hospital in Cardiff, South Wales, United Kingdom.. Thirty dependent patients (mean age 84.9) needing continuing inpatient care, 40 patients with falls attending a day hospital (mean age 84.2), 40 independent controls (mean age 82.7), and 30 young controls (mean age 23.3).. Functional status, including the five frailty indicators proposed by Fried et al., anthropometry, and serum markers of nutrition and inflammation.. The continuing care patients were frail, all having three to five frailty indicators. Day hospital patients were of intermediate frailty (mean Fried score 2.97), and the independent group was fittest (0.83). Body mass index, triceps skinfold thickness (TSF), and mid-arm muscle area were lowest in continuing care patients. With increasing patient frailty, albumin levels fell significantly (P<.005) and C-reactive protein (CRP) levels increased significantly (P<.005). Continuing care patients had significantly lower leptin levels (P<.005) and significantly higher interleukin (IL)-6 levels (P<.005). There was a significant correlation between log transformed leptin and TSF for each patient group.. The frailest older people displayed features of cachexia. Their leptin levels were appropriately low given their low body fat, and IL-6 and CRP levels were high. The mechanism of their cachexia may therefore be similar to that proposed in heart failure and cancer: disturbed hypothalamic feedback of leptin or effects of proinflammatory cytokines. Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; Chi-Square Distribution; Female; Frail Elderly; Geriatric Assessment; Humans; Inflammation; Interleukin-6; Leptin; Male; Nutritional Status; Skinfold Thickness; Statistics, Nonparametric | 2008 |
Endothelial lipase is increased in vivo by inflammation in humans.
Endothelial lipase (EL) is a plasma lipase that we previously reported to be significantly correlated with all features of the metabolic syndrome in humans, including directly with measures of adiposity and inversely with high-density lipoprotein cholesterol levels. We hypothesized that inflammation associated with obesity results in upregulation of EL. We determined the relationship between inflammatory markers and EL levels in a cohort of healthy persons recruited on the basis of family history of coronary disease. Furthermore, we directly tested the hypothesis that plasma EL concentrations would increase with induction of an inflammatory state by low-dose endotoxin in humans.. High-sensitivity C-reactive protein, interleukin 6, soluble tumor necrosis factor receptor II, soluble intercellular adhesion molecule 1, leptin, and adiponectin were measured in plasma of 858 subjects. Significant direct correlations (P<0.001 for all) were found between EL concentrations and high-sensitivity C-reactive protein (r=0.28), interleukin-6 (r=0.22), soluble tumor necrosis factor receptor II (r=0.22), soluble intercellular adhesion molecule 1 (r=0.24), and leptin (r=0.20). An inverse correlation was present with adiponectin (r=-0.15, P<0.001). Adiponectin inhibited the tumor necrosis factor-alpha-stimulated EL secretion from cultured human coronary endothelial cells in a dose-dependent manner. Experimental low-dose endotoxemia in 20 subjects resulted in a 2.5-fold increase in EL concentrations 12 to 16 hours after injection, which correlated temporally with decreases in both total and high-density lipoprotein phospholipid.. In humans, plasma inflammatory markers are directly correlated with plasma EL concentrations, and experimental endotoxemia significantly increases plasma EL concentrations, proving that EL is upregulated by inflammation in humans. This mechanism may partially explain the low high-density lipoprotein cholesterol levels seen in obesity and metabolic syndrome. Topics: Adiponectin; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Endothelium, Vascular; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Lipase; Male; Middle Aged; Receptors, Tumor Necrosis Factor, Type II | 2008 |
Visceral adipose tissue inflammation accelerates atherosclerosis in apolipoprotein E-deficient mice.
Fat inflammation may play an important role in comorbidities associated with obesity such as atherosclerosis.. To first establish feasibility of fat transplantation, epididymal fat pads were harvested from wild-type C57BL/6J mice and transplanted into leptin-deficient (Lep(ob/ob)) mice. Fat transplantation produced physiological leptin levels and prevented obesity and infertility in Lep(ob/ob) mice. However, the transplanted fat depots were associated with chronically increased macrophage infiltration with characteristics identical to those observed in fat harvested from obese animals. The inflammation in transplanted adipose depots was regulated by the same factors that have been implicated in endogenous fat inflammation such as monocyte chemoattractant protein-1. To determine whether this inflamed adipose depot could affect vascular disease in mice, epididymal fat depots were transplanted into atherosclerosis-prone apolipoprotein E-deficient ApoE(-/-) mice. Plasma from ApoE(-/-) mice receiving fat transplants contained increased leptin, resistin, and monocyte chemoattractant protein-1 compared with plasma from sham-operated ApoE(-/-) mice. Furthermore, mice transplanted with visceral fat developed significantly more atherosclerosis compared with sham-operated animals, whereas transplants with subcutaneous fat did not affect atherosclerosis despite a similar degree of fat inflammation. Treatment of transplanted ApoE(-/-) mice with pioglitazone decreased macrophage content of the transplanted visceral fat pad and reduced plasma monocyte chemoattractant protein-1. Importantly, pioglitazone also reduced atherosclerosis triggered by inflammatory visceral fat but had no protective effect on atherosclerosis in the absence of the visceral fat transplantation.. Our results indicate that visceral adipose-related inflammation accelerates atherosclerosis in mice. Drugs such as thiazolidinediones might be a useful strategy to specifically attenuate the vascular disease induced by visceral inflammatory fat. Topics: Adiponectin; Animals; Apolipoproteins E; Atherosclerosis; Inflammation; Intra-Abdominal Fat; Leptin; Macrophages; Mice; Mice, Inbred C57BL; Pioglitazone; Thiazolidinediones | 2008 |
Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo.
Protein-tyrosine phosphatase 1B (PTP1B) is a major negative regulator of insulin and leptin sensitivity. PTP1B overexpression in adipose tissue and skeletal muscle of humans and rodents may contribute to insulin resistance and obesity. The mechanisms mediating PTP1B overexpression in obese and diabetic states have been unclear. We find that adipose tissue inflammation and the pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha) regulate PTP1B expression in vivo. High fat feeding of mice increased PTP1B expression 1.5- to 7-fold in adipose tissue, liver, skeletal muscle, and arcuate nucleus of hypothalamus. PTP1B overexpression in high fat-fed mice coincided with increased adipose tissue expression of the macrophage marker CD68 and TNFalpha, which is implicated in causing obesity-induced insulin resistance. TNFalpha increased PTP1B mRNA and protein levels by 2- to 5-fold in a dose- and time-dependent manner in adipocyte and hepatocyte cell lines. TNFalpha administration in mice increased PTP1B mRNA 1.4- to 4-fold in adipose tissue, liver, skeletal muscle, and hypothalamic arcuate nucleus and PTP1B protein 2-fold in liver. Actinomycin D treatment blocked, and high dose salicylate treatment inhibited by 80%, TNFalpha-induced PTP1B expression in adipocyte cell lines, suggesting TNFalpha may induce PTP1B transcription via nuclear factor kappaB (NFkappaB) activation. Chromatin immunoprecipitation from adipocyte cell lines and liver of mice demonstrated TNFalpha-induced recruitment of NFkappaB subunit p65 to the PTP1B promoter in vitro and in vivo. In mice with diet-induced obesity, TNFalpha deficiency also partly blocked PTP1B overexpression in adipose tissue. Our data suggest that PTP1B overexpression in multiple tissues in obesity is regulated by inflammation and that PTP1B may be a target of anti-inflammatory therapies. Topics: Animal Feed; Animals; Base Sequence; Cells, Cultured; Diabetes Mellitus; Gene Expression Regulation, Enzymologic; Inflammation; Insulin; Insulin Resistance; Leptin; Mice; Molecular Sequence Data; Obesity; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Rats; Transcription, Genetic; Tumor Necrosis Factor-alpha | 2008 |
Serum concentrations and expressions of serum amyloid A and leptin in adipose tissue are interrelated: the Genobin Study.
Serum amyloid A (SAA) is a novel link between increased adipose tissue mass and low-grade inflammation in obesity. Little is known about the factors regulating its serum concentration and mRNA levels. We investigated the association between SAA and leptin in obese and normal weight subjects and analyzed the effect of weight reduction on serum SAA concentration and gene expression in adipose tissue of the obese subjects.. Seventy-five obese subjects (60+/-7 years, body mass index (BMI) 32.9+/-2.8 kg/m(2), mean+/-s.d.) with impaired fasting plasma glucose or impaired glucose tolerance and other features of metabolic syndrome, and 11 normal weight control subjects (48+/-9 years, BMI 23.7+/-1.9 kg/m(2)) were studied at the baseline. Twenty-eight obese subjects underwent a 12-week intensive weight reduction program followed by 5 months of weight maintenance. Blood samples and abdominal s.c. adipose tissue biopsies were taken at the baseline and after the follow-up. Gene expression was studied using real-time quantitative PCR.. The gene expressions in women and serum concentrations of leptin and SAA were interrelated independently of body fat mass in the obese subjects (r=0.54, P=0.001; r=0.24, P=0.039 respectively). In multiple linear regression analyses, leptin mRNA explained 38% of the variance in SAA mRNA (P=0.002) in the obese women. Weight loss of at least 5% increased SAA mRNA expression by 48 and 36% in men and women, but serum SAA concentrations did not change.. The association between SAA and leptin suggests an interaction between these two adipokines, which may have implications in inflammatory processes related to obesity and the metabolic syndrome. Topics: Adipocytes; Adipose Tissue; Aged; Body Weight; Female; Gene Expression; Glucose Intolerance; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; RNA, Messenger; Serum Amyloid A Protein; Weight Loss | 2008 |
Leptin induces the expression of functional tissue factor in human neutrophils and peripheral blood mononuclear cells through JAK2-dependent mechanisms and TNFalpha involvement.
Leptin is an adipocyte-derived cytokine primarily involved in the regulation of body weight and energy balance. In vivo studies suggest that leptin promotes platelet aggregation and thrombosis. Neutrophils are involved in the crosstalk between inflammation and thrombosis in clinical disorders. Leptin is also involved in the regulation of inflammation.. We examined the in vitro effects of leptin on the expression of tissue factor (TF), the primary initiator of coagulation, in healthy neutrophils.. The effects on TF expression were assayed functionally using a modified prothrombin time (mPT), as well as at mRNA and protein levels. The same experiments were performed in parallel with PBMC. Leptin induced functional TF and increased TF mRNA and protein expression in both cell types, as determined by mPT, real-time RT-PCR, western blot, flow cytometry, immunocytochemistry. Inhibition studies revealed that the effect of leptin on TF expression is mediated, at least in part, by JAK2 and PI3K. Our findings, after neutralising TNFalpha in supernatants of leptin-treated cells, also suggest the involvement of TNFalpha in the leptin-induced TF expression in leukocytes.. This study indicates a novel link between inflammation, obesity and thrombosis by showing that leptin is able to trigger the extrinsic coagulation cascade. This work suggests a possible mechanism of the thrombotic effects of hyperleptinemic-associated clinical disorders. Topics: Blood Coagulation; Humans; Inflammation; Janus Kinase 2; Leptin; Leukocytes, Mononuclear; Neutrophils; Obesity; Phosphatidylinositol 3-Kinases; Platelet Aggregation; Prothrombin Time; RNA, Messenger; Thromboplastin; Thrombosis; Tumor Necrosis Factor-alpha | 2008 |
Fat may fuel breast cancer growth.
Topics: Adipose Tissue; Biomarkers, Tumor; Body Mass Index; Body Weight; Breast Neoplasms; Disease-Free Survival; Estrogens; Exercise; Female; Humans; Inflammation; Insulin; Insulin-Like Growth Factor I; Leptin; Neoplasms; Obesity; Overweight; Recurrence; Risk Assessment; Risk Factors; United Kingdom; Weight Gain | 2008 |
Effect of weight loss on proinflammatory state of mononuclear cells in obese women.
In order to investigate whether weight loss can lead to improvement of the mononuclear cell (MNC) proinflammatory state, 21 nondiabetic obese women with mean age 34+/-2 years (mean+/-s.e.m.) and BMI 32.5+/-1.2 kg/m2 were enrolled in a 12-week caloric restriction and light exercise-based weight loss program. Ten lean women served as controls. Reverse transcription-PCR of proinflammatory cytokines and adipocytokines as well as homeostasis model assessment of insulin resistance (HOMA-IR) were determined before and after weight reduction. Nuclear factor kappaB (NF-kappaB) binding to DNA and inhibitors of NF-kappaB (IkappaB-alpha and IkappaB-beta) obtained from peripheral MNCs were measured. Overall, subjects lost a mean of 4.0+/-0.4 kg (5.0+/-0.3% of their initial body weight) (P<0.01). In addition to significant reductions in BMI, fasting glucose and insulin concentrations, mean serum high-sensitivity C-reactive protein (hs-CRP), migration inhibitor factor (MIF), leptin and visfatin levels decreased by 49.0, 66.6, 17.2, and 50.2%, respectively (all P<0.05), while adiponectin concentrations rose by 33.9% (P<0.05). The DNA binding of the transcriptionally active NF-kappaB from (p65/p50) decreased by 38.1% (P<0.05). Elevated levels of mRNA of NF-kappaB related proinflammatory genes, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), MIF, and matrix metalloproteinase-9 (MMP-9), decreased significantly after weight loss. Although mRNA expression of Rel-A, p105, IkappaB-alpha, IkappaB-beta decreased significantly, their protein levels did not change after weight loss. As a group, NF-kappaB binding activity correlated with HOMA-IR (r=0.332, P=0.049) and marginally with values of BMI (r=0.308, P=0.059). In conclusion, weight loss by 5% of initial weight in nondiabetic obese women led to significant improvement in activated intranuclear NF-kappaB binding as well as several transcriptions of proinflammatory genes regulated by NF-kappaB. Topics: Adult; Blood Glucose; C-Reactive Protein; Case-Control Studies; Female; Humans; I-kappa B Proteins; Inflammation; Insulin; Interleukin-6; Intramolecular Oxidoreductases; Leptin; Leukocytes, Mononuclear; Macrophage Migration-Inhibitory Factors; Matrix Metalloproteinase 9; NF-kappa B; NF-KappaB Inhibitor alpha; Nicotinamide Phosphoribosyltransferase; Obesity; Tumor Necrosis Factor-alpha; Weight Loss | 2008 |
Corticotropin-releasing hormone deficiency is associated with reduced local inflammation in a mouse model of experimental colitis.
CRH, the hypothalamic component of the hypothalamic-pituitary adrenal axis, attenuates inflammation through stimulation of glucocorticoid release, whereas peripherally expressed CRH acts as a proinflammatory mediator. CRH is expressed in the intestine and up-regulated in patients with ulcerative colitis. However, its pathophysiological significance in intestinal inflammatory diseases has just started to emerge. In a mouse model of acute, trinitrobenzene sulfonic acid-induced experimental colitis, we demonstrate that, despite low glucocorticoid levels, CRH-deficient mice develop substantially reduced local inflammatory responses. These effects were shown by histological scoring of tissue damage and neutrophil infiltration. At the same time, CRH deficiency was found to be associated with higher serum leptin and IL-6 levels along with sustained anorexia and weight loss, although central CRH has been reported to be a strong appetite suppressor. Taken together, our results support an important proinflammatory role for CRH during mouse experimental colitis and possibly in inflammatory bowel disease in humans. Moreover, the results suggest that CRH is involved in homeostatic pathways that link inflammation and metabolism. Topics: Animals; Anorexia; Colitis, Ulcerative; Corticotropin-Releasing Hormone; Disease Models, Animal; Female; Gene Expression; Inflammation; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Reverse Transcriptase Polymerase Chain Reaction; Trinitrobenzenesulfonic Acid; Weight Loss | 2008 |
Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines.
In obesity, decreases in adiponectin and increases in proinflammatory adipokines are associated with heart disease. Because adipocytes express mineralocorticoid receptor (MR) and MR blockade reduces cardiovascular inflammation and injury, we tested the hypothesis that MR blockade reduces inflammation and expression of proinflammatory cytokines in adipose tissue and increases adiponectin expression in adipose tissue and hearts of obese mice.. We determined the effect of MR blockade (eplerenone, 100 mg/kg per day for 16 weeks) on gene expression in retroperitoneal adipose and heart tissue from obese, diabetic db/db mice (n=8) compared with untreated obese, diabetic db/db mice (n=10) and lean, nondiabetic db/+ littermates (n=11). Expression of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, plasminogen activator inhibitor type 1, and macrophage protein CD68 increased, and expression of adiponectin and peroxisome proliferator-activated receptor-gamma decreased in retroperitoneal adipose tissue from obese versus lean mice. In addition, adiponectin expression in heart was reduced in obese versus lean mice. MR blockade prevented these obesity-related changes in gene expression. Furthermore, treatment of undifferentiated preadipocytes with aldosterone (10(-8) mol/L for 24 hours) increased mRNA levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 and reduced mRNA and protein levels of peroxisome proliferator-activated receptor-gamma and adiponectin, supporting a direct aldosterone effect on gene expression.. MR blockade reduced expression of proinflammatory and prothrombotic factors in adipose tissue and increased expression of adiponectin in heart and adipose tissue of obese, diabetic mice. These effects on adiponectin and adipokine gene expression may represent a novel mechanism for the cardioprotective effects of MR blockade. Topics: 3T3-L1 Cells; Adipokines; Adiponectin; Adipose Tissue; Aldosterone; Animals; Biomarkers; Body Weight; Diabetes Mellitus, Experimental; Homeostasis; Inflammation; Leptin; Male; Mice; Mice, Mutant Strains; Mineralocorticoid Receptor Antagonists; Myocardium; Obesity; PPAR gamma; Receptors, Mineralocorticoid; RNA, Messenger; Triglycerides | 2008 |
Inflammation is associated with a decrease of lipogenic factors in omental fat in women.
Obesity is characterized by systemic low-grade inflammation in which adipose tissue, especially the omental depot, is thought to play a key role. We have previously shown that inflammation impairs 3T3-L1 preadipocyte cell line differentiation. To explore whether this interaction also takes place in vivo, the expression of several genes related to inflammation and adipocyte differentiation was assessed in human samples. Paired adipose tissue biopsies (from omental and subcutaneous depots) were obtained from 24 women: 6 lean normoglycemic and 18 obese volunteers with different glycemic states (normoglycemic, glucose-intolerant, or type 2 diabetic). The expression levels of CD14, IL-18, leptin, adiponectin, sterol regulatory element binding transcription factor 1 (SREBP1), peroxisome proliferator-activated receptor gamma (PPARgamma), pre-B-cell colony enhancing factor 1 (PBEF1) (or visfatin), glycerol-3-phosphate dehydrogenase 1 (soluble) (GPD1), lipoprotein lipase (LPL), fatty acid binding protein 4, adipocyte (FABP4), and hypoxia-inducible factor 1alpha were determined by quantitative real-time PCR. CD14 and IL-18 were overexpressed in omental adipose tissue compared with the subcutaneous depot, irrespective of the subject's obesity or diabetes status. A significant decrease of LPL, GPD1, and leptin expression was observed in omental tissue, and an inverse correlation between expression of CD14 and IL-18 and that of PPARgamma, LPL, and FABP4 was observed. The underexpression of omental lipogenic markers was more accentuated in the presence of glucose intolerance. Furthermore, adiponectin and SREBP1 expression was also significantly decreased in omental tissue of type 2 diabetic patients. PBEF1 and HIF1alpha expression remained comparable in all samples. Therefore, in humans, inflammation is increased in the omental depot, as evidenced by CD14 and IL-18 expression. In this localization, the inflammatory state is associated with a decreased expression of lipogenic markers, which is more pronounced in diabetic subjects. Topics: Adiponectin; Adipose Tissue; Adult; Body Composition; Cytokines; Diabetes Mellitus, Type 2; Fatty Acid-Binding Proteins; Female; Gene Expression Regulation; Glucose Intolerance; Glycerolphosphate Dehydrogenase; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Interleukin-18; Leptin; Lipogenesis; Lipopolysaccharide Receptors; Lipoprotein Lipase; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Omentum; PPAR gamma; RNA, Messenger; Sterol Regulatory Element Binding Protein 1 | 2008 |
Contribution of adipocytokines to low-grade inflammatory state as expressed by circulating C-reactive protein in Japanese men: comparison of leptin and adiponectin.
Circulating C-reactive protein (CRP) is a marker of inflammation and is associated with the incidence of cardiovascular events. Although it has been known that adiponectin protects, whereas leptin accelerates, the development of atherosclerotic diseases, the comparative strength of their reciprocal effects on circulating CRP remains unclear.. We studied a population of 2049 Japanese men aged 35 to 66. For all subjects, multiple regression analysis performed with log-transformed CRP concentration as the dependent variable, and with log-transformed leptin, log-transformed adiponectin, age, BMI, smoking status, and components of metabolic syndrome as independent variables.. Both leptin (positively) and adiponectin (negatively) were significantly and independently associated with CRP concentration. The absolute value of the standardized regression coefficient (st-beta) of leptin (st-beta=0.201) was higher than that of adiponectin (st-beta=-0.082). After subjects were stratified by current BMI level, both of the adipocytokines were significantly associated with CRP concentration among subjects with BMI <25 kg/m(2), whereas only leptin was significantly associated with CRP concentration among subjects with BMI >=25 kg/m(2).. Both leptin and adiponectin were independently associated with CRP concentration. Leptin was more strongly related to CRP levels than adiponectin was, especially among obese subjects. Topics: Adiponectin; Adult; Aged; Asian People; Biomarkers; C-Reactive Protein; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Middle Aged; Obesity | 2008 |
Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels.
Cellular and animal studies suggest that leptin has proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis. To investigate this hypothesis, we examined the effect of genetic variability at the leptin receptor (LEPR) locus on the plasma levels of fibrinogen and CRP--two markers of inflammation and susceptibility to atherosclerosis.. Linkage disequilibrium analysis of 71 single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian individuals, variability in block #4 was significantly associated with plasma fibrinogen (p=0.005), accounting for 3% of its variance (r2=0.030). The same block was also associated with CRP levels (p=0.049, r2=0.022). The effect was strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10% higher in minor allele homozygotes than in major allele homozygotes and intermediate in heterozygotes (p=0.015). At rs1805096, it was 5% higher (p=0.007) and CRP 32% higher (p=0.011) in major allele homozygotes than in minor allele carriers. This pattern of association was also evident in the haplotype analysis.. Association of leptin receptor variability with inflammatory traits supports the hypothesis that leptin may play a role in atherogenesis. Topics: Adipose Tissue; Adult; Atherosclerosis; C-Reactive Protein; Female; Fibrinogen; Humans; Inflammation; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Cell Surface; Receptors, Leptin; White People | 2007 |
Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease.
Leptin, an adipocyte-derived protein, regulating food intake and metabolism has been implicated in the development of coronary heart disease. We have examined the relationship between leptin and vascular risk factors including insulin resistance, metabolic, inflammatory and haemostatic risk factors.. The study was carried out in 3640 non-diabetic men aged 60-79 years drawn from general practices in 24 British towns and who were not on warfarin. Leptin was strongly positively correlated with waist circumference (r=0.58; p<0.0001). Leptin concentrations decreased significantly with increasing physical activity and were lowered in cigarette smokers and elevated in men with pre-existing coronary heart disease and stroke; alcohol intake showed no association with leptin concentration. After adjustment for waist circumference and these lifestyle factors, increased leptin was independently associated with significant increases in insulin resistance, triglycerides, inflammatory markers (interleukin-6, C-reactive protein, fibrinogen, plasma viscosity), coagulation factor VIII, endothelial markers von Willebrand factor, tissue plasminogen activator, and fibrin D-dimer levels; and a decrease in HDL-cholesterol. No association was seen between leptin and blood pressure, total cholesterol, glucose or white cell count after adjusting for waist circumference. Further adjustment for insulin resistance abolished the relationships between leptin and triglycerides and HDL-cholesterol, weakened the associations with the haemostatic factors although they remained significant, but made minor differences to the associations with inflammatory markers.. Plasma leptin is associated with insulin resistance, inflammation and disturbances in haemostasis independent of waist circumference, suggesting possible pathways by which leptin may influence risk of cardiovascular disease. Topics: Aged; Biomarkers; Cardiovascular Diseases; Endothelium, Vascular; Follow-Up Studies; Hemostasis; Humans; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Male; Middle Aged; Obesity; Prospective Studies; Registries; Risk Assessment; Risk Factors; Time Factors; United Kingdom | 2007 |
Drug residues store in the body following cessation of use: impacts on neuroendocrine balance and behavior--use of the Hubbard sauna regimen to remove toxins and restore health.
For decades, scientists have investigated the environmental and human health effects of synthetic chemicals. A growing body of research has illuminated the spectrum of consequences deriving from our reliance these substances and their proliferation in air, water, soil and the food chain. Of particular concern is the fact that residues of many man-made chemicals are now detectible in virtually every person. A key to a chemical's tendency to persist in tissues once it has entered the body is its lipophilicity. Substances that are poorly soluble in water and quite soluble in fat have relatively free access, via lipid-rich cellular membranes, to the cells of all organs including the ability to cross the blood-brain and placental barriers. Substantial data exist demonstrating that in addition to pollutants, drugs and their metabolites dispose to tissues high in fat content, including brain and adipose. While their characteristic lipophilicity permits drugs and medications to reach target tissues, thereby producing therapeutic effects in the present, current perceptions of risk may be ignoring the possibility that adipose accumulations of illicit drugs and pharmaceuticals may lead to future patterns of ill health similar to those associated with exposure to other categories of xenobiotic chemicals. Empirical data are beginning to characterize the myriad regulatory functions of adipose hormones, including roles in cravings, cognitive function, energy level, and inflammation as well as changes in adipose hormone levels associated with drug use. Included in this data are the observation that a rehabilitative treatment intervention introduced by L. Ron Hubbard in 1978 to aid in the broad elimination of chemicals from body stores improves symptoms common to both chemical exposure and drug addiction. The regimen, which includes exercise, sauna bathing, and vitamin and mineral supplementation, is utilized by nearly 70 drug rehabilitation and medical practices in over 20 countries. At present, much more is unknown than is known regarding long-term drug retention and effects. This subject deserves careful evaluation given its potential implications for health and chronic illnesses of poorly defined etiology (such as chronic fatigue syndrome), as well as drug abuse prevention, drug rehabilitation, forensic and legal areas. Topics: Dietary Supplements; Drug Residues; Food; Human Body; Humans; Illicit Drugs; Inflammation; Leptin; Models, Biological; Neurosecretory Systems; Pharmaceutical Preparations; Steam Bath; Toxins, Biological; Tumor Necrosis Factor-alpha | 2007 |
Sex differences in the association between leptin and CRP: results from the Dallas Heart Study.
Higher C-reactive protein (CRP) levels in women compared with men may reflect sex differences in the relationship between obesity and inflammation. We evaluated how the adipokine leptin influenced these relationships.. Dual energy X-ray absorptometry measurements of fat mass and plasma levels of leptin and CRP were measured in 1188 women and 1102 men from the Dallas Heart Study. Analyses were stratified by sex and a leptin/percent fat index was created to evaluate the association between leptin and CRP independent of fat mass. Women had higher body mass index, percent fat mass, and plasma levels of CRP and leptin. CRP levels correlated with leptin levels in both women (Spearman rho=0.48, p<0.0001) and in men (rho=0.27, p<0.0001). In multivariable models adjusting for confounders including total fat mass, leptin/percent fat index remained significantly associated with logCRP in women (p=0.005), but not in men (p=0.95). A significant interaction was observed between sex and leptin levels on CRP (p(interaction)=0.03).. Leptin was associated with CRP independent of other measures of obesity in women, but not in men. These findings suggest that sex differences in CRP may reflect sex-related differences in the inflammatory responses to obesity, and may in part, be mediated by leptin. Topics: Adult; Body Composition; Body Mass Index; C-Reactive Protein; Cross-Sectional Studies; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Obesity; Sex Factors; Statistics as Topic | 2007 |
Insulin-like growth factor-1, leptin, body composition, and clinical status interactions in children with cystic fibrosis.
Children with cystic fibrosis (CF) are of increased risk of reduced fat body mass (FBM) and lean body mass (LBM). Serum concentrations of insulin-like growth factor-1 (IGF-1)and leptin could be markers of LBM and/or FBM depletion. To evaluate the relationships between disease activity, body composition, IGF-1 and leptin concentrations in CF children.. A cross-sectional study with 26 CF children aged 5.0-15.5 years and 33 healthy controls, mean age 9.4 years. Body composition was evaluated by dual-energy X-ray absorptiometry. Fasting blood samples were analyzed for leptin, IGF-1 and IGFBP-3.. FBM standard deviation score (SDS; CF boys -0.02 +/- 0.88 vs. 0.78 +/- 0.65, p < 0.01; CF girls -0.37 +/- 1.15 vs. 0.70 +/- 0.97, p < 0.05), leptin concentration (CF boys 2.07 +/- 0.79 vs. 3.07 +/- 1.28 ng/ml, p < 0.05; CF girls 2.71 +/- 0.86 vs. 5.00 +/- 2.95 ng/ml, p < 0.05) and IGF-1SDS (CF boys -1.43 +/- 1.50 vs. -0.32 +/- 0.88, p < 0.05; CF girls -0.66 +/- 1.66 vs. 0.64 +/- 0.57, p < 0.01) were lower in CF children compared to controls. Shwachman score was the strongest predictor of lean body mass (R = 0.63). Leptin levels explain 60% of the variability in FBM.. Serum concentrations of IGF-1 and leptin are decreased in children with CF and are associated with clinical conditions and body composition. Topics: Adipose Tissue; Adolescent; Biomarkers; Body Composition; Child; Child Development; Child, Preschool; Cross-Sectional Studies; Cystic Fibrosis; Female; Humans; Inflammation; Insulin-Like Growth Factor I; Leptin; Male | 2007 |
Body composition, insulin, and leptin levels in patients with ankylosing spondylitis.
The aim of this study was to compare the effect of chronic inflammation on insulin resistance, serum leptin levels, and body composition (BC) in patients with ankylosing spondylitis (AS) and healthy controls. Twenty-eight AS patients and 17 healthy controls were included in this study. Subjects with hypertension, diabetes, hyperlipidemia, and obesity were excluded. Acute phase reactants and serum levels of glucose, insulin, lipids, and leptin were studied. BC was determined anthropometrically and by foot-to-foot body fat analyzer (BIA, bioelectrical impedance analysis). Quantitative insulin-sensitivity check index, homeostasis model assessment for insulin resistance, and McAuley indices were calculated. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Age, sex distribution, smoking status, serum lipids, insulin concentrations, and insulin resistance indices were comparable between AS patients and controls (p > 0.05). However, acute phase reactants were significantly higher and leptin levels were significantly lower in the AS patients than in controls (p < 0.05). Fat percent assessed by both BIA and anthropometrical methods was lower in the male and female AS patients than in controls, and this reduced fat level reached statistical significance for men (p < 0.05). There were significant correlations between percent body fat, body mass index, leptin, age, and BASMI (p < 0.05; r = 0.6, 0.75, 0.35, -0.41, respectively). On the other hand, body fat percent, waist-to-hip ratio, C-reactive protein, and BASMI were significantly correlated with serum leptin levels (p < 0.05; r = 0.75, -0.42, -0.52, -0.47, respectively). Chronic inflammatory condition in AS may be responsible for the reduced body fat content and lower circulating leptin concentrations. Insulin levels and insulin resistance indices seem similar in patients and controls in the absence of classic vascular risk factors. Topics: Adult; Body Composition; Body Mass Index; C-Reactive Protein; Case-Control Studies; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Middle Aged; Spondylitis, Ankylosing | 2007 |
Hyperleptinaemia and chronic inflammation after peritonitis predicts poor nutritional status and mortality in patients on peritoneal dialysis.
The serum leptin level is elevated in patients undergoing peritoneal dialysis (PD) and associated with a loss of lean body mass. The nutritional status of PD patients may further be worsened following peritonitis. We investigated the association between hyperleptinaemia, inflammation and malnourishment in PD-related peritonitis.. We conducted a prospective study on PD patients who developed peritonitis. Blood samples were obtained as baseline (D0) before the onset of peritonitis, and once peritonitis developed, leptin, adiponectin (ADPN) and other inflammatory markers were collected, on day 1 (D1), day 7 (D7) and day 42 (D42) of peritonitis. Patients were followed-up for any censor event or 1 year after peritonitis.. Forty-two patients with a mean age of 62.9+/-13.2 years were recruited. Fourteen (33.3%) were diabetic. The serum leptin levels increased significantly from baseline to day 1 and 7, but fell back to the premorbid state at day 42. In contrast, the ADPN level decreased from a baseline value of 15.60+/-10.4 microg/ml to 13.01+/-8.1 microg/ml on day 1 (P=0.01) but rose to 14.39+/-8.9 microg/ml on day 7 (P=0.28) and 13.87+/-7.9 microg/ml on day 42 (P=0.21). High-sensitivity C-reactive protein (hs-CRP) increased significantly from baseline to day 1, 7 and even at day 42. The lean body mass (LBM) and nutritional markers decreased significantly after peritonitis. For patients with high hs-CRP (>3.0 mg/l) at day 42, there was a higher mortality rate than for those with lower hs-CRP (<3.0 mg/l, P=0.02), even if they were in clinical remission of peritonitis.. Our study confirmed an increase in serum leptin during acute peritonitis and a prolonged course of systemic inflammation after apparent clinical remission of peritonitis. These factors related to the persistent chronic inflammation may contribute to the development of malnourishment and poor survival rate. Topics: Adiponectin; Aged; C-Reactive Protein; Chronic Disease; Female; Follow-Up Studies; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Peritonitis; Predictive Value of Tests; Prognosis; Prospective Studies; Protein-Energy Malnutrition; Tumor Necrosis Factor-alpha | 2007 |
Leptin and C-reactive protein levels correlate during minor infection in children.
Leptin, a pleiotropic hormone, has been suggested to be part of an acute-phase response during an inflammatory stimulus. Its correlation with other acute-phase reactants during minor infection in children has not been investigated.. To study the correlation between levels of serum leptin and those of C-reactive protein, a well-documented acute-phase reactant, in a series of pediatric patients with acute minor infections.. Leptin and CRP levels were measured in 62 blood samples of pediatric patients presenting with mild febrile illness who were admitted to Dana Children's Hospital in Israel. All children were finally diagnosed as having minor infection based on the negative blood/urine cultures and favorable outcome.. Serum leptin level was positively correlated with CRP (r2 = 0.5), total white blood cells (r2 = 0.33) and absolute neutrophil count (r2 = 0.31). The regression coefficient was the highest between leptin and CRP.. Circulating leptin concentrations are positively correlated with CRP levels during acute minor infection in children visiting the emergency room for febrile illnesses. Our observation suggests that leptin is indeed a part of acute-phase proteins. The wide scattering showed that it is not a better marker in minor infections than CRP, but it may contribute to weight loss and anorexia seen in a minority of patients during mild infections. Topics: Acute Disease; Acute-Phase Proteins; Adolescent; Age Factors; Bacterial Infections; Biomarkers; C-Reactive Protein; Child; Child, Preschool; Female; Humans; Inflammation; Leptin; Male; Risk Factors; Statistics as Topic | 2007 |
Signs of proinflammatory/genotoxic switch (adipogenotoxicosis) in mammary fat of breast cancer patients: role of menopausal status, estrogens and hyperglycemia.
The abundance of fat tissue surrounding normal and malignant epithelial mammary cells raises the questions whether such "adipose milieu" is important in the local proinflammatory/genotoxic shift, which apparently promotes tumor development and worsens prognosis, and what conditions stimulate this shift, or "adipogenotoxicosis." We studied 95 mammary fat samples from 70 postmenopausal and 25 premenopausal breast cancer (BC) patients at a distance of 1.5-2.0 cm from tumors. The levels of leptin, adiponectin, TNFalpha and IL-6 release after 4-hr incubation of the samples were evaluated with ELISA, nitric oxide (NO) production by Griess reaction and lipid peroxidation by determination of thiobarbiturate-reactive products (TBRP). Infiltration of fat with macrophages (CD68-positive cells) and expression of cytochrome P450 1B1/estrogen 4-hydroxylase (CYP1B1) were detected by immunohistochemistry. Aromatase (CYP19) activity in mammary fat was measured by (3)H(2)O release from (3)H-1beta-androstenedione. In the postmenopausal BC patients, NO and TNFalpha production by adipose tissue explants increased independent of BMI and in parallel with decreasing leptin and, especially, adiponectin release. In the premenopausal patients, higher CYP1B1 expression and TBRP level were found in mammary fat, while higher aromatase activity was combined with higher CYP1B1 expression as well as NO and IL-6 production. In the postmenopausal group, impaired glucose tolerance was associated with higher IL-6 release production by fat and with higher IL-6/adiponectin ratio. Thus, signs of adipogenotoxicosis in mammary fat can be found in both pre- and postmenopausal BC patients. This condition is likely being maintained through estrogen- and glucose-related factors and mechanisms presumably associated with less favorable types of hormonal carcinogenesis. Topics: Adipose Tissue; Adult; Aged; Aged, 80 and over; Aromatase; Breast Neoplasms; Cytochrome P-450 Enzyme System; Estrogens; Female; Humans; Hyperglycemia; Inflammation; Leptin; Macrophages; Mammary Glands, Human; Middle Aged; Postmenopause; Premenopause | 2007 |
Adiponectin, resistin and subclinical inflammation--the metabolic burden in Launois Bensaude Syndrome, a rare form of obesity.
The aim of the study was to investigate, whether the degree of metabolic risk factors for atherosclerotic complications in a very rare kind of obesity, the Multiple Symmetrical Lipomatosis, also known as the Launois-Bensaude Syndrome (LBS), are comparable or different from "simple" truncal obesity. 10 patients with LBS (Body mass index 34.4 +/- 1.8 kg/m(2), age: 62 +/- 3 yrs) were compared with 19 BMI - matched patients with "simple" truncal obesity and obstructive sleep apnoea syndrome (OSAS) and 20 BMI- matched patients with "simple" truncal obesity without OSAS. Markers of subclinical inflammation and thrombocyte activation (sCD62p = soluble p-selectin, highly sensitive C-Reactive protein = CRP, Interleukin-6 = IL-6, ICAM-1 = Intracellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule = VCAM -1, leptin), as well as adiponectin and resistin were studied. The prevalence of atherogenic risk factors as hypertension (80%), type 2 diabetes (30%), OSAS (50%), smoking (30%) and alcohol abuse (80%) was high in the (obese) LBS group. The markers of subclinical inflammation and thrombocyte activation showed an indifferent picture with lower levels of circulating IL-6 and sCD62p, comparable CRP and higher ICAM-1 and VCAM-1 than in controls. Leptin and adiponectin were higher than in controls. However, the accumulation of "classic" cardiovascular risk factors in the LBS group was well reflected by the presence of symptomatic cardiovascular disease in 3 of the 10 LBS patients, putting LBS patients - if obese - at an atherosclerotic risk at least comparable to obese persons. Topics: Adiponectin; Atherosclerosis; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Lipomatosis, Multiple Symmetrical; Male; Middle Aged; Obesity; P-Selectin; Resistin; Sleep Apnea, Obstructive; Vascular Cell Adhesion Molecule-1 | 2007 |
Neonatal immune challenge does not affect body weight regulation in rats.
The perinatal environment plays a crucial role in programming many aspects of adult physiology. Myriad stressors during pregnancy, from maternal immune challenge to nutritional deficiency, can alter long-term body weight set points of the offspring. In light of the increasing concern over body weight issues, such as obesity and anorexia, in modern societies and accumulating evidence that developmental stressors have long-lasting effects on other aspects of physiology (e.g., fever, pain), we explored the role of immune system activation during neonatal development and its impact on body weight regulation in adulthood. Here we present a thorough evaluation of the effects of immune system activation (LPS, 100 microg/kg ip) at postnatal days 3, 7, or 14 on long-term body weight, adiposity, and body weight regulation after a further LPS injection (50 microg/kg ip) or fasting and basal and LPS-induced circulating levels of the appetite-regulating proinflammatory cytokine leptin. We show that neonatal exposure to LPS at various times during the neonatal period has no long-term effects on growth, body weight, or adiposity. We also observed no effects on body weight regulation in response to a short fasting period or a further exposure to LPS. Despite reductions in circulating leptin levels in response to LPS during the neonatal period, no long-term effects on leptin were seen. These results convincingly demonstrate that adult body weight and weight regulation are, unlike many other aspects of adult physiology, resistant to programming by a febrile-dose neonatal immune challenge. Topics: Acute Disease; Adipose Tissue; Age Factors; Animals; Animals, Newborn; Anorexia; Body Weight; Critical Period, Psychological; Fasting; Female; Inflammation; Leptin; Lipopolysaccharides; Male; Obesity; Pregnancy; Rats; Rats, Sprague-Dawley; Satiation; Sodium Chloride | 2007 |
Leptin induces inflammation-related genes in RINm5F insulinoma cells.
Leptin acts not only on hypothalamic centers to control food intake but has additional functions in peripheral tissues, e.g. inhibition of insulin secretion from pancreatic islets. The leptin receptor (LEPRb) is a class I cytokine receptor that mediates activation of STAT transcription factors. In this study, we characterise the regulation of inflammation-related genes by leptin in insulinoma cells and compare the effect of transcriptional regulation by leptin with that of other cytokines.. We have used RINm5F insulinoma cells as a model system for a peripheral target cell of leptin. Six transcripts encoding inflammation-related proteins were found to be upregulated by activation of LEPRb, namely lipocalin-2, pancreatitis-associated protein, preprotachykinin-1, fibrinogen-beta, tissue-type plasminogen activator (tPA) and manganese-dependent superoxide dismutase (MnSOD). Four of these transcripts (fibrinogen-beta, lipocalin-2, tPA, MnSOD) were also induced by the proinflammatory cytokine interleukin-1beta (IL-1beta). Interferon-gamma alone had no effect on the leptin-induced transcripts but enhanced the upregulation by IL-1beta of lipocalin-2, tPA and MnSOD mRNA levels. Experiments with LEPRb point mutants revealed that the upregulation of the inflammation-related genes depended on the presence of tyrosine-1138 which mediates the activation of the transcription factors STAT1 and STAT3. Reporter gene assays showed that leptin induced the expression of preprotachykinin-1 and lipocalin-2 on the level of promoter regulation. Finally, leptin treatment increased caspase 3-like proteolytic activity in RINm5F cells.. The present data show that leptin induces a cytokine-like transcriptional response in RINm5F cells, consistent with the proposed function of leptin as a modulator of immune and inflammatory responses. Topics: Animals; Carrier Proteins; Caspases; Cell Line, Tumor; Cricetinae; Gene Expression Regulation, Neoplastic; Genes, Reporter; Inflammation; Insulinoma; Interferon-gamma; Interleukin-1beta; Leptin; Lipocalin-2; Lipocalins; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Pancreatitis-Associated Proteins; Point Mutation; Promoter Regions, Genetic; Protein Precursors; Rats; Receptors, Cell Surface; Receptors, Leptin; Signal Transduction; STAT1 Transcription Factor; STAT3 Transcription Factor; Tachykinins; Tyrosine | 2007 |
Molecular characterization of inflammatory genes in sentinel and nonsentinel nodes in melanoma.
Identification of regional node metastasis is important for accurate staging and optimal treatment of early melanoma. We hypothesize that the nodal profile of immunoregulatory cytokines can confirm the identity of the first tumor-draining regional node, i.e., the sentinel node (SN) and indicate its tumor status.. RNA was extracted from freshly dissected and preserved nodal tissue of 13 tumor-negative SNs, 10 tumor-positive SNs (micrometastases <2 mm), and 11 tumor-negative non-SNs (NSN). RNA was converted into cDNA and then amplified by PCR. Expression of 96 cytokines and chemokines was assessed using cDNA microarray and compared by using hierarchical clustering.. Fifty-seven genes were expressed at significantly (P < 0.05) different levels in SNs and NSNs (4 genes had higher expression, and 53 genes had lower expression in SNs). Expression levels of interleukin-13 (IL-13), leptin, lymphotoxin beta receptor (LTbR), and macrophage inflammatory protein 1b (MIP1b) were significantly higher (P < 0.04, P < 0.01, P < 0.05, and P < 0.01, respectively), and expression level of IL-11Ra was lower (P < 0.03) for tumor-positive as compared with tumor-negative SN. Receiver-operator characteristics curve analyses showed that the area under the curve (AUC) for IL-13, leptin, LTbR, MIP1b, and IL-11Ra was 0.79, 0.83, 0.75, 0.81, and 0.77, respectively. The AUC for the five genes in combination was 0.973, suggesting high concordance of gene-expression profiles with SN staging.. SNs have a different immunoregulatory cytokine profile than NSNs. The cytokine profile of tumor-positive SNs; increased expression of IL-13, leptin, LTbR, and MIP1b and decreased expression of IL-11Ra, may provide clues to the local tumor lymph node interaction seen in the earliest steps of melanoma metastasis. Topics: CD3 Complex; Cell Line, Tumor; Chemokines; Cytokines; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Interleukin-13; Leptin; Lymph Nodes; Melanoma; Neoplasm Metastasis; Receptors, Interleukin-11; Sentinel Lymph Node Biopsy; Skin Neoplasms | 2007 |
Serum adipokines are associated with cholesterol metabolism in the metabolic syndrome.
The purpose of this study was to investigate whether cholesterol metabolism is associated with serum adipokines and inflammatory markers.. In fifty-eight subjects with impaired fasting glucose or impaired glucose tolerance and features of the metabolic syndrome cholesterol metabolism was assayed with serum non-cholesterol sterol ratios to cholesterol, surrogate markers of synthesis (cholesterol precursors) and dietary absorption % of cholesterol (cholestanol and plant sterols) and related them to serum adiponectin, leptin, high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).. Adiponectin was negatively related to synthesis markers (e.g. desmosterol r=-0.371, P<0.01), and positively to absorption markers (e.g. cholestanol r=0.269, P<0.05). Leptin was associated with synthesis markers (e.g. desmosterol r=0.271, P<0.05) and negatively with absorption markers (e.g. sitosterol r=-0.278, P<0.05). Hs-CRP was negatively associated with absorption markers (e.g. sitosterol r=-0.407, P<0.001). IL-6 and TNF-alpha were not related to cholesterol metabolism. When dividing the subjects into tertiles by the serum desmosterol/cholestanol ratio, the I tertile (high synthesis/low absorption) was associated with low adiponectin concentrations, high BMI and serum leptin concentrations (P<0.05 for all).. Adiponectin, leptin and hs-CRP were associated with variables of cholesterol metabolism. A high ratio of cholesterol synthesis to absorption is characterized by high serum leptin and low adiponectin concentrations. Topics: Adipocytes; Adiponectin; Biomarkers; C-Reactive Protein; Cholesterol; Cytokines; Female; Humans; Inflammation; Leptin; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged | 2007 |
Adiposity dependent apelin gene expression: relationships with oxidative and inflammation markers.
It has been reported that apelin functions as an adipokine, which has been associated to obesity and insulin resistance. The objective of this study was to analyze the apelin mRNA expression in white adipose tissue (WAT) from high-fat (Cafeteria) fed rats, in order to examine potential relationships with obesity markers and other related risk factors. Animals fed on the high-fat diet during 56 days increased their body weight, total body fat and WAT depots weights when compared to controls. Apelin subcutaneous mRNA expression was higher in the Cafeteria than in the Control fed group and this increase was partially reversed by dietary vitamin C supplementation. Statistically significant associations between subcutaneous apelin gene expression and almost all the studied variables were identified, being of special interest the correlations found with serum leptin (r=0.517), liver malondialdehyde (MDA) levels (r=0.477), and leptin, IRS-3 and IL-1ra retroperitoneal mRNA expression (r=0.701; r=0.692 and r=0.561, respectively). These associations evidence a possible role for apelin in the excessive weight gain induced by high-fat feeding and increased adiposity, insulin-resistance, liver oxidative stress and inflammation. Topics: Adiposity; Animals; Apelin; Ascorbic Acid; Biomarkers; Carrier Proteins; Diet, Atherogenic; Inflammation; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Intra-Abdominal Fat; Leptin; Liver; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Wistar; Subcutaneous Fat | 2007 |
Leptin-mediated cytokine release and migration of eosinophils: implications for immunopathophysiology of allergic inflammation.
Leptin is a pleiotropic adipocyte-derived cytokine used in hypothalamic regulation of body weight and modulation of immune response by stimulating T cells, macrophages and neutrophils. Leptin has been shown to be an eosinophil survival factor. We examined the immunopathological mechanisms for the activation of human eosinophils from healthy volunteers by leptin in allergic inflammation. Adhesion molecules, cytokines and cell migration were assessed by flow cytometry, ELISA and Boyden chamber assay, respectively. Intracellular signaling molecules were investigated by membrane array and Western blot. Leptin could up-regulate cell surface expression of adhesion molecule ICAM-1 and CD18 but suppress ICAM-3 and L-selectin on eosinophils. Leptin could also stimulate the chemokinesis of eosinophils, and induce the release of inflammatory cytokines IL-1beta and IL-6, and chemokines IL-8, growth-related oncogene-alpha and MCP-1. We found that leptin-mediated induction of adhesion molecules, release of cytokines and chemokines, and chemokinesis were differentially regulated by the activation of ERK, p38 MAPK and NF-kappaB. In view of the above results and elevated production of leptin in patients with allergic diseases such as atopic asthma and atopic dermatitis, leptin could play crucial immunopathophysiological roles in allergic inflammation by activation of eosinophils via differential intracellular signaling cascades. Topics: Blotting, Western; Cell Adhesion Molecules; Chemotaxis, Leukocyte; Cytokines; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Eosinophils; Extracellular Signal-Regulated MAP Kinases; Flow Cytometry; Humans; Hypersensitivity; Inflammation; Leptin; NF-kappa B; p38 Mitogen-Activated Protein Kinases | 2007 |
Components of metabolic syndrome predicting diabetes: no role of inflammation or dyslipidemia.
The diagnostic criteria and the clinical usefulness of the metabolic syndrome (MetSy) are currently questioned. The objective was to describe the structure of MetSy and to evaluate its components for prediction of diabetes type 2 (T2DM).. This was a case-referent study nested within a population-based health survey. Among 33,336 participants, we identified 177 initially non-diabetic individuals who developed T2DM after 0.1 to 10.5 years (mean, 5.4 years), and, for each diabetes case, two referents matched for sex, age, and year of health survey. Baseline variables included oral glucose tolerance test, BMI, blood pressure, blood lipids, adipokines, inflammatory markers, insulin resistance, and beta-cell function. Exploratory and confirmative factor analyses were applied to hypothesize the structure of the MetSy. The prediction of T2DM by the different factors was evaluated by multivariate logistic regression analysis.. A hypothetical five-factor model of intercorrelated composite factors was generated. The inflammation, dyslipidemia, and blood pressure factors were predicitive only in univariate analysis. In multivariable analyses, two factors independently and significantly predicted T2DM: an obesity/insulin resistance factor and a glycemia factor. The composite factors did not improve the prediction of T2DM compared with single variables. Among the original variables, fasting glucose, proinsulin, BMI, and blood pressure values were predictive of T2DM.. Our data support the concept of a MetSy, and we propose five separate clusters of components. The inflammation and dyslipidemia factors were not independently associated with diabetes risk. In contrast, obesity and accompanying insulin resistance and beta-cell decompensation seem to be two core perturbations promoting and predicting progression to T2DM. Topics: Adult; Analysis of Variance; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Diabetes Mellitus; Dyslipidemias; Female; Health Surveys; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Middle Aged; Predictive Value of Tests; Proinsulin; Risk Factors; Sweden | 2007 |
Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice.
Chronic inflammation and reduced adiponectin are widely observed in the white adipose tissue in obesity. However, the cause of the changes remains to be identified. In this study, we provide experimental evidence that hypoxia occurs in adipose tissue in obese mice and that adipose hypoxia may contribute to the endocrine alterations. The adipose hypoxia was demonstrated by a reduction in the interstitial partial oxygen pressure (Po(2)), an increase in the hypoxia probe signal, and an elevation in expression of the hypoxia response genes in ob/ob mice. The adipose hypoxia was confirmed in dietary obese mice by expression of hypoxia response genes. In the adipose tissue, hypoxia was associated with an increased expression of inflammatory genes and decreased expression of adiponectin. In dietary obese mice, reduction in body weight by calorie restriction was associated with an improvement of oxygenation and a reduction in inflammation. In cell culture, inflammatory cytokines were induced by hypoxia in primary adipocytes and primary macrophages of lean mice. The transcription factor NF-kappaB and the TNF-alpha gene promoter were activated by hypoxia in 3T3-L1 adipocytes and NIH3T3 fibroblasts. In addition, adiponectin expression was reduced by hypoxia, and the reduction was observed in the gene promoter in adipocytes. These data suggest a potential role of hypoxia in the induction of chronic inflammation and inhibition of adiponectin in the adipose tissue in obesity. Topics: 3T3-L1 Cells; Adipocytes, White; Adiponectin; Adipose Tissue; Animals; Body Weight; Cell Hypoxia; Diet, Atherogenic; Down-Regulation; Inflammation; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; NIH 3T3 Cells; Obesity; Risk Factors | 2007 |
Obesity-induced inflammation in white adipose tissue is attenuated by loss of melanocortin-3 receptor signaling.
Metabolic syndrome, a complex of highly debilitating disorders that includes insulin resistance, hypertension, and dyslipidemia, is associated with the development of obesity in humans as well as rodent models. White adipose tissue (WAT) inflammation, caused in part by macrophage infiltration, and fat accumulation in the liver are both linked to development of the metabolic syndrome. Despite large increases in body fat, melanocortin 3-receptor (MC3-R)-deficient mice do not get fatty liver disease or severe insulin resistance. This is in contrast to obese melanocortin 4-receptor (MC4-R)-deficient mice and diet-induced obese (DIO) mice, which show increased adiposity, fatty liver disease, and insulin resistance. We hypothesized that defects in the inflammatory response to obesity may underlie the protection from metabolic syndrome seen in MC3-R null mice. MC4-R mice fed a chow diet show increased proinflammatory gene expression and macrophage infiltration in WAT, as do wild-type (WT) DIO mice. In contrast, MC3-R-deficient mice fed a normal chow diet show neither of these inflammatory changes, despite their elevated adiposity and a comparable degree of adipocyte hypertrophy to the MC4-R null and DIO mice. Furthermore, even when challenged with high-fat chow for 4 wk, a period of time shown to induce an inflammatory response in WAT of WT animals, MC3-R nulls showed an attenuated up-regulation in both monocyte chemoattractant protein-1 (MCP-1) and TNFalpha mRNA in WAT compared with WT high-fat-fed animals. Topics: Adipose Tissue, White; Adiposity; Animals; Chemokine CCL2; Dietary Fats; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Inflammation; Insulin Resistance; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Receptor, Melanocortin, Type 3; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Triglycerides; Tumor Necrosis Factor-alpha | 2007 |
Adipokines in diabetes and cardiovascular diseases.
Recent studies suggest that adipocyte-secreted factors called adipokines are involved in obesity-associated complications including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Among those, adiponectin is an antidiabetic and antiatherogenic protein, concentrations of which are decreased in obesity-associated metabolic and vascular disorders. In contrast, leptin, tumor necrosis factor a, interleukin-6, monocyte chemoattractant protein-1, and plasminogen activator inhibitor-1 are upregulated in obesity and contribute to the development of diabetes and vascular disease. In this review, the relevance of adipokines in obesity, insulin resistance, diabetes mellitus, atherosclerosis, and cardiovascular diseases is discussed. Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Atherosclerosis; Cardiovascular Diseases; Chemokine CCL2; Diabetes Mellitus; Humans; Inflammation; Interleukin-6; Leptin; Metabolic Syndrome; Mice; Obesity; Plasminogen Activator Inhibitor 1; Species Specificity; Tumor Necrosis Factor-alpha | 2007 |
Physiology. An integrative view of obesity.
Topics: Acyl Coenzyme A; Adipose Tissue; Animals; Diabetes Mellitus, Type 2; Endothelium, Vascular; Energy Intake; Energy Metabolism; Homeostasis; Humans; Hypothalamus; Inflammation; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Leptin; Nitric Oxide; Obesity; Oxidative Stress; Phosphatidylinositol 3-Kinases; Reactive Oxygen Species; Receptor, Insulin; Signal Transduction | 2007 |
Reduced expression of the KATP channel subunit, Kir6.2, is associated with decreased expression of neuropeptide Y and agouti-related protein in the hypothalami of Zucker diabetic fatty rats.
The link between obesity and diabetes is not fully understood but there is evidence to suggest that hypothalamic signalling pathways may be involved. The hypothalamic neuropeptides, pro-opiomelanocortin (POMC), neuropeptide Y (NPY) and agouti-related protein (AGRP) are central to the regulation of food intake and have been implicated in glucose homeostasis. Therefore, the expression of these genes was quantified in hypothalami from diabetic Zucker fatty (ZDF) rats and nondiabetic Zucker fatty (ZF) rats at 6, 8, 10 and 14 weeks of age. Although both strains are obese, only ZDF rats develop pancreatic degeneration and diabetes over this time period. In both ZF and ZDF rats, POMC gene expression was decreased in obese versus lean rats at all ages. By contrast, although there was the expected increase in both NPY and AGRP expression in obese 14-week-old ZF rats, the expression of NPY and AGRP was decreased in 6-week-old obese ZDF rats with hyperinsulinaemia and in 14-week-old rats with the additional hyperglycaemia. Therefore, candidate genes involved in glucose, and insulin signalling pathways were examined in obese ZDF rats over this age range. We found that expression of the ATP-sensitive potassium (K(ATP)) channel component, Kir6.2, was decreased in obese ZDF rats and was lower compared to ZF rats in each age group tested. Furthermore, immunofluorescence analysis showed that Kir6.2 protein expression was reduced in the dorsomedial and ventromedial hypothalamic nuclei of 6-week-old prediabetic ZDF rats compared to ZF rats. The Kir6.2 immunofluorescence colocalised with NPY throughout the hypothalamus. The differences in Kir6.2 expression in ZF and ZDF rats mimic those of NPY and AGRP, which could infer that the changes occur in the same neurones. Overall, these data suggest that chronic changes in hypothalamic Kir6.2 expression may be associated with the development of hyperinsulinaemia and hyperglycaemia in ZDF rats. Topics: Agouti-Related Protein; Animals; Diabetes Mellitus; Gene Expression; Glucose; Hyperglycemia; Hyperinsulinism; Hypothalamus; Immunohistochemistry; Inflammation; Insulin; Leptin; Male; Neuropeptide Y; Obesity; Pancreas; Potassium Channels, Inwardly Rectifying; Pro-Opiomelanocortin; Rats; Rats, Wistar; Rats, Zucker; Signal Transduction | 2007 |
Structural equation modeling of sleep apnea, inflammation, and metabolic dysfunction in children.
Obstructive sleep apnea (OSA), often concomitant with obesity, increases the risk for the metabolic syndrome. One mechanism that may participate in this association is upregulation of inflammatory pathways. We used structural equation modeling to assess the interrelations between childhood obesity, OSA, inflammation, and metabolic dysfunction. One hundred and eighty-four children (127 boys, mean age: 8.5 +/- 4.1 years) had height and weight measured, underwent overnight polysomnography and had fasting blood taken. The blood was analyzed for insulin, glucose, lipids, leptin, and cytokines [interferon (IFN)-gamma, granulocyte macrophage-colony stimulating factor, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha]. Structural equation modeling (SEM) was used to evaluate associations between the outcomes of interest including hypoxia, arousal (related to respiratory and spontaneous), obesity, metabolic dysfunction, and inflammatory markers. Two cytokine factors and one metabolic factor were derived for the SEM. These factors provided good fit in the structural equation model (chi(2)/df = 2.855; comparative fit index = 0.90, root mean squared error of approximation = 0.10) and all factor loadings were significantly different from zero (P < or = 0.01). Overall, our results indicate that while obesity (as measured by body mass index z-score) has a major influence on the metabolic dysfunction associated with OSA, arousal indices, and cytokine markers may also influence this association. Our results support the hypothesis that OSA is a contributor to the mechanisms that link sleep, systemic inflammation and insulin resistance, and show that the interrelations may begin in childhood. Topics: Adolescent; Arousal; Blood Glucose; Child; Child, Preschool; Cytokines; Female; Humans; Infant; Inflammation; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Models, Statistical; Obesity; Oxygen; Polysomnography; Signal Processing, Computer-Assisted; Sleep Apnea, Obstructive; Software | 2007 |
Role of adiponectin and inflammation in insulin resistance of Mc3r and Mc4r knockout mice.
To investigate the involvement of hypoadiponectinemia and inflammation in coupling obesity to insulin resistance in melanocortin-3 receptor and melanocortin-4 receptor knockout (KO) mice (Mc3/4rKO).. Sera and tissue were collected from 6-month-old Mc3rKO, Mc4rKO, and wild-type C57BL6J litter mates maintained on low-fat diet or exposed to high-fat diet (HFD) for 1 or 3 months. Inflammation was assessed by both real-time polymerase chain reaction analysis of macrophage-specific gene expression and immunohistochemistry.. Mc4rKO exhibited hypoadiponectinemia, exacerbated by HFD and obesity, previously reported in murine models of obesity. Mc4r deficiency was also associated with high levels of macrophage infiltration of adipose tissue, again exacerbated by HFD. In contrast, Mc3rKO exhibited normal serum adiponectin levels, irrespective of diet or obesity, and a delayed inflammatory response to HFD relative to Mc4rKO.. Our findings suggest that severe insulin resistance of Mc4rKO fed a HFD, as reported in other models of obesity such as leptin-deficient (Lep(ob)/Lep(ob)) and KK-A(y) mice, is linked to reduced serum adiponectin and high levels of inflammation in adipose tissue. Conversely, maintenance of normal serum adiponectin may be a factor in the relatively mild insulin-resistant phenotype of severely obese Mc3rKO. Mc3rKO are, thus, a unique mouse model where obesity is not associated with reduced serum adiponectin levels. A delay in macrophage infiltration of adipose tissue of Mc3rKO during exposure to HFD may also be a factor contributing to the mild insulin resistance in this model. Topics: Adipocytes; Adiponectin; Animals; Body Composition; Dietary Fats; Disease Models, Animal; Humans; Inflammation; Insulin Resistance; Leptin; Male; Mice; Mice, Knockout; Obesity; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4 | 2007 |
Peritoneal fluid leptin is associated with chronic pelvic pain but not infertility in endometriosis patients.
Leptin influences the proinflammatory immune responses and has angiogenic activity in vitro and in vivo. The objective of this study was to evaluate the peritoneal fluid levels of leptin in patients with endometriosis and idiopathic infertility and compare them with a control group of tubal ligation/reanastomosis patients.. In this observational, prospective controlled study, peritoneal fluid from 108 women was obtained while they underwent laparoscopy for pelvic pain, infertility, tubal ligation or sterilization reversal. We measured the concentration of leptin in the peritoneal fluid and compared the levels among women who were divided into groups according to their post-surgical diagnosis. Sixty patients were diagnosed with endometriosis, 10 with idiopathic infertility and 38 had undergone tubal ligation or reanastomosis (control group).. Peritoneal fluid leptin was significantly higher in endometriosis 14.62+/-9.79 (mean+/-SD) ng/ml compared to idiopathic infertility [0.92+/-1.57 ng/ml (P=0.0007)] and to controls [0.78+/-1.94 ng/ml (P<0.0001)]. Leptin levels were positively correlated with the stage of endometriosis (r=0.45; P=0.03), and with pelvic pain in endometriosis patients (r=0.49; P=0.001). Peritoneal fluid leptin levels in patients with idiopathic infertility were comparable to controls.. Higher levels of leptin were observed in peritoneal fluid of patients with endometriosis compared to those without the disease. These data suggest that the proinflammatory and neoangiogenic action of leptin may contribute to the pathogenesis of endometriosis. Moreover, leptin may play a role in endometriosis-associated pain. Topics: Ascitic Fluid; Biomarkers; Body Mass Index; Endometriosis; Female; Humans; Infertility, Female; Inflammation; Leptin; Pain; Pelvis; Sterilization Reversal; Sterilization, Tubal | 2006 |
Hyperhomocysteinemia correlates with insulin resistance and low-grade systemic inflammation in obese prepubertal children.
Obesity is an independent risk factor for the development of cardiovascular disease frequently associated with hypertension, dyslipemia, diabetes, and insulin resistance. Higher homocysteine (Hcy) levels are observed in the hyperinsulinemic obese adults and suggest that Hcy could play a role in the higher risk of cardiovascular disease in obesity. We analyzed total Hcy levels in obese prepubertal children and their possible association with both metabolic syndrome and various inflammatory biomarkers and leptin. We studied 43 obese children (aged 6-9 years) and an equal number of nonobese children, paired by age and sex. The obese subjects presented significantly elevated values for insulin (P = .003), C-reactive protein (P = .033), and leptin (P < .001). No significant differences were found in Hcy levels between the obese and nonobese children. However, Hcy concentration was significantly higher in the hyperinsulinemic obese children than in the normoinsulinemic group (P = .002). Using multivariant regression analysis, in the obese group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .001) and leptin (P partial = .02) are independent predictive factors for Hcy. In the control group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .005) and leptin (P partial = .031) also are independent predictive factor for Hcy. Increased plasma Hcy, particularly in hyperinsulinemic obese children, may be causally involved in the pathogenesis of atherosclerosis and/or cardiovascular disease, both of which are common in obesity. Topics: Anthropometry; Biomarkers; Body Weight; Case-Control Studies; Child; Female; Fluorescence Polarization Immunoassay; Homocysteine; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Puberty | 2006 |
Whole grains, bran, and germ in relation to homocysteine and markers of glycemic control, lipids, and inflammation 1.
Intake of whole grains is inversely associated with risk of diabetes and ischemic heart disease in observational studies. The lower risk associated with high whole-grain intakes may be mediated through improvements in glycemic control, lipid profiles, or reduced inflammation.. The aim was to examine whether the intake of whole grains, bran, and germ is related to homocysteine, plasma markers of glycemic control (fasting insulin, hemoglobin A1c, C-peptide, and leptin), lipids (total cholesterol, triacylglycerol, HDL cholesterol, and LDL cholesterol), and inflammation (C-reactive protein, fibrinogen, and interleukin 6).. This was a cross-sectional study of the relations of whole grains, bran, and germ intakes with homocysteine and markers of glycemic control, lipids, and inflammation in 938 healthy men and women.. Whole-grain intake was inversely associated with homocysteine and markers of glycemic control. Compared with participants in the bottom quintile of whole-grain intake, participants in the highest quintile had 17%, 14%, 14%, and 11% lower concentrations of homocysteine (P < 0.01), insulin (P = 0.12), C-peptide (P = 0.03), and leptin (P = 0.03), respectively. Inverse associations were also observed with total cholesterol (P = 0.02), HDL cholesterol (P = 0.05), and LDL cholesterol (P = 0.10). Whole-grain intake was not associated with the markers of inflammation. Whole-grain intake was most strongly inversely associated with markers of glycemic control in this population.. The results suggest a lower risk of diabetes and heart disease in persons who consume diets high in whole grains. Topics: Adult; Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Edible Grain; Female; Fibrinogen; Health Surveys; Heart Diseases; Homocysteine; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Lipid Metabolism; Male; Middle Aged; Risk Factors | 2006 |
Microarray profiling of human white adipose tissue after exogenous leptin injection.
Leptin is a secreted adipocyte hormone that plays a key role in the regulation of body weight homeostasis. The leptin effect on human white adipose tissue (WAT) is still debated.. The aim of this study was to assess whether the administration of polyethylene glycol-leptin (PEG-OB) in a single supraphysiological dose has transcriptional effects on genes of WAT and to identify its target genes and functional pathways in WAT.. Blood samples and WAT biopsies were obtained from 10 healthy nonobese men before treatment and 72 h after the PEG-OB injection, leading to an approximate 809-fold increase in circulating leptin. The WAT gene expression profile before and after the PEG-OB injection was compared using pangenomic microarrays. Functional gene annotations based on the gene ontology of the PEG-OB regulated genes were performed using both an 'in house' automated procedure and GenMAPP (Gene Microarray Pathway Profiler), designed for viewing and analyzing gene expression data in the context of biological pathways.. Statistical analysis of microarray data revealed that PEG-OB had a major down-regulated effect on WAT gene expression, as we obtained 1,822 and 100 down- and up-regulated genes, respectively. Microarray data were validated using reverse transcription quantitative PCR. Functional gene annotations of PEG-OB regulated genes revealed that the functional class related to immunity and inflammation was among the most mobilized PEG-OB pathway in WAT. These genes are mainly expressed in the cell of the stroma vascular fraction in comparison with adipocytes.. Our observations support the hypothesis that leptin could act on WAT, particularly on genes related to inflammation and immunity, which may suggest a novel leptin target pathway in human WAT. Topics: Adipocytes; Adipose Tissue; Adult; Cytokines; DNA, Circular; Gene Expression Regulation; Humans; Inflammation; Injections; Leptin; Male; Oligonucleotide Array Sequence Analysis; Polyethylene Glycols; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger | 2006 |
Relationship between increasing body weight, insulin resistance, inflammation, adipocytokine leptin, and coronary circulatory function.
We sought to evaluate effects of obesity, insulin resistance, and inflammation on coronary circulatory function and its relationship to leptin plasma levels.. It is not known whether obesity, commonly paralleled by insulin resistance, inflammation, and leptin, is independently associated with coronary circulatory dysfunction.. Myocardial blood flow (MBF) responses to cold pressor test (CPT) and pharmacologic vasodilation was measured with positron emission tomography and 13N-ammonia. Study participants were divided into three groups based on their body mass index (BMI, kg/m2): control, 20 < or = BMI <25 (n = 19); overweight, 25 < or = BMI <30 (n = 21); and obese, BMI >30 (n = 32).. Body mass index was significantly correlated to the Homeostasis Model Assessment Index of insulin resistance and C-reactive protein levels (r = 0.60 and r = 0.47, p < 0.0001). Compared with control subjects, endothelium-related change in MBF (DeltaMBF) to CPT progressively declined in overweight and obese groups (0.32 +/- 0.09 vs. 0.21 +/- 0.19 and 0.07 +/- 0.16 ml/g/min; p < 0.03 and p < 0.0001). The dipyridamole-induced total vasodilator capacity was significantly lower in obese than in control subjects (1.77 +/- 0.51 vs. 2.04 +/- 0.37 ml/g/min, p < 0.02). On multivariate analysis, BMI (p < 0.012) and age (p < 0.035) were significant independent predictors of DeltaMBF. Finally, only in the obese group leptin plasma levels significantly correlated with DeltaMBF (r = 0.37, p < 0.036).. Increased body weight is independently associated with abnormal coronary circulatory function that progresses from an impairment in endothelium-related coronary vasomotion in overweight individuals to an impairment of the total vasodilator capacity in obese individuals. The findings that elevated leptin plasma levels in patients that are obese might exert beneficial effects on the coronary endothelium to counterbalance the adverse effects of increases in body weight on coronary circulatory function should be tested. Topics: Adult; Coronary Circulation; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Obesity; Overweight | 2006 |
Increased T-helper interferon-gamma-secreting cells in obese children.
Leptin, an adipocyte-secreted hormone, has emerged as a potential candidate for the link between obesity and the proinflammatory state. Specifically, leptin modulates T-helper (Th) cells toward a Th1 phenotype, with the secretion of proinflammatory cytokines. The aim of this study was to evaluate the Th1/Th2 balance in obese children and its relation with hormonal and metabolic features.. In 50 obese children and 20 control children, we measured the CD4-positive Th cells that secrete interferon (IFN)-gamma or interleukin (IL)-2 (taken as an index of Th1 cells), and IL-4 (taken as an index of Th2 cells) as well as serum glucose, insulin, insulin resistance (IR) index (as homeostasis model assessment model (HOMA)), lipid profile, aminotransferases, leptin and ghrelin. Obese children also underwent dual energy X-ray absorptiometry scan measurements, and liver ultrasound scanning.. Geometric mean percentages of IL-2- and IL-4-CD4 secreting cells in obese children were not significantly different from those found in control children. However, the geometric mean percentage of CD4-positive T cells secreting IFN-gamma was significantly higher in the obese than in the control (P < 0.0001, t-test) group. Within the entire group of study children, the percentage of IFN-gamma-positive cells was positively associated with leptin (P = 0.002), insulin (P < 0.00 005), and HOMA-IR values (P < 0.00 005). However, when these associations were restricted to the group of obese subjects, insulin and HOMA-IR values, but not leptin, retained statistical significance. Yet, in the obese group, the percentage of IFN-gamma-positive cells was associated with nonalcoholic steatohepatitis (NASH) (P = 0.001), but not with body mass index-standard deviation score and total body fat mass.. In obese children, a shift to Th1-cytokine profile dominated by the production of IFN-gamma is related to insulin resistance as well as to NASH independently of anthropometric features and other metabolic characteristics. The prevalent Th1 pattern of secreted cytokines may be regarded as a mechanism contributing to inflammation in obesity. Topics: Biomarkers; Child; Female; Humans; Inflammation; Interferon-gamma; Interleukin-2; Interleukin-4; Leptin; Male; Obesity; Th1 Cells; Th2 Cells | 2006 |
Leptin and host defense against Gram-positive and Gram-negative pneumonia in mice.
Leptin is a pleiotrophic protein mainly produced by adipocytes that has been implicated as a link between nutritional status and immune function. Severe bacterial infection is associated with elevated plasma levels of leptin. To determine the role of leptin in the host response to bacterial pneumonia leptin deficient ob/ob mice and normal wild-type (WT) mice were intranasally infected with different doses of the Gram-positive pathogen Streptococcus (S.) pneumoniae or the Gram-negative bacterium Klebsiella (K.) pneumoniae. After infection with lower doses of either pathogen ob/ob mice displayed lower pulmonary levels of proinflammatory cytokines, in particular tumor necrosis factor-alpha and chemokines. However, after infection with a higher dose of S. pneumoniae or K. pneumoniae the lung concentrations of these inflammatory mediators did not differ between ob/ob and WT mice. In addition, the extent and severity of lung inflammation, as assessed by semi-quantitative histopathology scores, were similar in both mouse strains. Finally, leptin deficiency did not impact on the bacterial outgrowth in the lungs during either Gram-positive or Gram-negative pneumonia irrespective of the infective dose. These data suggest that although leptin may play a modest role in the regulation of inflammation during bacterial pneumonia, it does not contribute to host defense mechanisms that act to limit the outgrowth of S. pneumoniae or K. pneumoniae in the lower airways. Topics: Animals; Immunity; Inflammation; Klebsiella Infections; Klebsiella pneumoniae; Leptin; Male; Mice; Mice, Inbred C57BL; Pneumonia, Pneumococcal | 2006 |
Accelerated tumor formation in a fatless mouse with type 2 diabetes and inflammation.
Epidemiologic studies show a positive association between obesity and cancer risk. In addition to increased body adiposity and secretion of fat-derived hormones, obesity is also linked to insulin resistance, type 2 diabetes, and chronic inflammation. We used the fatless A-ZIP/F-1 transgenic mouse to dissociate the relative role of each of these underlying factors in the development of cancer. These mice are unique in that they do not have white fat but do develop type 2 diabetes. In two cancer models, the classic two-stage skin carcinogenesis protocol and the C3(1)/T-Ag transgenic mouse mammary tumor model, A-ZIP/F-1 mice displayed higher tumor incidence, tumor multiplicity, and decreased tumor latency than wild-type mice. We examined circulating levels of adipokines, growth factors, and cytokines. As expected, adipokines (i.e., leptin, adiponectin, and resistin) were undetectable or found at very low levels in the blood of fatless mice. However, insulin, insulin-like growth factor-I, growth hormone, vascular endothelial growth factor, and proinflammatory Th2 cytokines, such as interleukin (IL)-1beta, IL-4, and IL-6, were elevated in A-ZIP/F-1 mice. Additionally, we examined multiple phosphorylated proteins (i.e., protein kinase B/Akt and ErbB2/HER-2 kinase) associated with cancer development. Results show that many of these phosphorylated proteins were activated specifically in the A-ZIP/F-1 skin but not in the wild-type skin. These findings suggest that adipokines are not required for the promotion of tumor development and thus contradict the epidemiologic data linking obesity to carcinogenesis. We postulate that insulin resistance and inflammation are responsible for the positive correlation with cancer observed in A-ZIP/F-1 mice. Topics: Adiponectin; Adipose Tissue; Animals; Cytokines; Diabetes Mellitus, Type 2; Disease Susceptibility; Female; Inflammation; Insulin Resistance; Leptin; Mammary Neoplasms, Experimental; Mice; Mice, Transgenic; Obesity; Resistin; Skin Neoplasms; Transcription Factors | 2006 |
Effects of short-term supplementation with ascorbate, folate, and vitamins B6 and B12 on inflammatory factors and estrogen levels in obese postmenopausal women.
Little is known about the effects of commonly used vitamins on serum inflammatory markers and the hormonal balance in obese postmenopausal women. We studied the effects of an 8-week open-label supplementation with vitamins C (500 mg), B6 (25 mg), B12 (1 mg), and folate (5 mg) on C-reactive protein, interleukin-6, and estradiol levels in 20 obese (body mass index > or = 30) postmenopausal women. Outcomes were assessed in a blinded fashion. Folate and vitamin B12 levels rose significantly, suggesting that the supplement was well absorbed and that participants adhered to the protocol. Weight, blood pressure, and serum lipids remained stable. C-reactive protein, interleukin-6, and leptin levels remained unchanged. Estradiol levels rose from a median of 22.0 pg/mL (IQR = 15.9-25.8) at baseline to a median of 27.8 pg/mL (IQR = 23.1-33.9) at follow-up (p = 0.003). Increments in serum estradiol caused by vitamin supplementation in postmenopausal women have not been previously described and probably merit further investigation. Topics: Ascorbic Acid; C-Reactive Protein; Dietary Supplements; Estradiol; Folic Acid; Inflammation; Interleukin-6; Leptin; Obesity; Postmenopause; Vitamin B 12; Vitamin B 6; Vitamin B Complex | 2006 |
Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue.
Conjugated linoleic acids (CLAs) are conjugated dienoic isomers of linoleic acid. Many people supplement their diets with CLAs to attempt weight loss, and the trans-10,cis-12 isomer (t10,c12-CLA) of CLA reduces adiposity in animal models and humans. However, CLA treatment in mice causes insulin resistance that has been attributed to the lipoatrophic state, which is associated with hyperinsulinemia and hepatic steatosis. Here, we investigated the effect of t10,c12-CLA on adipose tissue inflammation, another factor promoting insulin resistance. We confirmed that t10,c12-CLA daily gavage performed in mice reduces white adipose tissue (WAT) mass and adiponectin and leptin serum levels and provokes hyperinsulinemia. In parallel, we demonstrated that this CLA isomer led to a rapid induction of inflammatory factors such as tumor necrosis factor-alpha and interleukin-6 gene expression in WAT without affecting their serum levels. In vitro, t10,c12-CLA directly induced IL-6 secretion in 3T3-L1 adipocytes by an nuclear factor-kappaB-dependent mechanism. In vivo, however, the lipoatrophic adipose tissue of CLA-treated mice was notable for a dramatic increase in macrophage infiltration and gene expression. Thus, CLA supplementation directly induces inflammatory gene expression in adipocytes and also promotes macrophage infiltration into adipose tissue to a local inflammatory state that contributes to insulin resistance. Topics: 3T3-L1 Cells; Adiponectin; Adipose Tissue, White; Animals; Dietary Supplements; Enzyme-Linked Immunosorbent Assay; Female; Hyperinsulinism; Immunohistochemistry; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Linoleic Acids, Conjugated; Macrophages; Mice; Mice, Inbred C57BL; NF-kappa B; PPAR gamma; Resistin; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha | 2006 |
Relationships of physical activity with metabolic syndrome features and low-grade inflammation in adolescents.
Physical activity has beneficial effects on symptoms of the metabolic syndrome and low-grade inflammation in adults. These associations have rarely been studied in adolescents. Moreover, it has not been established whether they depend on adiposity, fat localisation and adipokines.. We used cross-sectional data of 640 12-year-old adolescents participating in the Intervention Centred on Adolescents' Physical Activity and Sedentary Behaviour Study (ICAPS). Weight, height, body fat mass and WHR were measured. Metabolic syndrome components, two inflammatory markers (IL-6 and C-reactive protein), plasma leptin, adiponectin and soluble TNF-alpha receptor 1 (sTNF-alpha R1) were determined. Insulin resistance was estimated by homeostasis model assessment (HOMA) and energy expenditure due to organised leisure-time physical activity (PAE) assessed by questionnaire.. The metabolic syndrome was present in 5.8% of the adolescents. After adjustment for sex, sexual maturity and socio-economic status, a beneficial relationship between PAE and all metabolic syndrome features was found, but only the associations with HOMA and IL-6 were independent of body fat mass and WHR. Adjusted means from the lowest to the highest tertile of PAE were 1.99, 1.80 and 1.78 for HOMA (p=0.04), and 0.88, 0.69 and 0.70 pg/ml for IL-6 (p=0.02). PAE was inversely associated with leptin, independently of body fat mass and WHR (p<10(-2)), but not with adiponectin or sTNF-alpha R1. Further adjustment for adipokines did not change the relationships of PAE with HOMA and IL-6.. In adolescents, physical activity is inversely related to HOMA and IL-6, independently of adiposity and fat localisation. These relationships are not accounted for by adipokines. Topics: Adipocytes; Adiponectin; Adiposity; Body Weight; C-Reactive Protein; Child; Cross-Sectional Studies; Female; Humans; Inflammation; Interleukin-6; Least-Squares Analysis; Leptin; Male; Metabolic Syndrome; Motor Activity; Receptors, Tumor Necrosis Factor, Type I; Socioeconomic Factors; Surveys and Questionnaires | 2006 |
[Effect of intestinal ischemia/reperfusion injury on leptin and orexin-A levels].
To explore the effect of intestinal ischemia/reperfusion (I/R) injury on leptin and orexin-A levels in peripheral blood and central secretory tissues, and investigate the roles of leptin and orexin-A in acute inflammatory responses.. An intestinal I/R injury rat model was established, and the rats were grouped according to duration of the reperfusion time following a 60-min ischemia. Radioimmunoassay was used to examine the protein levels of leptin in the serum and adipose tissue, and the protein levels of orexin-A in the plasma and hypothalamus. Reverse transcriptase-polymerase chain reaction was also performed to detect the mRNA expressions of adipose leptin and hypothalamus orexin-A.. Compared with that before injury, serum leptin level of 60-min ischemia with 30-min reperfusion (I60'R30') group decreased significantly and that of I60'R360' increased significantly. Compared with the sham-operation group (sham) after injury, serum leptin level of I60'R360' group increased significantly, and adipose leptin protein levels of I60'R30' and I60'R90' groups decreased significantly, whereas that of I60'R360' group increased obviously. Compared with sham group after injury, adipose leptin mRNA expressions of I60'R30', I60'R240' and I60'R360' groups all increased significantly, while that of I60'R150' showed significant decrease. No significant changes were noted in the protein levels of orexin-A either in the plasma or hypothalamus after I/R injury. In comparison with sham group after injury, hypothalamus orexin-A mRNA expressions of I60'R30' and I60'R90' groups showed gradual but significant decrease, and till 150 min of reperfusion, the expression reached its lowest, followed then by slow recovery at 240 and 360 min, though still remaining significantly lower than that of sham group.. Leptin and orexin-A have a time-dependent response to intestinal I/R injury, but the former appears to exhibit a faster response, and they may play a certain role in the metabolic disorders of acute inflammation. Topics: Animals; Female; Inflammation; Intestine, Small; Intracellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptides; Orexins; Rabbits; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger | 2006 |
Insulinemia and leptinemia in geriatric patients: markers of the metabolic syndrome or of undernutrition?
The metabolic syndrome (MS) describes a cluster of metabolic disturbances including type 2 diabetes and/or insulin resistance, hypertension, dyslipidemia and obesity, which predict a high risk of cardiovascular disorders. The associated hyperinsulinemia and hyperleptinemia may contribute to the cardiovascular risk. However, the operational value of the MS in elderly patients is questionable. We therefore investigated the prevalence and significance of the MS in geriatric care. In a survey of 98 consecutive admissions of diabetic patients, <40% had a MS; this is a low value compared to younger diabetic adults, due to a low prevalence of obesity and dyslipidemia. We found a high prevalence of low BMI (<20 kg/m2), hypoalbuminemia and low total cholesterol levels, suggesting that the MS may be modified by undernutrition. The interplay between the MS and undernutrition was further studied in 30 non-diabetic patients. Both leptinemia and insulin resistance indexes (HOMA-IR and QUICKI) were strongly associated with BMI and body fat (measured by Bioelectrical impedance Analysis). BMI, leptinemia and insulin resistance indexes were associated with the Mini Nutritional Assessment (MNA) score. Thus, undernutrition is associated with low leptin and insulin levels and may obscure the association of these parameters with cardiovascular risk. In conclusion, the MS has a low prevalence in our population of elderly diabetic patients, and is of questionable prognostic value. It can be oveshadowed by undernutrition, which is associated with low body weight, leptinemia and insulin resistance indexes. Prevention of undernutrition and/or adjustment to its consequences should receive higher priority in the care of elderly diabetic patients. Topics: Aged; Biomarkers; Cardiovascular Diseases; Hospitals, Special; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Malnutrition; Metabolic Syndrome; Nutrition Assessment; Risk Factors | 2006 |
Leptin and incident type 2 diabetes: risk or protection?
The aim of this study was to investigate the association of leptin levels with incident diabetes in middle-aged adults, taking into account factors purportedly related to leptin resistance.. We conducted a case-cohort study (570 incident diabetes cases and 530 non-cases) representing the 9-year experience of 10,275 participants of the Atherosclerosis Risk in Communities Study. Plasma leptin was measured by direct sandwich ELISA.. In proportional hazards models adjusting for age, study centre, ethnicity and sex, high leptin levels (defined by sex-specific cut-off points) predicted an increased risk of diabetes, with a hazard ratio (HR) comparing the upper with the lower quartile of 3.9 (95% CI 2.6-5.6). However, after further adjusting additionally for obesity indices, fasting insulin, inflammation score, hypertension, triglycerides and adiponectin, high leptin predicted a lower diabetes risk (HR=0.40, 95% CI 0.23-0.67). Additional inclusion of fasting glucose attenuated this protective association (HR=0.59, 95% CI 0.32-1.08, p<0.03 for linear trend across quartiles). In similar models, protective associations were generally seen across subgroups of sex, race, nutritional status and smoking, though not among those with lower inflammation scores or impaired fasting glucose (interaction p=0.03 for both).. High leptin levels, probably reflecting leptin resistance, predict an increased risk of diabetes. Adjusting for factors purportedly related to leptin resistance unveils a protective association, independent of adiponectin and consistent with some of leptin's described protective effects against diabetes. Topics: Adiponectin; Black or African American; Blood Glucose; Body Mass Index; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Incidence; Inflammation; Insulin; Leptin; Linear Models; Male; Middle Aged; Obesity; Risk Factors; Smoking; Triglycerides; United States; White People | 2006 |
Inflammation, obesity and cardiovascular function in African and Caucasian women from South Africa: the POWIRS study.
The integrated relationship between inflammation, obesity and cardiovascular disease is currently a subject of much research interest. These specific relationships, however, have not been studied in-depth in South African population groups in order to determine the role of ethnicity. It is known that Africans, compared to Caucasians, suffer from a high prevalence of hypertension. It was therefore hypothesized that the levels of inflammatory markers (high-sensitivity C-reactive protein (hsCRP), fibrinogen and leptin) are higher in Africans compared to Caucasians and are notably associated with cardiovascular dysfunction in Africans. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index (BMI), were recruited. Leptin, hsCRP, fibrinogen and lipid levels, waist circumference (WC), BMI, systolic and diastolic blood pressure, cardiac output (CO), total peripheral resistance (TPR) and Windkessel compliance were measured. Results showed that the levels of leptin, hsCRP and fibrinogen were significantly higher (P<0.05) in the African women. The inflammatory markers correlated strongly with cardiovascular parameters, age and obesity (BMI, WC) in both groups, but after adjusting for age and obesity, none of the correlations were significant anymore. Multiple regression analyses (with leptin, hsCRP or fibrinogen as dependent variable) showed that only leptin levels of African women were explained by cardiovascular parameters (BP, TPR and CO). In conclusion, even though African women had significantly higher leptin, hsCRP, fibrinogen and blood pressure levels than Caucasian women, no cardiovascular parameters explained the variation in the inflammatory markers (except for leptin levels of African women). Topics: Adult; Analysis of Variance; Biomarkers; Black People; Blood Pressure; Body Mass Index; C-Reactive Protein; Cardiac Output; Cardiovascular Physiological Phenomena; Case-Control Studies; Cholesterol, HDL; Female; Fibrinogen; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Leptin; Middle Aged; Obesity; Regression Analysis; South Africa; Triglycerides; Vascular Resistance; Waist-Hip Ratio; White People | 2006 |
Similar effects of general and spinal anaesthesia on perioperative stress response in patients undergoing haemorrhoidectomy.
Surgery induces release of neuroendocrine hormones (cortisol), cytokines (interleukin-6: IL-6, tumour necrosis factor-alpha: TNF-alpha), acute phase proteins (C-reactive protein: CRP, leptin). We studied the effects of general and spinal anaesthesia on stress response to haemorrhoidectomy. Patients were assigned to general and spinal anaesthesia groups (n = 7). Blood samples were drawn before induction and 24 hours after surgery. Perioperative levels of IL-6, TNF-alpha, CRP, cortisol, and leptin were comparable among the groups. Twenty four hours after surgery, TNF-alpha and cortisol did not change; IL-6 and CRP increased significantly in all patients. Significant increase in leptin levels was found in patients undergoing spinal anaesthesia. Except for the increase in leptin levels, there was no significant difference related to the effects of general and spinal anaesthesia. Topics: Adult; Anesthesia, General; Anesthesia, Spinal; C-Reactive Protein; Female; Hemorrhoids; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Stress, Physiological; Time Factors; Tumor Necrosis Factor-alpha | 2006 |
Is leptin related to systemic inflammatory response in acute pancreatitis?
To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis.. Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-alpha, IL-6, -8 and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria.. Fifty-two (29 females) patients were studied. Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index (P = 0.04) and men showed higher body mass index (P = 0.05). No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis (P = 0.1). A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6. Correlations of leptin with another cytokines only showed a trend for IL-8 (P = 0.058).. High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity. Topics: Acute Disease; Adiposity; Adult; Body Mass Index; Disease Progression; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Pancreatitis; Prognosis; Severity of Illness Index; Sex Characteristics; Tumor Necrosis Factor-alpha | 2006 |
Effect of PEA on LPS inflammatory action in human adipocytes.
N-Palmitoylethanolamide (PEA) is an endogenous lipid secreted by human adipocytes that possesses numerous anti-inflammatory properties. Human adipose tissue can be subjected to modulation of its inflammatory state by lipopolysaccharide (LPS). Here we demonstrate that LPS increases the secretion of interleukin-6 (IL-6) by human mature adipocytes via activation of the NFkappaB pathway. This effect is not inhibited by PEA. Inversely, LPS strongly inhibits adipose cell leptin release, with PEA acting as a potentiator of this inhibitory effect. These actions are not linked to a reduction in leptin gene transcription. Thus, PEA does not have an anti-inflammatory role in the secretion of IL-6 via NFkappaB at the adipocyte level, but instead seems to act at the heart of the LPS-stimulated pathway, which, independently of NFkappaB, inhibits the secretion of leptin. Topics: Adipocytes; Adult; Amides; Cells, Cultured; Endocannabinoids; Ethanolamines; Humans; Inflammation; Interleukin-6; Leptin; Lipopolysaccharides; Middle Aged; NF-kappa B; Palmitic Acids | 2006 |
Early obesity and age-related mimicry of metabolic syndrome in female mice with sex hormonal imbalances.
To investigate the relationship of early obesity to metabolic syndrome during sex hormonal imbalances in mutant female mice at different ages.. Hormonal imbalances, accumulation and nature of adipose tissue, food intake, glucose tolerance, and expression of candidate genes and markers of inflammation were studied by comparing wild-type, null, and haploinsufficient follitropin receptor knockout female mice at different ages.. Follitropin receptor deletion in mice produced null females that are infertile and haploinsufficient mice that undergo accelerated biological aging. Both types of mutants with sex hormonal imbalances have central obesity without hyperphagia, but circulating leptin is elevated. Adipocyte hyperplasia and hypertrophy is attributed to elevated peroxisome proliferator-activated receptor gamma expression. Adiponectin protein levels increase in fat tissue and plasma. Only mutants but not controls acquire age-dependent decline in glucose tolerance with high insulin and altered pancreatic beta cells. Changes in inflammation markers, decreased muscle insulin receptor phosphorylation, and increase of the enzyme protein tyrosine phosphatase 1B indicate insulin resistance.. In this animal model, the chronological appearance of early obesity induced by hormonal imbalances culminates in characteristics that are attributable to metabolic syndrome, including cardiovascular abnormalities. Dissection of the depot-specific alterations and defining molecular interrelationships could help in developing targeted remedies and resolving complications and controversies related to health benefits and adversities of current hormone replacement therapy. Topics: Adiponectin; Adipose Tissue; Aging; Animals; Disease Models, Animal; Female; Follicle Stimulating Hormone; Gene Expression Regulation; Glucose Tolerance Test; Gonadal Steroid Hormones; Inflammation; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Mice; Mice, Knockout; Obesity; PPAR gamma; Receptors, FSH | 2006 |
Dietary intakes of fat and antioxidant vitamins are predictors of subclinical inflammation in overweight Swiss children.
In obese children, subclinical inflammation is often present and is correlated with the metabolic syndrome. Dietary factors, such as fatty acids and antioxidants, potentially modulate the association between adiposity and subclinical inflammation, but few data are available in children.. The aim of the study was to determine whether dietary fat or antioxidant intakes influence circulating tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), C-reactive protein (CRP), and leptin concentrations in overweight children.. In a cross-sectional study of 6-14-y-old normal-weight (n = 33), overweight (n = 19), and obese (n = 27) Swiss children, nutritional intakes were assessed from two 24-h dietary recalls and a 1-d dietary record. Percentage body fat from skinfold thicknesses, waist-hip ratio, and blood pressure were measured. Fasting blood samples were collected for the measurement of insulin, glucose, HDL-cholesterol, triacylglycerol, CRP, IL-6, TNF-alpha, and leptin concentrations.. CRP, IL-6, and leptin increased significantly (P < 0.02) with increasing adiposity, independent of age; TNF-alpha did not increase. Total dietary fat and the percentage of energy from fat were significant predictors of CRP concentration, independent of body mass index (P < 0.05). Meat intake was a significant predictor of IL-6 and leptin, independent of body mass index (P < 0.05). Intakes of antioxidant vitamins (vitamins E and C and beta-carotene) were significant predictors of leptin (P < 0.05) but not of CRP, IL-6, or TNF-alpha.. Overweight Swiss children as young as 6 y have elevated concentrations of inflammatory markers. Intakes of total fat and antioxidant vitamins are determinants of subclinical inflammation in this age group. Topics: Adolescent; Antioxidants; Ascorbic Acid; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Carotenoids; Child; Cholesterol, HDL; Dietary Fats; Female; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Male; Multivariate Analysis; Overweight; Predictive Value of Tests; Skinfold Thickness; Switzerland; Triglycerides; Tumor Necrosis Factor-alpha; Vitamin E; Vitamins; Waist-Hip Ratio | 2006 |
Leptin induces cyclooxygenase-2 via an interaction with interleukin-1beta in the rat brain.
In addition to its central effects on appetite regulation, leptin has been implicated in immune function and inflammation. Previous data suggested that leptin acts as an inflammatory signal within the brain, as exogenously administered leptin induced fever, a typical brain-regulated inflammatory response. The present study aimed to delineate the inflammatory actions and cellular targets of leptin in the brain by examining its effects on the expression of interleukin (IL)-1beta and cyclooxygenase (COX)-2, two important inflammatory components of the fever response. Intracerebroventricular injection of leptin (5 microg/rat) induced IL-1beta and COX-2 mRNA and protein in the hypothalamus between 1 and 3 h after treatment as determined by reverse transcription-polymerase chain reaction and immunohistochemistry. Coinjection of IL-1 receptor antagonist (100 microg/rat, intracerebroventricular) attenuated leptin-induced COX-2, whereas IL-1 receptor antagonist had no effect on endogenous IL-1beta levels, suggesting that leptin induces COX-2 via, at least partly, IL-1beta action. IL-1beta protein expression was induced in macrophages in the meningis and perivascular space after leptin treatment, whereas COX-2 induction was observed in endothelial cells, indicating the roles for these non-neuronal cells in mediating inflammatory actions of leptin. In addition, neutralization of endogenous circulating leptin with anti-leptin antiserum attenuated intraperitoneal lipopolysaccharide (100 microg/kg)-induced brain IL-1beta and COX-2 upregulation, suggesting that leptin indeed acts as an inflammatory signal to the brain during systemic inflammation. These findings are in contrast to the effects of leptin on appetite regulation where it is believed to act primarily on neurons, thus presenting a distinct anatomical basis for the inflammatory and appetite regulatory actions of leptin in the brain. Topics: Animals; Appetite; Brain; Cyclooxygenase 2; Endothelial Cells; Enzyme Induction; Hypothalamus; Immunohistochemistry; Inflammation; Injections, Intraventricular; Interleukin-1beta; Leptin; Lipopolysaccharides; Macrophages; Male; Mice; Neurons; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; STAT3 Transcription Factor | 2006 |
Percutaneous coronary intervention increases leptin and decreases adiponectin levels.
The study was designed to examine the effect of percutaneous coronary intervention (PCI) on adiponectin and leptin levels. We have previously demonstrated that PCI triggers a systemic inflammatory response. We hypothesized that inflammation participates in the pathogenesis of diabetes mellitus and the metabolic syndrome by modulating levels of adiponectin and leptin.. Prospective study in which inflammation was induced by PCI.. Forty-eight patients with stable coronary artery disease and without diabetes mellitus.. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), leptin and adiponectin were measured at baseline and 48 h after the procedure.. Following PCI, hs-CRP increased by 211%, IL-6 by 87% and leptin by 19%, while adiponectin decreased by 14% (P < 0.001 for all). The change in IL-6 correlated with that in hs-CRP (rho = 0.32; P = 0.027), as did the changes in IL-6 and leptin (rho = 0.31; P = 0.03). The change in adiponectin, however, did not correlate with the change in any of the other markers.. This study demonstrates that PCI affects the levels of adiponectin and leptin within 48 h. These effects may be secondary to the inflammatory response triggered by PCI. Topics: Adiponectin; Aged; Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Coronary Disease; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Postoperative Period; Prospective Studies; Statistics, Nonparametric | 2006 |
Sympathetic overactivity, endothelial dysfunction, inflammation, and metabolic abnormalities cluster in grade III (World Health Organization) obesity: reversal through sustained weight loss obtained with laparoscopic adjustable gastric banding.
Topics: Body Mass Index; Endothelium, Vascular; Gastroplasty; Humans; Inflammation; Laparoscopy; Leptin; Obesity; Regression Analysis; Sympathetic Nervous System; Weight Loss; World Health Organization | 2006 |
Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte.
Berberine (BBR), an isoquinoline alkaloid, has a wide range of pharmacological effects, yet its exact mechanism is unknown. In order to understand the anti-adipogenic effect of BBR, we studied the change of expression of several adipogenic enzymes of 3T3-L1 cells by BBR treatment. First, we measured the change of leptin and glycerol in the medium of 3T3-L1 cells treated with 1 micrometer, 5 micrometer and 10 micrometer concentrations of BBR. We also measured the changes of adipogenic and lipolytic factors of 3T3-L1. In 3T3-L1 cells, both leptin and adipogenic factors (SREBP-1c, C/EBP-alpha, PPAR-gamma, fatty acid synthase, acetyl-CoA carboxylase, acyl-CoA synthase and lipoprotein lipase) were reduced by BBR treatment. Glycerol secretion was increased, whereas expression of lipolytic enzymes (hormone-sensitive lipase and perilipin) mRNA was slightly decreased. Next, we measured the change of inflammation markers of 3T3-L1 cells by BBR treatment. This resulted in the down-regulation of mRNA level of inflammation markers such as TNF-alpha, IL-6, C- reactive protein and haptoglobin. Taken together, our data shows that BBR has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect seems to be due to the down-regulation of adipogenic enzymes and transcription factors. Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Berberine; Cytokines; Gene Expression Regulation; Glycerol; Inflammation; Inflammation Mediators; Leptin; Mice; RNA, Messenger | 2006 |
Serum leptin levels in children with acute viral hepatitis A.
In acute viral hepatitis A (AVH-A), involvement of the liver is through cytotoxic cells and cytokine levels are increased Immune response of the host determines the severity of the disease. Leptin stimulates cytokines, therefore, the authors hypothesized that the relationship between leptin and cellular immunity might cause different clinical presentations of the disease.. Twenty-eight children with AVH-A and 10 healthy children formed the basis of the study. Serum leptin, C-reactive protein (CRP) and alpha-1-antitrypsin (A1AT) levels were determined. There was significant positive correlation between body mass index (BMI) and leptin levels both in patients and controls (p = 0.003 and p = 0.001 respectively). No significant difference in serum leptin, CRP or A1AT levels between patients and controls was detected (p > 0.05). Presence of icterus or fulminant hepatic failure (FHF) did not affect serum leptin level (p > 0.05). Mean A1AT level was significantly higher in children with FHF (p < 0.05). On the 30th day of admission, mean BMI, weight and leptin levels increased (p < 0.01, p < 0.01 and p < 0.05 respectively) and mean A1AT level decreased (p < 0.01).. Leptin levels are not altered in children with AVH-A. In the convalescence period, leptin increased parallel to BMI. It is suggested that expected increment in leptin due to inflammation might be balanced with the decrease due to loss of appetite during acute illness or it might be entirely due to loss of production. Topics: Acute Disease; Adolescent; alpha 1-Antitrypsin; Body Mass Index; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Female; Hepatitis A; Humans; Infant; Inflammation; Leptin; Liver; Male | 2006 |
Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats.
Chronic arthritis induces hypermetabolism and cachexia. Ghrelin is a gastrointestinal hormone that has been proposed as a treatment to prevent cachexia. The aim of this work was to examine the effect of administration of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) to arthritic rats. Male Wistar rats were injected with Freund's adjuvant, and 15 days later arthritic and control rats were daily injected with GHRP-2 (100 microg/kg) or with saline for 8 days. Arthritis induced an increase in serum ghrelin (P < 0.01) and a decrease in serum concentrations of leptin (P < 0.01), whereas GHRP-2 administration increased serum concentrations of leptin. GHRP-2 increased food intake in control rats but not in arthritic rats. However, in arthritic rats GHRP-2 administration ameliorated the external symptoms of arthritis, as it decreased the arthritis score (10.4 +/- 0.8 vs. 13.42 +/- 0.47, P < 0.01) and the paw volume. In addition, circulating IL-6 and nitrites/nitrates were increased by arthritis, and GHRP-2 treatment decreased the serum IL-6 levels (P < 0.01). To elucidate whether GHRP-2 is able to modulate IL-6 release directly on immune cells, peritoneal macrophage cultures were incubated with GHRP-2 or ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor. Both GHRP-2 (10(-7) M) and ghrelin (10(-7) M) prevented endotoxin-induced IL-6 and decreased nitrite/nitrate release from peritoneal macrophages in vitro. These data suggest that GHRP-2 administration has an anti-inflammatory effect in arthritic rats that seems to be mediated by ghrelin receptors directly on immune cells. Topics: Adrenocorticotropic Hormone; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Blood; Body Weight; Corticosterone; Eating; Foot; Freund's Adjuvant; Ghrelin; Inflammation; Interleukin-6; Leptin; Lipopolysaccharides; Macrophages, Peritoneal; Male; Nitrates; Nitrites; Oligopeptides; Peptide Hormones; Rats; Rats, Wistar | 2005 |
Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro.
There is much evidence to indicate a role for adipocytokines in insulin resistance and/or type 2 diabetes mellitus. In experimental models, oral salicylates, through their ability to interfere with the nuclear factor-kappa B (NF-kappa B) transcription pathway, have been demonstrated to reverse insulin resistance. The aim of this study was to investigate whether NF-kappa B regulates the release of adipocytokines in human adipose tissue and skeletal muscle. Human sc adipose tissue and skeletal muscle (obtained from normal pregnant women) were incubated in the absence (control) or presence of two NF-kappa B inhibitors sulfasalazine (1.25, 2.5, and 5 mm) and BAY 11-7082 (25, 50, and 100 microm). After an 18-h incubation, the tissues were collected, and NF-kappa B p65 DNA-binding activity and I kappa B kinase (IKK-beta) and insulin receptor-beta protein expression were assessed by ELISA and Western blotting, respectively. The incubation medium was collected, and the release of TNF-alpha, IL-6, IL-8, resistin, adiponectin, and leptin was quantified by ELISA. Treatment of adipose tissue and skeletal muscle with sulfasalazine and BAY 11-7082 significantly inhibited the release of IL-6, IL-8, and TNF-alpha; NF-kappa B p65 DNA-binding activity; and IKK-beta protein expression (P < 0.05, by Newman-Keuls test). There was no effect of sulfasalazine and BAY 11-7082 on resistin, adiponectin, or leptin release. Both sulfasalazine and BAY 11-7082 increased the adipose tissue and skeletal muscle expression of insulin receptor-beta. The data presented in this study demonstrate that the IKK-beta/NF-kappa B transcription pathway is a key regulator of IL-6, IL-8, and TNF-alpha release from adipose tissue and skeletal muscle. Control of the IKK-beta/NF-kappa B pathway may therefore provide an alternative therapeutic strategy for regulating aberrant cytokine release and thereby alleviating insulin resistance in type 2 diabetes mellitus. Topics: Adiponectin; Adipose Tissue; Adult; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Cell Survival; Cytokines; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation; Hormones, Ectopic; Humans; I-kappa B Kinase; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-6; Interleukin-8; Leptin; Muscle, Skeletal; NF-kappa B; Nitriles; Pregnancy; Protein Binding; Protein Serine-Threonine Kinases; Receptor, Insulin; Resistin; Sulfasalazine; Sulfones; Time Factors; Tissue Distribution; Transcription, Genetic; Tumor Necrosis Factor-alpha | 2005 |
Leptin ameliorates burn-induced multiple organ damage and modulates postburn immune response in rats.
The present study was designed to determine whether exogenous leptin reduces remote organ injury in the rats with thermal burn trauma. Leptin (10 microg/kg) or saline was administered intraperitoneally after burn injury, and the rats were decapitated at either 6 or 24 h. Plasma samples of 24-h burn group were assayed for the determination of monocyte and neutrophil apoptosis. Thermal injury increased tissue-associated myeloperoxidase (MPO) activity and microscopic damage scores in the lung, liver, stomach, colon and kidney of both 6- and 24-h burn groups. In the 6-h burn group, leptin reduced microscopic damage score in the liver and kidney only, while damage scores in the 24-h burn group were reduced in all the tissues except the lung. Also, in both burn groups, leptin reduced elevated MPO activity in all tissues except the lung. The percentage of mononuclear cells was significantly reduced at the 24 h of burn injury, while the granulocyte percentage was increased. Leptin treatment, however, had no significant effect on burn-induced reversal of white blood cell ratios. On the other hand, burn-induced increase in the death of mononuclear cells and granulocytes was significantly reduced in leptin-treated rats. The results of the present study suggest that leptin may provide a therapeutic benefit in diminishing burn-induced inflammation and associated multiple organ failure. Topics: Animals; Apoptosis; Burns; Flow Cytometry; Granulocytes; Immune System; Inflammation; Kidney; Leptin; Leukocytes; Leukocytes, Mononuclear; Liver; Monocytes; Neutrophils; Peroxidase; Rats; Rats, Sprague-Dawley; Time Factors; Tissue Distribution | 2005 |
How obesity causes diabetes: not a tall tale.
The epidemic of obesity-associated diabetes is a major crisis in modern societies, in which food is plentiful and exercise is optional. The biological basis of this problem has been explored from evolutionary and mechanistic perspectives. Evolutionary theories, focusing on the potential survival advantages of "thrifty" genes that are now maladaptive, are of great interest but are inherently speculative and difficult to prove. Mechanistic studies have revealed numerous fat-derived molecules and a link to inflammation that, together, are hypothesized to underlie the obesity-diabetes connection and thereby represent prospective targets for therapeutic intervention. Topics: Adipocytes; Adipose Tissue; Animals; Biological Evolution; Cytokines; Diabetes Mellitus, Type 2; Epigenesis, Genetic; Fetal Nutrition Disorders; Glucose; Humans; Immunity, Innate; Inflammation; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Macrophages; Obesity; Phenotype; Proteins | 2005 |
Low-grade systemic inflammation, hypoadiponectinemia and a high concentration of leptin are present in very young obese children, and correlate with metabolic syndrome.
To determine the concentration levels of C-reactive protein (CRP), leptin and adiponectin in obese pre-pubertal children, and their possible relation with metabolic syndrome, fibrinogen and plasminogen activator inhibitor-1.. A study was carried out in 51 obese children (aged 6 to 9 years) and the same number of non-obese children (control group), matched by age and sex. (Cross-sectional study of obese children). Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined for each child. Serum CRP, leptin, adiponectin, glucose, insulin, lipid profile, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were all measured.. The levels of CRP serum (1.67+/-0.222 vs 0.92+/-0.16 mg/l) and leptin (15.56+/-1.27 vs 4.68+/-0.62 ng/ml) were significantly higher in obese children. The adiponectin level was significantly higher in non-obese children (11.58+/-0.63 vs 9.64+/-0.49 microg/dl). In the obese group, log. CRP showed a positive correlation with BMI, insulin, homeostasis model assessment (HOMA), triglycerides, alanine aminotransferase (ALT), uric acid, PAI-1, fibrinogen and interleukin 6 (IL-6), and correlated negatively with apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-C). The leptin was positively correlated with BMI, insulin, HOMA, triglycerides and PAI-1 and negatively with Apo A-I and HDL-C. Adiponectin correlated negatively with BMI, insulin, HOMA, and triglycerides.. Low-grade systemic inflammation, elevated leptin concentration and low adiponectin level are described in very young obese children, correlating with a range of variables of metabolic syndrome. Inflammation and adipocytokines can play an important role in the etiopathogeny of metabolic syndrome. Topics: Adiponectin; Blood Glucose; Blood Pressure; C-Reactive Protein; Child; Cross-Sectional Studies; Female; Fibrinogen; Homeostasis; Humans; Inflammation; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Lipids; Male; Metabolic Syndrome; Obesity; Plasminogen Activator Inhibitor 1 | 2005 |
White adipose tissue, inert no more!
Topics: Adiponectin; Adipose Tissue; Animals; Cytokines; Hepatitis; Humans; Immunity; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Lipodystrophy; Mice; Mice, Transgenic; Obesity; T-Lymphocytes; Tumor Necrosis Factor-alpha | 2005 |
Application of pregnancy-related proteins in prenatal and tumor diagnostics--a workshop report.
Topics: Biomarkers; Biomarkers, Tumor; Chorionic Gonadotropin; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Inflammation; Interleukin-10; Killer Cells, Natural; Leptin; Luteinizing Hormone; Neoplasms; Pre-Eclampsia; Pregnancy; Pregnancy Proteins | 2005 |
Wound inflammation in diabetic ob/ob mice: functional coupling of prostaglandin biosynthesis to cyclooxygenase-1 activity in diabetes-impaired wound healing.
This study focused on the regulation of prostaglandin (PG) production in diabetes-impaired wound tissue. Cyclooxygenase (COX)-1 and -2 expression and activity were severely dysregulated in chronic wounds of diabetic ob/ob mice. Those wounds were characterized by a reduced expression of COX-1 and the presence of strongly elevated levels of COX-2 when compared with conditions observed in healthy animals. Resolution of the diabetic and impaired wound-healing phenotype by systemic administration of leptin into ob/ob mice increased COX-1 expression in wound margin keratinocytes and decreased COX-2 expression in inner wound areas to levels found in wild-type animals. Notably, improved wound healing was characterized by a marked increase in PGE2/PGD2 biosynthesis that colocalized with induced COX-1 in new tissue at the margin of the wound. COX-2 expression did not significantly contribute to PGE2/PGD2 production in impaired wound tissue. Accordingly, only late wound tissue from SC-560-treated (selective COX-1 inhibitor) but not celecoxib-treated (selective COX-2 inhibitor) ob/ob mice exhibited a severe loss in PGE2, PGD2, and prostacyclin at the wound site, and this change was associated with reduced keratinocyte numbers in the neo-epithelia. These data constitute strong evidence that a dysregulation of COX-1-coupled prostaglandin contributes to diabetes-impaired wound healing. Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Diabetes Mellitus, Type 2; Dinoprostone; Disease Models, Animal; Inflammation; Leptin; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Recombinant Proteins; Wound Healing; Wounds and Injuries | 2005 |
Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase
Beyond their effects on central metabolic functions, leptin, resistin, and adiponectin have profound effects on a number of other physiologic processes, including immune function and inflammation. Although leptin, resistin, and adiponectin are produced in human placenta and adipose tissue, their immunoregulatory actions in these tissues are not known. Therefore, the aim of this study was to determine the effect of leptin, resistin, and adiponectin on the release of proinflammatory mediators in human placenta and sc adipose tissue. Samples were obtained from normal pregnancies at the time of cesarean section. Tissue explants (n = 5) were incubated in the absence (basal control) or presence of a leptin (1, 10, and 100 ng/ml), resistin (1, 10, and 100 ng/ml), and adiponectin (0.1 and 0.5 microg/ml). After 6 h incubation, the medium was collected, and the release of IL-1beta, IL-6, TNFalpha, prostaglandin (PG)F2alpha and PGE2 was quantified by ELISA. There was no effect of resistin on proinflammatory cytokine or prostaglandin release; however, leptin at 100 ng/ml and adiponectin at 0.1 and/or 0.5 microg/ml significantly increased the release of IL-1beta, IL-6, TNFalpha, and PGE2 from human placenta and adipose tissue. Although both leptin and adiponectin significantly increased PGF2alpha release from human placenta, there was no effect of these hormones on PGF2alpha release from adipose tissue. Furthermore, this leptin- and adiponectin-induced proinflammatory response could be abrogated by treatment with the antiinflammatory ERK1/2 MAPK inhibitor U0126, the peroxisomal proliferator-activated receptor-gamma ligand troglitazone, and the nuclear factor-kappaB inhibitor BAY 11-7082. Collectively, these data indicate that leptin and adiponectin activate proinflammatory cytokine release and phospholipid metabolism in human placenta and adipose tissue, and antiinflammatory agents can abrogate leptin- and adiponectin-induced inflammation. Topics: Adiponectin; Adipose Tissue; Cell Survival; Cytokines; Female; Hormones, Ectopic; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Leptin; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Organ Culture Techniques; Placenta; PPAR gamma; Pregnancy; Prostaglandins; Resistin | 2005 |
Lipopolysaccharide-induced leptin synthesis and release are differentially controlled by alpha-melanocyte-stimulating hormone.
Since alpha-melanocyte-stimulating hormone (alpha-MSH) inhibits the synthesis and release of proinflammatory cytokines and stimulates the synthesis and release of anti-inflammatory cytokines, and leptin is a cytokine that has anti-inflammatory actions in the presence of lipopolysaccharide (LPS), we hypothesized that alpha-MSH increases leptin synthesis and release.. alpha-MSH or 0.9% NaCl (saline) were injected intraperitoneally 15 min prior to intravenous injection of 0.5 ml of saline or LPS (0.15 mg/kg). Thereafter, repeated blood samples were withdrawn over a period of 6 h and plasma leptin concentrations determined. The rats were sacrificed at 6 h and leptin mRNA was measured in epididymal fat pads.. Plasma leptin concentrations of the saline-injected control group were unaltered during the 6 h, whereas in the LPS group, leptin was unaltered between 0 and 30 min and thereafter progressively increased between 30 and 360 min by 2.5-fold. alpha-MSH slightly increased plasma leptin concentrations by 15 min and then increased them further by 120 min, after which they declined towards baseline. The pattern of plasma leptin concentrations in the alpha-MSH + LPS group was similar to that of the LPS group, except that higher concentrations were observed at 120 min in the rats injected with alpha-MSH + LPS. LPS increased leptin mRNA by 3-fold at 6 h, whereas it was unaffected in the MSH-treated animals. On the contrary, alpha-MSH completely blocked the LPS-induced leptin mRNA.. Our results suggest that alpha-MSH increased leptin release without altering its synthesis, but when LPS increased release and synthesis of leptin, alpha-MSH, although further increasing release, blocked the enhanced synthesis of leptin elicited by LPS. Topics: Adipose Tissue; alpha-MSH; Animals; Bacterial Infections; Down-Regulation; Epididymis; Immunity, Innate; Inflammation; Leptin; Lipopolysaccharides; Male; Rats; Rats, Sprague-Dawley; RNA, Messenger; Up-Regulation | 2005 |
Leptin therapy does not affect inflammatory markers.
Topics: Biomarkers; C-Reactive Protein; Female; Humans; Inflammation; Leptin; Male | 2005 |
Fat apoptosis through targeted activation of caspase 8: a new mouse model of inducible and reversible lipoatrophy.
We describe the generation and characterization of the first inducible 'fatless' model system, the FAT-ATTAC mouse (fat apoptosis through targeted activation of caspase 8). This transgenic mouse develops identically to wild-type littermates. Apoptosis of adipocytes can be induced at any developmental stage by administration of a FK1012 analog leading to the dimerization of a membrane-bound, adipocyte-specific caspase 8-FKBP fusion protein. Within 2 weeks of dimerizer administration, FAT-ATTAC mice show near-knockout levels of circulating adipokines and markedly reduced levels of adipose tissue. FAT-ATTAC mice are glucose intolerant, have diminished basal and endotoxin-stimulated systemic inflammation, are less responsive to glucose-stimulated insulin secretion and show increased food intake independent of the effects of leptin. Most importantly, we show that functional adipocytes can be recovered upon cessation of treatment, allowing the study of adipogenesis in vivo, as well as a detailed examination of the importance of the adipocyte in the regulation of multiple physiological functions and pathological states. Topics: Adipocytes; Adipose Tissue; Animals; Apoptosis; Caspase 8; Caspases; Dimerization; Eating; Enzyme Activation; Glucose Intolerance; Inflammation; Insulin; Insulin Secretion; Leptin; Lipodystrophy; Lipopolysaccharides; Mice; Mice, Transgenic; Recombinant Fusion Proteins; Tacrolimus; Tacrolimus Binding Proteins | 2005 |
Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes.
Aldosterone is a mineralocorticoid hormone that regulates blood pressure and salt/water balance. Increased aldosterone levels are found in states of disturbed energy balance such as the metabolic syndrome. Adipose tissue has been recognized to play a pivotal role in the regulation of energy homeostasis. We investigated direct aldosterone effects on brown adipocyte function. Aldosterone dose-dependently inhibited expression of uncoupling protein-1 (UCP-1) by 30% (p < 0.01). Furthermore, aldosterone dose-dependently impaired insulin-induced glucose uptake by about 25% (p < 0.01). On a transcriptional level, mRNA of the proinflammatory adipokines leptin and monocyte chemoattractant protein-1 (MCP-1) was increased by 5,000% and 40%, respectively, by aldosterone exposure (p < 0.05). This study demonstrates that aldosterone directly impacts on major adipose functions including stimulation of proinflammatory adipokines. Topics: Adipocytes; Adipose Tissue, Brown; Aldosterone; Animals; Blotting, Western; Carrier Proteins; Chemokine CCL2; Dose-Response Relationship, Drug; Energy Metabolism; Gene Expression; Glucose; Inflammation; Insect Hormones; Insulin Resistance; Ion Channels; Leptin; Membrane Proteins; Mice; Mitochondrial Proteins; Oligopeptides; Pyrrolidonecarboxylic Acid; RNA, Messenger; Thermogenesis; Uncoupling Protein 1 | 2005 |
Differential expression of immune system-related components in midtrimester amniotic fluid from singleton and twin pregnancies.
We investigated differences between singleton and twin gestations in immune mediators in midtrimester amniotic fluid.. Amniotic fluid from 252 singleton and 46 twin gestations were tested by enzyme-linked immunosorbent assay for interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, tumor necrosis factor-alpha, nitric oxide, Clara cell protein 16, leptin, and the 70-kDa heat shock protein. A subset of amniotic fluid was also tested for leukemia inhibitory factor, angiogenin, and migration inhibitory factor-related protein 8 and migration inhibitory factor-related protein 14. Data were analyzed by the Mann-Whitney U test and Spearman rank correlation.. Median concentrations of interleukin-1beta, tumor necrosis factor-alpha, interleukin-4, Clara cell protein 16, leptin, and angiogenin were increased in amniotic fluid from twins; median levels of the 70-kDa heat shock protein, leukemia inhibitory factor, migration inhibitory factor-related protein 8, and migration inhibitory factor-related protein 14 were highest in amniotic fluid from singletons (P < .001).. Elevated levels of immune activators may contribute to the increased rate of preterm premature rupture of membranes and spontaneous preterm birth in twin populations. Topics: Adult; Amniotic Fluid; Female; Fetal Membranes, Premature Rupture; HSP70 Heat-Shock Proteins; Humans; Inflammation; Interleukin-1; Interleukins; Leptin; Macrophage Migration-Inhibitory Factors; Phospholipases A; Pregnancy; Pregnancy Trimester, Second; Pregnancy, Multiple; Twins; Uteroglobin | 2005 |
Body fat mass and serum leptin levels influence epoetin sensitivity in patients with ESRD.
Dose requirements of epoetin vary considerably among patients with end-stage renal disease (ESRD), whereas determinants of epoetin sensitivity are poorly understood. Fat mass is an important source of adipokines, including interleukin 6 (IL-6), which is associated with decreased epoetin sensitivity. Furthermore, the adipokine leptin stimulates human erythroid development in vitro. In the present study, we investigate the impact of fat mass and leptin level on epoetin sensitivity in patients with ESRD.. One hundred sixty-six patients with ESRD (107 men; 64%) with a mean age of 56.9 +/- 0.9 years were studied in a post hoc cross-sectional analysis. Body composition was analyzed by dual-energy X-ray absorptiometry and correlated with serum markers of inflammation and leptin (analyzed by enzyme-linked immunosorbent assays), as well as with epoetin dose, in international units administered per week (IU/wk). To correct for differences in body mass and hemoglobin (Hb) levels, epoetin sensitivity was approximated as epoetin/Hb ratio, ie, epoetin dose per unit of Hb (IU/wk/g/dL) and epoetin/Hb/kg ratio, ie, epoetin dose per unit of Hb and kilogram of patient body weight (IU/wk/Hb/kg).. Patients were divided into 3 groups according to epoetin/Hb/kg ratio (no-epoetin group, low-epoetin group, and high-epoetin group). The 3 groups had significantly different serum levels of high-sensitivity C-reactive protein (hsCRP; median, 8.6 versus 3.1 and 8.0 mg/L, respectively; P < 0.05), neopterin (median, 112.4 versus 94.3 and 96.1 ng/L, respectively; P < 0.05), and IL-6 (median, 6.8 versus 4.1 and 6.5 ng/mL, respectively; P < 0.05). Significant between-group differences also were found in fat mass and leptin levels (median, 14.8 versus 10.5 and 7.9 ng/mL, respectively; P = 0.02). In univariate analyses, significant relationships between epoetin sensitivity indices, leptin levels, and levels of the inflammatory markers hsCRP and IL-6 were found. In a multivariate stepwise regression model, log ferritin, parathyroid hormone, log leptin, log IL-6, and polycystic kidney disease were significantly associated with the epoetin/Hb ratio.. The present study shows that leptin level may be a predictor of epoetin sensitivity. The effect could be either direct stimulation of erythropoiesis or indirect stimulation by associated adipokines. Although truncal fat is associated with secretion of proinflammatory cytokines, this secretion appears not to have inhibitory effects on epoetin sensitivity in the presence of high leptin levels. Topics: Adipose Tissue; Anemia; Body Composition; C-Reactive Protein; Cross-Sectional Studies; Darbepoetin alfa; Drug Resistance; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Organ Size; Polycystic Kidney Diseases; Renal Dialysis; Sweden | 2005 |
Resistin in preterm and term newborns: relation to anthropometry, leptin, and insulin.
This study aimed to investigate 1) the plasma resistin concentration at birth, 2) the relationship of resistin with leptin and insulin, and 3) the association of resistin with anthropometric indexes in newborn infants. Blood samples for hormonal assay were obtained from preterm and term newborns within the first 2 h of life and before milk feeding or energy intake. Although these infants required blood sampling for clinical reasons, all were proved to be noninfected. Plasma resistin was significantly higher in term than in preterm infants. It was also significantly correlated with serum leptin, and both hormones were significantly associated with gestational age and anthropometric indexes. Infants who were born vaginally were found to have significantly higher plasma resistin levels compared with those who were born by cesarean section. In the multivariate forward stepwise regression models, resistin was found to be significantly associated with the mode of delivery and gestational age or birth weight. The association among resistin, leptin, and anthropometric indexes suggested that both hormones might be gestation related. A high circulating resistin level at term gestation could be advantageous to the infant by promoting hepatic glucose production and preventing hypoglycemia after birth. Infants who were born vaginally had significantly higher plasma resistin levels, suggesting that this hormone might also be associated with stress or inflammation induced by the birth process. Topics: Anthropometry; Blood Glucose; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Hormones; Humans; Hypoglycemia; Infant, Newborn; Infant, Premature; Inflammation; Insulin; Leptin; Male; Multivariate Analysis; Premature Birth; Regression Analysis; Resistin; Sex Factors; Time Factors | 2005 |
The anti-inflammatory effect of leptin on experimental colitis: involvement of endogenous glucocorticoids.
The present study was designed to compare the effect of leptin on acute colonic inflammation with that of acute stress exposure, which acts via the hypothalamic-pituitary-adrenal (HPA) axis. Sprague-Dawley rats of both sexes were administered intrarectally with acetic acid. Either leptin (10 microg/kg; i.p.) or saline was injected immediately before and 6 h after the induction of colitis. A group of rats was exposed to water avoidance stress (WAS) for 30 min at the 6th h of colitis induction. RU-486 (2 mg/kg; i.p.), a glucocorticoid receptor antagonist, was injected intraperitoneally, at 12 and 1 h before the initial leptin injection, and at 1 h before the second leptin injection or exposure to WAS. Rats were decapitated at 24 h and the distal 8 cm of the colon were removed for macroscopic and microscopic scoring, determination of tissue wet weight index (WI) and tissue myeloperoxidase activity (MPO). Acetic acid-induced colitis significantly increased macroscopic and microscopic damage scores, WI and MPO, compared to control group. Exposure to acute WAS or treatment with leptin reduced the elevations in damage scores, WI and MPO induced by colitis, but no additive inhibitory effect was observed when WAS and leptin were applied together. RU-486 treatment reversed the inhibitory effects of leptin or WAS on colonic inflammation. Our results demonstrate that exogenous leptin mimics the effects of HPA axis activation on colitis-induced inflammatory process. The results also suggest that the anti-inflammatory effect of leptin involves a tissue neutrophil-dependent mechanism and is dependent on the release of glucocorticoids. Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Colitis; Colon; Dehydration; Female; Glucocorticoids; Inflammation; Leptin; Male; Peroxidase; Rats; Rats, Sprague-Dawley | 2004 |
The relationship between leptin concentrations, the systemic inflammatory response and illness severity in surgical patients admitted to ITU.
The relationship between circulation leptin concentrations, mediators of the systemic inflammatory response and illness severity in critically ill patients remains unclear. The aim of the present study was to examine these relationships in critically ill surgical patients admitted to the intensive therapy unit (ITU).. Patients (n = 38) who had undergone surgery and subsequently admitted to ITU were prospectively entered into a cross-sectional study. Circulating concentrations of leptin, cortisol, growth hormone, interleukin-6, C-reactive protein and albumin were measured. Sex and age matched controls (n = 14) were also studied.. On day 1, the critically ill group had lower BMI and leptin concentrations and a pronounced systemic inflammatory response compared with controls. There was a weak positive correlation between leptin concentrations and BMI in the critically ill patients (r = 0.42, P<0.10). In contrast, leptin was inversely correlated with C-reactive protein (r = -0.59, P<0.05) but not with cortisol, growth hormone, interleukin-6, APACHE II or predicted mortality. Leptin concentrations did not alter with the day of admission to ITU.. On ITU admission, leptin concentrations appeared to be low for BMI, related to the magnitude of the systemic inflammatory response but did not appear to be regulated by proposed mediators in critically ill surgical patients. Topics: Adult; Aged; Body Mass Index; Critical Illness; Female; Humans; Inflammation; Intensive Care Units; Leptin; Male; Middle Aged; Postoperative Care; Respiration, Artificial; Severity of Illness Index | 2004 |
Anti-inflammatory and growth-stimulating effects precede nutritional restitution during enteral feeding in Crohn disease.
Exclusive enteral feeding reduces inflammation and improves well being, nutrition and growth in children with active Crohn disease. Whether improved growth and increases in growth-related proteins are a consequence of improved nutrition or a reduced inflammation is not known. This study was undertaken to test the hypothesis that changes in growth-related proteins are related to decreased inflammation, rather than improvement in nutritional status.. Twelve children with active Crohn disease treated for 6-weeks with exclusive enteral feeding were studied at days 0, 3, 7, 14, 21, 28, and 56. The Paediatric Crohn's Disease Activity Index (PCDAI), weight, triceps skinfold thickness, and midupper arm circumference were recorded. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), insulin-like growth factor (IGF-I), IGF-binding protein (IGFBP-3), and leptin were measured at each visit. Wilcoxon matched-pairs signed-rank test was used to compare day 0 with follow-up data.. Significant improvements (P < 0.05) occurred by day 3 in inflammatory parameters (ESR, IL-6) and by day 7 in PCDAI, CRP, and IGF-I. These changes preceded any significant changes in nutritional parameters (weight-for-age Z score and midupper arm circumference day 14, triceps skinfold thickness day 21).. Early increases in IGF-I during treatment of Crohn disease are attributable to the anti-inflammatory effect of the enteral feed rather than nutritional restitution. Topics: Adolescent; Anthropometry; Biomarkers; Blood Sedimentation; C-Reactive Protein; Child; Crohn Disease; Enteral Nutrition; Female; Humans; Inflammation; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Male; Nutritional Status; Statistics, Nonparametric; Time Factors; Treatment Outcome | 2004 |
Independent association between plasma leptin and C-reactive protein in healthy humans.
C-reactive protein (CRP) is synthesized from the liver and is regulated by cytokines, especially interleukin-6. Leptin, the adipocyte-derived protein product of the ob gene, is related to amount of body fat. The long form of the leptin receptor resembles cytokine receptors, which include the interleukin-6 receptor. Both leptin and CRP may be increased in women, in obesity, and in inflammation, and both have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk. We tested the hypothesis that leptin is associated with CRP levels independently of the influences of gender, body mass index (BMI), waist-to-hip ratio, and other variables.. We studied 100 healthy volunteers (48 men, and 52 women). For all subjects, leptin was independently associated with CRP after adjustment for age, gender, BMI, waist-to-hip ratio, smoking, and alcohol consumption (F=12.39, P=0.0007). There was a strong and significant positive relationship between leptin and CRP in both women (R=0.61, P<0.0001) and men (R=0.55, P<0.0001) considered separately. The association between leptin and CRP was significant even after adjustment for age, BMI, waist-to-hip ratio, smoking, and alcohol consumption in women (F=7.13, P=0.01) and men (F=5.69, P=0.02). When only subjects with BMI <25 kg/m2 were considered (n=47), CRP was not linked to BMI (R=0.02, P=0.96), but a significant association between leptin and CRP was still evident (R=0.55, P<0.0001).. Leptin and CRP levels are independently associated in normal humans, providing further evidence linking metabolic and inflammatory cardiovascular disease mechanisms. Topics: Adult; Alcohol Drinking; Body Constitution; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Leptin; Male; Reference Values; Smoking | 2004 |
Delayed resolution of acute inflammation during zymosan-induced arthritis in leptin-deficient mice.
The severity of antigen-induced arthritis (AIA) is decreased in leptin-deficient ob/ob mice. However, joint inflammation in AIA depends on the immune response, which is impaired in ob/ob mice. In the present study we investigated the effects of leptin deficiency on zymosan-induced arthritis (ZIA), which is independent of adaptive immunity. Arthritis was induced by injection of zymosan into the knee joint. Joint swelling was similar after 6 and 24 hours in ob/ob and control mice. However, it remained elevated in ob/ob animals on day 3 whereas values normalized in controls. Histology revealed similar articular lesions in all animals on day 3, but on days 14 and 21 arthritis tended to be more severe in ob/ob mice. The acute phase response, reflected by circulating levels of IL-6 and serum amyloid A, was also more pronounced in ob/ob mice, although corticosterone was significantly elevated in these animals. Similar results were obtained in leptin receptor-deficient db/db mice. Thus, in contrast to AIA, ZIA is not impaired in leptin-deficient animals. On the contrary, resolution of acute inflammation appears to be delayed in the absence of leptin or leptin signalling, suggesting that chronic leptin deficiency interferes with adequate control of the inflammatory response in ZIA. Topics: Acute Disease; Acute-Phase Reaction; Animals; Arthritis, Experimental; Corticosterone; Cytokines; Edema; Inflammation; Knee Joint; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger; Severity of Illness Index; Zymosan | 2004 |
Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction.
Severe obesity increases the prevalence of the metabolic syndrome, and moderate acute weight loss with a very low-calorie diet in obese subjects with the metabolic syndrome leads to significant metabolic benefits. Adiponectin has been implicated in both the pathogenesis of obesity-related insulin resistance and increased inflammation. We analyzed the relationship of the adipocyte-derived hormone adiponectin with indices of inflammation, adiposity, and insulin resistance in obese subjects with (MS+, n = 40) and without (MS-, n = 40) the metabolic syndrome and examined the acute effects of rapid weight loss. MS+ subjects had significantly lower adiponectin (7.6 +/- 0.6 vs. 10.4 +/- 0.6 microg/ml; P = 0.003) and significantly higher TNF-alpha (3.3 +/- 0.2 vs. 2.8 +/- 0.3 pg/ml; P = 0.004) levels compared with MS- subjects matched for age and body mass index. Plasma adiponectin and TNF-alpha levels were inversely related to the number of metabolic syndrome factors in a stepwise manner. After 4-6 wk of weight loss, there was marked improvement in glucose, insulin, leptin, and triglycerides, whereas adiponectin and TNF-alpha concentrations did not change. Thus, increases in plasma levels of adiponectin or reductions in TNF-alpha are not required for marked improvements in glucose/insulin and lipid metabolism with acute weight loss. Topics: Adiponectin; Blood Glucose; Diet, Reducing; Energy Intake; Female; Humans; Inflammation; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Proteins; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss | 2004 |
Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women.
We assessed the relationships between four circulating acute phase proteins and the circulating and adipose tissue levels of three adipocytokines.. In all, 15 nondiabetic obese women with a body mass index (BMI) above 32 kg/m(2) were investigated.. Circulating concentrations of C-reactive protein (CRP), alpha 1 acid glycoprotein (AAG), fibrinogen, alpha 1 antitrypsin and both circulating and adipose tissue levels of interleukin (IL)-6, tumor necrosis factor (TNF)alpha and leptin were measured by either nephelometry or enzyme-linked immunosorbent assay.. We found a strong positive correlation between both circulating and adipose tissue levels of IL-6, TNFalpha and leptin and serum CRP levels. All these adipose tissue adipocytokines were also positively correlated with serum AAG levels. These correlations disappeared when adjusted for fat mass, suggesting that the relationship observed was dependent on fat amount.. Our results indicate a strong relationship between adipocytokines and inflammatory markers, and suggest that cytokines secreted by adipose tissue in obese subjects could play a role in increased inflammatory proteins secretion by the liver. Topics: Acute-Phase Proteins; Adipose Tissue; alpha 1-Antitrypsin; Biomarkers; C-Reactive Protein; Female; Fibrinogen; Humans; Inflammation; Interleukin-6; Leptin; Middle Aged; Obesity; Orosomucoid; Plasminogen Activator Inhibitor 1; Regression Analysis; Tumor Necrosis Factor-alpha | 2004 |
Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.
Ghrelin, a recently described endogenous ligand for the growth hormone secretagogue receptor (GHS-R), is produced by stomach cells and is a potent circulating orexigen, controlling energy expenditure, adiposity, and growth hormone secretion. However, the functional role of ghrelin in regulation of immune responses remains undefined. Here we report that GHS-R and ghrelin are expressed in human T lymphocytes and monocytes, where ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha. Ghrelin led to a dose-dependent inhibition of leptin-induced cytokine expression, while leptin upregulated GHS-R expression on human T lymphocytes. These data suggest the existence of a reciprocal regulatory network by which ghrelin and leptin control immune cell activation and inflammation. Moreover, ghrelin also exerts potent anti-inflammatory effects and attenuates endotoxin-induced anorexia in a murine endotoxemia model. We believe this to be the first report demonstrating that ghrelin functions as a key signal, coupling the metabolic axis to the immune system, and supporting the potential use of ghrelin and GHS-R agonists in the management of disease-associated cachexia. Topics: Cytokines; Dose-Response Relationship, Drug; Gene Expression Regulation; Ghrelin; Human Growth Hormone; Humans; Inflammation; Leptin; Lymphocyte Activation; Monocytes; Peptide Hormones; Receptors, G-Protein-Coupled; Receptors, Ghrelin; Receptors, Leptin; RNA, Messenger; T-Lymphocytes | 2004 |
Low grade inflammation in juvenile obesity and type 1 diabetes associated with early signs of atherosclerosis.
Subclinical inflammation has been implicated in the initiation and/or progression of atherosclerosis. Diabetes mellitus and obesity are risk factors for atherosclerosis, and asymptomatic low grade inflammation occurs prior to overt vascular lesions in these patients. In contrast to adults, little information exists concerning low grade inflammation in young type 1 diabetes and juvenile obesity.. To investigate low grade inflammation and immune activation in juvenile diabetes mellitus and obesity.. hs-CRP, soluble interleukin-2 receptor (sIL-2R), C-peptide, insulin, cortisol, vitamin B12, folic acid, leptin, and homocysteine were determined in 148 patients with juvenile type 1 diabetes, 86 obese children and 142 normal weighted age-matched healthy controls. Intima-media thickness (IMT) and lumen diameter of both common carotid arteries (CCA) was measured by ultrasonography in 52 healthy pediatric controls, 10 diabetics, and 34 obese juveniles.. Serum hs-CRP was significantly elevated in patients with type 1 diabetes (p < 0.0001), and obese children (p < 0.0001) as compared to the control group. The obese juveniles (p < 0.0001) and the diabetics (p < 0.0001) showed significantly increased values for IMT of CAAs. Levels of homocysteine, sIL-2R, insulin, cortisol, vitamin B12, and folic acid did not differ from the controls. The elevation of hs-CRP was more pronounced in obesity as compared to type 1 diabetes (p < 0.0001), and the hs-CRP values correlated significantly with body mass index standard deviation score (BMI-SDS) values. Furthermore, the IMT and the luminal diameter of CCAs showed significant correlations with BMI-SDS values.. A low grade inflammation as determined by serum hs-CRP is significantly increased in children with type 1 diabetes, and even more pronounced in apparently healthy juveniles with obesity. The increased IMT of CCAs strongly argues for an association between this low grade inflammation and early atherosclerotic vessel injury. Topics: Adolescent; Arteriosclerosis; Body Mass Index; C-Peptide; C-Reactive Protein; Carotid Artery, Common; Child; Diabetes Mellitus, Type 1; Female; Folic Acid; Homocysteine; Humans; Inflammation; Leptin; Male; Obesity; Receptors, Interleukin-2; Tunica Intima; Vitamin B 12 | 2004 |
Opposites detract.
Topics: Cytokines; Ghrelin; Humans; Inflammation; Leptin; Peptide Hormones; T-Lymphocytes | 2004 |
Resistin levels in patients with obstructive sleep apnoea syndrome--the link to subclinical inflammation?
The role of resistin, a "new" white adipose tissue hormone, still needs to be established. Its linkage to insulin sensitivity and body mass was controversial in previous studies.. Twenty obese patients (BMI: 32.1+/-6.9 kg/m2 ) with obstructive sleep apnoea syndrome (OSAS) (Apnoea-Hypopnoea Index: 48.6+/-19.1, underwent measurements of resistin, interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1), CRP and the insulin sensitivity index (ISI) by hyperinsulinaemic euglycaemic clamp before, 2 days and 2 months after onset of CPAP treatment.. Resistin remained unchanged during CPAP-therapy and was negatively correlated to ISI (r=-0.359; p=0.006), the latter was significantly improved by CPAP (p<0.001). In a correlation matrix, IL-6 and ICAM-1 were significantly (p=0.001) correlated to resistin (p=0.614 and 0.427). Changes of inflammatory markers under CPAP treatment were related to AHI, as well as resistin changes.. In agreement with previous investigations, we could only demonstrate a weak linkage between ISI and resistin. However, at least in obese patients with OSAS, there is a close relation to subclinical inflammation (IL-6) and endothelial activation (ICAM-1). Topics: Body Mass Index; C-Reactive Protein; Continuous Positive Airway Pressure; Hormones, Ectopic; Humans; Inflammation; Insulin Resistance; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Middle Aged; Obesity; Patient Compliance; Polysomnography; Resistin; Sleep Apnea, Obstructive; Statistics as Topic | 2004 |
Leptin, C-reactive protein, and nitric oxide production in healthy humans.
Topics: C-Reactive Protein; Cardiovascular Diseases; Electron Spin Resonance Spectroscopy; Female; Humans; Inflammation; Leptin; Male; Membrane Fluidity; Metabolic Syndrome; Nitric Oxide; Obesity; Reference Values | 2004 |
Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3T3-L1 cells and C57BL/6J and ob/ob mice.
Inflammation plays a major role in the development of chronic diseases such as cardiovascular disease and Type 2 diabetes. Further, it was demonstrated that obese animals and humans have significantly higher levels of circulating proinflammatory cytokines, such as interleukin-6 (IL-6). The aim of this study was to determine whether adipose tissue could be a major source of circulating IL-6 in leptin-deficient obese (ob/ob) mice by comparing the expression of IL-6 in different tissues of ob/ob mice. Our secondary goal was to determine whether preadipocytes are the source of adipose tissue IL-6. The ob/ob mice had higher levels of plasma IL-6 (P < 0.05) and adipose tissue IL-6 mRNA (P < 0.05) compared with lean mice. Interestingly, IL-6 mRNA levels of liver and spleen were not different between ob/ob and lean mice, whereas adipose tissue IL-6 mRNA levels were higher in the ob/ob mice compared with lean mice (P < 0.05). In addition, we showed that IL-6 secretion from the adipose tissue stromal vascular fraction cells was higher than that from fully differentiated adipocytes (P < 0.001). We further demonstrated that 3T3-L1 preadipocytes had significantly higher levels of lipopolysaccharide (LPS)-stimulated IL-6 mRNA and IL-6 secretion than differentiated 3T3-L1 adipocytes. Taken together, these data suggest that adipose tissue and preadipocytes from the adipose tissue stromal vascular fraction may contribute significantly to the increased plasma IL-6 levels in ob/ob mice. Topics: 3T3-L1 Cells; Adipocytes; Animals; Blood Glucose; Inflammation; Insulin; Interleukin-6; Leptin; Lipopolysaccharides; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity | 2004 |
Treatment with interleukin-11 affects plasma leptin levels in inflamed and non-inflamed rabbits.
Treatment with the anti-inflammatory cytokine, interleukin-11 (IL-11), in rabbits with TNBS-colitis reduces tissue damage but does not normalize body weight loss despite an increase in plasma levels of motilin, known to stimulate food intake. We investigated whether IL-11 could increase plasma levels of the anorectic peptide, leptin in non-inflamed and inflamed rabbits. In addition, the effect of IL-11 and leptin on motilin mRNA expression in the T84 cell line was tested. Five days post-inflammation, weight loss amounted 10.7+/-1.2%, but plasma leptin and motilin levels were unaffected. During IL-11 treatment, weight loss remained and plasma leptin levels dose-dependently increased with 27+/-5% (4 microg/kg day) and 108+/-7% (720 microg/kg day). Motilin levels increased in parallel with 23+/-12% or 256+/-97%. In non-inflamed animals, a prompt decrease in weight (-11.9+/-1%) was observed after treatment with the highest dose of IL-11 and this was associated with an increase in plasma leptin (70+/-18%) and motilin levels (113+/-7%). Both IL-11 and leptin stimulated motilin mRNA expression in T84 cells with a different time profile. In conclusion, the increase in plasma leptin levels during IL-11 treatment induces wasting in normal rabbits and may be one of the major factors involved in the maintenance of body weight loss in rabbits with colitis. Increase of motilin expression by leptin may be part of a feedback mechanism. Topics: Animals; Cell Line; Colitis; Gene Expression Regulation; Inflammation; Interleukin-11; Leptin; Motilin; Rabbits; RNA, Messenger; Weight Loss | 2004 |
Weight-loss-associated induction of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice.
Weight loss in obese insulin-resistant but not in insulin-sensitive persons reduces coronary heart disease risk. To what extent changes in gene expression are related to atherosclerosis and cardiovascular function is unknown.. We studied the effect of diet restriction-induced weight loss on gene expression in the adipose tissue, the heart, and the aortic arch and on atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia, and insulin resistance are associated with hypertension, impaired left ventricular function, and accelerated atherosclerosis in those mice. Compared with lean mice, peroxisome proliferator-activated receptors (PPAR)-alpha and PPAR-gamma expression was downregulated in obese double-knockout mice. Diet restriction caused a 45% weight loss, an upregulation of PPAR-alpha and PPAR-gamma, and a change in the expression of genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress, and inflammation, most of which are under the transcriptional control of these PPARs. Changes in gene expression were associated with increased insulin sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. PPAR-alpha and PPAR-gamma expression was inversely related to plaque volume and to oxidized LDL content in the plaques.. Induction of PPAR-alpha and PPAR-gamma in adipose tissue, heart, and aortic arch is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight loss. Improved lipid metabolism and insulin signaling is associated with decreased tissue deposition of oxidized LDL that increases cardiovascular risk in persons with the metabolic syndrome. Topics: Adipose Tissue; Animals; Aorta, Thoracic; Arteriosclerosis; Autoantibodies; Circadian Rhythm; Echocardiography; Gene Expression Regulation; Genotype; Glucose; Heart Function Tests; Hypertriglyceridemia; Inflammation; Insulin Resistance; Leptin; Lipoproteins, LDL; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Myocardium; Obesity; Oxidative Stress; PPAR alpha; PPAR gamma; Receptors, LDL; Transcription, Genetic; Up-Regulation; Weight Loss | 2004 |
Is there any link between insulin resistance and inflammation in established preeclampsia?
Both insulin resistance and inflammation may contribute to the onset of preeclampsia. They also could be interrelated. We studied the relationship between inflammatory cytokines and markers of insulin resistance. During their third trimester, 22 proteinuric preeclamptic women and 16 normotensive controls underwent intravenous glucose tolerance test (minimal model). Preeclamptic women were more insulin-resistant (P = .009), and they had higher levels of serum soluble tumor necrosis alpha receptor II (TNFalpha RII) (P = .002), triglycerides (P = .006), uric acid (P = .001), and leptin (P = .002) than did the controls. However, the study groups did not differ in serum TNFalpha, C-reactive protein (CRP), interleukin-6 (IL-6), sex hormone-binding globulin (SHBG), and high-density lipoprotein-2 (HDL(2))-cholesterol. In multiple regression analysis only SHBG (P = .01) and triglycerides (P = .0036) were associated with insulin sensitivity independently of body mass index (BMI), weight gain, HDL(2)-cholesterol, CRP, TNFalpha, and TNFalpha RII, IL-6, and leptin. We conclude that insulin resistance and the inflammatory markers studied were not associated in established preeclampsia. Topics: Biomarkers; Case-Control Studies; Female; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Leptin; Pre-Eclampsia; Pregnancy; Receptors, Tumor Necrosis Factor; Regression Analysis; Risk Factors; Sex Hormone-Binding Globulin; Triglycerides; Uric Acid | 2004 |
The relationship between inflammatory markers, leptin and adiponectin in chronic hemodialysis patients.
Chronic inflammation is prevalent in dialysis patients. We investigated the relationship between inflammation and newly identified adipokines: leptin and adiponectin in this population. A total of 129 chronic hemodialysis patients were collected. Serum high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), leptin and adiponectin levels were determined as well as other metabolic variables. Correlation studies and multiple regression analysis were performed among variables. Our results showed that hemodialysis patients had elevated levels of inflammatory markers, leptin and adiponectin. Diabetic subjects had higher serum CRP and lower albumin levels than non-diabetics. Serum CRP levels were positively correlated with IL-6 levels and negatively correlated with albumin levels. Serum leptin levels were directly related to CRP levels while adiponectin levels were inversely related to CRP levels. A significant negative correlation was observed between serum leptin and adiponectin levels. Serum IL-6 levels were the single independent factor affecting CRP levels. Body mass index can predict both serum leptin and adiponectin levels. We conclude that hemodialysis patients are at an increased risk of chronic inflammation and diabetes patients are even more susceptible to this status. Both serum leptin and adiponectin levels are associated with inflammatory markers. As adipose tissue is the major secreting site of these adipokines, our results suggest that adipose tissue plays an important role in the pathogenesis of chronic inflammation in dialysis patients. Topics: Adiponectin; Age Factors; Biomarkers; Body Mass Index; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Middle Aged; Regression Analysis; Renal Dialysis; Renal Insufficiency; Serum Albumin; Sex Factors | 2004 |
Leptin fluctuates in intestinal ischemia-reperfusion injury as inflammatory cytokine.
As leptin is an active mediator mainly secreted by adipose tissue and is closely related with energy metabolism, we evaluate both the changes of leptin levels in serum and adipose tissue with a concise radioimmunoassay and the changes of leptin mRNA expression in adipose tissue with RT-PCR, during the severe metabolic impediment in rat intestinal ischemia-reperfusion (I/R) injury. Results show that not only leptin levels in serum and adipose tissue but also its mRNA expression in adipose tissue undergo a fluctuation according to different injury times. Therefore, we conclude that leptin has a time-dependent response to acute inflammatory stimuli and acts as an anti-inflammatory cytokine. Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Base Sequence; Cytokines; Inflammation; Intestines; Leptin; Male; Rabbits; Radioimmunoassay; Rats; Reperfusion Injury; RNA, Messenger; Sensitivity and Specificity | 2004 |
Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression.
To explore the links between tumor necrosis factor alpha (TNFalpha) and leptin adipose tissue expression and low-grade systemic inflammation and to determine the relationship between inflammation and the degree of adiposity, the presence of type 2 diabetes, and other cardiovascular risk factors.. Ninety-one women (BMI 19 to 65 kg/m(2)) were divided into tertiles of CRP. Insulin resistance was calculated using the HOMA method. Albumin, fibrinogen, C-reactive protein (CRP), interleukin-6, sTNFR1, sTNFR2, and leptin levels were measured in serum and plasma samples. TNFalpha and leptin expression were measured by reverse transcription-polymerase chain reaction in abdominal subcutaneous adipose tissue samples.. CRP was positively related to BMI and upper distribution of adiposity. TNFalpha and leptin adipose tissue expression were higher in the upper tertile of CRP. Also, peripheral levels of both soluble TNFRs and leptin were higher in patients with the greatest inflammation degree. Diabetes, dislipidemia, and hypertension were most prevalent in patients in the upper CRP tertile. Inflammatory markers of diabetic women were significantly different from those of nondiabetic women, even after adjusting for differences in body fat. BMI, type 2 diabetes, and adipose TNFalpha mRNA levels were significant predictors of serum CRP levels (r(2) = 0.28, p < 0.001).. These results are in agreement with the hypothesis that the synthesis of adipose tissue TNFalpha and leptin could induce the production of interleukin-6, CRP, and other acute-phase reactants, thus contributing to the maintenance of chronic low-grade inflammation state involved in the progression of obesity and its associated comorbidities. Topics: Adipose Tissue; Adult; Antigens, CD; Body Composition; Body Mass Index; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Gene Expression; Humans; Hyperlipidemias; Hypertension; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Leukocyte Count; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; RNA, Messenger; Tumor Necrosis Factor-alpha | 2003 |
Leptin and wound inflammation in diabetic ob/ob mice: differential regulation of neutrophil and macrophage influx and a potential role for the scab as a sink for inflammatory cells and mediators.
In this study, we investigated the role of leptin for the inflammatory response in diabetes-impaired skin repair. We demonstrated, that systemic treatment of diabetic ob/ob mice with leptin blunted polymorphonuclear neutrophil (PMN), but not macrophage influx into the wound site. Closed wounds of leptin-administered mice were characterized by tremendous numbers of macrophage within the granulation tissue. In line, leptin supplementation potently attenuated epithelium-derived CXC- but not CC-chemokine expression. PMNs were preferentially located in the scab, but macrophages predominantly resided within the wound stroma of the animals. The scabs of nonhealing wounds were most likely to serve as sinks for bioactive inflammatory mediators, which were still capable to drive gene expression in keratinocytes in vitro. Differential effects of leptin on PMN and macrophage axes of inflammation must be indirect, as topical administration of leptin onto wounds of ob/ob mice did not reduce PMN influx into the wounded areas. Moreover, caloric-restricted, pair-fed ob/ob mice were characterized by impaired healing conditions that were associated with persisting PMNs. Interestingly, we documented the absence of leptin receptor expression in human diabetic foot ulcers. Thus, we show that leptin might function as a regulatory link between the endocrine and the immune system in the context of skin repair. Topics: Administration, Topical; Animals; Blood Glucose; Chemokines; Diabetes Mellitus; Diabetes Mellitus, Type 2; Disease Models, Animal; Female; Gene Expression Regulation; Inflammation; Leptin; Macrophages; Mice; Mice, Inbred C57BL; Mice, Obese; Neutrophils; Obesity; Recombinant Proteins; RNA, Messenger; Transcription, Genetic; Wound Healing | 2003 |
Deteriorating fuel metabolism, inflammation and coronary disease: are we closer to an all-encompassing theory?
Topics: Animals; C-Reactive Protein; Coronary Disease; Diabetes Mellitus; Glucose Intolerance; Humans; Hypertension; Inflammation; Leptin; Lipoproteins, HDL; Matrix Metalloproteinase 9; Metabolic Syndrome; Mice; Mice, Knockout; Obesity; Oxidative Stress; Phosphatidylcholine-Sterol O-Acyltransferase; Receptors, LDL; Risk Factors; Smoking | 2003 |
Leptin increase is associated with markers of the hemostatic system in obese healthy women.
Leptin, a hormone secreted by the adipose tissue, might be a link between obesity and increased morbidity for cardiovascular disease. Leptin exerts proinflammatory, pro-angiogenic actions by activating a specific receptor (Ob-Rb) which is expressed in human endothelial cells. Thus, a link may exist between leptin expression and endothelial dysfunction.. We sought to determine whether in obese women there is a correlation between leptin levels, endothelial perturbation and coagulative activation.. Circulating levels of leptin, von Willebrand Factor (VWF), factor (F)VIIa, prothrombin fragment 1 + 2 (F1+2), were measured in 51 non-diabetic, obese women and in 51 normal-weight subjects, using immunoenzymatic assays.. Obese women had significantly higher levels of leptin, VWF, FVIIa, F1+2 compared with healthy women. Simple correlation coefficients showed significant correlation between leptin and either VWF, FVIIa, or F1+2 concentrations. A multiple linear regression analysis, performed to quantify further the relationship between leptin levels and the above-mentioned variables as well as the inflammatory marker C-reactive protein (CRP) and including age, body mass index (BMI), waist-hip ratio (WHR) and lipid parameters as potential confounders, revealed that only FVIIa and VWF were independently related to leptin levels. Reduction in adipose tissue after weight loss resulted in a decrease in both circulating leptin and endothelial and coagulative activation markers.. We suggest that leptin might have pro-atherogenic effects in vivo, with a mechanism involving endothelial cell activation. Topics: Adult; Anthropometry; Biomarkers; Blood Coagulation; Case-Control Studies; Endothelium, Vascular; Female; Hemostasis; Humans; Inflammation; Leptin; Middle Aged; Obesity; Thrombophilia; Weight Loss | 2003 |
Resistin - concentrations in persons with type 2 diabetes mellitus and in individuals with acute inflammatory disease.
Resistin is a recently discovered signal molecule, which could help elucidation of the pathophysiology of the insulin resistance and its correlation with obesity. As little information was available about resistin determination in venous blood at the time of our study, we focused on the question whether any correlation exists between persons with type 2 diabetes mellitus, with systemic inflammation, healthy persons and resistin concentrations and laboratory markers of inflammation, peptone, BMI. Differences of resistin values in these types of volunteers were studied as well.. Persons under study were divided into 3 groups: group A - with clinical signs of inflammatory disease of respiratory tract, leukocytosis > 10000/ul and CRP concentration > 50 mg/l (n = 35); group B - with well controlled type 2 DM treated by oral antidiabetic drugs, without clinical signs of inflammation and negative case history of acute disease (n = 12); group C - without clinical signs of inflammation and negative case history of acute disease (n = 77). For all volunteers we determined BMI index and examined resistin, leptin, interleukin 6, TNF-alpha, Na, K, Cl, insulin, cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, creatinine, uric acid, ALT, AST, GMT, P, Mg and albumin in serum.. Persons with clinical signs of severe inflammation had higher concentrations of Il6, CRP, resistin and a markedly lower BMI, decreased values of glucose, sodium, triacylglycerols, cholesterol, LDL-cholesterol and HDL-cholesterol compared to diabetics of type 2 (p < 0.05). Persons with clinical signs of severe inflammation showed significantly higher concentrations of TNF-alpha, Il6, CRP, resistin, glucose, leptin and considerably lower values of albumin, sodium and HDL-cholesterol than healthy individuals (p < 0.05). Persons with type 2 DM had markedly higher values of BMI, CRP, glucose, triacylglycerols, LDL-cholesterol, GMT and leptin, compared to healthy volunteers (p < 0.05). None of the three groups differed markedly in age or sex. Healthy volunteers show a significant correlation between leptin and resistin (correlation coefficient 0.82); this correlation was not found in patients with inflammation and type 2 DM. The group of volunteers with inflammations was found to have a significant positive correlation between resistin and inflammatory markers (correlation coefficient 0.3-0.5), negative correlation between resistin and cholesterol. We also found positive correlations between leptin and BMI as well as negative correlations between leptin and CRP. No significant correlations between resistin and other studied parameters were found in persons with type 2 DM.. In healthy population a correlation was found between leptin and resistin concentrations in serum. In patients with severe inflammatory disease a correlation between resistin concentration and laboratory markers of inflammation was shown, however, no correlation was found between leptin and resistin. Resistin concentration in the serum of these patients is significantly higher ( p < 0.01) compared to healthy subjects and well controlled persons with type 2 DM with signs of insulin resistance. This may be due to a direct effect of inflammatory cytokines on resistin production. In persons with type 2 DM no significant correlations were found between resistin and other individual parameters ( insulin sensitivity markers, BMI or leptin). Resistin concentrations in persons with type 2 DM do not differ from concentrations of common population. Topics: Acute Disease; Aged; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Resistin; Respiratory Tract Diseases | 2003 |
Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways.
Obesity is increasing in prevalence worldwide and in all age groups. In nonpregnant individuals, obesity is associated with dyslipidemia; hyperinsulinemia; vascular dysfunction; and, more recently, low-grade chronic inflammation. However, whether such effects are sustained during pregnancy has been sparsely investigated but is important to establish, given the association of maternal obesity with numerous adverse metabolic and vascular consequences. We consecutively recruited 47 healthy women in the third trimester of pregnancy and divided the participants into 2 groups, lean [n = 24; median body mass index (BMI), 22.1 kg/m(2)] and obese (n = 23; median BMI, 31.0 kg/m(2)) around the median first trimester BMI. The age, parity, and smoking history were comparable in both groups. A detailed panel of metabolic and inflammatory parameters was measured and an in vivo assessment of endothelial-dependent and -independent microvascular function made using laser doppler imaging. Although low-density lipoprotein cholesterol and glycosylated hemoglobin were similar, fasting triglyceride concentrations were higher [2.70 (interquartile range, 2.3-3.21) vs. 2.20 (IQ range, 2.0-2.6) mmol/liter, P = 0.02] and high-density lipoprotein concentrations were lower [1.55 (IQ range, 1.1-1.7) vs. 1.72 (IQ range, 1.4-2.0) mmol/liter, P = 0.02] in the obese group. Leptin [55.6 (range, 45-64.4) ng/ml vs. 23.8 (range, 13.2-35.2) ng/ml, P < 0.0001] and fasting insulin [14.5 (range, 11.4-27.3) vs. 6.5 (range, 4.6-9.7) mU/liter, P < 0.0001] levels were more than double. Similarly, levels of inflammatory parameters, IL-6 [3.15 (range, 2.4-3.5) vs. 2.1 (range, 1.73-2.85) pg/ml, P = 0.003], and sensitive C-reactive protein [4.45 (range, 2.9-6.6) vs. 2.25 (range, 0.92-3.65) mg/ml, P = 0.0015] were also substantially elevated. Both endothelial-dependent and -independent vasodilatory responses were significantly reduced in the obese group (P = 0.0003 and P = 0.02, respectively, ANOVA) and systolic blood pressure was higher (P = 0.01). Metabolic factors, C-reactive protein (r = 0.289, P = 0.049), and insulin (r = 0.339, P = 0.02) were related inversely to endothelial-dependent function. These comprehensive data demonstrate that, as in nonpregnant obese individuals, obesity in pregnancy is associated not only with marked hyperinsulinemia (without necessarily glucose dysregulation) and dyslipidemia but also impaired endothelial function, higher blood pressure, and inflammatory up-regulation. Su Topics: Adult; Blood Pressure; Body Mass Index; C-Reactive Protein; Cholesterol, LDL; Delivery, Obstetric; Endothelium, Vascular; Female; Glycated Hemoglobin; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Lipids; Lipoproteins; Obesity; Parity; Pregnancy; Pregnancy Complications; Reference Values; Regression Analysis; Smoking; Thinness; Triglycerides; Vasodilation | 2002 |
Decreased plasma leptin concentrations in tuberculosis patients are associated with wasting and inflammation.
Tuberculosis patients often suffer from severe weight loss, which is considered to be immunosuppressive and a major determinant of severity and outcome of disease. Because leptin is involved in weight regulation and cellular immunity, its possible role in tuberculosis-associated wasting was investigated. In an urban clinic in Indonesia, plasma leptin concentrations, indicators of adipocyte mass, appetite, C-reactive protein (CRP), tuberculin reactivity, and cytokine response were measured in tuberculosis patients and healthy controls. Plasma leptin concentrations were lower in patients than in controls (615 vs. 2,550 ng/liter; P < 0.001). Multivariate regression analysis showed that body fat mass and inflammation were two independent factors determining plasma leptin concentrations; there was a positive correlation between fat and leptin, whereas, unexpectedly, leptin was inversely associated with CRP and tumor necrosis factor-alpha production. Concentrations of both CRP and leptin were independently associated with loss of appetite. Our results do not support the concept that weight loss in tuberculosis is caused by enhanced production of leptin. Rather, loss of body fat leads to low plasma leptin concentrations, and prolonged inflammation may further suppress leptin production. Because leptin is important for cell-mediated immunity, low leptin production during active tuberculosis may contribute to increased disease severity, especially in cachectic patients. Topics: Adipose Tissue; Adult; Antitubercular Agents; Appetite; Body Weight; Cytokines; Female; Humans; Inflammation; Leptin; Male; Osmolar Concentration; Reference Values; Tuberculosis | 2002 |
Balancing susceptibility to infection and autoimmunity: a role for leptin?
The immune responses to many infections have long been known to share features with autoimmune responses. In particular, both types of response are typified by the enhanced reactivity of T helper 1 cells - with high levels of interleukin-2, interferon gamma and tumor necrosis factor alpha - and are accompanied often by organ-specific and/or systemic damage and the production of IgG. Paradoxically, the geographical distributions of incidence of infectious diseases and autoimmunity are complementary, rather than coincident. In less-developed societies, an epidemiological association between susceptibility to infection and malnutrition has been observed, whereas in affluent countries, an increased incidence of autoimmune diseases has been described. We suggest that these observations can be explained partly by taking into consideration the immune effects of the adipocyte-derived hormone leptin, which has been shown recently to act as a link between nutritional status and the immune response. Topics: Adipose Tissue; Animals; Autoimmune Diseases; Autoimmunity; Disease Susceptibility; Female; Humans; Infections; Inflammation; Leptin; Male; Mice; Models, Immunological; Nutritional Status; Rats | 2002 |
Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans.
Type 2 diabetes is associated with biochemical evidence of low-grade inflammation, and experimental studies have suggested that both insulin and glucose affect inflammatory responses. To determine the effect of in vivo changes in glucose availability and plasma insulin concentrations in humans, we administered 20 U/kg Escherichia coli lipopolysaccharide (LPS) or saline (control) to 14 subjects during a euglycemic hyperinsulinemic clamp (n = 6) or an infusion of sterile saline (n = 8). Parallel in vitro studies on human whole blood were undertaken to determine whether there was a direct effect of glucose, insulin, and leptin on proinflammatory cytokine production. Infusion of glucose and insulin significantly amplified and/or prolonged the cardiovascular, plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and counterregulatory hormone responses to LPS, whereas the effects on fever, plasma norepinephrine concentrations, and oxygen consumption were unaffected. In vitro studies showed no modulation of LPS-stimulated IL-6 or TNF-alpha production by glucose, insulin, or leptin at physiologically relevant concentrations. Hyperinsulinemia indirectly enhances key components of the systemic inflammatory and stress responses in this human model of infection. Topics: Adult; Blood Glucose; Blood Pressure; Body Temperature; Cytokines; Diabetes Mellitus, Type 2; Escherichia coli; Female; Glucose Clamp Technique; Humans; Hyperinsulinism; Inflammation; Insulin; Insulin-Like Growth Factor Binding Protein 1; Interleukin-6; Leptin; Lipopolysaccharides; Male; Norepinephrine; Oxygen Consumption; Pulse; Tumor Necrosis Factor-alpha | 2002 |
Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure.
Three measures--heart rate, a global index of the influence of the autonomic nervous system on the heart; circulating concentrations of adiponectin, an adipose-specific protein; and C-reactive protein (CRP), a sensitive marker of inflammation--have been reported to be closely associated with insulin resistance. Patients with borderline hypertension are known to be more insulin resistant and dyslipidemic than those with normal blood pressure (BP). BP can be classified into three categories: optimal, normal, and high-normal. The present study examined whether those with high-normal BP have any of these three conditions as compared with those with optimal BP in young healthy men.. Anthropometric, blood pressure, heart rate, and blood tests, including tests for adiponectin and CRP, were conducted in 198 male students, ages 18-26 years, who had fasted overnight. Insulin resistance (IR) and insulin secretion (beta-cell levels) were calculated using the homeostasis model assessment (HOMA), and LDL size was measured by PAGE.. Compared with the 90 men who had optimal BP, the 46 men with high-normal BP had increased heart rate, BMI, percent body fat, and serum leptin levels. In addition, they had greater serum insulin, HOMA IR, and beta-cell levels, lower adiponectin levels, and comparable CRP levels. Furthermore, the 46 men with high-normal BP had higher serum triglyceride and apolipoprotein (apo) B levels, and smaller LDL size; however, there was no difference in LDL and HDL cholesterol and apoA-I between men with optimal and high-normal BP. After adjusting for BMI, differences were still significant in serum adiponectin, heart rate, and LDL particle size. As BP rose, there was an increase in heart rate (BMI-adjusted least square means were 63, 65, and 70 bpm in men with optimal, normal, and high-normal BP, respectively; P = 0.005), whereas serum adiponectin (7.5, 6.6, and 6.4 mg/l; P = 0.007) and LDL particle size (271, 269, and 269 A; P = 0.008) decreased.. Young men with high-normal BP have a faster heart rate, lower serum adiponectin levels, and smaller LDL size than men with optimal BP, even after adjustment for BMI. These results suggest the necessity of preventing further development of cardiac and metabolic diseases in young people who have high-normal BP. Topics: Adiponectin; Adolescent; Adult; Asian People; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Fasting; Heart Rate; Humans; Inflammation; Insulin; Intercellular Signaling Peptides and Proteins; Japan; Leptin; Lipoproteins, LDL; Male; Proteins; Reference Values | 2002 |
Markers of chronic inflammation and obesity: a prospective study on the reversibility of this association in middle-aged women undergoing weight loss by surgical intervention.
Human adipose tissue expresses and releases proinflammatory cytokines and these measures of chronic inflammation have recently been associated with obesity.. To test whether the proinflammatory state is reversible in subjects undergoing weight loss by surgical measures.. Twenty morbidly obese women participated in this prospective study. Subjects were examined for fat mass, high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) before and 1 y after Swedish adjustable gastric banding.. Anthropometric measures displayed a significant reduction of the body mass index (BMI) from 41.6+/-5.4 to 30.8+/-6.1 kg/m(2) and the fat mass from 53.9+/-10.3 to 29.8+/-12.1 kg (mean+/-s.d.). Hs-CRP levels decreased significantly from 1.33+/-1.21 mg/dl in pre-gastric banding subjects to 0.40+/-0.61 mg/dl in post-gastric banding subjects, respectively. IL-6 and TNF-alpha levels did not differ significantly between pre- and post-gastric banding subjects.. We speculate that in these patients the marked reduction in C-reactive protein might be beneficial in reducing their cardiovascular risk and is not solely mediated by IL-6 and TNF-alpha. Topics: Adipose Tissue; Adult; Biomarkers; Body Composition; C-Reactive Protein; Cholesterol; Female; Gastroplasty; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Middle Aged; Obesity; Prospective Studies; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss | 2002 |
Altered macrophage-like functions of preadipocytes in inflammation and genetic obesity.
We recently demonstrated that preadipocytes exhibit functional features of macrophages, such as phagocytosis and anti-microbial activity, suggesting that preadipose cells could play a role in the inflammatory process or immune response. The aim of this study was to compare these functions of both macrophages and cells from stroma-vascular fraction (SVF) of the adipose tissue in two different situations, obesity and inflammation, characterized by alterations in immune responsiveness. We demonstrated that ob/ob mice exhibited strong decrease in antimicrobial activity of both macrophages and SVF. This defect is compensated in SVF, at least in part, by an enhancement of phagocytosis that does not seem to be due to an increased macrophage number. In vitro leptin treatment of SVF and macrophages from obese mice did not restore their immune defects. Thioglycollate treatment of lean and obese mice induced an inflammatory process that led to an increase in macrophage activity in both strains. This stimulation also observed in SVF from lean mice is not present in obese ones. This work demonstrated that SVF immune functions could be modified in different pathological situations such as inflammation and obesity and sustained the new physiological role of preadipocytes in these processes. Topics: Adipocytes; Adipose Tissue; Animals; Cell Survival; Cells, Cultured; Female; Homozygote; Inflammation; Leptin; Macrophages; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Ovary; Phagocytosis; Stromal Cells; Thinness | 2001 |
Regulation of free and bound leptin and soluble leptin receptors during inflammation in mice.
Leptin, an appetite-regulating hormone/cytokine, circulates both free and bound to soluble leptin receptors (s-leptin R). An electrochemiluminescence (ECL) assay for the quantitative measurement of murine s-leptin R was developed. The absence of s-leptin R immunoreactivity in the serum of db(pas)/db(pas)mice demonstrated the specificity of the assay, which detected s-leptin R both in the free form and complexed with leptin. The distribution of free vs bound leptin and the regulation of s-leptin R were evaluated in mice following administration of the pro-inflammatory stimuli endotoxin (100 microg/mouse) and turpentine (100 microl/mouse). Both endotoxin and turpentine significantly increased serum leptin and s-leptin R levels compared to control mice. The distribution of free vs bound leptin was not altered by administration of endotoxin or turpentine. In fact, approximately 50% of total leptin was present in the free form in either control, endotoxin- or turpentine-injected mice. On the contrary, during the hyperleptinemia of pregnancy, only 10% of total leptin was present in the free form. We conclude that inflammation leads to the increase of both bound and free leptin. Therefore, the total amount of bioactive leptin is increased during acute inflammation, suggesting that leptin participates in the host response to inflammation. Topics: Animals; Carrier Proteins; Chromatography, Gel; Electrochemistry; Female; Inflammation; Leptin; Lipopolysaccharides; Luminescent Measurements; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Pregnancy; Receptors, Cell Surface; Receptors, Leptin; Solubility; Thinness; Turpentine | 2001 |
[Skeletal muscle dysfunction in COPD. Cell mechanisms. A.G.N].
Topics: Apoptosis; Cachexia; Cell Hypoxia; Genetic Predisposition to Disease; Humans; Inflammation; Leptin; Life Style; Lung Diseases, Obstructive; Muscle Contraction; Muscle Proteins; Muscle, Skeletal; Nitric Oxide; Nutrition Disorders; Oxidative Stress | 2001 |
Does leptin modulate immune and endocrine response in the time of LPS-induced acute inflammation?
In many studies it has been reported, that leptin may play an important role not only in the regulation of food intake and body weight but can modify immune response. The aim of our study was to estimate the effects of the administration of exogenous leptin on serum concentration of proinflammatory cytokines (interleukin 6-IL 6 and tumor necrosis factor alpha-TNF alpha) and anti-inflammatory cytokine (interleukin 10 - IL 10) during LPS induced acute inflammation. We also estimated leptin's influence on pituitary, thyroid, adrenal and gonadal hormones in response to lipopolysaccharide (LPS) induced acute inflammation.. Male rats Wistar-Kyoto were divided into four groups, which received respectively: placebo (0.9% NaCl), LPS, leptin and leptin with LPS. The TNF alpha and IL 6 serum concentrations were measured after 2 hours and IL 10 after 4 hours. The pituitary, thyroid, adrenal and gonadal hormones serum concentrations were measured after 2 and 4 hours. Cytokine concentrations were estimated using ELISA tests and hormones concentrations using RIA tests.. Leptin did not have an effect on both cytokine responses (proinflammatory and anti-inflammatory) in the time of LPS-induced acute inflammation. Leptin enhanced LPS-induced increasing of corticosterone secretion after 2 hours and decreased LPS-induced inhibition of testosterone secretion after 4 hours.. Leptin can modulate hormone response during LPS-induced acute inflammation. Topics: Animals; Corticosterone; Cytokines; Hormones; Inflammation; Interleukin-10; Interleukin-6; Kinetics; Leptin; Lipopolysaccharides; Luteinizing Hormone; Male; Prolactin; Rats; Rats, Inbred WKY; Testosterone; Thyroxine; Triiodothyronine; Tumor Necrosis Factor-alpha | 2001 |
Effects of ultrapure dialysis fluid on nutritional status and inflammatory parameters.
Malnutrition and chronic systemic inflammatory response syndrome not only coexist in uraemia, but may also have a bi-directional cause-and-effect relationship. To evaluate the role of dialysate-related cytokine induction in inflammatory response and nutritional status, we conducted a prospective comparison of two dialysis fluids differing in their microbiological quality.. Forty-eight early haemodialysis patients were assigned to either treatment with conventional (potentially microbiologically contaminated) or on-line produced ultrapure dialysis fluid. Study parameters were bacterial growth, markers of systemic inflammation (C-reactive protein (CRP) and interleukin 6), and parameters of nutritional status (estimated dry weight, upper mid-arm muscle circumference, serum albumin concentration, insulin-like growth factor 1, leptin, and protein catabolic rate). Patients were followed for 12 months.. There were no statistically significant differences in demographic and treatment characteristics, degree of bacterial contamination of the dialysate, markers of systemic inflammation, or parameters of nutritional status among the two treatment groups at recruitment. Changing from conventional to ultrapure dialysis fluid reduced significantly the levels of IL-6 (19+/-3 pg/ml to 13+/-3 pg/ml) and CRP (1.0+/- 0.4 mg/dl to 0.5+/-0.2 mg/dl), and resulted in significant increases in estimated dry body weight, mid-arm muscle circumference, serum albumin concentration, levels of the humoral factors, and in protein catabolic rate after 12 months. Continuous use of conventional dialysis fluid (median 40-60 c.f.u./ml) was not associated with significant alterations in markers of inflammation (IL-6 21+/-4 pg/ml vs 24+/-6 pg/ml, CRP 0.9+/-0.3 mg/dl vs 1.1+/-0.4 mg/dl) or of nutritional status at any time of the study. All differences in systemic inflammation and nutritional parameters observed during the study period (from recruitment to month 12) were significant between the two patient groups.. Cytokine induction by microbiologically contaminated dialysis fluid has a negative impact on nutritional parameters of early haemodialysis patients. The microbiological quality of the dialysis fluid represents an independent determinant of the nutritional status in addition to known factors, such as dose of dialysis and biocompatibility of the dialyser membrane. Ultrapure dialysis fluid adds to the cost of the dialytic treatment, but may improve the nutritional status in long-term haemodialysis patients. Topics: Aged; Body Weight; C-Reactive Protein; Dialysis Solutions; Drug Contamination; Female; Humans; Inflammation; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Male; Middle Aged; Muscle, Skeletal; Nutritional Status; Prospective Studies; Serum Albumin | 2001 |
Leptin does not influence the IgE response to ovalbumin in mice.
Leptin is important for maintenance of the body's energy homeostasis and it also increases Th1 and suppresses Th2 cytokine production. We have investigated the effect of leptin on the allergic immune response to the model allergen ovalbumin (OA) by using the popliteal lymph node assay (PLNA) and serum antibody determination in mice. Mice were injected with either leptin i.v. plus OA in one hind footpad, or leptin or OA alone. A booster dose of leptin was given twice and of OA once and the animals were exsanguinated on experimental day 19 when the PLNs also were removed. End-point measurements were serum levels of IgE, IgG1, and IgG2a anti-OA and weight and cell number of the excised PLNs. Leptin given i.v. with the protocol employed altered neither the cellular PLN response nor the specific serum IgE, IgG1, or IgG2a anti-OA levels compared with the group given OA without leptin. Our data indicate that systemic administration of leptin neither suppresses nor enhances the Th2-dependent antibody responses in the present mouse model. Topics: Allergens; Animals; Cells, Cultured; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Inflammation; Leptin; Lymph Nodes; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Ovalbumin; Th1 Cells; Th2 Cells | 2001 |
Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individuals.
To study whether an increase of plasma leptin concentrations, as observed in the case of increased body weight, is associated with an inflammatory state.. Sixty-three healthy subjects with body mass index (BMI) ranging from 20 to 61 kg/m2.. Plasma concentrations of leptin, the inflammatory parameter soluble TNF-alpha receptors (TNFR55 and TNFR75), the acute phase proteins lipopolysaccharide binding protein (LBP), serum amyloid A (SAA), alpha-acid glycoprotein (AGP), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1) and the anti-inflammatory soluble Interleukin-1 decoy receptor (sIL-1RII) were measured.. As expected, BMI correlated significantly with leptin (r=0.823, P<0.001), but also with all acute phase proteins, both soluble TNF receptors and PAI concentrations. After correction for BMI and sex, no significant correlation between leptin and the acute phase proteins was seen. Interestingly, however, leptin strongly correlated with both TNF receptors (r=0.523, P<0.001 for TNFR55 and r=0.438, P<0.001 for TNFR75).. This study shows the development of a pro-inflammatory state with increasing body weight. The BMI independent relationship between leptin and both soluble TNF-receptors is consistent with a regulatory role for leptin in the inflammatory state in morbidly obese subjects. Topics: Acute-Phase Proteins; Adipose Tissue; Adult; Body Mass Index; Female; Humans; Inflammation; Leptin; Male; Obesity, Morbid; Plasminogen Activator Inhibitor 1; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha | 2001 |
Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease.
Low-grade chronic inflammation, characterized by elevated plasma concentrations of C-reactive protein (CRP), is associated with an increased risk of atherosclerotic cardiovascular disease. Endothelial cell activation is an early event in atherogenesis, and previous studies have reported correlations between indirect markers of endothelial cell activation and CRP concentration. Therefore, in the present study, we measured CRP concentration (and leptin concentration as an index of fat mass) in nine healthy subjects (mean age 53+/-8.1 years; body mass index 27+/-3.2 kg/m(2); mean arterial blood pressure 101+/-9.0 mmHg) undergoing measurement of basal endothelial nitric oxide (NO) synthesis using intra-brachial infusions of N(G)-monomethyl-L-arginine (L-NMMA; a substrate inhibitor of endothelial NO synthase) and noradrenaline (a non-specific control vasoconstrictor). In univariate analysis, CRP concentration was correlated with (i) the percentage decrease in forearm blood flow (FBF) during L-NMMA infusion (r=0.85, P=0.004); and (ii) the serum leptin concentration (r=0.65, P=0.05). In multivariate analysis, the relationship between CRP concentration and the FBF response to L-NMMA remained significant when age and leptin (t=2.65, P=0.045), age and BMI (t=3.69, P=0.014), or age and low-density-lipoprotein-cholesterol plus high-density-lipoprotein-cholesterol (t=3.37, P=0.044), were included in regression models. In contrast, the response of FBF to noradrenaline was not significantly related to CRP concentration. These data demonstrate for the first time a relationship between low-grade chronic inflammation and basal endothelial NO synthesis (measured using an invasive method), and support the notion that endothelial dysfunction is a critical intermediate phenotype in the relationship between inflammation and cardiovascular disease. Topics: Adult; Aged; Arteriosclerosis; Biomarkers; C-Reactive Protein; Chronic Disease; Endothelium, Vascular; Enzyme Inhibitors; Female; Humans; Inflammation; Leptin; Lipids; Male; Middle Aged; omega-N-Methylarginine | 2000 |
Leptin is an endogenous protective protein against the toxicity exerted by tumor necrosis factor.
Tumor necrosis factor (TNF) is a central mediator of a number of important pathologies such as the systemic inflammatory response syndrome. Administration of high TNF doses induces acute anorexia, metabolic derangement, inflammation, and eventually shock and death. The in vivo effects of TNF are largely mediated by a complex network of TNF-induced cytokines and hormones acting together or antagonistically. Since TNF also induces leptin, a hormone secreted by adipocytes that modulates food intake and metabolism, we questioned the role of leptin in TNF-induced pathology. To address this question, we tested mouse strains that were defective either in leptin gene (ob/ob) or in functional leptin receptor gene (db/db), and made use of a receptor antagonist of leptin. Ob/ob and db/db mice, as well as normal mice treated with antagonist, exhibited increased sensitivity to the lethal effect of TNF. Exogenous leptin afforded protection to TNF in ob/ob mice, but failed to enhance the protective effect of endogenous leptin in normal mice. We conclude that leptin is involved in the protective mechanisms that allow an organism to cope with the potentially autoaggressive effects of its immune system. Topics: Animals; Carrier Proteins; Inflammation; Leptin; Mice; Mice, Inbred NOD; Mice, Obese; Proteins; Receptors, Cell Surface; Receptors, Leptin; Recombinant Proteins; Time Factors; Tumor Necrosis Factor-alpha | 1999 |
Leptin regulates proinflammatory immune responses.
Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor alpha expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity. Topics: Animals; Carrier Proteins; Cytokines; Gene Expression Regulation; Inflammation; Leptin; Lipopolysaccharides; Macrophages; Mice; Mice, Obese; Phagocytosis; Proteins; Receptors, Cell Surface; Receptors, Leptin; Recombinant Proteins | 1998 |
IL-1 beta mediates leptin induction during inflammation.
Interleukins (IL) are key mediators of the host response to infection and inflammation. Leptin is secreted by adipose tissue and plays an important role in the control of food intake. Administration of lipopolysaccharide (LPS), tumor necrosis factor (TNF), or IL-1 acutely increases leptin mRNA and protein levels. To investigate the role of IL-1 beta and IL-6 in leptin expression during inflammation, we used IL-1 beta-deficient (-/-) and IL-6 -/- mice. Mice were injected intraperitoneally with LPS or subcutaneously with turpentine, as models of systemic or local inflammation, respectively. In IL-1 beta +/+ mice, both LPS and turpentine increased leptin mRNA and circulating leptin. In contrast, neither LPS nor turpentine increased leptin levels in IL-1 beta -/- mice. In IL-6 +/+ or IL-6 -/- mice, turpentine increased leptin protein to comparable levels. We conclude that IL-1 beta is essential for leptin induction by both LPS and turpentine in mice, but IL-6 is not. Topics: Animals; Gene Expression Regulation; Inflammation; Interleukin-1; Interleukin-6; Leptin; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Models, Biological; Protein Biosynthesis; RNA, Messenger; Transcription, Genetic; Turpentine | 1998 |
Low leptin gene expression and hyperleptinemia in chronic renal failure.
The ob gene product leptin is thought to be a key regulator of food intake and body weight. Patients having advanced chronic renal failure (CRF) have markedly higher serum leptin levels. It is not known whether the increase in leptin levels in CRF is caused by a decreased plasma clearance and/or increased production.. In the present study serum leptin levels and glomerular filtration rate (GFR) were measured in 219 patients having various degrees of renal failure. In addition, serum leptin levels, C-reactive protein (CRP), body composition (by dual-energy x-ray absorptiometry) and ob gene expression (by in situ hybridization histochemistry) were determined in 15 patients with advanced CRF. Seven of the patients were re-evaluated following 12 months of peritoneal dialysis (PD) treatment.. Serum leptin levels correlated negatively to GFR (r = -0.26; P < 0.0001). The ob gene expression was significantly lower in patients with CRF than in healthy controls. A negative correlation between serum leptin levels and ob gene expression (r = -0.66; P < 0.05) was found in patients with CRP < 25 mg/liter. The ob gene expression (20.0 +/- 1.8 vs. 15.0 +/- 1.0 nCi/g; P < 0.05) was significantly higher in 5 patients with CRP > 25 mg/liter than in 10 patients with CRP < 25 mg/liter. Following 12 months of PD, the amount of body fat increased by 30% while the ob gene expression remained unchanged.. The present study shows a correlation between serum leptin levels and GFR, and our results suggest that elevated leptin levels, due to a decreased plasma clearance, down-regulate the expression of the ob gene. We also found that an ongoing inflammation stimulates ob gene expression in patients with CRF. Therefore, it is suggested that the hyperleptinemia induced feedback inhibition of ob gene expression is overcome by inflammatory cytokines. Topics: Adipose Tissue; Adult; Aged; Aged, 80 and over; Case-Control Studies; Down-Regulation; Feedback; Female; Gene Expression; Glomerular Filtration Rate; Humans; Inflammation; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Obesity; Peritoneal Dialysis; Proteins | 1998 |
Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia.
Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions. Topics: Adipose Tissue; Animals; Anorexia; Ciliary Neurotrophic Factor; Cytokines; Escherichia coli; Female; Growth Inhibitors; Humans; Inflammation; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukins; Kinetics; Leptin; Leukemia Inhibitory Factor; Lipopolysaccharides; Lymphokines; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Protein Biosynthesis; Proteins; Recombinant Proteins; RNA, Messenger; Transcription, Genetic; Tumor Necrosis Factor-alpha | 1997 |
Transforming growth factor-beta enhances and pro-inflammatory cytokines inhibit ob gene expression in 3T3-L1 adipocytes.
Leptin is a protein which is encoded by the obese (ob) gene. It is synthesized by adipocytes and binds to receptors in the hypothalamus, thereby suppressing appetite and increasing the metabolic rate. When mouse 3T3-L1 cells are induced to differentiate into adipocytes, they begin to constitutively express low levels of ob mRNA. Using reverse transcription and a semi-quantitative polymerase chain reaction, the experiments described herein demonstrate that the anti-inflammatory cytokine transforming growth factor-beta increases steady state ob mRNA. Conversely, treatment of 3T3-L1 adipocytes with the pro-inflammatory cytokines interleukin-1 beta, interleukin-6, interleukin-11, and tumor necrosis factor-alpha results in a decrease in ob transcripts. When considered in the context of animal studies showing that interleukin-1 and tumor necrosis factor-alpha induce leptin and ob mRNA, these results suggest that pro-inflammatory cytokines induce ob gene transcription in vivo via secondary mediators such as transforming growth factor-beta. Topics: 3T3 Cells; Adipocytes; Adipose Tissue; Animals; Cytokines; DNA Primers; Drug Synergism; Inflammation; Interleukin-1; Interleukin-11; Interleukin-6; Leptin; Mice; Polymerase Chain Reaction; Protein Biosynthesis; RNA, Messenger; Transcription, Genetic; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha | 1997 |