leptin and Chronic-Disease

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; Auditory Threshold; Aurora Kinase B; Australia; Autophagy; Autophagy-Related Protein 5; Autotrophic Processes; Bacillus cereus; Bacillus thuringiensis; Bacterial Proteins; Beclin-1; Belgium; Benzene; Benzene Derivatives; Benzhydryl Compounds; beta Catenin; beta-Arrestin 2; Biliary Tract Diseases; Biofilms; Biofuels; Biomarkers; Biomarkers, Tumor; Biomass; Biomechanical Phenomena; Bioreactors; Biosensing Techniques; Biosynthetic Pathways; Bismuth; Blood Platelets; Bone and Bones; Bone Regeneration; Bortezomib; Botulinum Toxins, Type A; Brain; Brain Injuries; Brain Ischemia; Brain Neoplasms; Breast Neoplasms; Breath Tests; Bronchodilator Agents; Calcium Phosphates; Cannabis; Carbon Dioxide; Carbon Isotopes; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiomyopathies; Cardiovascular Diseases; Cariostatic Agents; Case Managers; Case-Control Studies; Catalysis; Cation Transport Proteins; CD8-Positive T-Lymphocytes; Cecropia Plant; Cell Adhesion; Cell Count; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Self Renewal; Cell Survival; Cells, Cultured; Cellular Reprogramming; Cellulose; Charcoal; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemokines; Chemoradiotherapy; Chemoreceptor Cells; Child; Child Abuse; Child, Preschool; China; Chlorogenic Acid; Chloroquine; Chromatography, Gas; Chronic Disease; Clinical Competence; Coated Materials, Biocompatible; Cochlea; Cohort Studies; Color; Comorbidity; Computer Simulation; Computer-Aided Design; Contraception; Contraceptive Agents, Female; Contrast Media; COP-Coated Vesicles; Coronavirus Infections; Cost of Illness; Coturnix; COVID-19; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Culex; Curriculum; Cyclic N-Oxides; Cytokines; Cytoplasm; Cytotoxicity, Immunologic; Cytotoxins; Databases, Factual; Deep Learning; Delivery, Obstetric; Denitrification; Dental Caries; Denture, Complete; Dexamethasone; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dielectric Spectroscopy; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Disease Progression; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Dog Diseases; Dogs; Dopaminergic Neurons; Double-Blind Method; Down-Regulation; Doxorubicin; Drug Carriers; Drug Design; Drug Interactions; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Dry Powder Inhalers; Dust; E2F1 Transcription Factor; Ecosystem; Education, Nursing; Education, Nursing, Baccalaureate; Electric Impedance; Electricity; Electrocardiography; Electrochemical Techniques; Electrochemistry; Electrodes; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum; Endothelial Cells; Environmental Monitoring; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Estrogen Receptor Modulators; Europe; Evoked Potentials, Auditory, Brain Stem; Exosomes; Feasibility Studies; Female; Ferricyanides; Ferrocyanides; Fibrinogen; Finite Element Analysis; Fistula; Fluorescent Dyes; Fluorides, Topical; Fluorodeoxyglucose F18; Fluticasone; Follow-Up Studies; Food Contamination; Food Microbiology; Foods, Specialized; Forensic Medicine; Frail Elderly; France; Free Radicals; Fresh Water; Fungi; Fungicides, Industrial; Galactosamine; Gastrointestinal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Gingival Hemorrhage; Glioblastoma; Glioma; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucose; Glucose Transport Proteins, Facilitative; Glucosides; Glutamine; Glycolysis; Gold; GPI-Linked Proteins; Gram-Negative Bacteria; Gram-Positive Bacteria; Graphite; Haplotypes; HCT116 Cells; Healthy Volunteers; 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

Chronic liver disease (CLD) is a major health problem worldwide. Non-alcoholic fatty liver disease (NAFLD), chronic hepatitis C (CHC), chronic hepatitis B (CHB), and alcoholic liver disease (ALD) are the most common etiologies of CLD. Liver biopsy is the gold standard for assessment of liver fibrosis, however, it is an invasive method. This review attempts to evaluate the usefulness of serum adiponectin, serum leptin, serum ferritin, serum transforming growth factor-β1 (TGF-β1), and serum platelet derived growth factor-BB (PDGF-BB) as non-invasive markers in the diagnosis of liver fibrosis/cirrhosis. A systematic search in MEDLINE, Web of Science, Scopus, and local databases was performed to identify articles published in English or Persian as of November 2017. Studies conducted among CLD patients, with biopsy proven fibrosis/cirrhosis, and providing sufficient details of patients' clinicopathological characteristics were included. In the 95 studies included, there were a total of 15,548 CLD patients. More than 83% of studies were carried out in Asia and Europe. The relationship between liver fibrosis/cirrhosis and serum levels of ferritin, adiponectin, leptin, TGF-β1, and PDGF-BB was assessed in 42, 33, 27, nine, and three studies, respectively. Serum levels of the markers, particularly ferritin, could successfully predict liver fibrosis/cirrhosis, however, these data might not be clinically replicated and further studies are needed.

Topics: Adiponectin; Becaplermin; Biomarkers; Chronic Disease; Ferritins; Humans; Leptin; Liver Cirrhosis; Transforming Growth Factor beta1

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

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

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

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

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

Chronic heart failure (CHF) is a major health problem that carries a devastating prognosis. The prognosis worsens considerably once cardiac cachexia has been diagnosed. Neurohormonal, metabolic, hemodynamic and immunological alterations are involved in the initiation and progression of cardiac cachexia. Cachexia is characterized by a hypothalamic inappropriate response to the mechanisms controlling energy homeostasis. Levels of the anorexigenic hormone leptin are decreased whereas the orexigenic gherlin hormone levels are normal or elevated. Nevertheless, energy intake is not increased as expected due to a persistent activation of the proopiomelanocortin (POMC) system (anorexigenic) paralleled by a decreased activity of the neuropeptide Y (NPY, orexigenic) neurons. Cachexia is also characterized by an imbalance in anabolic (impairment in the growth hormone/insulin-like growth factor-I axis, insulin resistance) and catabolic (increased levels of catecholamines, increased cortisol/dehydroepiandrosterone ratio and activation of proinflammatory cytokines such as tumor necrosis factor-alpha, interleuchin-6, interleuchin-1') at the basis of the wasting process. This review discusses the complex role of the endocrine system in modulating energy balance, appetite and metabolism in patients with chronic heart failure. A joint multidisciplinary effort of the cardiologists, immunologists and endocrinologists might be useful to identify the precise mechanisms involved in the neuroendocrine alteration and to develop therapeutic strategies able to improve the prognosis of CHF patients.

Topics: Appetite; Biomarkers; Cachexia; Chronic Disease; Cytokines; Endocrine System; Ghrelin; Heart Failure; Humans; Hypothalamus; Leptin; Neuropeptide Y; Pro-Opiomelanocortin; Prognosis

Chronic heart failure (CHF) is a major public health problem. The failure to provide peripheral tissues with sufficient amounts of oxygen is accompanied by maladaptive responses that include pathophysiological pathways that may lead to an anabolic-catabolic imbalance with the development of cardiac cachexia. This review aims to highlight players of the catabolic-anabolic imbalance, regulators or appetite, and other mediators that are involved in the progression of CHF to cachexia.. Clinical research has buttressed the view that deficiencies or resistance to growth hormone and testosterone plays an important role in the pathophysiology of CHF. The role of appetite regulation in the development of cardiac cachexia is also subject of recent studies. The resistance of CHF patients to the effects of appetite-stimulating peptide ghrelin may be one of the contributing factors. These circumstances drive muscle, bone, and fat wasting. Plasma levels of the adipokines leptin and adiponectin may have a role in the detection of such wasting processes.. Hormonal signaling pathways play an essential role in the development of cardiac cachexia. Recent findings enhance our understanding of the complex interplay between these regulators and may serve as a hub for the development of therapeutic interventions to prevent or potentially even to treat cardiac cachexia.

Topics: Adiponectin; Appetite; Cachexia; Chronic Disease; Ghrelin; Heart Failure; Human Growth Hormone; Humans; Leptin; Peptide Hormones; Prognosis; Signal Transduction; Testosterone

The estimated prevalence of anorexia nervosa is highest in teenagers and probably increasing in prepubertal girls, while morbidity rates in female adults remain constant. Childhood and adolescent AN often take a chronic and disabling course with severe consequences for somatic and mental health in adulthood and an eventually high mortality. Besides a reduced growth, diminished reproduction rate and an increased risk of osteoporosis a prolonged course of the disorder may impact on the development of the adolescent brain, probably by hormonal dysfunctions such as those of the corticoid and gonadal system and by severe changes in neuropeptides such as leptin. Thus, besides a genetic disposition, longer lasting effects of starvation on brain development might explain the high prevalence of mental disorders in adulthood of former AN patients. Neuropsychological findings resembling those in obsessive-compulsive disorder and autism spectrum disorders are of growing importance because they might contribute to more effective and specific interventions in both adolescent and adult eating disorders.

Topics: Adolescent; Adult; Anorexia Nervosa; Brain; Child; Chronic Disease; Cross-Sectional Studies; Female; Hormones; Humans; Incidence; Leptin; Male; Neuropsychological Tests; Prognosis; Risk Factors; Young Adult

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

Obesity is a chronic metabolic disorder that affects one third of American adults. Modest weight losses of just 5% to 10% of body weight, which are achievable with lifestyle modification and pharmacotherapy, can lead to remarkable improvements in many obesity-associated co-morbidities, including dyslipidemia, hypertension, and type 2 diabetes. In this review, the indications for pharmacotherapy and the goals of treatment are discussed, and current and future pharmacologic approaches to the treatment of obesity are examined. Current pharmacologic therapies for obesity are limited, but recent advances in our understanding of the complex and overlapping endocrine pathways that regulate body weight have led to new opportunities for antiobesity drug development. Important drug targets that are highlighted in this review include adipocyte-derived hormones, hypothalamic neuropeptides, and gastrointestinal hormones.

Topics: Amyloid; Anti-Obesity Agents; Appetite Depressants; Body Weight; Chronic Disease; Comorbidity; Cyclobutanes; Exenatide; Gastrointestinal Hormones; Humans; Islet Amyloid Polypeptide; Lactones; Leptin; Metformin; Obesity; Orlistat; Peptides; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Venoms

Topics: Adipocytes; Adiponectin; Antibody Formation; Chronic Disease; Diabetes Mellitus, Type 2; Humans; Leptin

Leptin and adiponectin, the main metabolic products of adipose tissue, have been implicated in a wide spectrum of human diseases. Given the frequent presence of hepatic steatosis in several chronic liver diseases, there is currently increasing interest in the role of these adipokines in the development of hepatic steatosis and also in necroinflammation and fibrosis, mostly in patients with nonalcoholic fatty liver disease or chronic hepatitis C. According to experimental data, reduced adiponectin levels and increased leptin levels associated with leptin resistance, which are usually observed in obese patients with or without metabolic syndrome, may result in fat accumulation in the liver and in the enhancement of liver inflammation and mostly fibrogenesis. Increased leptin and decreased adiponectin serum levels have been detected initially in patients with nonalcoholic steatohepatitis and more recently in patients with chronic hepatitis C compared to healthy controls in most but not all studies, while the data on the associations between these adipokine levels and the severity of hepatic steatosis or fibrosis are still rather conflicting. However, several potential confounding parameters were not evaluated in all studies. Therefore, the associations between adipokines and liver histological lesions and their effects on liver cells should be evaluated further in prospective, carefully designed studies, including larger cohorts of patients with detailed assessment of metabolic and other potential confounding factors.

Topics: Adiponectin; Chronic Disease; Fats; Fatty Liver; Hepatitis C, Chronic; Humans; Leptin; Liver; Liver Cirrhosis; Liver Diseases

Leptin is a 16-kDa nonglycosylated protein primarily secreted from the adipocytes of white fat; minor levels of regulated leptin expression also occurs at other sites such as placenta, skeletal muscle, the stomach fundus, and culture-activated hepatic stellate cells (HSCs). Leptin is primarily involved in the regulation of food intake and body composition through a central feedback mechanism linking food ingestion, hypothalamus, and adipose tissue mass. In recent years, however, emerging evidence has suggested a critical role of leptin in hepatic inflammation and fibrogenesis and the influence of leptin on chronic liver disease has been an area of active research worldwide. In this review the data on the in vivo and in vitro actions of leptin on liver cells in experimental animal models of liver injury and the effects of leptin on human liver are discussed, with a focus on three distinct fields of chronic liver diseases: nonalcoholic steatohepatitis, alcoholic liver disease, chronic viral hepatitis, and, especially, hepatitis C.

Topics: Animals; Chronic Disease; Hepatocytes; Humans; Leptin; Liver Diseases; Rats

Malnutrition is defined as abnormalities caused by an inadequate diet, but this term is often used inappropriately to describe the syndrome of loss of body weight with muscle mass being replaced by fatty tissue and declining serum proteins present in adults and children with chronic kidney disease (CKD). This syndrome is more accurately described as cachexia, and manifests as growth failure in children with CKD. Cachexia is common and is an important risk factor for poor quality of life and increased mortality and morbidity in both adults and children with CKD. Anorexia, acidosis and inflammation are important causes of cachexia, but the underlying molecular mechanism is not well understood. Dietary intake is often poor and resting metabolic rate is increased in CKD. The energy cost of growth is increased in experimental CKD. Circulating concentrations of cytokines, such as leptin, tumor necrosis factor-alpha and interleukins 1 and 6 are increased in patients with CKD and correlate with the degree of cachexia in these individuals. We hypothesize that cytokines signal through orexigenic neuropetides such as agouti-related peptide and neuropeptide Y (NPY), and anorexigenic neuropetides such as proopiomelanocortin and alpha-melanocyte-stimulating hormone in the arcuate nucleus in the hypothalamus. This signaling system also involves the NPY receptor and the melanocortin receptors and controls appetite and metabolic rate in health and disease. Furthermore, the first order neurons of this system are located outside the blood-brain barrier and can therefore sense the circulating levels of cytokines, as well as long-term satiety hormones such as leptin and insulin and short-term satiety hormones such as ghrelin and peptide (P) YY. There is experimental evidence that this hypothalamic neuropeptide signaling system may have an important role in the pathogenesis of cachexia in CKD. Understanding the molecular mechanism of cachexia in CKD may lead to novel therapeutic strategies.

Topics: Cachexia; Child; Chronic Disease; Cytokines; Ghrelin; Humans; Kidney Diseases; Kidney Failure, Chronic; Leptin; Malnutrition; Peptide Hormones

None of the synonyms of nonalcoholic fatty liver disease (NAFLD) include clinical correlates nor do they mention insulin resistance, a recognized determinant of the etiopathogenesis and natural history of NAFLD.. The literature concerning the pathogenesis and definition of NAFLD is reviewed.. The reasons why NAFLD should be renamed are: (a) clinically meaningful hepatic steatosis could be present at less than 5% triglyceride hepatic content; (b) steatosis is usually no longer observed in the most advanced forms of NAFLD ('cryptogenic cirrhosis'); (c) the concurrence of metabolic derangements could be more important than alcohol in the pathogenesis of alcoholic liver disease; (d) a concurrent metabolic etiology might worsen the course of chronic HCV and autoimmune hepatitis; (e) in NAFLD the liver is a target organ of the metabolic syndrome, a systemic subclinical inflammatory state.. The introduction of a positive criterion also mentioned in its definition would benefit the diagnosis of NAFLD and of steatohepatitis observed in the setting of other liver diseases, help to estimate the risk of its progression and aid the treatment of metabolic (fatty) liver disorders. There is a compelling need for an experts' agreement on a new definition of insulin resistance/metabolic-related liver disease.

Topics: Chronic Disease; Diagnosis, Differential; Disease Progression; Fatty Liver; Humans; Insulin Resistance; Leptin; Risk Factors; Terminology as Topic

Leptin, the product of the ob-gene, regulates cellular homeostasis and glycemic control. While initially described as an adipocyte-derived protein with expression and secretion restricted to adipose tissue, recent reports have shown local expression of leptin in several tissues including the skeletal muscle, heart, vessels and brain. Leptin acts through the different isoforms of its receptor which are ubiquitously expressed and can be detected in endothelium, vascular smooth muscle and myocardium. In addition to its metabolic effects, leptin has distinct effects in the cardiovascular system leading to increased production of proinflammatory cytokines and oxidative stress, vascular remodeling and neointima formation as well as cardiomyocyte hypertrophy. Notably, recent clinical studies have linked serum levels of leptin to the occurrence of cardiovascular events such as myocardial infarction and stroke suggesting that leptin promotes pro-atherogenic vascular mechanisms. In contrast, less is known about the role and effects of leptin in the setting of chronic heart failure. We here review the current knowledge on cardiovascular effects of leptin and discuss its potential as a new therapeutic tool in chronic heart failure.

Topics: Animals; Biomarkers; Chronic Disease; Heart Diseases; Humans; Leptin; Receptors, Cell Surface; Receptors, Leptin; Risk Factors

Although catecholamine is a well-known classical hormone, its precise pathophysiological role remains obscure. Recently, growing evidence suggests that this hormone plays a causative role in several common diseases such as hypertension, diabetes, and dyslipidemia (metabolic syndrome). Thus, the discussion that follows will mainly focus on our data, including: 1) leptin as well Ang II subtype-2 receptor (AT2), assumed to be a key molecule for metabolic syndrome, much involved in regulating catecholamine synthesis and secretion. 2) Recent progress of pheochromocytoma (SDHX and Peptidergic Regulation). 3) Chromogranin A, as a possible marker for chronic sympatho-adrenal activities.

Topics: Adrenal Gland Neoplasms; Autonomic Nervous System Diseases; Biomarkers; Catecholamines; Chromogranin A; Chromogranins; Chronic Disease; Humans; Iron-Sulfur Proteins; Leptin; Membrane Proteins; Metabolic Syndrome; Mutation; Pheochromocytoma; Protein Subunits; Receptor, Angiotensin, Type 2; Succinate Dehydrogenase

Systemic thermal therapy, such as taking a warm-water bath and sauna, induces systemic vasodilation. It was found that repeated sauna therapy (60 degrees C for 15 min) improved hemodynamic parameters, clinical symptoms, cardiac function, and vascular endothelial function in patients with congestive heart failure. Vascular endothelial function is impaired in subjects with lifestyle-related diseases, such as hypertension, hyperlipidemia, diabetes mellitus, obesity, and smoking. Sauna therapy also improved endothelial dysfunction in these subjects, suggesting a preventive role for atherosclerosis. In animal experiments, sauna therapy increases mRNA and protein levels of endothelial nitric oxide synthase (eNOS) in aortas. In normal-weight patients with appetite loss, repeated sauna therapy increased plasma ghrelin concentrations and daily caloric intake and improved feeding behavior. In obese patients, the body weight and body fat significantly decreased after 2 weeks of sauna therapy without increase of plasma ghrelin concentrations. On the basis of these data, sauna therapy may be a promising therapy for patients with lifestyle-related diseases.

Topics: Animals; Cardiovascular Diseases; Chronic Disease; Endothelium, Vascular; Feeding Behavior; Ghrelin; Humans; Leptin; Life Style; Nitric Oxide Synthase; Obesity; Peptide Hormones; Steam Bath

Metabolic and nutritional derangements are prominent features of the uremic syndrome. Recent evidence suggest that several large-molecular-weight molecules that often are elevated in uremia, such as leptin, ghrelin, and proinflammatory cytokines, may have nutritional impact in this patient group. On the basis of present knowledge, these compounds could be regarded as suspected but not established uremic toxins. The discovery of the ob gene, its product leptin, and cerebral leptin receptors has undoubtedly widened our understanding of obesity and the underlying molecular and physiologic mechanisms that regulate food intake and body weight. Moreover, the recent discovery of leptin receptor isoforms in several peripheral organs suggests that leptin besides having a central function also has several important peripheral biological functions. Because uremic patients in general have an inappropriate elevation of circulatory leptin, further research is necessary to determine the potential biological effects of elevated leptin levels in end-stage renal disease. Also, because many symptoms and findings prevalent in the uremic syndrome are known to be associated with elevated levels of proinflammatory cytokines, such as interleukin-6, future studies are needed to evaluate the role of specific anti-inflammatory treatment strategies in malnourished uremic patients.

Topics: Animals; Chronic Disease; Cytokines; Ghrelin; Humans; Inflammation Mediators; Kidney Diseases; Leptin; Nutritional Status; Peptide Hormones

Poor periodontal health is known to be associated with Type 2 diabetes mellitus (DM). This relationship and underlying mechanisms are discussed elsewhere in this issue. Less is known concerning the link between the metabolic precursors to DM, including insulin resistance (IR), and its possible association with periodontitis. Indeed, there has been relatively little research to date in human populations concerning periodontal disease, IR, and the subsequent risk of chronic diseases, including DM. This paper will present an epidemiologist's view of how IR may link periodontal disease with DM and suggest several avenues of investigation to help clarify some of the outstanding issues.

Topics: Adipocytes; Animals; Chronic Disease; Diabetes Mellitus, Type 2; Disease Models, Animal; Epidemiologic Methods; Forecasting; Glucose Clamp Technique; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Models, Biological; Periodontal Diseases; Periodontitis; Research Design; Risk Factors; Tumor Necrosis Factor-alpha

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; Auditory Threshold; Aurora Kinase B; Australia; Autophagy; Autophagy-Related Protein 5; Autotrophic Processes; Bacillus cereus; Bacillus thuringiensis; Bacterial Proteins; Beclin-1; Belgium; Benzene; Benzene Derivatives; Benzhydryl Compounds; beta Catenin; beta-Arrestin 2; Biliary Tract Diseases; Biofilms; Biofuels; Biomarkers; Biomarkers, Tumor; Biomass; Biomechanical Phenomena; Bioreactors; Biosensing Techniques; Biosynthetic Pathways; Bismuth; Blood Platelets; Bone and Bones; Bone Regeneration; Bortezomib; Botulinum Toxins, Type A; Brain; Brain Injuries; Brain Ischemia; Brain Neoplasms; Breast Neoplasms; Breath Tests; Bronchodilator Agents; Calcium Phosphates; Cannabis; Carbon Dioxide; Carbon Isotopes; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiomyopathies; Cardiovascular Diseases; Cariostatic Agents; Case Managers; Case-Control Studies; Catalysis; Cation Transport Proteins; CD8-Positive T-Lymphocytes; Cecropia Plant; Cell Adhesion; Cell Count; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Self Renewal; Cell Survival; Cells, Cultured; Cellular Reprogramming; Cellulose; Charcoal; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemokines; Chemoradiotherapy; Chemoreceptor Cells; Child; Child Abuse; Child, Preschool; China; Chlorogenic Acid; Chloroquine; Chromatography, Gas; Chronic Disease; Clinical Competence; Coated Materials, Biocompatible; Cochlea; Cohort Studies; Color; Comorbidity; Computer Simulation; Computer-Aided Design; Contraception; Contraceptive Agents, Female; Contrast Media; COP-Coated Vesicles; Coronavirus Infections; Cost of Illness; Coturnix; COVID-19; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Culex; Curriculum; Cyclic N-Oxides; Cytokines; Cytoplasm; Cytotoxicity, Immunologic; Cytotoxins; Databases, Factual; Deep Learning; Delivery, Obstetric; Denitrification; Dental Caries; Denture, Complete; Dexamethasone; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dielectric Spectroscopy; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Disease Progression; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Dog Diseases; Dogs; Dopaminergic Neurons; Double-Blind Method; Down-Regulation; Doxorubicin; Drug Carriers; Drug Design; Drug Interactions; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Dry Powder Inhalers; Dust; E2F1 Transcription Factor; Ecosystem; Education, Nursing; Education, Nursing, Baccalaureate; Electric Impedance; Electricity; Electrocardiography; Electrochemical Techniques; Electrochemistry; Electrodes; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum; Endothelial Cells; Environmental Monitoring; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Estrogen Receptor Modulators; Europe; Evoked Potentials, Auditory, Brain Stem; Exosomes; Feasibility Studies; Female; Ferricyanides; Ferrocyanides; Fibrinogen; Finite Element Analysis; Fistula; Fluorescent Dyes; Fluorides, Topical; Fluorodeoxyglucose F18; Fluticasone; Follow-Up Studies; Food Contamination; Food Microbiology; Foods, Specialized; Forensic Medicine; Frail Elderly; France; Free Radicals; Fresh Water; Fungi; Fungicides, Industrial; Galactosamine; Gastrointestinal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Gingival Hemorrhage; Glioblastoma; Glioma; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucose; Glucose Transport Proteins, Facilitative; Glucosides; Glutamine; Glycolysis; Gold; GPI-Linked Proteins; Gram-Negative Bacteria; Gram-Positive Bacteria; Graphite; Haplotypes; HCT116 Cells; Healthy Volunteers; 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

The gut microbiota is known to be related to type 2 diabetes (T2D), psychiatric conditions, and opioid use. In this study, we tested the hypothesis that variability in gut microbiota in T2D is associated with psycho-metabolic health.. A cross-sectional study was conducted among African American men (AAM) (n = 99) that were outpatients at a Chicago VA Medical Center. The main outcome measures included fecal microbiota ecology (by 16S rRNA gene sequencing), psychiatric disorders including opioid use, and circulating leptin and oxytocin as representative hormone biomarkers for obesity and psychological pro-social behavior.. The study subjects had prevalent overweight/obesity (78%), T2D (50%) and co-morbid psychiatric (65%) and opioid use (45%) disorders. In the analysis of microbiota, the data showed interactions of opioids, T2D and metformin with Bifidobacterium and Prevotella genera. The differential analysis of Bifidobacterium stratified by opioids, T2D and metformin, showed significant interactions among these factors indicating that the effect of one factor was changed by the other (FDR-adjusted p [q] < 0.01). In addition, the pair-wise comparison showed that participants with T2D not taking metformin had a significant 6.74 log2 fold increase in Bifidobacterium in opioid users as compared to non-users (q = 2.2 x 10-8). Since metformin was not included in this pair-wise comparison, the significant 'q' suggested association of opioid use with Bifidobacterium abundance. The differences in Bifidobacterium abundance could possibly be explained by opioids acting as organic cation transporter 1 (OCT1) inhibitors. Analysis stratified by lower and higher leptin and oxytocin (divided by the 50th percentile) in the subgroup without T2D showed lower Dialister in High-Leptin vs. Low-Leptin (p = 0.03). Contrary, the opposite was shown for oxytocin, higher Dialister in High-Oxytocin vs. Low-Oxytocin (p = 0.04).. The study demonstrated for the first time that Bifidobacterium and Prevotella abundance was affected by interactions of T2D, metformin and opioid use. Also, in subjects without T2D Dialister abundance varied according to circulating leptin and oxytocin.

Topics: Bacteria; Black or African American; Chronic Disease; Cost of Illness; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Humans; Leptin; Male; Metformin; Opioid-Related Disorders; Oxytocin

Some angiotensin receptor blockers (ARBs), including irbesartan, increase the peroxisome proliferator-activated receptor (PPAR)-g activity in vitro. The aim of this study was to evaluate the interactions between obesity and the effects of irbesartan on inflammatory cytokines in chronic glomerulonephritis patients without diabetes.. The anti-inflammatory effects of irbesartan were evaluated in 29 hypertensive chronic glomerulonephritis patients without diabetes in a prospective, single-arm study.. Following treatment with irbesartan for 26 weeks, blood pressure and proteinuria significantly decreased, as previously reported (blood pressure decreased from 142±1/87±1 to 131±1/81±1 mmHg and the urine protein/creatinine ratio decreased from 1030±143 to 779±121 mg/g Cr). BMI did not significantly change after the study. Among the inflammatory parameters, the concentrations of adiponectin and high-sensitivity C-reactive protein (hsCRP) significantly improved after treatment; however, the changes in the concentrations of interleukin-6 (IL-6), tumor necrosis factor (TNF)-a and leptin did not reach statistical significance. Moreover, the changes in these five parameters following treatment were moderately correlated with the BMI values obtained at the initiation of the study, and the improvements were particularly prominent in those with a BMI greater than 25. Improvements in proteinuria were significantly correlated with increases in the adiponectin concentration, but not with BMI. There was also a moderate correlation between the changes in the adiponectin and insulin concentrations.. Irbesartan improves metabolic parameters in nondiabetic hypertensive chronic glomerulonephritis patients, especially those with a high BMI. Improving the adiponectin concentration may be important for reducing proteinuria.

Topics: Adiponectin; Angiotensin II Type 1 Receptor Blockers; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Body Mass Index; C-Reactive Protein; Chronic Disease; Cytokines; Female; Glomerulonephritis; Humans; Hypertension; Inflammation Mediators; Interleukin-6; Irbesartan; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Proteinuria; Tetrazoles; Tumor Necrosis Factor-alpha

Chronic heart failure (CHF) is characterized by increased insulin resistance and hyperleptinaemia. We aimed to study effects of selective and non-selective beta-blockers on body weight, insulin resistance, plasma concentrations of leptin and resistin in patients with CHF.. Twenty-six non-cachectic beta-blocker-naive patients with CHF were randomized and treated with either carvedilol or bisoprolol. Body weight, plasma concentrations of leptin, resistin, fasting glucose and insulin were measured at baseline and after 6 months of therapy. Insulin resistance was estimated by homeostasis model assessment- estimated insulin resistance (HOMA-IR).. Body weight increased significantly in the carvedilol group (mean change + 2.30 kg, p = 0.023) while it did not change in the bisoprolol group (mean change -0.30 kg, p = 0.623) (ns between groups). Plasma leptin concentration increased only in the carvedilol group (mean change + 4.20 ng/ml, p = 0.019) (ns between groups). Fasting glucose and resistin remained unchanged in both groups. After 6 months, mean plasma insulin concentration changed significantly differently (p = 0.015) in the bisoprolol (mean change +3.1 microU/ml) compared to the carvedilol group (mean change -6.3 microU/ml) and HOMA-IR was consequently higher in the bisoprolol compared to the carvedilol group (5.2 +/- 4.2 vs 2.8 +/- 1.6, p = 0.046).. This study found different metabolic effects of carvedilol and bisoprolol in non-cachectic patients with CHF. With unchanged fasting plasma glucose concentration after 6 months of treatment, carvedilol significantly decreased plasma insulin concentration and insulin resistance compared to bisoprolol.

Topics: Adrenergic beta-Antagonists; Aged; Bisoprolol; Blood Glucose; Body Weight; Carbazoles; Carvedilol; Chronic Disease; Female; Heart Failure; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Propanolamines; Resistin

Acute immune thrombocytopenic purpura (ITP) induces thrombocytopenia by means of an autoimmune mechanism. Recent studies suggested that T helper immune response is responsible for the pathogenesis of chronic ITP. Despite several studies that were carried out, we do not have a clue as to what triggers the autoimmunity. Leptin is a 16-kd protein secreted from the adipose tissue. Leptin is structurally similar to interleukin (IL)-2, IL-6, and IL-15. The structural similarities between leptin receptor and hematopoietic cytokine receptors suggested that leptin could play a role in hematopoiesis and immune function. Recent studies suggested that leptin could play an important role in autoimmunity. We made a prospective analysis of a series of 39 newly diagnosed acute childhood ITP in a year period. Serum leptin levels were obtained after diagnosis and before treatment and all patients were followed up at least 6 months to designate acute or chronic event. We conclude that in childhood acute ITP, leptin did not play a role in the pathophysiology of the disease. Further investigations are needed to examine what triggers T cells and how the autoimmune disease became.

Topics: Acute Disease; Autoimmunity; Child; Child, Preschool; Chronic Disease; Cytokines; Female; Follow-Up Studies; Humans; Infant; Leptin; Male; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Structural Homology, Protein; T-Lymphocytes, Helper-Inducer

Weight gain is a problem commonly encountered with antipsychotic treatment and has become more apparent with increasing use of the newer atypical antipsychotics. The adipocyte-derived hormone, leptin, has been associated with body weight and energy homeostasis, and abnormal regulation of leptin could play a role in weight gain induced by antipsychotics. We investigated whether a leptin gene promoter variant affected weight gain after long-term treatment with clozapine in chronic schizophrenia. Leptin G2548A polymorphism was genotyped in 102 Chinese Han inpatients with chronic schizophrenia treated with clozapine. Weight gains, expressed as change in body mass index (BMI), were monitored after long-term clozapine treatment. We found a significant relationship between the 3 leptin G/A genotypes and mean BMI gain (F(2,99) = 3.35, P = 0.039, r(2) = 0.09). Moreover, genotype had a strong effect on BMI gain in male (P = 0.004, r(2) = 0.16), but not in female patients (P > 0.05). Thus, variation in the leptin gene may be a risk factor for weight gain in male patients with schizophrenia on long-term clozapine treatment.

Topics: Antipsychotic Agents; Asian People; Body Mass Index; China; Chronic Disease; Clozapine; Female; Genotype; Humans; Leptin; Male; Middle Aged; Pharmacogenetics; Polymorphism, Genetic; Promoter Regions, Genetic; Schizophrenia; Weight Gain

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

Abnormal regulation of the adipocyte-derived hormone leptin could play a role in body weight gain induced by antipsychotics.. To study the effects of long-term antipsychotic treatment on leptin levels in patients with schizophrenia.. Serum leptin levels were determined in 59 out-patients with chronic schizophrenia and in the same number of healthy subjects controlled by gender, age and body mass index.. Leptin levels did not differ between patients and controls. Leptin levels in patients with schizophrenia correlated with weight gain, even after controlling for current weight, but did not show any association with clinical variables. Antipsychotic class tended to exert different effects over leptin levels (among atypicals, olanzapine induced a greater increase).. Elevation of leptin levels induced by chronic antipsychotic treatment can be attributed to weight gain, but other mechanisms could be involved.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Chronic Disease; Female; Humans; Leptin; Male; Schizophrenia; Weight Gain

Leptin plays a role in central nervous system developmental programs and intercurrent physiological processes related to body fat regulation. The timing and neuromolecular mechanisms for these effects are relevant to the prevention and treatment of obesity. Factors implicated in a body weight "set point" including dietary fat, circulating leptin, and other adipokines tend to covary with adiposity and are difficult to disarticulate experimentally. To dissociate leptin effects from adiposity and diet, we created a transgenic mouse in which leptin expression is regulated by doxycycline exposure. Using this system, we investigated the physiological consequences of developmentally-timed transient hyperleptinemia on subsequent adiposity. We evaluated physiological effects of leptin elevation during adulthood (9 to 29 weeks old), "adolescence" (3 to 8 weeks old), and the immediate postnatal period [postnatal days 0 to 22 (P0 to P22)] on long-term adiposity and susceptibility to gain weight on high-fat diet (HFD) fed ad libitum. We found that inducing chronic hyperleptinemia in adult or "adolescent" mice did not alter body weight when excess leptin was discontinued, and upon later exposure to HFD, weight gain did not differ from controls. However, transient elevation of circulating leptin from P0 to P22 increased weight and fat gain in response to HFD, indicating greater susceptibility to obesity as adults. Thus, transient plasma leptin elevations-mimicking one aspect of transient adiposity-increased later susceptibility to diet-induced obesity, although these effects were restricted to a critical developmental (P0 to P22) time window. These findings may have clinical implications for weight management in infancy.

Topics: Aging; Animals; Animals, Newborn; Body Weight; Chronic Disease; Doxycycline; Female; Leptin; Male; Mice, Inbred C57BL; Mice, Transgenic; Reproducibility of Results

Leptin and ghrelin and a "cross-talk" between both hormones were implicated in the pathophysiology of alcohol dependence, both modulating alcohol craving and drug-seeking. To date, the neurobiological mechanisms underlying those effects are still little-known. We thus investigated the effect of leptin and ghrelin on alcohol cue-induced brain response, alcohol craving and relapse risk in alcohol-dependent subjects. Seventy abstinent alcohol dependent individuals underwent a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task and patients` alcohol craving was assessed. Plasma levels of leptin, total and acylated, active ghrelin were measured prior to the fMRI session. Additionally, relapse data was collected during a three-month follow-up. Associations between hormone levels, mesolimbic cue-reactivity, alcohol craving and relapse risk were tested. Leptin levels showed a significant negative association to alcohol cue-induced brain response in the striatum and alcohol craving. In addition, there was a significant effect of leptin on time to first heavy relapse in which higher leptin levels predicted longer times to first heavy relapse. Moreover, positive associations between acylated ghrelin and increased cue-reactivity in bilateral insulae as well as increased craving for alcohol during the fMRI task were revealed. Leptin and acylated ghrelin show opposing effects on mesolimbic cue-reactivity and alcohol craving. We suspect that the reduced striatal cue-reactivity might be the neurobiological correlate of leptin's effect on relapse-risk. The reported results further support the relevance of appetite regulating hormones in the pathophysiology of addiction and their potential role as future treatment targets.

Topics: Adolescent; Adult; Aged; Alcohol Abstinence; Alcohol Drinking; Alcoholism; Brain; Chronic Disease; Conditioning, Psychological; Craving; Cues; Ethanol; Ghrelin; Humans; Leptin; Magnetic Resonance Imaging; Middle Aged; Nerve Net; Recurrence; Young Adult

Introduction: Over the years, heart failure remains one of the most common and prognostically unfavorable conditions. The aim of our study was to determine the frequency of complications in patients with CHF depending on the body weight and intoxication syndrome of varying degrees of severity.. Materials and methods: A complete clinical examination was performed in 58 patients (41 (70.6%) men and 17 (29.4%) women) with CHF. In addition to the standard examination in accordance with the protocol, the level of endogenous intoxication was determined by the level of medium-weight molecules (MWM254) and leptin. The patients were randomized into 4 groups depending on their body mass index and the degree of endogenous intoxication. Statistical processing of the results was carried out using the methods of variation statistics "Statistica 6.0".. Results: It was revealed that the worst survival rate is observed in patients with normal body mass against the background of the expressed endogenous intoxication syndrome, the best survival rate is observed provided that there are a normal body mass and endogenous intoxication of a minimum degree. An inverse correlation between the body mass index and the endogenous intoxication indicator (blood MWM) was detected. Patients with CHF should have their leptin level evaluated. An increase in its level was associated with arterial hypertension, an increase in blood glucose levels and lipid metabolism disorders.. Conclusions: Increased level of blood MWM worsens the forecast of CHF. The unfavorable outcome was observed in patients with the combination of hypoleptinemia with severe endogenous intoxication.

Topics: Body Mass Index; Body Weight; Chronic Disease; Female; Heart Failure; Humans; Leptin; Male; Prognosis

Stress exposure is known to trigger and exacerbate functional dyspepsia (FD) symptoms. Increased gastric sensitivity to food-related stimuli is widely observed in FD patients and is associated with stress and psychological disorders. The mechanisms underlying the hypersensitivity are not clear. Gastric vagal afferents (GVAs) play an important role in sensing meal-related mechanical stimulation to modulate gastrointestinal function and food intake. This study aimed to determine whether GVAs display hypersensitivity after chronic stress, and whether its interaction with leptin was altered by stress.. Eight-week-old male C57BL/6 mice were exposed to unpredictable chronic mild stress or no stress (control) for 8 weeks. The metabolic rate, gastric emptying rate, and anxiety- and depression-like behaviors were determined. GVA mechanosensitivity, and its modulation by leptin, was determined using an in vitro single fiber recording technique. QRT-PCR was used to establish the levels of leptin and leptin receptor mRNA in the stomach and nodose ganglion, respectively.. The stressed mice had lower body weight and food intake, and increased anxiety-like behavior compared to the control mice. The mechanosensitivity of mucosal and tension-sensitive GVAs was higher in the stressed mice. Leptin potentiated mucosal GVA mechanosensitivity in control but not stressed mice. The expression of leptin mRNA in the gastric mucosa was lower in the stressed mice.. In conclusion, chronic stress enhances GVA mechanosensitivity, which may contribute to the gastric hypersensitivity in FD. In addition, the modulatory effect of leptin on GVA signaling is lost after chronic stress exposure.

Topics: Afferent Pathways; Animals; Anxiety; Blood Glucose; Chronic Disease; Corticosterone; Depression; Exploratory Behavior; Feeding Behavior; Gastric Emptying; Humans; Leptin; Male; Maze Learning; Mechanoreceptors; Mice; Mice, Inbred C57BL; Noxae; Stress, Psychological; Sucrose; Swimming; Vagus Nerve

Leptin is an adipo-myokine that regulates appetite and energy expenditure by a neuroendocrine feedback loop. Leptin levels are positively correlated with BMI in the spinal cord injury population and leptin levels are greater in individuals with spinal cord injury compared to uninjured controls. Leptin is produced in multiple tissues, including fat, bone, and skeletal muscle and is a putative biomarker of sedentary behavior in older adults. We assessed body composition leptin, adiponectin, and IL-6 levels in 205 men with chronic spinal cord injury. We found no association between age, injury duration, injury level, injury completeness, or walking status and leptin. There was a significant positive association between lean mass and leptin in men with SCI that was independent of fat. Adjusting for body composition, leptin levels were positively associated with IL-6 and negatively associated with adiponectin levels. When considering men with SCI and sarcopenic obesity, only fat mass remained positively associated with leptin. We found no association between IL-6, adiponectin, or lean mass and leptin in the sarcopenic obesity group. Our findings suggest that lean mass is an under recognized, but substantial, source of circulating leptin. Furthermore, SCI-related sarcopenic obesity may result in dysregulated adipo-myokine metabolism with local and systemic physiologic effects.

Topics: Adult; Aged; Aged, 80 and over; Body Composition; Chronic Disease; Humans; Leptin; Male; Middle Aged; Spinal Cord Injuries; Young Adult

Overweight, obesity and some chronic diseases have become more prevalent recently. It is well known that their causes may be genetic, epigenetic, environmental, or a mixture of these. . To analyze the relationship between nine single nucleotide polymorphisms of genes LEP (rs2167270), LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) and APOA4 (rs5095, rs675, rs5110) with obesity-related phenotypes and other comorbidities. . We recruited 144 adults (76 males and 68 females, with average ages of 29.93±8.29 and 32.49±11.15 years, respectively) in the State of Sucre, Venezuela. Clinical and anthropometric parameters were obtained. Genotype-risk associations were studied. We then compared the averages registered for anthropometric and biochemical variables previously adjusted for biological and environmental factors. . According to the body mass index, 38.9% of the individuals in the sample were overweight (25≤BMI≤29.9 kg/m2) and 20.1% were obese (BMI≥30 kg/m2). Genotype and allele frequencies did not differ statistically for groups with normal and high body mass index (overweight plus obesity). The association between LDLR rs5742911 ancestral genotype A/A and high risk condition related to HDL-cholesterol was the only one found to be significant (OR=2.944, 95% CI: 1.446-5.996; p=0.003). The difference in adjusted mean HDL-cholesterol for LDLR rs5742911 genotypes was statistically significant (p=0.005) (A/A: 41.50±14.81 mg/dL; A/G: 45.00±12.07 mg/dL; G/G: 47.17±9.43 mg/dL). . For most of the genetic variants studied, there was an association with the presence of overweight and obesity among ancestral genotype carriers, although this was not statistically significant. The rs5742911 polymorphism may be useful as an indicator of a risk of chronic diseases.

Topics: Adolescent; Adult; Aged; Anthropometry; Apolipoproteins A; Blood Glucose; Chronic Disease; Dyslipidemias; Female; Genetic Association Studies; Habits; Humans; Leptin; Life Style; Lipids; Male; Middle Aged; Obesity; Overweight; Polymorphism, Single Nucleotide; Receptors, LDL; Socioeconomic Factors; Venezuela; Young Adult

Disruption of the circadian system can lead to metabolic dysfunction as a response to environmental alterations. This study assessed the effects of the association between obesity and chronic stress on the temporal pattern of serum levels of adipogenic markers and corticosterone in rats. We evaluated weekly weight, delta weight, Lee index, and weight fractions of adipose tissue (mesenteric, MAT; subcutaneous, SAT; and pericardial, PAT) to control for hypercaloric diet-induced obesity model efficacy. Wistar rats were divided into four groups: standard chow (C), hypercaloric diet (HD), stress plus standard chow (S), and stress plus hypercaloric diet (SHD), and analyzed at three time points: ZT0, ZT12, and ZT18. Stressed animals were subjected to chronic stress for 1h per day, 5 days per week, during 80 days. The chronic exposure to a hypercaloric diet was an effective model for the induction of obesity and metabolic syndrome, increasing delta weight, Lee index, weight fractions of adipose tissue, and triglycerides and leptin levels. We confirmed the presence of a temporal pattern in the release of triglycerides, corticosterone, leptin, and adiponectin in naïve animals. Chronic stress reduced delta weight, MAT weight, and levels of triglycerides, total cholesterol, and leptin. There were interactions between chronic stress and obesity and serum total cholesterol levels, between time points and obesity and adiponectin and corticosterone levels, and between time points and chronic stress and serum leptin levels. In conclusion, both parameters were able to desynchronize the temporal pattern of leptin and triglyceride release, which could contribute to the development of metabolic diseases such as obesity and metabolic syndrome.

Topics: Adiponectin; Adipose Tissue, White; Adiposity; Animals; Cholesterol; Chronic Disease; Circadian Rhythm; Corticosterone; Leptin; Male; Obesity; Rats; Rats, Wistar; Restraint, Physical; Stress, Psychological; Triglycerides; Weight Gain

Sugar intake may be causally associated with chronic disease risk, either directly or by contributing to obesity. However, evidence from observational studies is mixed, in part due to the error and bias inherent in self-reported measures of sugar intake. Objective biomarkers may clarify the relationship between sugar intake and chronic disease risk. We have recently validated a biomarker of sugar intake in an Alaska Native (Yup'ik) study population that incorporates red blood cell carbon and nitrogen isotope ratios in a predictive model. This study tested associations of isotopic estimates of sugar intake with body mass index (BMI), waist circumference (WC) and a broad array of other physiological and biochemical measures of chronic disease risk in Yup'ik people.. In a cross-sectional sample of 1076 Yup'ik people, multiple linear regression was used to examine associations of sugar intake with BMI, WC and other chronic disease risk factors.. Isotopic estimates of sugar intake were not associated with BMI (P=0.50) or WC (P=0.85). They were positively associated with blood pressure, triglycerides (TG) and leptin, and are inversely associated with total-, high-density lipoprotein- and low-density lipoprotein-cholesterol and adiponectin.. Isotopic estimates of sugar intake were not associated with obesity, but were adversely associated with other chronic disease risk factors in this Yup'ik study population. This first use of stable isotope markers of sugar intake may influence recommendations for sugar intake by Yup'ik people; however, longitudinal studies are required to understand associations with chronic disease incidence.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Alaska; Biomarkers; Blood Pressure; Body Mass Index; Carbon Isotopes; Chronic Disease; Cross-Sectional Studies; Dietary Carbohydrates; Female; Humans; Indians, North American; Leptin; Linear Models; Male; Middle Aged; Nitrogen Isotopes; Obesity; Risk Factors; Triglycerides; Waist Circumference; Young Adult

Suppression of body weight and symptom of anorexia are major symptoms of depression. Recently, we reported that chronic social defeat stress (CSDS) induced suppression of body weight gain and anorexic feeding behavior in rats. These abnormalities were the result of disrupted malonyl-coenzyme A (CoA) signaling pathway in the hypothalamus. However, the condition of peripheral leptin and its hypothalamic downstream signal molecules which regulate hypothalamic malonyl-CoA level in the CSDS-exposed rats (CSDS rats) is still unknown.. CSDS rats showed suppressed body weight gain and food intake. The weight of the CSDS rats' epididymal white adipose tissues was decreased when compared to the control rats. The plasma cholesterol concentration was decreased significantly in the CSDS rats compared to the control rats (P < 0.05). The plasma glucose concentration was slightly decreased in the CSDS rats compared to the control rats (P < 0.1). The expression of leptin mRNA in epididymal white adipose tissues and the plasma leptin concentration were decreased in CSDS rats. Furthermore, the phosphorylation of the hypothalamic downstream signals of leptin, including extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3), was decreased in CSDS rats.. Our results indicated that decreased peripheral leptin expression in CSDS rats could down-regulate the hypothalamic downstream signaling pathways of leptin while suppressed food intake. These data indicate that CSDS induces the down-regulation of hypothalamic AMPK following the elevation of hypothalamic malonyl-CoA levels and is independent of peripheral leptin and glucose.

Topics: Adaptation, Psychological; Animals; Anorexia; Chronic Disease; Depression; Eating; Hypothalamus; Leptin; Male; Rats; Rats, Wistar; Social Dominance; Stress, Psychological; Weight Gain

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

We investigated the associations of the LEP-2548A/G and HTR2C-759C/T polymorphisms with long-term clozapine-induced weight changes and baseline BMI in chronic patients with schizophrenia.. A total of 113 patients receiving clozapine for at least 1 year were enrolled. Body weight was measured cross-sectionally and data on body weight just before starting clozapine were retrospectively extracted from medical records.. Clozapine-induced change in BMI was correlated inversely with the baseline BMI (P<0.001, ρ=-0.347). The LEP-2548A/G polymorphism was associated significantly with the change in BMI (F=4.380, P=0.015) during clozapine use; those with the AA genotype had the highest BMI gain (1.4±3.1 kg/m), followed by those with the AG (-0.2±3.3 kg/m) and GG (-1.6±3.4 kg/m) genotypes. We also found a significant association between the leptin genotype and BMI at baseline (F=3.499, P=0.034); those with the AA genotype had the lowest baseline BMI (23.4±4.3 kg/m), followed by those with the AG (24.1±4.4 kg/m) and GG (28.8±7.3 kg/m) genotypes. In the case of the HTR2C-759C/T polymorphism, we found a trend in which T alleles were more prevalent in male patients with up to 7% increase in BMI than in those with a greater than 7% increase in BMI [12/54 (22.7%) vs. 1/27 (3.7%); Fisher's exact test: P=0.051].. This study shows an inverse correlation between the baseline BMI and change in BMI during long-term clozapine use in patients with schizophrenia, and the LEP-2548A/G polymorphism was associated significantly with both these measures.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Chronic Disease; Clozapine; Humans; Leptin; Middle Aged; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2C; Schizophrenia; Weight Gain

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

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

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

Although the etiology of two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are unknown and evidence suggests that chronic intestinal inflammation is caused by an excessive immune response to mucosal antigens. Previous studies support the role for TGF-β1 through 3 in the initiation and maintenance of tolerance via the induction of regulatory T cells (Tregs) to control intestinal inflammation. Leptin, a satiety hormone produced primarily by adipose tissue, has been shown to increase during colitis progression and is believed to contribute to disease genesis and/or progression.. We investigated the ability of a pegylated leptin antagonist (PG-MLA) to ameliorate the development of chronic experimental colitis.. Compared to vehicle control animals, PG-MLA treatment of mice resulted in an (1) attenuated clinical score; (2) reversed colitis-associated pathogenesis including a decrease in body weight; (3) reduced systemic and mucosal inflammatory cytokine expression; (4) increased insulin levels and (5) enhanced systemic and mucosal Tregs and CD39⁺ Tregs in mice with chronic colitis. The percentage of systemic and mucosal TGF-β1, -β2 and -β3 expressing CD4⁺ T cells were augmented after PG-MLA treatment. The activation of STAT1 and STAT3 and the expression of Smad7 were also reduced after PG-MLA treatment in the colitic mice. These findings clearly suggest that PG-MLA treatment reduces intestinal Smad7 expression, restores TGF-β1-3 signaling and reduces STAT1/STAT3 activation that may increase the number of Tregs to ameliorate chronic colitis.. This study clearly links inflammation with the metabolic hormone leptin suggesting that nutritional status influences immune tolerance through the induction of functional Tregs. Inhibiting leptin activity through PG-MLA might provide a new and novel therapeutic strategy for the treatment of IBD.

Topics: Animals; Antigens, CD; Apyrase; Body Weight; Chronic Disease; Colitis; Down-Regulation; Female; Insulin; Interleukin-10; Intestinal Mucosa; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Polyethylene Glycols; Recombinant Proteins; Signal Transduction; Smad7 Protein; STAT1 Transcription Factor; STAT3 Transcription Factor; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

The aim of this study was assess the role of chronic stress on the metabolic and nutritional profile of rats exposed to a high-fat diet.. Thirty-day-old male Wistar rats (70-100 g) were distributed into four groups: normal-diet (NC), chronic stress (St), high-fat diet (HD), and chronic stress/high-fat diet (HD/St). Stress consisted at immobilization during 15 weeks, 5 times per week, 1h per day; and exposure to the high-fat diet lasted 15 weeks. Nutritional and metabolic parameters were assessed. The level of significance was 5%.. The HD group had final body weight, total fat, as well as insulin and leptin increased, and they were insulin resistant. The St and HD/St had arterial hypertension and increased levels of corticosterone. Stress blocked the effects of the high-fat diet.. Chronic stress prevented the appearance of obesity. Our results help to clarify the mechanisms involved in metabolic and nutritional dysfunction, and contribute to clinical cases linked to stress and high-fat diet.

Topics: Adiposity; Analysis of Variance; Animals; Anti-Inflammatory Agents; Blood Glucose; Body Composition; Chronic Disease; Corticosterone; Diet, High-Fat; Eating; Energy Intake; Hypoglycemic Agents; Immobilization; Insulin; Leptin; Male; Nutritional Status; Obesity; Rats, Wistar; Stress, Physiological

Both chronic stress and antidepressant medications have been associated with changes in body weight. In the current study, we investigate mechanisms by which stress and antidepressants interact to affect meal patterns. A group of mice was subjected to the chronic social defeat stress model of major depression followed by fluoxetine treatment and was subsequently analyzed for food intake using metabolic cages. We report that chronic social defeat stress increases food intake by specifically increasing meal size, an effect that is reversed by fluoxetine treatment. In an attempt to gain mechanistic insight into changes in meal patterning induced by stress and fluoxetine, fasting serum samples were collected every 4h over a 24-h period, and acyl-ghrelin, leptin, and corticosterone levels were measured. Chronic stress induces a peak in acyl-ghrelin levels just prior to the onset of the dark phase, which is shifted in mice treated with fluoxetine. Taken together, these results indicate that stress increases food intake by decreasing satiation, and that fluoxetine can reverse stress-induced changes in meal patterns.

Topics: Animals; Antidepressive Agents, Second-Generation; Chronic Disease; Corticosterone; Eating; Energy Intake; Fluoxetine; Ghrelin; Leptin; Meals; Mice; Obesity; Satiation; Selective Serotonin Reuptake Inhibitors; Social Environment; Stress, Psychological

Across species obesity is associated with several disorders but in companion animals little information is available on the impact of chronic obesity on immune competence. The aim of the present study was to investigate whether weight gain and stable obese bodyweight affects the immune cell response. Obesity was induced in eight adult healthy beagle dogs (weight gain group; WGG) by a weight gain period (WGP) of 47 weeks, which was immediately followed by a period (stable period: SP) of stable obesity of 26 weeks. Eight adult healthy beagle dogs were included as a control group (CG) and remained at their ideal bodyweight throughout the entire study. Body composition was measured at five intervening time-points. Concentration of serum leptin and inflammatory cytokines, functionality of lymphocytes and phagocytic activity of neutrophils and monocytes were evaluated at ten intervening time-points. Serum leptin concentration was rising during the WGP in the WGG but went to lower concentrations during the SP. At the end of long-term weight gain, a decreased mitogen-induced proliferation of T-lymphocytes was noted but this alteration seemed to be transient after stabilization of bodyweight. This finding may imply an altered immune response for dogs with different energy balances. However, no systemic low grade inflammation or alteration in other immune cell functions was observed. Consequently it is suggested that the change in energy balance during the onset of obesity (becoming obese versus being obese), evokes an additional obesity-related disorder in dogs, i.e. impaired T-lymphocyte immune function.

Topics: Animals; Case-Control Studies; Cell Proliferation; Chronic Disease; Cytokines; Dog Diseases; Dogs; Energy Intake; Female; Leptin; Lymphocyte Activation; Male; Obesity; T-Lymphocytes; Weight Gain

Chronic stress and diet can independently or in concert influence the body's homeostasis over time. Thus, it is crucial to investigate the interplay of these parameters to gain insight into the evolution of stress-induced metabolic and eating disorders.. C57BL/6J mice were subjected to chronic psychosocial (mixed model of social defeat and overcrowding) stress in combination with either a high- or low-fat diet for three or six weeks. To determine the evolution of stress and dietary effects, changes in body weight, caloric intake and caloric efficiency were determined as well as circulating leptin, insulin, glucose and corticosterone levels and social avoidance behaviour.. Exposure to stress for three weeks caused an increase in weight gain, in caloric intake and in caloric efficiency only in mice on a low-fat diet. However, after six weeks, only stressed mice on a high-fat diet displayed a pronounced inhibition of body weight gain, accompanied by reduced caloric intake and caloric efficiency. Stress decreased circulating leptin levels in mice on a low-fat diet after three weeks and in mice on a high-fat diet after three and six weeks of exposure. Plasma levels of insulin and markers of insulin resistance were blunted in mice on high-fat diet following six weeks of stress exposure. Social avoidance following chronic stress was present in all mice after three and six weeks.. This study describes the evolution of the chronic effects of social defeat/overcrowding stress in combination with exposure to high- or low-fat diet. Most importantly, we demonstrate that a six week chronic exposure to social defeat stress prevents the metabolic effects of high-fat diet, by inhibiting an increase in weight gain, caloric intake and efficiency and insulin resistance as well as in plasma leptin and insulin levels. This study highlights the importance of considering the chronic aspects of both parameters and their time-dependent interplay.

Topics: Animals; Blood Glucose; Body Weight; Chronic Disease; Corticosterone; Crowding; Diet, High-Fat; Energy Intake; Insulin; Interpersonal Relations; Leptin; Male; Mice; Mice, Inbred C57BL; Social Dominance; Social Environment; Stress, Psychological; Weight Gain

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

Leptin is an adipokine with both protective and harmful effects on the cardiovascular (CV) system. Prior studies evaluating the association between leptin and CV outcomes have yielded conflicting results. Thus, we sought to investigate the relationship between leptin and CV events and mortality in patients with chronic stable coronary artery disease (CAD).. We performed a prospective cohort study of 981 outpatients with stable CAD. Leptin levels were measured in fasting venous samples at baseline. We used proportional hazards models to evaluate the association of baseline leptin with subsequent CV events (myocardial infarction, stroke, transient ischemic attack) and death.. During a mean follow-up of 6.2±2.1 years, there were 304 deaths, 112 myocardial infarctions, and 52 strokes/TIAs. In models adjusted for age, sex, and race, low leptin was associated with a 30% increased risk of the combined outcome (HR 1.30, CI 1.05-1.59, p=0.01). After further adjustment for obesity, traditional CV risk factors and biomarkers, low leptin remained associated with a 37% increased risk of events (HR 1.37, CI 1.06-1.76, p=0.02).. Low leptin is associated with increased CV events and mortality in patients with stable coronary artery disease. This association is independent of known factors affecting leptin levels, including gender and obesity.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Chronic Disease; Coronary Artery Disease; Down-Regulation; Female; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Leptin; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; San Francisco; Stroke

Chronic intermittent hypoxia (IH) during sleep can result from obstructive sleep apnea (OSA), a disorder that is particularly prevalent in obesity. OSA is associated with high levels of circulating leptin, cardiovascular dysfunction, and dyslipidemia. Relationships between leptin and cardiovascular function in OSA and chronic IH are poorly understood. We exposed lean wild-type (WT) and obese leptin-deficient ob/ob mice to IH for 4 wk, with and without leptin infusion, and measured cardiovascular indices including aortic vascular stiffness, endothelial function, cardiac myocyte morphology, and contractile properties. At baseline, ob/ob mice had decreased vascular compliance and endothelial function vs. WT mice. We found that 4 wk of IH decreased vascular compliance and endothelial relaxation responses to acetylcholine in both WT and leptin-deficient ob/ob animals. Recombinant leptin infusion in both strains restored IH-induced vascular abnormalities toward normoxic WT levels. Cardiac myocyte morphology and function were unaltered by IH. Serum cholesterol and triglyceride levels were significantly decreased by leptin treatment in IH mice, as was hepatic stearoyl-Coenzyme A desaturase 1 expression. Taken together, these data suggest that restoring normal leptin signaling can reduce vascular stiffness, increase endothelial relaxation, and correct dyslipidemia associated with IH.

Topics: Acetylcholine; Animals; Chronic Disease; Hyperlipidemias; Hypoxia; Leptin; Lipids; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Myocytes, Cardiac; Signal Transduction; Stearoyl-CoA Desaturase; Vascular Resistance

To characterize clinicopathogenetically factors influencing development of early chronic kidney disease (CKD) and impairment of other target organs in obese patients.. The examination of 86 obese patients (64 males and 22 females, mean age 44 +/- 11 years) included standard clinical tests, test for albuminuria, calculation of glomerular filtration rate (GFR) by MDRD formula, ultrasound investigation of the carotid arteries to detect atherosclerotic lesion of the carotid arteries, assessment of insulin resistance - IR (plasma concentration of insulin before meal and blood C-peptide, HOMA-index), test for plasma adipokinins (leptin, adiponectin).. Significant direct correlations were found between blood plasma leptin concentration, body mass index (BMI), plasma concentration of insulin and C-peptide, HOMA index, adiponectinemia and albuminuria. CKD patients have significantly higher than patients free of CKD levels of IR markers, waist circumference, BMI, leptinemia (38.2 +/- 28.8 and 21.6 +/- 19.8 ng/ml, respectively; p < 0.01). Obstructive sleep apnea syndrome was associated with higher IR and albuminuria, significantly lower estimated GFR (81 +/- 2 and 95 +/- 2 ml/min/1.73 m2, respectively; p < 0.05). Ultrasound evidence for atherosclerotic lesions of the carotid arteries was associated with a significant increase in blood plasma concentration of C-peptide, reduction of adiponectinemia (14.9 +/- 10.8 and 32.5 +/- 22.5 mcg/ml; p < 0.01), a rise in proportion fasting insulinemia/adiponectinemia (1.6 +/- 1.2 and 0.6 +/- 0.8, respectively; p < 0.05) and reduction of estimated GFR (86 +/- 19 and 102 +/- 25 ml/min/1.73 m2, respectively; p = 0.001).. In obesity, CKD at early stages develops in parallel with atherosclerotic lesion of the carotid arteries, which correlates with progression of leptinemia, IR and attenuation of organ-protecting properties of adiponectin.

Topics: Adiponectin; Atherosclerosis; Biomarkers; Carotid Artery Diseases; Chronic Disease; Female; Humans; Insulin Resistance; Kidney Diseases; Leptin; Male; Obesity

Leptin is a hormone secreted by adipocytes that plays an important role in regulating appetite and energy expenditure. Our aim was to evaluate serum leptin level in hemodialysis (HD) patients with or without chronic liver disease (CLD) and study the relationship between serum leptin level and bone mineral density in these groups of patients.. we recruited 20 healthy volunteers as controls (group I), 20 patients on regular HD with normal liver function (group II), 20 CLD patients with normal kidney function (group III) and 20 patients on regular HD with CLD (group IV). We measured serum calcium, phosphorus, parathyroid hormone (PTH), total alkaline phosphatase (ALP), serum leptin, 24-hours urinary hydroxyproline and bone mineral density (BMD) of the lumber spine and femoral neck by DEXA scan.. Serum leptin level was significantly higher (p < 0.001) in HD patients and CLD patients compared to controls. Its level was also significantly elevated in HD patients without liver disease (group II) compared to patients with CLD who had no renal failure (group III). Urinary hydroxyproline level was increased in both HD patients and CLD patients. We detected a positive correlation between serum leptin level and urinary hydroxyproline in all patient groups. There was a significant decrease in BMD in HD and CLD patients. BMD was significantly lower in HD patients without CLD compared to HD patients with CLD. There was a significant negative correlation between serum leptin level and BMD in CLD patients without renal disease but not in other groups (r = - 0.6, P = 0.01).. Serum leptin is elevated in HD patients with or without liver disease and in CLD patients. Serum leptin level is inversely correlated with BMD in CLD patients without renal disease.

Topics: Absorptiometry, Photon; Adult; Analysis of Variance; Bone Density; Chronic Disease; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Hydroxyproline; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Schistosomiasis; Young Adult

Anorexia is a common complication of chronic kidney disease (CKD), while novel animal and human data suggest a role for visfatin in regulating feeding behavior. We hypothesized that increased visfatin levels in CKD patients may be involved in the regulation of appetite and nutrient homeostasis.. This is a cross-sectional study where circulating visfatin levels were analysed in 246 incident CKD stage 5 patients starting dialysis therapy. The associations between visfatin (enzyme-linked immunosorbent assay, ELISA) and anthropometric and biochemical nutritional status, self-reported appetite, fasting serum amino acids (high-performance liquid chromatography) and circulating cytokine levels (ELISAs) were assessed. We also performed genotyping (Pyrosequencing(R)) of two polymorphisms (rs1319501 and rs9770242) in the visfatin gene.. Serum visfatin concentrations were not associated with either body mass index or serum leptin. Across groups with worsening appetite, median visfatin levels were incrementally higher (P < 0.05). With increasing visfatin tertiles, patients proved to be more often anorectic (P < 0.05) and to have incrementally lower serum albumin, cholesterol and triglycerides as well as lower essential and non-essential serum amino acids (P < 0.05 for all). A polymorphism in the visfatin gene was associated with increased circulating visfatin levels and, at the same time, a higher prevalence of poor appetite (P < 0.05 for both).. Our study suggests novel links between visfatin and anorexia in CKD patients. Based on recent studies, we speculate that high visfatin in CKD patients may constitute a counter-regulatory response to central visfatin resistance in uremia. Future studies should examine a putative role of visfatin as a regulator of nutrient homeostasis in uremia.

Topics: Adult; Aged; Amino Acids; Appetite; Body Mass Index; Chronic Disease; Cross-Sectional Studies; Feeding Behavior; Female; Homeostasis; Humans; Kidney Diseases; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Polymorphism, Genetic; Triglycerides; Uremia

Chronic kidney disease (CKD) is a significant public health problem that leads to end-stage renal disease (ESRD) with as many as 2 million people predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimental studies have suggested a link between serum leptin and kidney disease. We hypothesised that variants in the leptin gene (LEP) may be associated with markers of CKD in indigenous black Africans.. Black South Africans of Xhosa (distinct cultural Bantu-speaking population) descent were recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-U43653 [ENSSNP5824596]) were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), Serum creatinine (Scr) and serum leptin level. In one of the four single nucleotide polymorphisms (SNPs) we examined, an association with the renal phenotypes was observed. Hypertensive subjects with the T allele (CT genotype) of the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141), and significantly lower Scr (p = 0.0137). This was confirmed by haplotype analysis. Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio in normotensive subjects (p = 0.0482).. These results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans.

Topics: Adult; Albuminuria; Alleles; Base Sequence; Black People; Chronic Disease; Creatinine; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glomerular Filtration Rate; Haplotypes; Humans; Hypertension; Kidney Diseases; Leptin; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Single Nucleotide; South Africa

The aim of the study was to investigate the associations of adiponectin and leptin to bone mass and bone specific surrogates in elderly males with chronic heart failure (CHF).. Seventy-three males (mean age 68 +/- 7 years) with stable mild to moderate CHF and 20 healthy individuals age- and body mass index-matching underwent dual energy x-ray absorptiometry measurements (bone mineral density (BMD) at hip and lumbar spine, total bone mineral content, and body composition); echocardiography; 6-minute walk test; grip strength; and biochemical assessment including adiponectin, leptin, bone specific surrogates (osteocalcin, beta-CrossLaps, osteoprotegerin [OPG], receptor activator of nuclear factor kappaB ligand [RANKL]), parathyroid hormone, 25-hydroxy vitamin D, testosterone, sex hormone-binding globulin, and NT-pro-BNP. Serum adiponectin, osteocalcin, beta-CrossLaps, OPG, RANKL, and parathyroid hormone were significantly increased in CHF patients, whereas 25-hydroxy vitamin D was significantly lower compared to healthy controls. The significant positive association was found between adiponectin level with osteocalcin, beta-CrossLaps, OPG, and RANKL among CHF patients. In multivariate regression analysis, adiponectin was a significant determinant of total hip BMD, although the variance was small (r(2) = 0.239), whereas leptin was determinant for total bone mineral content (r(2) = 0.469) in patients with CHF.. Serum adiponectin is an independent predictor of BMD in elderly males with mild to moderate CHF, and showed a positive correlation to bone specific surrogates. Adiponectin, as cardioprotective hormone, seems to be able to exert a negative effect on bone mass in chronic heart failure. Further research is needed to confirm the potential for adipokines in the crosstalk between bone and energy metabolism in CHF patients.

Topics: Adiponectin; Aged; Biomarkers; Bone and Bones; Bone Density; Chronic Disease; Heart Failure; Humans; Leptin; Lumbar Vertebrae; Male; Middle Aged; Predictive Value of Tests; Radiography

This cross-sectional study set out to compare total and acyl ghrelin levels in children with mild chronic kidney disease (CKD) undergoing conservative treatment (n = 19) with children with end-stage renal disease (ESRD) undergoing hemodialysis (n = 24), and with healthy controls (n = 20). The relationship between ghrelin levels and parameters of renal function, nutritional status, and selective hormones were investigated. ESRD patients had higher total ghrelin levels than those with mild CKD or control individuals. However, acyl ghrelin did not differ between groups, indicating that the excess circulating ghrelin was desacylated. Since desacyl ghrelin has been shown to inhibit appetite, increased levels might contribute to protein-energy wasting in pediatric renal patients. When all 43 renal patients were combined, multiple regression analysis found age and glomerular filtration rate (GFR) to be significant negative predictors of total ghrelin. Acyl ghrelin was influenced negatively by age and positively by energy intake. Acyl to total ghrelin ratio related positively to GFR and energy intake. The results indicate that total but not acyl ghrelin is influenced by low GFR in children with CKD and suggests that ghrelin activation may be impaired in these patients. Since energy intake is a positive predictor of acyl ghrelin, the physiological control of ghrelin secretion appears to be altered in pediatric renal patients.

Topics: Acylation; Adolescent; Biomarkers; Brazil; Child; Child, Preschool; Chronic Disease; Cross-Sectional Studies; Energy Intake; Female; Ghrelin; Glomerular Filtration Rate; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Kidney Diseases; Kidney Failure, Chronic; Leptin; Male; Nutritional Status; Protein Processing, Post-Translational; Protein-Energy Malnutrition; Renal Dialysis; Severity of Illness Index

Topics: Adult; Chemokines; Chronic Disease; Cyclosporine; Dermatitis; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Psoriasis; Skin; Up-Regulation

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

The aim of this study was to investigate the relationship between plasma leptin levels and the chronic complications in type 2 diabetic (T2DM) patients.. There were 157 T2DM patients (age, 56.7 ± 11.4 years; mean diabetes duration, 8.9 ± 3.6 years; mean body mass index, 28.1 ± 4.3 kg/m(2)) included to the study. Microvascular and macrovascular complications of diabetes were evaluated in all patients. There were 46 healthy subjects as control group. Plasma leptin levels were measured in both diabetic and healthy subjects.. Plasma leptin levels of the diabetic patients were not significantly different from the healthy subjects (26.4 ± 18.2 vs. 29.1 ± 13.1 ng/mL, P > 0.05). Plasma leptin levels in obese diabetic patients were higher than in nonobese (37.6 ± 20.9 vs. 20.0 ± 17.2 ng/mL, P = 0.001); in hypertensive diabetic patients than normotensive (35.2 ± 19.3 vs. 19.4 ± 13.9 ng/mL, P < 0.001); dyslipidemic diabetic patients than normolipidemic diabetic subjects (38.5 ± 18.3 vs. 31.3 ± 19.5 ng/mL, P = 0.038); diabetic patients with metabolic syndrome than diabetic patients without metabolic syndrome (37.9 ± 20.1 vs. 23.2 ± 15.3 ng/mL, P = 0.001). Plasma leptin levels were lower in diabetic patients who were smokers than nonsmokers (20.0 ± 15.5 vs. 24.7 ± 17.4 ng/mL, P = 0.023). There was no significant difference between patients with and without diabetic nephropathy, retinopathy, neuropathy, coronary artery disease or peripheral vascular disease (P > 0.05).. Our data suggest that obesity, hypertension, dyslipidemia, and metabolic syndrome in T2DM were associated with increased plasma leptin levels. We conclude that plasma leptin levels may not be strongly associated with microangiopathy and macroangiopathy in T2DM individuals.

Topics: Adult; Aged; Body Mass Index; Case-Control Studies; Chronic Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Leptin; Male; Middle Aged; Obesity

Experimental sleep deprivation in healthy humans affects levels of ghrelin and leptin, two primary hormones involved in energy balance that regulate appetite and body weight. No study to date has examined levels of these hormones in patients with chronic insomnia. In this study, men diagnosed with primary insomnia using DSM-IV criteria (n=14) and age and body weight comparable healthy control men (n=24) underwent polysomnography. Circulating levels of ghrelin and leptin were measured at 2300h, 0200h and 0600h. As compared to controls, insomnia patients showed less total sleep time, stage 2 and REM sleep and decreased sleep efficiency and more stage 1 sleep than controls (p's<.05). Ghrelin levels across the night were significantly lower in insomnia patients (p<.0001). Leptin was not significantly different between the groups. In conclusion, decreased nocturnal ghrelin in insomnia is consistent with findings for nighttime levels in sleep deprivation studies in healthy sleepers. These findings suggest that insomnia patients have a dysregulation in energy balance that may play a role in explaining prospective weight gain in this population.

Topics: Adult; Case-Control Studies; Chronic Disease; Circadian Rhythm; Ghrelin; Humans; Leptin; Male; Middle Aged; Reference Values; Sleep; Sleep Initiation and Maintenance Disorders

Both ghrelin and leptin are important appetite hormones secreted from the stomach. We examined whether demographic background, Helicobacter pylori infection, or its related gastritis severity could be associated with circulating ghrelin and leptin levels.. This study prospectively enrolled 341 dyspeptic patients (196 females, 145 males), who had received endoscopy to provide the gastric specimens over both antrum and corpus for histology reviewed by the updated Sydney's system. The fasting blood sample of each patient was obtained for total ghrelin and leptin analysis.. Without H. pylori infection, there were similar ghrelin levels between female and male patients. In the H. pylori-infected patients, the males had lower plasma ghrelin levels than females (1053 vs. 1419 pg/mL, p < .001). Only in males, not in females, the H. pylori infection and its related acute and chronic inflammation scores were significantly associated with a lower ghrelin level (p < or = .04). The multivariate regression disclosed that only the chronic inflammation score independently related to a lower ghrelin level. Only in males, the ghrelin levels ranked in a downward trend for the gastritis feature as with limited-gastritis, with antrum-predominant gastritis, and with corpus-gastritis (1236, 1101, and 977 pg/mL). Leptin level was not related to H. pylori-related gastritis, but positively related to body mass index.. There should be a gender difference to circulating total ghrelin levels, but not leptin levels, in response to H. pylori infection and its related chronic gastritis.

Topics: Adult; Aged; Body Mass Index; Chronic Disease; Female; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Middle Aged; Prospective Studies; Sex Characteristics

Altered regulation of adiponectin and leptin may be relevant to endothelial dysfunction and cardiovascular complications in patients with chronic glomerulonephritis.. The relationship between the levels of plasma adiponectin, leptin and proteinuria, glomerular filtration rate and metabolic risk factors was investigated in 38 patients with chronic glomerulonephritis.. Plasma adiponectin was much higher in patients with heavy proteinuria (38.8 +/- 27.8 microg/mL) than in patients with mild proteinuria (13.3 +/- 5.1 microg/mL, P < 0.001) and with moderate proteinuria (18.1 +/- 8.0 microg/mL, P < 0.01). The levels of serum leptin were not changed among these groups. Proteinuria and lipoprotein(a) were a strong and direct correlate of plasma adiponectin (r = 0.75, P < 0.0001), while serum albumin and the glomerular filtration rate correlated inversely with this protein (r = -0.56, P = 0.0002; r = 0.38, P = 0.02). Body mass index and triglyceride were direct correlates (r = 0.37, P = 0.02 and r = 0.37, P = 0.02, respectively) of plasma leptin in patients with glomerulonephritis.. Plasma adiponectin but not plasma leptin levels correlate with proteinuria in patients with chronic glomerulonephritis.

Topics: Adiponectin; Adult; Aged; Chronic Disease; Female; Glomerulonephritis; Humans; Leptin; Male; Middle Aged; Proteinuria

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

Patients with chronic heart failure (CHF) express enhanced catabolic metabolism finally resulting in overall weight loss, whereas adipokines might play a crucial role in signaling among tissues. The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. The case-control study comprised a total of 372 patients of Caucasian origin with chronic heart failure (New York Heart Association [NYHA] functional classes II-IV, ejection fraction (EF) <40%) and 407 healthy controls. They were genotyped for the leptin (LEP) -2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5'-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. No case-control differences in genotype as well as allele frequencies were observed between CHF patients and controls. We constructed POMC RsaI/C1032G haplotypes, having found no significant association with body mass index (BMI), left ventricle ejection fraction (LVEF), left ventricle hypertrophy (LVH) and diabetes mellitus (DM). Multivariate regression analyses revealed an approximately 2-fold risk for NYHA class IV associated with the LEPR Gln223Arg (P = 0.0000001, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.56-2.84); it also displayed an independent prediction role for LVEF in heart failure cases of all etiologies (P = 0.002, OR = 4.05, 95% CI = 1.36-10.06). In subanalyses according to CHF etiology the LEPR Gln223Arg showed an independent prediction role for NYHA IV in IHD patients (P = 0.0001, OR = 2.50, 95% CI = 1.69-3.82) and both for NYHA IV(P = 0.007, OR = 2.04, 95% CI = 1.20-3.84) and LVEF (P = 0.004, OR = 11.87, 95% CI = 2.08-55.6) in DCMP patients. The role of the polymorphic variants in the genes encoding for adipokines as potential CHF susceptibility genes is unclear. Based on our findings, the LEPR Gln223Arg polymorphism could be considered a disease susceptibility modulating factor both in ischemic heart disease or dilated cardiomyopathy patients.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Chronic Disease; Czech Republic; Female; Gene Frequency; Genetic Predisposition to Disease; Heart Failure; Humans; Leptin; Male; Middle Aged; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Pro-Opiomelanocortin; Receptors, Leptin; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Ventricular Function, Left; White People; Young Adult

Osteocalcin, a small peptide secreted by osteoblasts, has been recently described as a circulating hormone involved in the regulation of energy metabolism. In addition, experimental data suggest a regulation of adipocytes by bone, with a stimulation of adiponectin synthesis by osteocalcin and an inverse relationship between serum adiponectin level and bone mineral density (BMD). However, this relationship has not been explored during chronic kidney disease (CKD).. Osteocalcin, adiponectin and leptin were prospectively measured in a cohort of 61 CKD patients. A new non-invasive 3D bone imaging technique was performed (high-resolution peripheral quantitative computed tomography, HR-pQCT), measuring volumetric BMD (vBMD) and microarchitecture parameters at the distal tibia.. Patients' mean age was 67.2 +/- 13.9 years and mean GFR 33 +/- 12 mL/min/1.73 m(2). We found a positive association between serum osteocalcin and adiponectin (r = 0.29, P = 0.021). Univariate analysis showed inverse correlations between serum adiponectin and total vBMD (r = -0.33, P = 0.01), cortical thickness (r = -0.34, P = 0.008) and trabecular vBMD (r = -0.27, P = 0.04). These associations remained significant in multivariate analysis between serum adiponectin and total vBMD, cortical vBMD and cortical thickness.. We report for the first time an inverse relationship between bone density and adiponectin, as well as a positive association between osteocalcin and adiponectin in CKD II-IV patients.

Topics: Adiponectin; Aged; Bone Density; Chronic Disease; Humans; Kidney Diseases; Leptin; Osteocalcin; Prospective Studies

Understanding the early factors affecting obesity development in males and females may help to prevent obesity and may lead to the discovery of more effective treatments for those already obese. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of obesity is characterized by hyperphagia-induced obesity, due to a spontaneous lack of CCK(1) receptors. In the present study, we focused on the behavioral and physiological aspects of obesity development from weaning to adulthood. We examined body weight, feeding efficiency, fat pad [brown, retroperitoneal, inguinal and epydidimal (in males)] weight, inguinal adipocyte size and number, leptin and oxytocin levels, body mass index, waist circumference, and females' estrous cycle structure. In the males, central hypothalamic gene expression was also examined. OLETF rats presented overall higher fat and leptin levels, larger adipocytes, and increased waist circumference and BMI from weaning until adulthood, compared with controls. Analysis of developmental patterns of gene expression for hypothalamic neuropeptides revealed peptide-specific patterns that may underlie or be a consequence of the obesity development. Analysis of the developmental trajectories toward obesity within the OLETF strain revealed that OLETF females developed obesity in a more gradual manner than the males, presenting delayed obesity-related "turning points," with reduced adipocyte size but larger postweaning fat pads and increased adipocyte hyperplasia compared with the males. Intake decrease in estrus vs. proestrus was significantly less in OLETF vs. Long-Evans Tokushima Otsuka females. The findings highlight the importance of using different sex-appropriate approaches to increase the efficacy of therapeutic interventions in the treatment and prevention of chronic early-onset obesity.

Topics: Adipocytes; Adipose Tissue; Age Factors; Aging; Animals; Blood Glucose; Body Mass Index; Body Weight; Chronic Disease; Disease Models, Animal; Disease Progression; Eating; Estrus; Feeding Behavior; Female; Gene Expression Regulation, Developmental; Hyperphagia; Hypothalamus; Leptin; Male; Neuropeptides; Obesity; Oxytocin; Rats; Rats, Inbred OLETF; Receptor, Cholecystokinin A; RNA, Messenger

Obesity is a significant risk factor for psoriasis and body mass index (BMI) correlates with disease severity. Objectives To investigate the relationship between obesity and psoriasis, focusing on the role of adipokines such as leptin and resistin.. Patients with psoriasis (n = 30) were recruited and their BMI, waist circumference and disease severity [Psoriasis Area and Severity Index (PASI)] were recorded. Fasting serum samples were obtained on enrolment and after a course of ultraviolet (UV) B treatment. Age-, sex- and BMI-matched healthy controls were also recruited.. On enrolment, serum leptin and soluble leptin receptor levels were not raised compared with the controls. However, resistin, interleukin (IL)-1beta, IL-6, and chemokines CCL2, CXCL8 and CXCL9 were all significantly elevated in the patient group and serum resistin correlated with disease severity (r = 0.372, P = 0.043). Improvement after UVB treatment was accompanied by decreased serum CXCL8. In vitro, both leptin and resistin could induce CXCL8 and tumour necrosis factor-alpha production by blood monocytes, and leptin could additionally induce IL-1beta and IL-1 receptor antagonist production. Leptin also dose dependently increased secretion of the growth factor amphiregulin by ex vivo-cultured lesional psoriasis skin.. These data support the view that leptin and resistin may be involved in the pathogenesis of psoriasis in overweight individuals, possibly by augmenting the cytokine expression by the inflammatory infiltrate.

Topics: Adipokines; Adult; Aged; Aged, 80 and over; Amphiregulin; Body Constitution; Body Mass Index; Chronic Disease; Cytokines; Down-Regulation; EGF Family of Proteins; Female; Glycoproteins; Humans; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Obesity; Psoriasis; Receptors, Leptin; Resistin; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index; Skin; Tissue Culture Techniques; Ultraviolet Therapy

Muscle wasting is a hallmark of uremic cachexia and has frequently been attributed to malnutrition that manifests as anorexia in chronic kidney disease. However, recent evidence indicates that proteolytic mechanisms are responsible for atrophy. Cheung and colleagues have reexamined the links between loss of lean body mass and nutrition. They demonstrate that neuropeptide signaling pathways, which regulate appetite and energy expenditure, also affect expression of key proteins involved in muscle mass maintenance.

Topics: Animals; Appetite Regulation; Cachexia; Chronic Disease; Humans; Leptin; Male; Melanocortins; Mice; Muscle, Skeletal; Muscular Atrophy; Nutritional Requirements; Signal Transduction; Uremia

The most unique feature of ghrelin is the acyl-modification of a hydroxyl group of the Ser3 in the N-terminus. The Ser3 is commonly modified by n-octanoic acid in vertebrates being needed for its biological effects, at least in terms of feeding. Therefore, a critical question regarding the role of ghrelin was to characterize the mechanism involved in its acylation. The acyltransferase that catalyzes ghrelin octanoylation has been recently identified and named ghrelin O-acyltransferase (GOAT). The aim of this study was to clarify the physiological implications of GOAT in the regulation of energy balance, by assessing the effect of undernutrition, as well as fasting in adult male rats. We have determined GOAT mRNA expression levels by real time-PCR in the stomach mucosa. Our results show that chronic food restriction led to an increase in GOAT mRNA, particularly following long-term chronic malnutrition (21 days). Furthermore, following 48 h complete fasting, a situation with high-circulating ghrelin levels, we found similar mRNA expression of GOAT in fed and fasted rats; exogenous leptin administration markedly increase GOAT mRNA levels in the stomach mucosa of fasted rats. These findings suggest that increased GOAT mRNA levels may have a role in mediating the physiological responses to chronic undernutrition and could represent an adaptive response to prevent long-lasting alterations in energy balance and body weight homeostasis. Furthermore, our data also offer mechanistic insights into the reason why during fasting acylated ghrelin levels are not increased at a time when a marked increase in an orexigenic signal as important as acylated ghrelin will be expected.

Topics: Acyltransferases; Animals; Base Sequence; Chronic Disease; DNA Primers; Gastric Mucosa; Ghrelin; Leptin; Male; Malnutrition; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Cross-sectional comparison.. The mortality rate is higher in individuals with spinal cord injury (SCI), and one major cause is cardiovascular disease (CVD). In the general population, the metabolic syndrome (MetS) is associated with an increased risk of CVD, and abdominal obesity is a major feature. Adipokines, secreted by adipose tissue, contribute to obesity-linked metabolic diseases. The aim of this study is to evaluate the prevalence of MetS, the components of this syndrome, especially body composition, and the relations between adipokines and body composition, in SCI individuals.. Kanagawa Rehabilitation Hospital, Kanagawa, Japan.. Forty-four male SCI individuals (57+/-13 years and 28 paraplegia) and age-matched able-bodied controls were studied. Body composition was assessed by dual-energy X-ray absorptiometry (DXA) and anthropometry (waist circumference). The visceral fat area (VFA) was measured by computed tomography (CT). Plasma adipokine levels, including that of leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1), were measured.. Overall, 43% of SCI individuals met the criteria for MetS. Total and regional fat mass (FM), as well as VFA, were higher, whereas total and regional lean mass, except for arm, were lower than able-bodied controls. In the SCI, leptin and PAI-1 levels were positively associated and adiponectin levels were negatively associated with waist circumference, VFA and trunk FM. In multiple regression models, only leptin level was independently associated with waist circumference, VFA and trunk FM.. SCI individuals were predisposed to excessive abdominal obesity, and higher leptin levels were strongly associated with higher prevalence of abdominal obesity in this population.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Aged; Aged, 80 and over; Anthropometry; Body Composition; Body Mass Index; Case-Control Studies; Chi-Square Distribution; Chronic Disease; Humans; Intra-Abdominal Fat; Leptin; Male; Metabolic Diseases; Middle Aged; Obesity; Spinal Cord Injuries; Tomography, X-Ray Computed

S100B protein is mainly synthesized in glial cells and modulates the balance between cell proliferation and differentiation in neurons and glial cells. However, S100B is not CNS-specific since its production was detected in numerous non-cerebral tissues e.g. adipocytes. In this study we investigated the influence of chronic fasting and subsequent weight gain on serum levels of S100B in patients with anorexia nervosa. We found that nutritional status was an important factor influencing serum levels of S100B.

Topics: Adolescent; Age Factors; Anorexia Nervosa; Biomarkers; Body Composition; Body Mass Index; Chronic Disease; Dietary Proteins; Down-Regulation; Female; Humans; Leptin; Nerve Growth Factors; Nutritional Status; Predictive Value of Tests; Recovery of Function; Reference Values; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Starvation; Weight Gain

Stress-induced alterations in feeding behavior are sexually dimorphic and have been related to changes in monoamine levels. Fluoxetine is commonly used as an antidepressant and has also been suggested as an adjunct to other strategies to treat obese individuals. Leptin may interact with stress hormones and with the brain serotonergic system, possibly affecting the feeding behavior of stressed rats. The aim of this study is to evaluate the interaction between chronic fluoxetine treatment and leptin levels in adult female Wistar rats submitted to chronic variable stress. After 30 days of stress, control and stressed groups were subdivided into two groups that received daily injections of vehicle or fluoxetine (8 mg/kg, i.p.). Body weight was evaluated before and after fluoxetine treatment. The animals gained weight with time, signifying that there is a difference in weight gain over time when fluoxetine-treated animals are, or not, subjected to the stress model. Both fluoxetine and stress induced a decrease in sweet food consumption. On the 60th day of fluoxetine treatment, leptin levels were decreased in fluoxetine-treated animals and there was no effect of stress. We conclude that chronic fluoxetine treatment induced a decreased intake of sweet food, as well as a reduction in leptin levels, and that this result could represent a compensatory response to reduced food intake rather than a direct anorectic mechanism. No interaction with chronic stress was observed.

Topics: Animals; Body Weight; Chronic Disease; Estrous Cycle; Feeding Behavior; Female; Fluoxetine; Leptin; Nutritional Physiological Phenomena; Rats; Rats, Wistar; Selective Serotonin Reuptake Inhibitors; Stress, Psychological

Insulin-like growth factor (IGF)-I increases muscle mass while myostatin inhibits its development. Muscle wasting is common in patients with uremic cachexia and may be due to imbalance of this regulation. We had proposed a central mechanism involving leptin and melanocortin signaling in the pathogenesis of uremic cachexia since agouti-related peptide (AgRP), a melanocortin-4 receptor antagonist, reduced uremic cachexia. Here we found that injection of AgRP into the cerebral ventricles resulted in a gain of body mass and improved metabolic rate regulation in a mouse model of uremic cachexia. These salutary effects occurred independent of increased protein and calorie intake. Myostatin mRNA and protein concentrations were increased while those of IGF-I were decreased in the skeletal muscle of uremic mice. AgRP treatment partially corrected these uremia-induced changes. Suppressor of cytokine signaling-2 gene expression (SOCS2) was significantly increased in uremic animals and AgRP reduced this expression. We suggest that AgRP improves uremic cachexia and muscle wasting by a peripheral mechanism involving the balance between myostatin and IGF-I.

Topics: Agouti-Related Protein; Animals; Appetite Regulation; Cachexia; Chronic Disease; Gene Expression; Humans; Insulin-Like Growth Factor I; Leptin; Male; Melanocortins; Mice; Mice, Inbred C57BL; Muscular Atrophy; Myostatin; Nephrectomy; RNA, Messenger; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Transforming Growth Factor beta; Uremia

The purpose of this study was to examine the association of age (young, midlife, and older) and activity level (active and sedentary), determined by a pedometer, with risk factors of chronic disease, including body composition, dietary intake, serum lipids, insulin, leptin, C-reactive protein (CRP), plasma glucose, and resting metabolic rate (RMR) in women across the adult life cycle.. Young (aged 20 to 30 years) (n=49), midlife (aged 40 to 50 years) (n=62), and older (aged 60 years and older) (n=47) women were recruited for this cross-sectional study. For 7 days, participants completed weighed food records and wore a pedometer. Based on the average number of steps per day, the women were further classified as active (>/=7,500 steps per day) or sedentary (<7,500 steps per day). Height, weight, and waist circumference were determined for each participant. Fasting blood samples were taken to assess serum lipid, CRP, insulin, leptin, thyroid stimulating hormone, and plasma glucose levels. RMR and body composition (via dual-energy x-ray absorptiometry) were assessed.. Young and midlife women had lower concentrations compared to older women for serum cholesterol (P<0.01), low-density lipoprotein cholesterol (P<0.01), triglycerides (P<0.01), leptin (P<0.01), and plasma glucose (P<0.01); midlife women had lower serum insulin concentrations vs young and older groups (P=0.01); young women had smaller waist circumference compared to midlife and older groups (P<0.01); percent body fat (P<0.01) and percent fat-free mass (P<0.01) differed between all ages. Lower values were found in active vs sedentary women for serum insulin (P=0.02), serum leptin (P<0.01), waist circumference (P<0.01) and percent body fat (P<0.01). A higher percent fat-free mass (P<0.01) was also found in active compared to sedentary women. No differences were found between activity groups for serum cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, CRP, plasma glucose levels, or RMR. RMR was higher in young and midlife vs the older women (P<0.01). Significant inverse correlations were found between activity (steps per day) and body mass index, insulin level, CRP concentration, leptin level, waist circumference, and body fat. Significant positive correlations were found between age and body mass index, total serum cholesterol level, low-density lipoprotein cholesterol level, serum triglyceride level, leptin level, plasma glucose level, CRP concentration, waist circumference, and body fat. Young and midlife women reported consuming more relative energy (kilocalories per kilogram body weight) and protein (grams per kilogram body weight) than older women (P<0.01). The midlife women reported consuming more dietary cholesterol compared to the young and older women (P<0.01). Active women reported a higher relative energy (kilocalories per kilogram body weight) and protein (grams per kilogram body weight) intake vs the sedentary women (P<0.01). Active women also reported a higher intake of dietary carbohydrates (grams per day, P<0.01; percent of energy, P=0.04).. Overall, these results indicate that younger age and greater physical activity, despite age, are associated with fewer risk factors for chronic disease, such as cardiovascular disease, type 2 diabetes, and obesity.

Topics: Adult; Age Factors; Aged; Basal Metabolism; Blood Glucose; Body Composition; C-Reactive Protein; Chronic Disease; Cross-Sectional Studies; Diet Records; Energy Intake; Energy Metabolism; Exercise; Female; Humans; Insulin; Leptin; Lipid Metabolism; Middle Aged; Risk Factors; Walking

The disease presentation of chronic heart failure (CHF) is considered to progress with metabolic deterioration, underlined by changes in adipose associated hormones (adipocytokines). However, little is known about ethnic variations of adipocytokines amongst CHF patients, in particular South Asians, who are at an increased risk of CHF.. Using a cross-sectional study, South Asians (n=106) and Caucasians (n=105) living in the UK were compared by CHF status. We investigated ethnic differences in adipocytokines (leptin, adiponectin, tumor necrosis factor (TNF)alpha), and their association with CHF. Patients with mild to moderate CHF were recruited from heart failure clinics (47 Caucasian, 54 South Asian), and compared to healthy controls. Metabolic parameters (including insulin resistance using HOMA modelling), echocardiography and brain natriuretic peptide (BNP) were measured amongst patients and healthy controls, and compared across and within ethnic groups.. Mean (log transformed) plasma leptin concentrations were highest amongst South Asian patients, being 5.25% (95%CI: 1.50-9.02) higher than Caucasian patients (P=0.007), and similarly raised with respect to controls (P< or =0.04). Indices of insulin resistance were higher amongst CHF patients compared with controls, with no ethnic variation. In addition to age, female gender and body-mass index, levels of leptin were also associated with South Asian ethnicity (P<0.001), insulin resistance (P=0.02), smoking habit (P=0.01) and HDL cholesterol (P=0.004). Levels of adiponectin showed no ethnic variation, but were associated with CHF and a previous history of myocardial infarction (P<0.001). On multivariate regression analysis of patients and healthy controls, CHF was independently associated with smoking habit, adiponectin and insulin resistance (all P<0.01).. Metabolic abnormalities are present in CHF, which in turn, are influenced by ethnicity. The role of adipocytokines in CHF pathophysiology and prognosis merits further study.

Topics: Adiponectin; Adult; Aged; Asia, Western; Asian People; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; Female; Heart Failure; Humans; Insulin Resistance; Leptin; Male; Middle Aged; United Kingdom; White People

To demonstrate the hypothesis that dexamethasone (Dex) could improve chronic heart failure (CHF) by inhibiting the downstream signaling transduction of leptin but had no influence on the upregulation of leptin and its receptor in myocardium.. CHF was induced by left coronary artery ligation for 6 weeks. CHF rats were treated with Dex 50 mg.kg/d. Hemodynamics, histology, reactive oxygen species (ROS)-related parameters, and leptin concentrations in serum were measured. The mRNA expression of matrix metalloproteinases (MMP)2/9, tissue inhibitor of metalloproteinases (TIMP)1/2, tumor necrosis factor (TNF)-alpha, and OB-Rb were measured by RT-PCR.. In the CHF rats, hemodynamic functions were deteriorated, which was accompanied with myocardium remodeling and histological changes. CHF rats showed hyperleptinemia and excessive ROS in the serum, and the upregulation of MMP-2/9, TNF-alpha, and leptin receptor mRNA and downregulation of TIMP-1/2 mRNA in the myocardium compared with the sham operation group. Dex treatment significantly ameliorated CHF in association with the reversion of the abnormalities of MMP-2/9, TIMP-1/2, TNF-alpha, and ROS. But Dex had no influence on the hyperleptinemia and the upregulated leptin and its receptor in the myocardium during CHF.. Dex improves CHF by inhibiting TNF-alpha, MMP-2, MMP-9, and ROS. Dex had no effects on upregulated leptin and its receptor expression and hyperleptinemia induced by CHF.

Topics: Animals; Chronic Disease; Dexamethasone; Down-Regulation; Heart Failure; Leptin; Male; Matrix Metalloproteinases; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, Leptin; RNA, Messenger; STAT Transcription Factors; Tissue Inhibitor of Metalloproteinases; Tumor Necrosis Factor-alpha; Ventricular Remodeling

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

Leptin is a pleiotrophic hormone produced by adipose tissue and it plays an important role in protection of the host from inflammation and infection. The purpose of this study is to determine the presence of leptin in gingival crevicular fluid (GCF) and serum samples and to find out their association, if any.. Forty two subjects were selected based on their body mass index and were divided into three groups of 14 each; healthy (Group I), chronic gingivitis (Group II) and chronic periodontitis (Group III). GCF samples (by microcapillary pipettes) and serum samples (by venipuncture) were collected to estimate the levels of leptin using enzyme linked immunosorbent assay kit.. The highest mean leptin concentration in GCF was obtained for Group I (2658 pg/ml) and the least for Group III (1312 pg/ml). In contrast, the lowest serum leptin concentration was obtained for the Group I (8783 pg/ml), and the highest for Group III (12082 pg/ml). This suggests a negative correlation of GCF leptin concentration and a positive correlation of serum leptin concentration as the clinical attachment level progresses (p<0.05).. These results suggest that greater the periodontal destruction, lesser is the GCF leptin concentration and greater the serum leptin concentration.

Topics: Adult; Case-Control Studies; Chronic Disease; Female; Gingiva; Gingival Crevicular Fluid; Gingival Pocket; Gingivitis; Humans; Leptin; Male; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis

A high concentration of leptin is associated with healthy gingival tissue, and the concentration of leptin decreases as periodontal disease progresses. However, to date, the leptin concentration in gingival crevicular fluid has not been documented. Hence, the present study was carried out to explore the presence of leptin in gingival crevicular fluid in periodontal health and disease, and to probe further into its possible role in periodontal disease progression.. A total of 45 adult patients were selected, based on their body mass index, for the study. They were categorized into three groups of 15 patients each, based on their periodontal tissue status, as follows: group I (clinically healthy gingiva with no loss of attachment); group II (chronic gingivitis with no loss of attachment); and group III (chronic periodontitis). Gingival crevicular fluid samples of 1 microL were collected extracrevicularly using white color-coded 1-5 microL calibrated volumetric microcapillary pipettes from one site in each person, and samples were analyzed for leptin using a commercially available enzyme-linked immunosorbent assay kit.. The concentration of leptin in gingival crevicular fluid of patients in group I (2292.69 pg/mL) was statistically higher (p < 0.05) than in those of groups II (1409.95 pg/mL) and III (1071.89 pg/mL). This suggests a negative correlation of gingival crevicular fluid leptin concentration with clinical attachment loss (p < 0.05).. As periodontal tissue destruction increased, there was a substantial decrease in gingival crevicular fluid leptin concentration. This observation extends our knowledge of the protective role of leptin in periodontal health.

Topics: Adult; Body Mass Index; Chronic Disease; Female; Gingival Crevicular Fluid; Gingivitis; Humans; Leptin; Male; Periodontal Index; Periodontitis; Statistics, Nonparametric

Peripheral infusions of physiological doses of leptin decrease body fat mass, but it is not known whether this results from direct effects on peripheral tissue or activation of central leptin receptors. In this study, we infused chronically decerebrate (CD) rats, in which the forebrain was surgically isolated from the caudal brainstem, with 60 microg leptin/d or PBS for 14 d from ip mini-osmotic pumps. The CD rats were tube fed an amount of food equivalent to the intake of ad libitum-fed intact controls or 75% of this amount to account for their reduced energy expenditure. Control rats fed ad libitum or tube fed 75, 100, or 125% of their ad libitum intake also were peripherally infused with leptin or PBS. CD rats had a lower serum testosterone, energy expenditure, and lean body mass compared with controls but had increased levels of adiponectin and leptin and were obese. Leptin increased body fat and decreased energy expenditure during the light period in 100%-fed CD rats, but not 75%-fed CD rats. Leptin decreased body fat of ad libitum- and 100%-fed but not 75%-fed or 125%-fed intact controls. Energy expenditure did not change in any control group. These results show that leptin can change body fat independent of a change in food intake or energy expenditure, that the forebrain normally prevents leptin from inhibiting energy expenditure through mechanisms initiated in the caudal brainstem or peripheral tissues, and that the leptin response in both intact and CD rats is determined by the energy status of the animal.

Topics: Adipose Tissue; Animals; Body Composition; Chronic Disease; Decerebrate State; Eating; Energy Metabolism; Infusion Pumps; Leptin; Male; Obesity; Oxygen Consumption; Prosencephalon; Rats; Rats, Sprague-Dawley; Testosterone

The inability to maintain body weight within prescribed ranges occurs in a significant portion of the human spinal cord injury (SCI) population. Using a rodent model of long-term high thoracic (spinal level T3) spinal cord transection (TX), we aimed to identify derangements in body weight, body composition, plasma insulin, glucose tolerance, and metabolic function, as measured by uncoupling protein 1 (UCP1) expression in interscapular brown adipose tissue (IBAT). Sixteen weeks after SCI, body weights of injured female rats stabilized and were significantly lower than surgical control animals. At the same time point, SCI rats had a significantly lower whole body fat:lean tissue mass ratio than controls, as measured indirectly by NMR. Despite lower body weight and fat mass, the cumulative consumption of standard laboratory chow (4.0 kcal/g) and mean energy intake (kcal.day(-1).100 g body wt(-1)) of chronic SCI rats was significantly more than controls. Glucose tolerance tests indicated a significant enhancement in glucose handling in 16-wk SCI rats, which were coupled with lower serum insulin levels. The post mortem weight of gonadal and retroperitoneal fat pads was significantly reduced after SCI and IBAT displayed significantly lower real-time PCR expression of UCP1 mRNA. The reduced fat mass and IBAT UCP1 mRNA expression are contraindicative of the cumulative caloric intake by the SCI rats. The prolonged postinjury loss of body weight, including fat mass, is not due to hypophagia but possibly to permanent changes in gastrointestinal transit and absorption, as well as whole body homeostatic mechanisms.

Topics: Adipose Tissue; Animals; Biomarkers; Body Composition; Body Weight; Chronic Disease; Diet; Energy Intake; Female; Glucose; Glucose Tolerance Test; Insulin; Ion Channels; Leptin; Mitochondrial Proteins; Motor Activity; Organ Size; Rats; Rats, Wistar; RNA; Spinal Cord Injuries; Thermogenesis; Uncoupling Protein 1

The aim of the present study was to evaluate gingival crevicular fluid (GCF) leptin levels and the influence of long-term and heavy smoking on GCF leptin levels in patients with chronic periodontitis.. In this study, 143 individuals were divided into three groups: non-smokers (NS), smokers (S), and control (C). Three subgroups of NS and S were grouped as follows: a) probing depth (PD) 5 mm. For each patient, PD, gingival index (GI), plaque index (PI), gingival bleeding time index (GBTI), and clinical attachment level (CAL) values were recorded. The GCF leptin levels obtained from sampling sites were determined by using enzyme-linked immunosorbent assay kits.. The GCF leptin levels were found significantly lower in the a and b subgroups in the S group than those in the NS group (P <0.05). The inflammatory markers GI and GBTI showed significant correlations with leptin in NS (P <0.05).. Our results suggest that higher leptin GCF levels in healthy sites in periodontitis patients may play a protective role in periodontal disease. Further studies are needed to determine the cellular origin of the leptin in the gingiva and the effect of plasma leptin levels on GCF leptin concentrations.

Topics: Adult; Case-Control Studies; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Gingival Crevicular Fluid; Humans; Leptin; Male; Periodontal Index; Periodontitis; Smoking; Statistics, Nonparametric

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

Topics: Adult; Antiretroviral Therapy, Highly Active; Case-Control Studies; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cholesterol; Chronic Disease; Drug Administration Schedule; Female; HIV Infections; HIV-1; Humans; Leptin; Male; Receptors, Leptin; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Reference Standards; RNA, Viral; Skinfold Thickness; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha; Viral Load

The objectives of this research were to investigate the leptin levels among Chronic Hepatitis B Virus (HBV), Chronic Hepatitis C Virus (HCV) and non-alcoholic steatosis hepatitis (NASH) diseases of Thai patients compared with controls. Twenty of each HBV, HCV and NASH patients compared with sixty people as the control group from the Outpatient Department at the Hospital for Tropical Diseases, Bangkok, Thailand were investigated. Fasting blood samples were collected for investigation of leptin concentration, liver enzyme function tests and hematological variables. The serum leptin concentration of liver patients was significantly higher than that of control subjects. It might be due to the accumulations of fat cells in liver disease patients. However, there is no relationship between leptin level and other parameters such as BMI, ALT, AST, ALP and hematological variables. Liver enzyme functions levels are much higher in patients groups. White blood cells counts, platelets and hematocrit values are slightly lower in liver disease patients. Therefore, it is concluded that physiological regulation of leptin maintains in relation to body fat, even in chronic viral liver diseases. This finding and the apparent stage suggest the possibility that in the course of chronic viral diseases, serum leptin levels may reflect the extent of liver dysfunction.

Topics: Adult; Aged; Case-Control Studies; Chronic Disease; Fatty Liver; Female; Hepatitis B; Hepatitis C; Humans; Leptin; Male; Middle Aged; Thailand

Chronic idiopathic thrombocytopenic purpura (ITP) is an organ-specific autoimmune disease characterized by the production of antibodies against antigens on the membranes of platelets, resulting in enhanced destruction of the platelets by macrophages. Leptin, a cytokine-like hormone, plays a role in the pathogenesis of several autoimmune diseases. In this study, we observed significantly increased plasma leptin levels combined with decreased soluble leptin receptor (sOB-R) levels in 18 chronic ITP patients compared with 14 controls. We also demonstrated significantly elevated mRNA expression of long form leptin receptor (Ob-Rb) on peripheral blood mononuclear cells (PBMCs) from chronic ITP patients. Treatment with recombinant leptin or serum with high leptin levels enhanced in vitro secretion of IgG antiplatelet antibodies by splenocytes and PBMCs from patients with chronic ITP. After depletion of CD4(+) T cells from splenocytes, leptin lost this function. Further studies showed that leptin could increase platelet reactive T cells. These findings suggest that leptin may be involved in the pathogenesis of chronic ITP and might offer a potential target for the treatment of this disease.

Topics: Adult; Autoantibodies; Blood Platelets; CD4-Positive T-Lymphocytes; Cells, Cultured; Chronic Disease; Female; Humans; Immunoglobulin G; Leptin; Leukocytes, Mononuclear; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Spleen

Growing evidence suggests that concentration of the adipocytokines leptin and adiponectin may be affected by risk of hypertension during pregnancy. Leptin and leptin receptor gene expression has been studied in placentas obtained from pre-eclamptic patients, but not in those with chronic high blood pressure (CHBP). Adiponectin receptors remain unstudied in placentas obtained from hypertensive patients.. Therefore, we investigated relative mRNA expression of selected adipocytokine genes (leptin, leptin receptors (LEPRA, LEPRB, LEPRC, LEPRD) and adiponectin receptors (ADIPOR1, ADIPOR2)) in placental tissues from women with pre-eclampsia (n = 6) or CHBP (n = 8). Placentas from 28 normotensive patients were analyzed as controls. mRNA extracted from biopsies taken from the maternal and fetal sides of the placenta was investigated using real-time polymerase chain reaction.. Compared with controls, significant increases in leptin mRNA expression were seen in placentas from pre-eclamptic patients on the maternal (p = 0.01) and fetal (p = 0.02) sides, and in placentas from CHBP mothers on the fetal side (p = 0.001). Maternal-side tissue from CHBP patients was not significantly different from that of controls (p = 0.08), but this might be due to the small sample size. No significant differences were seen in mRNA expression for most of the adipocytokine receptors tested for hypertensive cases compared with controls. However, there was a decrease in LEPRC (pre-eclamptic, maternal side, p = 0.03) and LEPRD (pre-eclamptic, maternal side, p = 0.01; CHBP, fetal side, p = 0.009) in case-control analysis.. This pilot study shows that increases seen in leptin expression in placentas from hypertensive mothers might be a consequence of defects in placentation associated with this disease, and motivates further region-specific adipocytokine gene expression analysis across this organ.

Topics: Adult; Chronic Disease; Cytokines; Female; Gene Expression; Humans; Hypertension; Leptin; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Receptors, Adiponectin; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger

In the past 10 years, 3 new metabolic compounds, leptin, adiponectin, and ghrelin, involved in energy metabolism, body composition, and appetite regulation, have been discovered. We have assessed their characteristics in 46 patients with stage 3 to 4 chronic kidney disease to evaluate the role of decreased renal function in the abnormal handling reported in more severe end-stage renal disease patients. In addition to the usual correlations with body mass index and body fat mass, the results show unexpected positive correlations between leptin and insulin, leptin and adiponectin, a weak inverse relationship between adiponectin and glomerular filtration rate, and no influence of C-reactive protein on either leptin or adiponectin in these noninflamed patients. Serum ghrelin was inversely correlated with body mass index and with glomerular filtration rate as measured by inulin clearance. Thus, ghrelin and leptin, 2 antagonist signals for energy balance, both seem to increase when glomerular filtration rate is reduced, potentially neutralizing their respective biologic effects in severe renal insufficiency.

Topics: Adiponectin; Adult; Appetite; Body Composition; Body Mass Index; C-Reactive Protein; Chronic Disease; Energy Metabolism; Fasting; Female; Ghrelin; Glomerular Filtration Rate; Homeostasis; Humans; Insulin; Kidney Diseases; Leptin; Male; Middle Aged; Nutritional Status; Peptide Hormones; Regression Analysis

Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs. 33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p 0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.

Topics: Adipocytes; Adiponectin; Adult; Body Mass Index; Chronic Disease; Female; Heroin Dependence; Hormones; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Methadone; Narcotics; Nutritional Status; Resistin

Recent literature has shown that circulating levels of insulin-like growth factor I (IGF-I) and/or IGF binding proteins (IGF-BPs) may be of importance in the risk assessment of several chronic diseases including cancer, cardiovascular disease, diabetes mellitus and so on. The present study examined the extent of genetic and environmental influences on the populational variation of circulating IGF-I and IGF-BP-1 in apparently healthy and ethnically homogeneous white families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 563 individuals aged 18 to 80 years. Quantitative genetic analysis showed that the IGF-I variation was appreciably attributable to genetic effects (47.1% +/- 9.0%), whereas for IGF-BP-1, only 23.3% +/- 7.8% of the interindividual variation was explained by genetic determinants. Common familial environment factors contributed significantly only to IGF-BP-1 variation (23.3% +/- 7.8%). In addition, we examined the covariations between these molecules and between them and IGF-BP-3 and leptin that were previously studied in the same sample. The analysis revealed that the pleiotropic genetic effects were significant for 2 pairs of traits, namely for IGF-I and IGF-BP-3, and for IGF-BP-1 and leptin. The bivariate heritability estimates were 0.21 +/- 0.04 and 0.15 +/- 0.05. The common environmental factors were consistently a significant source of correlation between all pairs (barring IGF-I and leptin) of the studied molecules; they were the sole predictors of correlation between IGF-I and IGF-BP-1, and between IGF-BP-1 and IGF-BP-3. Our results affirm the existence of specific and common genetic pathways that in combination determine a substantial proportion of the circulating variation of these molecules.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anthropometry; Chronic Disease; Female; Genetic Predisposition to Disease; Humans; Leptin; Male; Middle Aged; Somatomedins

The debate about whether obesity should be called a disease continues. From a clinical perspective, it meets the criteria needed to call it a disease. It has an etiology--an imbalance between energy intake and expenditure. It has a pathogenesis in the feedback systems involving leptin, neurochemicals in the brain, and the neural and endocrine messages that respond to the intake of food. The pathology of obesity lies in its enlarged fat cells, and the pathophysiology lies in the changes in the secretion of products from these enlarged fat cells, including cytokines, procoagulants, inflammatory peptides, and angiotensinogen. These secretory products of fat cells and the increased mass of fat are responsible for the associated metabolic diseases, such as diabetes, hypertension, heart disease, sleep apnea, and some sorts of cancer. Treatments consist of techniques to alter the balance between energy intake and energy expenditure. This constellation of factors leads to the conclusion that obesity should be called a disease.

Topics: Body Weight; Chronic Disease; Energy Metabolism; Female; Humans; Leptin; Male; Obesity; Recurrence; Risk Factors

Leptin regulates appetite through the long isoform of its receptor in the hypothalamus. Although leptin regulates immune responses, it is still unknown whether a direct effect of leptin on lymphocytes is required.. To clarify whether expression of leptin receptors on T lymphocytes modulates intestinal inflammation in mice.. The model of colitis induced by transfer of CD4(+)CD45RB(high) (RB(high)) cells into scid mice was used. Wild-type (WT) or leptin receptor deficient (db/db) RB(high) cells were transferred into scid mice and development of colitis evaluated.. Leptin receptors were expressed on both RB(high) and RB(low) cells. Intestinal lymphocytes of mice with colitis expressed high leptin levels compared with healthy controls whereas the opposite was true for serum leptin levels. Transfer of RB(high) cells from db/db mice induced delayed disease compared with transfer of WT cells. A high rate of apoptosis in lamina propria lymphocytes and reduced cytokine production were observed early on in scid mice receiving db/db RB(high) cells. These effects were not due to the high levels of glucocorticoids present in db/db mice as administration of corticosterone to WT mice failed to reproduce this phenomenon. High expression of peroxisome proliferator activated receptor gamma was observed in the colon of recipients of db/db compared with WT cells. Freshly isolated db/db RB(high) cells produced low levels of interferon gamma. Despite delayed onset of colitis, as disease progressed differences between mice receiving WT or db/db cells were no longer apparent.. These results suggest that leptin affects the immune response, partly by acting on the long isoform of its receptor expressed on T lymphocytes.

Topics: Animals; Chronic Disease; Colitis; Corticosterone; Cytokines; Disease Progression; Disease Susceptibility; Immunity, Mucosal; Leptin; Leukocyte Common Antigens; Lymphocyte Transfusion; Male; Mice; Mice, Inbred C57BL; Mice, SCID; Receptors, Cell Surface; Receptors, Leptin; T-Lymphocytes; Th1 Cells

Increased serum leptin has been described after various organ transplants, with a mechanism that is still unclear.. We measured serum leptin in 60 patients before and after allogeneic (allo) or autologous (auto) stem cell transplant (SCT) and in 60 healthy controls, matched for age and body mass index (BMI).. Serum leptin was higher in patients after SCT than before and in controls. Leptin production was higher after allo- than after auto-SCT; the presence of chronic graft-versus-host disease (cGVHD) was associated with the highest values. The physiological correlation with BMI was lost in the allogeneic setting, indicating a strong influence of factors other than the nutritional status on circulating leptin. No relationship was found between serum leptin levels and time from transplant, age, cortisol, C-reactive protein, and T-lymphocyte CD4-to-CD8 ratio. Among the cytokines secreted by type-1/type-2 T-helper lymphocytes, only serum interferon-gamma significantly correlated with serum leptin levels. Anti-leptin blocking antibodies partially inhibited T-cell activation in mixed lymphocyte reaction, suggesting a link between leptin and T-lymphocyte activation in the allo-SCT setting.. Taken together, these findings suggest that increased serum leptin concentrations may contribute to T-cell activation during development of cGVHD.

Topics: Adolescent; Adult; CD4-CD8 Ratio; Chronic Disease; Cytokines; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leptin; Lymphocyte Culture Test, Mixed; Male; Middle Aged

Diagnosis of pancreatitis is based on the determination of serum amylase and lipase levels. However, recent identification of specific leptin receptors in the pancreas suggests that this peptide may also play some roles in the modulation of pancreatic function. The objective of the present study was to investigate the relationship between serum leptin levels and pancreatitis. Thirty male Wistar rats were divided into 3 groups: the control group, acute pancreatitis group and chronic pancreatitis group. Pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. A sham laparotomy was performed in the control group. Control and acute pancreatitis groups were sacrificed 24 hours later, and chronic pancreatitis group was sacrificed on postoperative day 7. Blood was taken by cardiac puncture for the determination of plasma leptin levels, and the pancreatic tissue was excised for histopathologic confirmation of pancreatitis. Plasma leptin rose significantly from the median of 0.78 +/- 0.12 ng/ml in the control group to 1.92 +/- 0.10 ng/ml and 1.86 +/- 0.13 ng/ml in acute and chronic pancreatitis groups, respectively (p < 0.001, for both). There was no significant difference in the plasma leptin levels between the acute pancreatitis group and the chronic pancreatitis group (p > 0.05). These findings confirm that leptin has a role in pancreas inflammation, and the inflamed tissue can be the source of local production of leptin.

Topics: Acute Disease; Animals; Chronic Disease; Humans; Leptin; Male; Pancreatitis; Rats; Rats, Wistar

Pulmonary tuberculosis is the classic cause of "consumption," but the pathogenesis of such wasting is largely unknown. Animal studies in other conditions suggest that leptin may be a mediator between proinflammatory cytokine activity and wasting.. We tested whether the leptin concentration, after control for body fat mass, is higher during active pulmonary tuberculosis than after recovery and whether it correlates with energy metabolism and proinflammatory cytokine activity.. Nondiabetic adults with pulmonary tuberculosis (n = 32) were recruited into a prospective observational study. Patients found to be antibody positive for human immunodeficiency virus were excluded from the study. Dual-energy X-ray absorptiometry, indirect calorimetry, and food intake protocols were performed at baseline and after 1 and 6 mo of tuberculosis treatment. Fasting plasma leptin, tumor necrosis factor alpha and its soluble receptor, and interleukin 6 were measured by enzyme-linked immunosorbent assay.. Resting energy expenditure was close to Harris-Benedict predictions and did not change significantly during treatment, but energy intake increased. Leptin concentration was correlated in a log-linear fashion with percentage body fat but was independent of cytokines and energy intake. There was no significant difference in leptin, corrected for energy balance and fat mass, at baseline and after 1 and 6 mo of treatment.. These data are compatible with recovery from anorexia or starvation without discernible hyper- or hypometabolism. The close correlation of leptin with body fat mass is similar to observations in healthy subjects. No additional influence of disease state or proinflammatory cytokine activity was found. Leptin does not appear to be a component of the immune response to human pulmonary tuberculosis, and thus it cannot account for the weight loss and anorexia associated with tuberculosis.

Topics: Absorptiometry, Photon; Adipose Tissue; Adolescent; Adult; Aged; Aged, 80 and over; Body Composition; Body Water; Calorimetry, Indirect; Chronic Disease; Cytokines; Energy Intake; Energy Metabolism; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Tuberculosis, Pulmonary; Weight Loss

Patients with chronic heart failure (CHF) have metabolic abnormalities, leading to a catabolic syndrome, with progressive loss of skeletal muscle in advanced stages of the disease. Leptin, the product of an obesity gene, has been associated with energy expenditure and weight regulation. The aim of this study was to assess serum levels of leptin and its soluble receptor in relation to exercise intolerance and neurohumoral activation in patients with CHF. We investigated 53 patients with CHF left ventricular ejection fraction (LVEF) 25+/-1%, age 56.6+/-1.3 years, Maximal oxygen uptake (VO(2) max) 16.3+/-0.6 ml/min.kg) sub-classified according to peak oxygen consumption of > or 14 ml/min.kg and controls). Elevated levels of leptin correlated with an increased serum concentration of TNFalpha (r=0.749, P<0.01) in this subgroup of patients with CHF. We conclude that patients with advanced CHF show elevated serum levels of leptin and its soluble receptor. This finding indicates that leptin may participate in the catabolic state leading to the development of cardiac cachexia in the course of CHF.

Topics: Aged; Biomarkers; Blood Sedimentation; Body Mass Index; Case-Control Studies; Chronic Disease; Cytokines; Exercise Test; Exercise Tolerance; Heart Failure; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Myocardial Ischemia; Oxygen Consumption; Receptors, Cell Surface; Receptors, Leptin; Severity of Illness Index; Solubility; Statistics as Topic; Stroke Volume; Tumor Necrosis Factor-alpha

Obesity is an important risk factor of atherosclerosis; however, the mechanism of proatherogenic effect of obesity is not definitely established. Recent studies suggest an important role of leptin in obesity associated complications. We investigated the effect of chronic hyperleptinemia on two antioxidant enzymes contained in plasma lipoproteins: paraoxonase 1 (PON1) and platelet activating factor-acetylhydrolase (PAF-AH). The study was performed on three groups of male Wistar rats: (1) control, fed ad libitum, (2) leptin treated, receiving leptin (0.25 mg/kg twice daily s.c. for 7 days), (3) pair-fed, in which food intake was identical as in leptin-treated animals. PON1 activity toward paraoxon, phenyl acetate, gamma-decanolactone and homogentisic acid lactone was lower in leptin-treated than in control group by 30.4, 30.8, 34.5 and 62%, respectively. Leptin increased plasma concentration and urinary excretion of isoprostanes by 46.4 and 49.2%, respectively. Leptin treatment had no effect on plasma lipid profile and glucose level. Plasma leptin was 208.8% higher in leptin-treated and 51.5% lower in pair-fed than in control group. These data indicate that hyperleptinemia induced by exogenous leptin administration markedly decreases plasma PON1 activity and induces oxidative stress. These mechanisms may be involved in atherogenesis in hyperleptinemic obese individuals.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Animals; Antimetabolites, Antineoplastic; Antioxidants; Aryldialkylphosphatase; Biomarkers; Cholinesterase Inhibitors; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperlipidemias; Isoprostanes; Lactones; Leptin; Male; Models, Cardiovascular; Oxidative Stress; Paraoxon; Phenylacetates; Rats; Rats, Wistar; Statistics as Topic

Obesity has reached epidemic proportions and has become one of the major health problems in developed countries. Current theories consider obesity a result of overeating and sedentary life style and most efforts to treat or prevent weight gain concentrate on exercise and food intake. This approach does not improve the situation as may be seen from the steep increase in the prevalence of obesity. This encouraged us to reanalyse existing information and look for biochemical basis of obesity. Our approach was to ignore current theories and concentrate on experimental data which are described in scientific journals and are available from several databases. We developed and applied a Knowledge Discovery in Databases procedure to analyse metabolic data. We began with the contradictory information: in obesity, more calories are consumed than used up, suggesting that obese people should have excess energy. On the other side, obese people experience fatigue and decreased physical endurance that indicates diminished energy supply in the body. The result of our work is a chain of metabolic events leading to obesity. The crucial event is the inhibition of the TCA cycle at the step of aconitase. It disturbs energy metabolism and results in ATP deficiency with simultaneous fat accumulation. Further steps in obesity development are the consequences of diminished energy supply: inhibition of beta-oxidation, leptin resistance, increase in appetite and food intake and a decrease in physical activity. Thus, our theory shows that obesity does not have to be caused by overeating and sedentary life-style but may be the result of the "obese" change in metabolism which is forcing people to overeat and save energy to sustain metabolic functions of cells. This "obese" change is caused by environmental factors that activate chronic low-grade inflammatory process in the body linking obesity with the environment of developed countries.

Topics: Aconitate Hydratase; Adenosine Triphosphate; Adipose Tissue; Bacterial Infections; Chronic Disease; Cytokines; Data Collection; Developed Countries; Energy Metabolism; Fatigue; Fatty Acid Synthases; Humans; Leptin; Liver; Nitric Oxide; Obesity; PubMed

Exposure to stress may cause either an increase or a decrease in food intake. Behavioral and physiological responses to stress, including alterations in feeding behavior, are sexually dimorphic. This study aimed to evaluate the interaction between estradiol levels and chronic variate stress on the intake of sweet food and on serum levels of leptin, a hormone secreted by the adipose cells with a role in the regulation of body weight. Adult female Wistar rats were used. After ovariectomy, the animals received estradiol replacement (or oil) subcutaneously. Rats were then divided in controls and stressed (submitted to 30 days of variate stress). Consumption of sweet food and of serum leptin was measured. Although animals receiving estradiol replacement presented smaller weight gain, they showed an increased consumption of sweet food. Chronic variate stress decreased sweet food intake at 30, but not at 20, days of treatment. Estradiol replacement in the stressed group prevented both the reduction observed in sweet food intake and the increase in leptin levels. These results suggest that there is an interaction between chronic stress and estradiol replacement in feeding behavior concerning sweet food consumption, and this interaction may be related to altered leptin levels.

Topics: Animals; Body Weight; Chronic Disease; Estradiol; Estrogen Replacement Therapy; Feeding Behavior; Female; Food Preferences; Leptin; Ovariectomy; Rats; Rats, Wistar; Stress, Psychological; Weight Gain

Within the past years, an important role for nitric oxide (NO) in skin repair has been well defined. As NO is synthesized from L-arginine by NO synthases (NOS), the availability of L-arginine might be one rate-limiting factor of NO production at the wound site. Upon injury, arginase-1 and -2 mRNA, protein, and activity were strongly induced reaching a maximum between day 3 and day 7 postwounding. Immunohistochemistry colocalized both arginases and the inducible NOS (iNOS) at epithelial sites at the margins of the wound. Notably, diabetes-impaired skin repair in leptin-deficient mice (diabetes/diabetes, db/db; and obese/obese, ob/ob) was characterized by an abnormally elevated arginase activity in wound tissue in the absence of an expression of iNOS. Expression analyses demonstrated that arginase-1 contributed to increased arginase activities in impaired repair. Interestingly, an improved healing of chronic wound situations in leptin-supplemented ob/ob mice was strongly associated with an adjustment of the dysregulated expression of L-arginine-converting enzymes: an attenuated iNOS expression was upregulated early in repair and an augmented arginase-1 expression and activity was downregulated in the presence of markedly elevated numbers of macrophages during late repair. These data suggest a coordinated consumption of L-arginine by the NOS and arginase enzymatic pathways at the wound site as a prerequisite for a balanced NO (via iNOS) and polyamine (via arginases) synthesis that drives a normal skin repair.

Topics: Animals; Arginase; Arginine; Chronic Disease; Diabetes Complications; Diabetes Mellitus; Female; Gene Expression Regulation, Enzymologic; Isoenzymes; Leptin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Skin; Wound Healing

Leptin released by adipocytes has been implicated in the control of food intake but recent detection of specific leptin receptors in the pancreas suggests that this peptide may also play some role in the modulation of pancreatic function. This study was undertaken to examine the effect of exogenous leptin on pancreatic enzyme secretion in vitro using isolated pancreatic acini, or in vivo in conscious rats with chronic pancreatic fistulae. Leptin plasma level was measured by radioimmunoassay following leptin administration to the animals. Intraperitoneal (i.p.) administration of leptin (0.1, 1, 5, 10, 20 or 50 microg/kg), failed to affect significantly basal secretion of pancreatic protein, but markedly reduced that stimulated by feeding. The strongest inhibition has been observed at dose of 10 microg/kg of leptin. Under basal conditions plasma leptin level averaged about 0.15 +/- 0.04 ng/ml and was increased by feeding up to 1.8 +/- 0.4 ng/ml. Administration of leptin dose-dependently augmented this plasma leptin level, reaching about 0.65 +/- 0.04 ng/ml at dose of 10 microg/kg of leptin. This dose of leptin completely abolished increase of pancreatic protein output produced by ordinary feeding, sham feeding or by diversion of pancreatic juice to the exterior. Leptin (10(-10)-10(-7) M) also dose-dependently attenuated caerulein-induced amylase release from isolated pancreatic acini, whereas basal enzyme secretion was unaffected. We conclude that leptin could take a part in the inhibition of postprandial pancreatic secretion and this effect could be related, at least in part, to the direct action of this peptide on pancreatic acini.

Topics: Animals; Bethanechol Compounds; Ceruletide; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Therapy, Combination; Eating; Gastric Fistula; Injections, Intraperitoneal; Leptin; Pancreas; Pancreatic Fistula; Pancreatic Juice; Postprandial Period; Rats; Rats, Wistar

Cachexia is a common problem in chronic heart failure (CHF) that may be partly mediated by activation of the sympathetic nervous system. The effects of beta-adrenergic receptor blocker (BB) therapy on body weight in cachectic and noncachectic subjects with CHF has not been previously reported.. Body weight and plasma norepinephrine, leptin, and insulin levels were measured in 27 subjects with CHF before and after 6 months of beta-adrenergic receptor blockade with carvedilol or long-acting metoprolol. Before BB therapy, baseline weight, plasma leptin, and plasma insulin levels did not differ between cachectic and noncachectic subjects. Baseline plasma norepinephrine levels were increased in cachectic subjects when compared with noncachectic subjects (930+/-248 pg/mL versus 503+/-109 pg/mL, P=.063). After 6 months of BB therapy, subjects with baseline cachexia demonstrated significantly greater weight gain (+5.2+/-9.6 versus +0.8+/-5.0 kg, P=.027), greater increase in plasma leptin levels (+3.7+/-3.9 versus +1.2+/-4.3 ng/mL, P=.030), and greater decrease in plasma norepinephrine levels (-374+/-261 versus -41+/-122 pg/mL, P=.012) when compared with noncachectic subjects.. Six months of BB therapy with carvedilol or long-acting metoprolol is associated with differential effects on body weight and hormonal levels in cachectic and noncachectic subjects with CHF. Further work is needed to determine the role the sympathetic nervous system in the pathogenesis of cachexia in patients with CHF.

Topics: Adrenergic beta-Antagonists; Biomarkers; Blood Pressure; Body Weight; Cachexia; Carbazoles; Carvedilol; Chronic Disease; Female; Heart Failure; Heart Rate; Humans; Insulin; Leptin; Male; Metoprolol; Middle Aged; Norepinephrine; Propanolamines; Prospective Studies; Severity of Illness Index; Stroke Volume; Treatment Outcome

Obesity is associated with hyperleptinemia and is also a risk factor for fibrosis and severity of fibrosis in several chronic liver diseases. The correlation between increased leptin, obesity and hepatic fibrosis prompted us to hypothesise that leptin has profibrogenic effects on the liver.. We analysed the role of leptin in liver fibrosis in leptin-deficient mice fed a diet which generates steatohepatitis, and in chronic carbon tetrachloride-induced hepatic injury.. Leptin-deficient mice failed to develop fibrosis during steatohepatitis or in response to chronic toxic liver injury, and failed to up-regulate collagen-I while developing similar hepatic injury as their genetic controls. Restitution of physiological levels of circulating leptin by injection of exogenous leptin, but not correction of the obese phenotype by dietary manipulation, restored liver fibrosis in leptin-deficient mice during chronic liver injury. These results confirmed the absolute requirement of leptin for hepatic fibrosis. We showed that leptin deficiency did not alter hepatic TNF regulation but that leptin is necessary for induction of bioactive transforming growth factor beta 1 (TGFbeta1) protein in the context of chronic liver injury.. These data establish that leptin is an essential mediator of hepatic fibrosis in response to chronic liver injury, whether metabolic or toxic in aetiology.

Topics: Animals; Carbon Tetrachloride; Chronic Disease; Disease Progression; Fatty Liver; Female; Leptin; Liver Cirrhosis; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oxidative Stress; Phenotype; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Background Behçet's syndrome is a systemic, relapsing immuno-inflammatory disease with a generalized vasculitis of the microvasculature endothelial dysfunction. Leptin, a recently discovered neuroendocrine hormone, is a metabolic peptide that appears to be involved. Serum proinflammatory cytokines upregulate leptin levels and leptin itself directly induces nitric oxide production from endothelial cells with its specific receptors.. To detect changes of serum leptin concentrations in patients with Behçet's syndrome compared with age- and sex-matched healthy volunteers by using enzyme-linked immunosorbent assay. We also investigated whether disease activity or the duration of Behçet's syndrome correlates with leptin concentration.. Thirty-five consecutive patients with Behçet's syndrome (41.2 +/- 8.4 years, 16 male, 19 female) and 20 age- and sex-matched healthy control subjects (40.4 +/- 10.91 years, nine male, 11 female) were included in this study. The body mass index (BMI) [weight (kg) height(-1) (m(2))] was calculated for subjects at study enrollment. We measured serum leptin with a leptin enzyme immunoassay kit, and acute-phase reactants, including erythrocyte sedimentation rate, alpha1-antitrypsin, alpha 2-macroglobulin and neutrophil count. The Mann-Whitney U-test was used for statistical analysis and P < 0.05 was considered significant. Values were expressed as mean +/- SD.. The gender ratio, age and BMI were not substantially different among Behçet's patients and controls. The mean serum leptin concentrations in patients with Behçet's syndrome (16.8 +/- 7.49 ng mL(-1)) were significantly (P < 0.001) higher than in healthy control volunteers (7.5 +/- 2.77 ng mL(-1)). Active Behçet's patients had significantly (P = 0.001) higher leptin concentrations (20.5 +/- 7.99 ng mL(-1)) when compared with patients in inactive periods (12.8 +/- 4.43 ng mL(-1)). In addition, patients with longer disease duration (mean, 20.1 +/- 5.15 years) had also significantly (P = 0.013) higher leptin concentrations (20.2 +/- 8.52 ng mL(-1)) than those with shorter disease duration (13.4 +/- 4.52 ng mL(-1)) (mean, 7.4 +/- 3.29 years). All acute-phase reaction parameters were found to be significantly (for each, P < 0.01) increased in active disease.. Leptin may have a role in modulating endothelial function and may be involved in mechanisms for vessel endothelium repair, during an exacerbation as well as in chronic disease.

Topics: Adult; Behcet Syndrome; Biomarkers; Case-Control Studies; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Middle Aged; Statistics, Nonparametric

Topics: Adult; Antioxidants; Biomarkers; C-Reactive Protein; Chronic Disease; Complement System Proteins; Female; Glutathione Peroxidase; Humans; Immunoglobulins; Leptin; Male; Maxillary Sinusitis; Middle Aged; Superoxide Dismutase; Superoxide Dismutase-1

Chronic heart failure (CHF) has emerged as an insulin-resistant state, independently of ischaemic aetiology. The underlying mechanisms of this finding are not known. Catecholamines, tumor necrosis factor alpha (TNFalpha) and leptin, the adipocyte specific hormone, have all been implicated as mediators of impaired insulin sensitivity. The purpose of this study was to examine in patients with CHF and in comparison to healthy controls subjects whether norepinephrine, TNFalpha or leptin relate to insulin sensitivity.. 41 patients with CHF (age 60+/-2 years, NYHA I/II/III/IV 4/12/22/3, peak oxygen consumption 17.6+/-1.0 ml/kg per min) and 21 healthy controls of similar age and total and regional fat distribution were studied in a cross-sectional study. Insulin sensitivity was assessed by intravenous glucose tolerance testing using the minimal model approach; catecholamines, TNFalpha and soluble TNF receptors 1 and 2 were also measured. Total and regional body fat mass was assessed by dual energy X-ray absorptiometry.. Insulin sensitivity was reduced in CHF patients compared to controls by 31% (P<0.01) and fasting insulin was higher in patients than in controls (79.1+/-9.7 vs. 41.4+/-6.0 pmol/l, P<0.01). Patients had, compared to healthy controls, elevated serum leptin levels (8.28+/-0.84 vs. 4.83+/-0.68 ng/ml), norepinephrine (3.45+/-0.34 vs. 1.87+/-0.16 nmol/l, both P<0.01) and soluble TNF-receptors 1 (1280+/-141 vs. 639+/-52 pg/ml) and 2 (2605+/-184 vs. 1758+/-221 pg/ml, both P<0.01). Leptin levels corrected for total body fat mass were higher in CHF patients than in controls (41.3+/-3 vs. 24.3+/-2 pg/ml per 100 g, P<0.001). TNFalpha was not significantly different between the groups. In both groups there was an inverse correlation between insulin sensitivity and serum leptin (r=-0.65, P<0.0001 for pooled subjects); in contrast, no significant relation was found between insulin sensitivity and norepinephrine or TNFalpha. In multivariate regression analysis, leptin emerged as the only significant predictor of insulin sensitivity (standardised coefficient=-0.59, P<0.001), independent of body fat mass, age and peak VO2.. In moderate CHF, elevated leptin levels directly and independently predict insulin resistance. Elevated serum leptin levels could play a role in the impaired regulation of energy metabolism in CHF. In contrast to observations in other conditions, TNFalpha and norepinephrine are not related to insulin resistance in moderate CHF.

Topics: Adipose Tissue; Blood Glucose; Blood Pressure; Chronic Disease; Creatinine; Cross-Sectional Studies; Heart Failure; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Multivariate Analysis; Norepinephrine; Oxygen Consumption; Predictive Value of Tests; Sensitivity and Specificity; Sodium; Tumor Necrosis Factor-alpha

In addition to acting as a regulator of food intake and energy expenditure, leptin can also modulate immune and inflammatory responses. The role of leptin in intestinal inflammation is the focus of the present study.. Acute and chronic colitis were induced in leptin-deficient ob/ob or wild-type (WT) mice using dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS). The severity of colitis was evaluated, and possible mechanisms were studied.. Leptin directly stimulates intraepithelial lymphocytes (IELs) and lamina propria mononuclear cells (LPMCs). In the DSS acute model, ob/ob mice exhibited a 72% reduction of colitis severity and spontaneous release of proinflammatory cytokines from the colon compared with WT mice. Replacement of leptin in ob/ob mice converted disease resistance to susceptibility, indicating that leptin deficiency, not obesity, accounts for the resistance to acute DSS-induced colitis. During chronic DSS-induced colitis and TNBS-induced colitis, in addition to reduced disease severity, ob/ob mice exhibited a significant attenuation in intestinal inflammation, accompanied by reduced production of cytokines and chemokines. When compared with WT mice, CD8(+) IELs of ob/ob mice were reduced in number as well as in their ability to synthesize interferon gamma. In addition, LPMCs of ob/ob mice showed increased apoptosis in untreated as well as DSS- or TNBS-treated mice. Phosphorylation of signal transducer and activator of transcription 3 and induction of cyclooxygenase 2 were absent in the colon of DSS-fed ob/ob mice.. These results show that leptin represents a functional link between the endocrine and immune systems.

Topics: Animals; Cells, Cultured; Chemokines; Chronic Disease; Colitis; Colon; Cyclooxygenase 2; Cytokines; Dextran Sulfate; Disease Susceptibility; DNA-Binding Proteins; Enzyme Induction; Female; Intestinal Mucosa; Isoenzymes; Leptin; Lymphocytes; Mice; Mice, Inbred C57BL; Monocytes; Obesity; Prostaglandin-Endoperoxide Synthases; Reference Values; STAT3 Transcription Factor; Trans-Activators; Trinitrobenzenesulfonic Acid

Leptin can act as a satiety factor and exert neuroendocrine effects, but most studies have been performed in fasted animals. We aimed to determine the effect of chronic under-nutrition on the response to a 3-day intracerebroventricular infusion of leptin with regard to food intake and the secretion of pituitary hormones. Ovariectomised ewes (n=6) had a mean (+/-s.e.m. ) bodyweight of 56+/-0.8 kg on a diet available ad libitum (ad lib) or 33.4+/-1 kg on a restricted diet. The differential bodyweight was achieved by dietary means over a period of 6 months prior to the commencement of the study. Leptin (4 microg/h) or vehicle (artificial cerebrospinal fluid (aCSF)) was infused into the third cerebral ventricle for 3 days. Blood samples were taken prior to commencement and on day 3 of infusion for the assay of plasma hormone levels. The experiment was repeated one week later in a cross-over design. Food intake and metabolic status were monitored daily. The luteinising hormone (LH) pulse amplitude was lower (P<0.05) but plasma growth hormone (GH) levels were higher (P<0.05) in the food-restricted animals. Plasma levels of glucose, lactate, insulin, urea and triglycerides were similar in the two groups but non-esterified fatty acid levels were higher (P<0.01) in the animals on an ad lib diet. Leptin reduced (P<0.05) food intake only in the animals fed an ad lib diet. Leptin increased (P<0.05) the secretion of LH in the food-restricted group only and increased (P<0.05) GH irrespective of bodyweight. In conclusion, leptin does not alter food intake in animals on a restricted diet but can increase the secretion of LH in the same animals. The treatment of leptin was not sufficient to reduce plasma GH levels in the food-restricted animals, suggesting that other factors or mechanisms must be involved in the regulation of this axis.

Topics: Analysis of Variance; Animals; Chronic Disease; Cross-Over Studies; Fatty Acids, Nonesterified; Female; Follicle Stimulating Hormone; Growth Hormone; Injections, Intraventricular; Leptin; Luteinizing Hormone; Nutrition Disorders; Ovariectomy; Satiety Response; Sheep

Advanced chronic heart failure is a hypercatabolic state with an imbalance between anabolic and catabolic metabolism and finally progressive loss of both muscle mass and adipose tissue. Leptin, the product of the obesity gene, is a hormone secreted by adipocytes. Therefore, we tested the hypothesis that plasma leptin concentrations are reduced in advanced chronic heart failure.. In 20 patients with chronic congestive heart failure (LVEF 23 +/- 6%) and 20 healthy controls (LVEF 65 +/- 8%) matched for gender, age, and body mass index, fasting plasma leptin (ELISA) and TNF alpha (ELISA) were measured. Follow-up examination was performed after 1 year.. The fasting plasma leptin concentrations of patients with NYHA grade III (8.4 +/- 3.8 ng/ml*) and NYHA grade IV (4.6 +/- 2.4 ng/ml dagger) were significantly lower as compared with the controls (11.2 +/- 3.1 ng/ml; *p < 0.05, dagger p < 0.01). In patients with NYHA grade II plasma leptin levels were significantly elevated as compared with the healthy controls (14.9 +/- 4.2 ng/ml). TNF alpha was higher in heart failure patients than in healthy controls (8.6 +/- 3.6 pg/ml; 5.9 +/- 2.1 pg/ml; respectively; p < 0.05), but did not correlate with the NYHA functional class. Mortality of the controls was 0%, whereas 15% (n = 3) in the congestive heart failure group; one patient (5%) needs an urgent heart transplantation. All of those patients had leptin concentrations below 5 ng/ml.. Plasma leptin concentrations correlate with the NYHA functional class suggesting anabolic metabolism in NYHA class II and catabolic metabolism in advanced heart failure which might be of prognostic relevance.

Topics: Adult; Body Mass Index; Chronic Disease; Energy Metabolism; Female; Heart Failure; Humans; Leptin; Male; Matched-Pair Analysis; Middle Aged; Prognosis; Reference Values; Tumor Necrosis Factor-alpha

Regulation of growth hormone (GH) receptor expression and hence tissue GH sensitivity may be important for the conflicting results found in treatment studies with recombinant growth hormone in chronic heart failure (CHF). Growth hormone-binding protein (GHBP) corresponds to the extracellular domain of the GH receptor and is closely related to measures of body composition and, specifically, to size of visceral fat tissue. Leptin, the adipocyte specific (ob) gene product, has been proposed as the signal linking adipose tissue and GHBP/GH-receptor expression. CHF has recently been shown to be a hyperleptinaemic and insulin-resistant state regardless of aetiology. This study aimed to examine the influence of leptin on GHBP in CHF patients with and without cardiac cachexia compared with healthy control subjects.. We studied 47 male patients with CHF (mean age 61+/-2 years, New York Heart Association (NYHA)-class 2.7+/-0.1, left ventricular ejection fraction (LVEF) 28+/-2%, peak oxygen consumption 16.8+/-0.9 ml/kg/min) and 21 male healthy controls of similar age. Of the CHF patients, 19 were cachectic (cCHF; non-oedematous weight loss >7.5% over at least 6 months) and 28 non-cachectic (ncCHF; similar for age and LVEF). Insulin sensitivity was assessed by an intravenous glucose tolerance test using the minimal model approach.. Compared with healthy controls, patients had elevated levels of leptin (7.6+/-0.7 vs 4.8+/-0.7 ng/ml, P<0.05), insulin (76.2+/-8.9 vs 41.4+/-6.0 pmol/l, P<0.01), and reduced insulin sensitivity (2.43+/-0.2 vs 3.48+/-0.3 min(-1).microU.ml(-1).10(4), P<0.005) but similar GHBP levels (901+/-73 vs 903+/-95 pmol/l). Leptin levels were increased in ncCHF (9.11+/-1.0 ng/ml, P=0.001) but were not different from normal in cCHF (5.32+/-0.7 ng/ml, P>0.5). After correction for total body fat mass, both ncCHF and cCHF were hyperleptinaemic (41.8+/-3.8 and 37.9+/-0.38 vs 24.4+/-2.1 ng/ml/100 g, ANOVA P=0.001). In both patients and controls there was a direct correlation between leptin levels and GHBP (r=0.70 and r=0.71 respectively, both P<0.0001). This relationship was stronger than between GHBP and several parameters of body composition (body mass index (BMI), total and regional body fat mass or % body fat) and held true when sub-groups were tested individually (ncCHF r=0.62, P<0.001; cCHF r=0.79, P<0.0001). In multivariate regression analysis in all CHF patients, serum leptin levels emerged as the strongest predictor of GHBP, independent of age, BMI, total and regional fat mass or % body fat, fasting insulin level and insulin sensitivity.. Fat mass corrected leptin levels are elevated in CHF patients with and without cachexia. Reduced total fat mass may account for lower leptin levels in cachectic CHF patients compared with non cachectic patients. Leptin strongly predicts GHBP levels in CHF regardless of its hyperleptinaemic state or severely altered body composition as in cardiac cachexia. Leptin could be the signalling link between adipose tissue and GHBP/GH receptor expression in CHF.

Topics: Adipose Tissue; Body Composition; Body Mass Index; Cachexia; Cardiac Output, Low; Carrier Proteins; Chronic Disease; Fasting; Glucose Tolerance Test; Humans; Insulin; Leptin; Male; Middle Aged; Oxygen Consumption; Regression Analysis; Ventricular Function, Left; Weight Loss

The pathophysiology of osteoporosis complicating chronic liver disease is unknown. Recent animal studies have found leptin to be a potent inhibitor of bone formation. The aim of this study was to investigate the relationship between serum leptin levels and bone mineral density in patients with chronic liver disease.. Fifty-eight patients, 39 females and 19 males, and age- and gender-matched controls were included. Bone mineral density was measured by using dual energy X-ray absorptiometry. Serum leptin was measured by using a radioimmunoassay.. The mean serum leptin concentration was 10.4 +/- 11.3 and 15.2 +/- 17.9 ng/mL; P=0.11, in the patients and controls, respectively. Leptin correlated positively with body mass index in patients (r=0.40; P=0.003) and in controls (r=0.55; P < 0.0001). In patients classified as Child-Pugh grade B and C, serum leptin correlated negatively with bone mineral density in females at both the lumbar spine and the femoral neck (r=-0.78; P=0.04 and r=-0.86; P=0.03, respectively). In male patients, the correlation was only significant at the lumbar spine (r=-0.99; P=0.002 and r=-0.86; P=0.06, at the lumbar spine and femoral neck, respectively). No correlation was found between serum leptin and bone mineral density in the controls.. An inverse relationship between serum leptin and bone mineral density was found in patients with advanced chronic liver disease. The reasons for these findings are uncertain, but a pathophysiological role of circulating leptin in osteoporosis in chronic liver disease is possible.

Topics: Absorptiometry, Photon; Adult; Aged; Body Mass Index; Bone Density; Case-Control Studies; Chronic Disease; Cohort Studies; Female; Humans; Leptin; Liver Cirrhosis; Male; Middle Aged; Osteoporosis

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

The dysregulation of the immune and inflammatory systems observed in protein-energy malnutrition (PEM) may be partly due to perturbation of essential fatty acid metabolism. In this study, we assessed the calcium ionophore A23187-induced generation of the arachidonate metabolites leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in isolated granulocyte suspensions.. Case-control study.. A university-affiliated acute care hospital in urban Stockholm.. Fourteen severely malnourished elderly subjects with stable non-malignant disorders (age 74 +/- 1 years, mean +/- SEM) and 12 healthy age-matched controls were examined.. Leukotrienes were analysed by high-performance liquid chromatography. Body mass index (BMI, kg m-2) and delayed cutaneous hypersensitivity (DCH) reaction were determined.. BMI was 16. 5 +/- 0.5 and 26.2 +/- 0.9 kg m-2 (mean +/- SE) in the malnourished group and controls (P < 0.001), respectively. DCH was 8.5 mm (median) in patients and 29.5 mm in controls (P < 0.001). LTC4 generation in granulocytes from PEM patients was half of that of controls (9.1 +/- 2.0 vs. 17.8 +/- 5.2 pmol mL-1, P < 0.05) when cells were stimulated with 0.2 micromol L-1 of A23187, and 13.7 +/- 2.5 and 27.2 +/- 7.5 pmol mL-1, respectively (NS), upon stimulation with 1.0 micromol L-1 of A23187. LTB4 production in PEM patients and controls did not differ at any of the two calcium ionophore concentrations. LTC4 production correlated with BMI (r = 0.41, P < 0.05), but there was no significant correlation between DCH and LTB4 or LTC4 production.. Protein-energy malnutrition is accompanied by perturbation of leukotriene synthesis, which may be one factor underlying the dysregulation of inflammatory responses in the depleted patient.

Topics: Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Chromatography, High Pressure Liquid; Chronic Disease; Female; Granulocytes; Humans; Hypersensitivity, Delayed; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Leukotriene B4; Leukotriene C4; Male; Orosomucoid; Protein-Energy Malnutrition; Skin; Superoxides

Recently leptin, a protein released from adipocytes, has been identified as a potent circulating satiety factor. We therefore undertook this series of experiments to examine leptin's role in the anorexia associated with biliary obstruction.. Rats underwent either surgical bile duct resection (BDR) or sham resection (sham). Body weight, and food and water intake were measured during a baseline period and for 8 days after surgery. At 4, 8 and 16 h as well as on days 2, 4, 6, and 8 postsurgery, sham and BDR rats were sacrificed and sera collected for subsequent measurement of leptin hormone concentration by RIA. White adipose tissue was collected on days 2, 4, 6 and 8 for leptin mRNA determination by Northern blot.. Obstructive cholestasis in BDR rats caused significant anorexia for up to 7 days post-surgery, whereas in sham rats, a significant decrease in food intake was only observed in the first 24-h period following surgery. In both sham and BDR rats, water intake was significantly decreased during the first 24-h period after surgery, but had recovered to baseline levels by day 2 in both groups. Fat pad mass corrected to body weight was not significantly different between the two experimental groups. Serum leptin levels were significantly increased 4 and 8 h after surgery, had normalized by 16 h post-surgery, and were then decreased in BDR rats on days 2, 4, 6 and 8 compared with controls. Leptin mRNA levels in epididymal fat pads were decreased by approximately 2-fold in BDR rats compared with sham rats on days 2, 4, 6 and 8. Furthermore, day 5 BDR and sham rats demonstrated similar anorectic responses to centrally administered leptin.. Leptin production is significantly increased early after biliary obstruction but is reduced after prolonged biliary obstruction. Increased circulating leptin levels may contribute to the profound anorexia observed early after biliary obstruction but appear not to mediate the anorexia observed during more chronic biliary obstruction.

Topics: Acute Disease; Adipose Tissue; Animals; Anorexia; Cholestasis; Chronic Disease; Drinking; Eating; Epididymis; Interleukin-6; Leptin; Male; Rats; Rats, Sprague-Dawley; Reference Values; RNA, Messenger; Time Factors; Tumor Necrosis Factor-alpha

Topics: Adipose Tissue; Catecholamines; Chronic Disease; Heart Failure; Humans; Insulin; Leptin; Obesity; Proteins; Sympathetic Nervous System

Cardiac cachexia is a syndrome of generalised wasting which caries a poor prognosis and is associated with raised plasma concentrations of tumour necrosis factor alpha (TNFalpha). TNFalpha increases secretion of leptin, a hormone which decreases food intake and increases energy expenditure.. To determine whether an inappropriate increase in plasma leptin concentration contributes to the cachexia of chronic heart failure.. Retrospective case-control study.. Tertiary referral cardiology unit.. 110 human subjects comprising 29 cachectic chronic heart failure patients, 22 non-cachectic chronic heart failure patients, 33 patients with ischaemic heart disease but normal ventricular function, and 26 healthy controls.. Measurement of: body fat content by skinfold thickness (cachectic males < 27%, females < 29%); plasma leptin, TNFalpha, and noradrenaline (norepinephrine); central haemodynamics in chronic heart failure patients at right heart catheterisation.. Plasma leptin concentration corrected for body fat content, plasma TNFalpha and noradrenaline concentration, and central haemodynamics.. Mean (SEM) plasma leptin concentrations were: 6.2 (0.6) ng/ml (cachectic heart failure), 16.9 (3.6) ng/ml (non-cachectic heart failure), 16.8 (3.0) ng/ml (ischaemic heart disease), and 18.3 (3.5) ng/ml (control) (p < 0.001 for cachectic heart failure v all other groups). Plasma leptin concentration remained significantly lower in the cachectic heart failure group even after correcting for body fat content and in spite of significantly increased TNFalpha concentrations. Thus plasma leptin was inappropriately low in cachectic chronic heart failure in the face of a recognised stimulus to its secretion. There was no significant correlation between plasma leptin, New York Heart Association class, ejection fraction, or any haemodynamic indices.. Leptin does not contribute to the cachexia of chronic heart failure. One or more leptin suppressing mechanisms may operate in this syndrome-for example, the sympathetic nervous system.

Topics: Adipose Tissue; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cachexia; Case-Control Studies; Chronic Disease; Female; Heart Failure; Hemodynamics; Humans; Leptin; Male; Middle Aged; Norepinephrine; Proteins; Retrospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha

Chronic obstructive pulmonary disease (COPD) is a syndrome of chronic wasting, in part associated with a chronic inflammatory response. The aim of this study was to investigate cross-sectionally and prospectively the potential role of leptin in relation to systemic inflammation in the regulation of the energy balance in COPD. Body composition by deuterium dilution, resting energy expenditure (REE) by indirect calorimetry, and plasma concentrations of leptin and soluble tumor necrosis factor (TNF) receptors (sTNF-R) 55 and 75 by ELISA were measured in 27 male patients with emphysema and 15 male patients with chronic bronchitis (disease-subtype defined by high-resolution computed tomography [HRCT]). Emphysematous patients were characterized by a lower body mass index due to a lower fat mass (FM) (p = 0.001) and by lower mean (detectable) leptin concentrations (p = 0.020) compared with bronchitic patients. Leptin was exponentially related to FM in emphysema (r = 0.74, p < 0.001) and in chronic bronchitis (r = 0.80, p = 0.001). Furthermore, a significant partial correlation coefficient between leptin and sTNF-R55 adjusted for FM and oral corticosteroid use was seen in emphysema (r = 0.81, p < 0.001) but not in chronic bronchitis. In 17 predominantly emphysematous depleted male patients with COPD, baseline plasma leptin divided by FM was in addition logarithmically inversely related to baseline dietary intake (r = -0.50, p = 0.047) and to the degree of weight change after 8 wk of nutritional support (r = -0.60, p = 0.017). This proposed cytokine-leptin link in pulmonary cachexia may explain the poor response to nutritional support in some of the cachectic patients with COPD and may open a novel approach in combating this significant comorbidity in COPD. Schols AMWJ, Creutzberg EC, Buurman WA, Campfield LA, Saris WHM, Wouters EFM. Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease.

Topics: Aged; Body Composition; Body Mass Index; Body Water; Bronchitis; Calorimetry, Indirect; Chronic Disease; Cross-Sectional Studies; Diet; Energy Metabolism; Humans; Leptin; Lung Diseases, Obstructive; Male; Nutritional Support; Prospective Studies; Pulmonary Emphysema; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Respiratory Mechanics

Leptin, a product of the ob gene, is known to increase energy expenditure. Given that chronic heart failure is a hypercatabolic state, we sought to determine whether congestive heart failure involves elevations in plasma leptin levels. Since leptin secretion is up-regulated by insulin, we also explored whether in congestive heart failure, a hyperinsulinaemic state, plasma leptin levels relate to plasma insulin levels.. Male patients with weight-stable congestive heart failure (n = 25, aged 55.5 +/- 2.0, mean +/- SEM, body mass index = 27.4 +/- 0.8, radionuclide left ventricular ejection fraction = 29.3 +/- 3.0%) and 18 controls, matched for age, sex and body fat (dual energy X-ray absorptiometry), underwent measurement of fasting plasma leptin (radioimmunoassay) and insulin levels.. Compared to controls, patients with congestive heart failure had higher plasma leptin [8.12 (-1.12, +1.31) vs 4.48 (-0.61, +0.70) ng.ml-1, mean +/- asymmetrical SEM, P = 0.003], 41.5% higher plasma leptin per percent body fat mass (P < 0.001), and higher fasting insulin levels [67.8 (-11.1, +13.3) vs 32.9 (-5.7, +6.9) pmol.l-1, P = 0.010]. In the congestive heart failure group, plasma leptin correlated with total body fat (r = 0.66) and fasting insulin (r = 0.68) (both P < 0.001). In multivariate regression analyses of the congestive heart failure group, fasting insulin (standardized coefficient = 0.41, P = 0.011) emerged as a predictor of plasma leptin levels, independent of total body fat (standardized coefficient = 0.73, P = 0.002, R2 = 0.66, P < 0.001).. Plasma leptin levels are raised in patients with congestive heart failure. The observation of a positive relationship between plasma leptin and insulin concentrations suggests that the insulin-leptin axis may be related to the increased energy expenditure observed in patients with congestive heart failure.

Topics: Adipose Tissue; Biomarkers; Body Mass Index; Cardiomyopathy, Dilated; Chronic Disease; Coronary Disease; Heart Failure; Humans; Hyperinsulinism; Insulin; Leptin; Male; Middle Aged; Proteins; Radioimmunoassay

Hypoglycemia causes hyperphagia and weight gain, through unknown peripheral and central signals. We investigated the effect of hypoglycemia on NPY and leptin expression and the ability of leptin to inhibit hypoglycemia-induced hyperphagia. Acute hypoglycemia (60 U/kg SC insulin; n = 8) increased food intake (p < 0.01) compared with controls (n = 8). Insulin- and leptin-treated rats (300 microg/kg IP leptin; n = 8) had reduced hyperphagia (p < 0.05 vs. controls; p < 0.05 vs. insulin alone) and a 15% fall in NPY mRNA levels compared with controls (p < 0.01). Chronic hypoglycemia, (20-60 U/kg/day insulin; n = 8) increased food intake compared with vehicle-treated controls (p < 0.01). Leptin and insulin administration (300 microg/kg/day IP leptin; n = 8) reduced hyperphagia (p < 0.01 vs. controls, p < 0.05 vs. insulin alone), and NPY mRNA fell by 18% vs. controls (p < 0.01). We conclude that hypoglycemia-induced hyperphagia is not mediated by either a fall in leptin or an increase in hypothalamic NPY mRNA. Leptin can inhibit feeding in hyperphagic hypoglycemic rats, and this may partly be attributable to its inhibition of the NPY neurons.

Topics: Acute Disease; Analysis of Variance; Animals; Arcuate Nucleus of Hypothalamus; Blood Glucose; Body Weight; Chronic Disease; Eating; Hyperphagia; Hypoglycemia; Insulin; Leptin; Male; Models, Biological; Neuropeptide Y; Protein Biosynthesis; Proteins; Rats; Rats, Wistar; RNA, Messenger

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Body Weight; Chronic Disease; Fenfluramine; Forecasting; Humans; Leptin; Obesity; Phentermine; Proteins; United States; United States Food and Drug Administration

To evaluate serum leptin, a fat cell-derived protein, levels in relation to the malnutrition often observed in chronic disease.. A comparison of circulating leptin concentrations in malnourished chronically ill elderly and in age-matched controls.. A university-affiliated teaching hospital in Stockholm, Sweden.. Nineteen protein-energy malnourished elderly patients (74 +/- 1 years) with various chronic nonmalignant diseases and 18 healthy controls (72 +/- 1 years).. Serum leptin levels measured by radioimmunoassay technique, nutritional status as expressed by body mass index (kg m[-2]), triceps skin fold, arm muscle circumference and serum albumin, and serum orosomucoid concentrations indicating inflammatory status.. Patients and controls displayed body mass indexes of 17.4 +/- 0.7 and 25.0 +/- 1.1 (P < 0.001), respectively. Triceps skin fold (TSF) measurements revealed a pronounced fat depletion in the patients, being 8.5 +/- 0.9 and 22.3 +/- 1.5 mm (P < 0.001) in female and 6.1 +/- 0.7 and 10.8 +/- 0.8 mm (P < 0.001) in male patients and controls, respectively. Patient serum leptin concentrations were less than half of the corresponding concentrations in the controls, 4.3 +/- 1.1 and 9.3 +/- 1.3 ng mL(-1)(P < 0.01), respectively. The highest leptin concentrations were registered in female controls, 12.1 +/- 1.6 ng mL(-1). The serum leptin levels in the controls correlated with TSF (r = 0.74: P < 0.001). No such correlation was found in the patients.. Serum leptin levels were low and did not seem to be directly associated with fat and muscle depletion in elderly patients with chronic illness, whereas they appeared to be positively correlated to body fat in healthy elderly.

Topics: Adipose Tissue; Aged; Body Mass Index; Case-Control Studies; Chronic Disease; Female; Humans; Leptin; Male; Nutritional Status; Orosomucoid; Protein-Energy Malnutrition; Proteins; Radioimmunoassay; Serum Albumin