leptin and Cardiovascular-Diseases

Leptin polymorphism (LEP) has been associated with coronary heart disease (CAD), obesity, and high body mass index (BMI). However, we performed a systematic review and meta-analysis to discover the association because previous studies reached different conclusions.. Review Manager, version 5.3.5, and Stata, version 15.0, were used for statistical analysis. We calculated the effect size of the studies using the OR with the corresponding 95% CI, and two-sided (bilateral) p-values of 0.05 were considered significant. To determine heterogeneity among the selected studies, the Q test and I2 statistics were used. Meta-regression was used to examine the disease (heart disease, obesity, and high BMI) and heterogeneity between these subgroups.. Eleven studies with 18,984 subjects were included in this study. The G-2548A (rs12112075), rs7799039, and A19G (rs2167270) polymorphisms of the leptin gene (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Our pooled analysis revealed an association between the G-2548A (rs12112075) polymorphism and heart disease, high BMI, and obesity. This indicates that individuals carrying the AA allele are at an increased risk for heart disease, high BMI, and obesity. People with heart failure and coronary artery disease did not have the rs7799039 polymorphism or its alleles linked to them.. Combined analysis of data from current and published research suggests that the leptin gene polymorphisms G-2548A (rs12112075), rs7799039, and A19G (rs2167270) (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Further research is needed to understand this association.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Coronary Artery Disease; Humans; Leptin; Obesity; Polymorphism, Genetic; Receptors, Leptin

Obesity has recently emerged as one of the most severe health concerns. Obesity is a key autonomous risk factor for heart failure and contributes to cardiovascular disease (CVD) risk factors such as hypertension, type 2 diabetes, and metabolic abnormalities. Obesity is caused by a metabolic imbalance, which occurs when calories burnt are fewer than the number of calories consumed. There are several pathways accountable for the adverse impacts of obesity on the cardiovascular system. Inflammatory cell infiltration develops in the adipose tissue, the pancreas, and other issues similar to the progression of obesity. Inflammation is triggered by immune cells that invade dysfunctional adipose tissue. The atherosclerotic inflammation phase, related to obesity, induces coronary calcification. Obesity is linked to elevated levels of leptin and high blood pressure. Leptin causes systemic vasoconstriction, sodium retention, and increased blood pressure by influencing the synthesis of nitric oxide and activating the sympathetic nervous system. Obesity is a well-known risk factor for CVD and is one of the leading causes of the greater risk of diseases, including dyslipidemia, hypertension, depression, metabolic syndrome, atrial fibrillation, and heart failure in adults and children. When used with dietary improvements, antiobesity drugs improve the probability of experiencing clinically healthy (5%) weight loss. This review aimed to address the consequences of obesity on cardiac structure and function, risk factors, the impact of the obesity paradox, pharmacological treatment strategies for managing and recommended exercise and diet.

Topics: Adult; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypertension; Inflammation; Leptin; Obesity

The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines, cytokines, malondialdehyde (MDA) and liver function enzymes in patients at risk of cardiovascular disease.. Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods.. A pooled analysis of 13 randomized controlled trials (RCTs) revealed that CLA supplementation led to a significant increment in fasting blood glucose (FBG) (WMD: 4.49 mg/dL; 95%CI: 2.39 to 6.59; P < 0.001), and aspartate aminotransferase (AST) (WMD: 2.54 IU/L; 95%CI: 0.06 to 5.01; P = 0.044). Moreover, CLA supplementation decreased leptin (WMD: -1.69 ng/ml; 95% CI: -1.80 to -1.58; P < 0.001), and interleukin 6 (IL-6) (WMD: -0.44 pg/ml; 95%CI: -0.86 to -0.02; P = 0.037). However, there was no effect on hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and alanine aminotransferase (ALT) adiponectin compared to the control group.. Our findings showed the overall favorable effect of CLA supplementation on the adipokines and cytokines including serum IL-6, and leptin, while increasing FBG and AST. It should be noted that the mentioned metabolic effects of CLA consumption were small and may not reach clinical importance.. CRD42023426374.

Topics: Adipokines; Blood Glucose; Cardiovascular Diseases; Cytokines; Dietary Supplements; Glycemic Control; Humans; Interleukin-6; Leptin; Linoleic Acids, Conjugated; Liver; Malondialdehyde

Characterized by a surplus of whole-body adiposity, obesity is strongly associated with the prognosis of atherosclerosis, a hallmark of coronary artery disease (CAD) and the major contributor to cardiovascular disease (CVD) mortality. Adipose tissue serves a primary role as a lipid-storage organ, secreting cytokines known as adipokines that affect whole-body metabolism, inflammation, and endocrine functions. Emerging evidence suggests that adipokines can play important roles in atherosclerosis development, progression, as well as regression. Here, we review the versatile functions of various adipokines in atherosclerosis and divide these respective functions into three major groups: protective, deteriorative, and undefined. The protective adipokines represented here are adiponectin, fibroblast growth factor 21 (FGF-21), C1q tumor necrosis factor-related protein 9 (CTRP9), and progranulin, while the deteriorative adipokines listed include leptin, chemerin, resistin, Interleukin- 6 (IL-6), and more, with additional adipokines that have unclear roles denoted as undefined adipokines. Comprehensively categorizing adipokines in the context of atherosclerosis can help elucidate the various pathways involved and potentially pave novel therapeutic approaches to treat CVDs.

Topics: Adipokines; Adiponectin; Adiposity; Atherosclerosis; Cardiovascular Diseases; Humans; Interleukin-6; Leptin; Obesity

Obstructive sleep apnea (OSA) is a common respiratory disorder characterized by partial obstruction of upper respiratory tract and repetitive cessation of breathing during sleep. The etiology behind OSA is associated with the occurrence of intermittent hypoxemia, recurrent arousals and intrathoracic pressure swings. These contributing factors may turn on various signaling mechanisms including elevated sympathetic tone, oxidative stress, inflammation, endothelial dysfunction, cardiovascular variability, abnormal coagulation and metabolic defect (

Topics: Cardiovascular Diseases; Humans; Leptin; Positive-Pressure Respiration; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is associated with a rise in serum inflammatory markers, which may be attenuated by sleep surgery.. To evaluate whether sleep surgery was associated with improved levels of proinflammatory markers in adults with OSA.. Two authors independently searched Cochrane, Embase, and PubMed databases from inception through June 14, 2022.. Two authors searched the Cochrane, Embase, and PubMed databases for studies comparing preoperative and postoperative levels of serum biomarkers in patients undergoing sleep surgery.. Data were extracted from included articles into a structured proforma. Meta-analyses of the standardized mean difference (SMD) were conducted in random-effects models. To ensure relevance to clinicians and patients, the probability of benefit and number needed to treat were calculated for outcomes that demonstrated a statistically significant effect after sleep surgery.. The primary outcome was the preoperative and postoperative levels of serum biomarkers in patients undergoing sleep surgery, including C-reactive protein (CRP), glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and interleukin-6 (IL-6). Data analysis was performed from April to May 2022.. Of the 3218 studies screened, 26 studies with 1187 patients (mean [SD] age, 42.8 [11.1] years; 932 [78.5%] men and 255 [21.5%] women) were included. Soft-tissue sleep surgery was associated with a large decrease in CRP (SMD, -0.377; 95% CI, -0.617 to -0.137), total cholesterol (SMD, -0.267; 95% CI, -0.417 to -0.116), LDL (SMD, -0.201; 95% CI, -0.344 to -0.058), IL-6 (SMD, -1.086; 95% CI, -1.952 to -0.221), tumor necrosis factor-α (SMD, -0.822; 95% CI, -1.617 to -0.027), triglyceride (SMD, -0.186; 95% CI, -0.301 to -0.071), and leptin (SMD, -0.519; 95% CI, -0.954 to -0.083) in patients with OSA. Meta-regression highlighted that increased age, higher preoperative score for cumulative sleep time percentage with oxyhemoglobin saturation less than 90% (CT90), and greater change in CT90 postoperatively were associated with a greater decrease in serum CRP levels after soft-tissue sleep surgery. A greater reduction in apnea hypopnea index (AHI) was strongly associated with a greater reduction in total cholesterol and LDL. A greater reduction in body mass index and AHI were also associated with a greater increase in HDL.. The findings of this systematic review and meta-analysis of 26 studies suggest that sleep surgery is associated with decreased levels of CRP, total cholesterol, LDL, triglyceride, IL-6, leptin, and TNF-α, which may improve the inflammatory and cardiometabolic profile of patients who undergo sleep surgery.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Cholesterol; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Sleep; Sleep Apnea, Obstructive; Triglycerides

Circadian rhythm, an innate 24-h biological clock, regulates several mammalian physiological activities anticipating daily environmental variations and optimizing available energetic resources. The circadian machinery is a complex neuronal and endocrinological network primarily organized into a central clock, suprachiasmatic nucleus (SCN), and peripheral clocks. Several small molecules generate daily circadian fluctuations ensuring inter-organ communication and coordination between external stimuli, i.e., light, food, and exercise, and body metabolism. As an orchestra, this complex network can be out of tone. Circadian disruption is often associated with obesity development and, above all, with diabetes and cardiovascular disease onset. Moreover, accumulating data highlight a bidirectional relationship between circadian misalignment and cardiometabolic disease severity. Food intake abnormalities, especially timing and composition of meal, are crucial cause of circadian disruption, but evidence from preclinical and clinical studies has shown that food could represent a unique therapeutic approach to promote circadian resynchronization. In this review, we briefly summarize the structure of circadian system and discuss the role playing by different molecules [from leptin to ghrelin, incretins, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF15)] to guarantee circadian homeostasis. Based on the recent data, we discuss the innovative nutritional interventions aimed at circadian re-synchronization and, consequently, improvement of cardiometabolic health.

Topics: Animals; Cardiovascular Diseases; Circadian Rhythm; Ghrelin; Growth Differentiation Factor 15; Humans; Incretins; Leptin

Obstructive sleep apnea (OSA) as an independent cardiovascular risk factor has been proposed, but the mechanisms underlying cardiovascular disease is far from being completely elucidated. Leptin, an inflammatory cytokine produced by adipocytes, contributes to the modulation of metabolism, respiratory control, and inflammation, which are factors associated with cardiovascular disease. Serum levels of leptin in children with OSA have shown conflicting results in previous studies.. We performed a meta-analysis to clarify the correlation between leptin expression of the OSA patients following the PRISMA. PubMed, Embase, and Web of Science were systematically searched for relevant studies, and then independently screened by two researchers, and analyzed the data through STATA version 12.0.. In a total of 5 articles including 469 participants, the data analysis showed that serum leptin levels were elevated in children with OSA (MD, 6.36; 95% CI, 0.24-12.49, P < .001), compared to the control group. Subgroup analysis were performed based on body mass index. The results of subgroup analysis demonstrated that the serum leptin concentration was correlated with body mass index in children with OSA (MD, 9.70; 95% CI, 0.22-11.18, P < .001).. The serum leptin levels were elevated in children with OSA, compared to the control group. It could add to our developing understanding of the pathogenesis and potential treatments for children with OSA, and help us to recognize the relevance of OSA in determining cardiovascular issues among children.

Topics: Body Mass Index; Cardiovascular Diseases; Child; Cytokines; Humans; Leptin; Sleep Apnea, Obstructive

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 landmark discoveries of leptin and adiponectin firmly established adipose tissue as a sophisticated and highly active endocrine organ, opening a new era of investigating adipose-mediated tissue crosstalk. Both obesity-associated hyperleptinemia and hypoadiponectinemia are important biomarkers to predict cardiovascular outcomes, suggesting a crucial role for adiponectin and leptin in obesity-associated cardiovascular disorders. Normal physiological levels of adiponectin and leptin are indeed essential to maintain proper cardiovascular function. Insufficient adiponectin and leptin signaling results in cardiovascular dysfunction. However, a paradox of high levels of both leptin and adiponectin is emerging in the pathogenesis of cardiovascular disorders. Here, we (1) summarize the recent progress in the field of adiponectin and leptin and its association with cardiovascular disorders, (2) further discuss the underlying mechanisms for this new paradox of leptin and adiponectin action, and (3) explore the possible application of partial leptin reduction, in addition to increasing the adiponectin/leptin ratio as a means to prevent or reverse cardiovascular disorders.

Topics: Adiponectin; Adipose Tissue; Animals; Anti-Obesity Agents; Bariatric Surgery; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Humans; Leptin; Metabolism, Inborn Errors; Obesity; Signal Transduction

During aging, body adiposity increases with changes in the metabolism of lipids and their metabolite levels. Considering lipid metabolism, excess adiposity with increased lipotoxicity leads to various age-related diseases, including cardiovascular disease, cancer, arthritis, type 2 diabetes, and Alzheimer's disease. However, the multifaceted nature and complexities of lipid metabolism make it difficult to delineate its exact mechanism and role during aging. With advances in genetic engineering techniques, recent studies have demonstrated that changes in lipid metabolism are associated with aging and age-related diseases. Lipid accumulation and impaired fatty acid utilization in organs are associated with pathophysiological phenotypes of aging. Changes in adipokine levels contribute to aging by modulating changes in systemic metabolism and inflammation. Advances in lipidomic techniques have identified changes in lipid profiles that are associated with aging. Although it remains unclear how lipid metabolism is regulated during aging, or how lipid metabolites impact aging, evidence suggests a dynamic role for lipid metabolism and its metabolites as active participants of signaling pathways and regulators of gene expression. This review describes recent advances in our understanding of lipid metabolism in aging, including established findings and recent approaches.

Topics: Adiponectin; Adipose Tissue; Adiposity; Aging; Alzheimer Disease; Arthritis; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Acids; Gene Expression Regulation; Humans; Leptin; Lipid Metabolism; Lipidomics; Neoplasms; Obesity; Signal Transduction

The importance of cardiometabolic factors in the inception and progression of atherosclerotic cardiovascular disease is increasingly being recognized. Beyond diabetes mellitus and metabolic syndrome, other factors may be responsible in patients with chronic kidney disease (CKD) for the high prevalence of cardiovascular disease, which is estimated to be 5- to 20-fold higher than in the general population. Although undefined uremic toxins are often blamed for part of the increased risk, visceral adipose tissue, and in particular epicardial adipose tissue (EAT), have been the focus of intense research in the past two decades. In fact, several lines of evidence suggest their involvement in atherosclerosis development and its complications. EAT may promote atherosclerosis through paracrine and endocrine pathways exerted via the secretion of adipocytokines such as adiponectin and leptin. In this article we review the current knowledge of the impact of EAT on cardiovascular outcomes in the general population and in patients with CKD. Special reference will be made to adiponectin and leptin as possible mediators of the increased cardiovascular risk linked with EAT.

Topics: Adiponectin; Adipose Tissue; Cardiovascular Diseases; Humans; Leptin; Pericardium; Renal Insufficiency, Chronic

Leptin and adiponectin are two adipokines. Their circulating concentrations, high for leptin and low for adiponectin, are predictive of insulin resistance and of an unfavorable cardiometabolic evolution in patients with obesity, metabolic syndrome or type 2 diabetes. In addition, recently, the adiponectin/leptin ratio has been proposed as an index of adipose tissue dysfunction together with threshold values for cardiometabolic risk for this index. The relevance and potential applications of the adiponectin/leptin and leptin/adiponectin ratios are discussed in the light of recent literature in this brief update.

Topics: Adiponectin; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diagnostic Techniques, Endocrine; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Prognosis; Risk Factors

Elevated circulating leptin levels have been associated with an increased cardiovascular risk in humans. However, recent meta-analyses show that certain epidemiological studies did not find this association, suggesting distinct effects of leptin depending on the pathophysiological context. Studies performed in mice deficient in leptin or in leptin receptors are often contradictory, showing both protective and deleterious effects of leptin. These effects appear to vary depending on the genetic background of the animal and the doses of leptin administered, making interpretation of the results difficult. In humans, elevated adiponectinemia is associated with a favourable cardiovascular risk profile. Adiponectin exerts protective effects at all stages of development of atherosclerotic plaque. However, our knowledge of the pathophysiological mechanisms involved in these protective effects has been established from cellular models, which do not necessarily reproduce the pathology in all its complexity. In addition, mouse models have a very different lipoprotein metabolism from humans, which does not always allow extrapolation of results to humans. Finally, epidemiological studies evaluating adiponectin as a marker of cardiovascular risk show paradoxical results since a high serum adiponectin concentration has not been associated with a reduction in the number of cardiovascular events but with an increase of cardiovascular and all causes mortality in healthy subjects and coronary patients. These observations illustrate the paradox of adipokines actions and show the complexity to use these biomarkers in cardiovascular diseases. Resistance to the action of these adipokines is one of the hypotheses put forward to explain these discrepancies.

Topics: Adiponectin; Animals; Biomarkers; Cardiotonic Agents; Cardiovascular Diseases; Cardiovascular System; Humans; Leptin; Mice; Risk Factors

The adipocyte-derived adipokine leptin exerts pleiotropic effects, which are essential for the regulation of energy balance and cell metabolism, for controlling inflammatory and immune responses, and for the maintenance of homeostasis of the cardiovascular system. Leptin resistance in obese or type 2 diabetes mellitus (T2DM) patients is defined as a decrease in tissue response to leptin. In the cardiovascular system, leptin resistance exhibits the adverse effect on the heart's response to stress conditions and promoting cardiac remodeling due to impaired cardiac metabolism, increased fibrosis, vascular dysfunction, and enhanced inflammation. Leptin resistance or leptin signaling deficiency results in the risk increase of cardiac dysfunction and heart failure, which is a leading cause of obesity- and T2DM-related morbidity and mortality. Animal studies using leptin- and leptin receptor- (Lepr) deficient rodents have provided many useful insights into the underlying molecular and pathophysiological mechanisms of obese- and T2DM-associated metabolic and cardiovascular diseases. However, none of the animal models used so far can fully recapitulate the phenotypes of patients with obese or T2DM. Therefore, the role of leptin in the human cardiovascular system, and whether leptin affects cardiac function directly or acts through a leptin-regulated neurohumoral pathway, remain elusive. As the prevalence of obesity and diabetes is continuously increasing, strategies are needed to develop and apply human cell-based models to better understand the precise role of leptin directly in different cardiac cell types and to overcome the existing translational barriers. The purpose of this review is to discuss the mechanisms associated with leptin signaling deficiency or leptin resistance in the development of metabolic and cardiovascular diseases. We analyzed and comprehensively addressed substantial findings in pathophysiological mechanisms in commonly used leptin- or Lepr-deficient rodent models and highlighted the differences between rodents and humans. This may open up new strategies to develop directly and reliably applicable models, which resemble the human pathophysiology in order to advance health care management of obesity- and T2DM-related cardiovascular complications.

Topics: Animals; Cardiovascular Diseases; Humans; Leptin; Obesity

Leptin is associated with cardiovascular risk. Some studies analyzed the potential association between leptin and arterial stiffness, an independent cardiovascular risk factor. However, the studies that investigated this association provided inconsistent and heterogeneous results.. We performed a systematic review and a meta-analysis of the available studies on the relationship between leptin and arterial stiffness to achieve definitive conclusions.. A systematic search of the on-line databases available (up to December 2019) was conducted including the observational studies that reported the evaluation of the relationship between non-invasively assessed arterial stiffness (expressed by carotid-femoral pulse wave velocity) and leptin. For each study, the effect size was standardized and pooled using a random effect model. Sensitivity analysis, heterogeneity, publication bias, meta-regression and sub-group analyses were also assessed.. Ten studies met the pre-defined inclusion criteria and provided 11 cohorts with 7,580 total participants. Leptin levels were positively and significantly associated with risk of increased arterial stiffness (odds ratio 1.04; p < 0.01), with no significant heterogeneity among studies. Likewise, pooled analysis of correlation showed a significant and positive association between leptin and pulse wave velocity (z = 0.27, p < 0.01), with significant heterogeneity among studies.. The results of this meta-analysis indicate that leptin is positively associated with arterial stiffness. This association significantly adds to the recognized value of leptin in cardiovascular disease.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Female; Humans; Leptin; Male; Middle Aged; Observational Studies as Topic; Prognosis; Risk Assessment; Risk Factors; Vascular Stiffness

It is now established that adipose tissue, skeletal muscle, and heart are endocrine organs and secrete in normal and in pathological conditions several molecules, called, respectively, adipokines, myokines, and cardiokines. These secretory proteins constitute a closed network that plays a crucial role in obesity and above all in cardiac diseases associated with obesity. In particular, the interaction between adipokines, myokines, and cardiokines is mainly involved in inflammatory and oxidative damage characterized obesity condition. Identifying new therapeutic agents or treatment having a positive action on the expression of these molecules could have a key positive effect on the management of obesity and its cardiac complications. Results from recent studies indicate that several nutritional interventions, including nutraceutical supplements, could represent new therapeutic agents on the adipo-myo-cardiokines network. This review focuses the biological action on the main adipokines, myokines and cardiokines involved in obesity and cardiovascular diseases and describe the principal nutraceutical approaches able to regulate leptin, adiponectin, apelin, irisin, natriuretic peptides, and follistatin-like 1 expression.

Topics: Adipokines; Adipose Tissue; Animals; Caloric Restriction; Cardiovascular Diseases; Dietary Supplements; Humans; Leptin; Mice; Models, Biological; Muscle, Skeletal; Myocardium; Obesity; Peptide Hormones; Prebiotics; Probiotics

Obesity as an independent risk factor for cardiovascular diseases (CVDs) leads to an increase in morbidity, mortality, and a shortening of life span. The changes in heart structure and function as well as metabolic profile are caused by obese people, including those free of metabolic disorders. Obesity alters heart function structure and affects lipid and glucose metabolism, blood pressure, and increase inflammatory cytokines. Adipokines, specific cytokines of adipocytes, are involved in the progression of obesity and the associated co-morbidities. In the current study, we review the scientific evidence on the effects of obesity on CVDs, focusing on the changes in adipokines. Several adipokines have anti-inflammatory and cardioprotective effects comprising omentin, apelin, adiponectin, and secreted frizzled-related protein (Sfrp-5). Other adipokines have pro-inflammatory impacts on the cardiovascular system and obesity including leptin, tumor necrosis factor (TNF), retinol-binding protein4 (RBP-4), visfatin, resistin, and osteopontin. We found that obesity is associated with multiple CVDs, but can only occur in unhealthy metabolic patients. However, more studies should be designed to clarify the association between obesity, adipokine changes, and the occurrence of CVDs.

Topics: Adipokines; Adiponectin; Animals; Biomarkers; Cardiovascular Diseases; Genome; Humans; Inflammation; Leptin; Metabolic Syndrome; Obesity; Resistin; Risk Factors

Lipodystrophy is a disease characterized by a partial or total absence of adipose tissue leading to severe metabolic derangements including marked insulin resistance, type 2 diabetes, hypertriglyceridemia, and steatohepatitis. Lipodystrophy is also a source of major cardiovascular disorders which, in addition to hepatic failure and infection, contribute to a significant reduction in life expectancy. Metreleptin, the synthetic analog of the adipocyte-derived hormone leptin and current therapy of choice for patients with lipodystrophy, successfully improves metabolic function. However, while leptin has been associated with hypertension, vascular diseases, and inflammation in the context of obesity, it remains unknown whether its daily administration could further impair cardiovascular function in patients with lipodystrophy. The goal of this short review is to describe the cardiovascular phenotype of patients with lipodystrophy, speculate on the etiology of the disorders, and discuss how the use of murine models of lipodystrophy could be beneficial to address the question of the contribution of leptin to lipodystrophy-associated cardiovascular disease.

Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Liver; Humans; Hypertriglyceridemia; Insulin Resistance; Leptin; Lipodystrophy; Mice

Obesity, which is a worldwide epidemic, confers increased risk for multiple serious conditions including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue only for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins, and growth and vasoactive factors, which are collectively called adipokines known to influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. This review describes the relevance of specific adipokines in the obesity-associated cardiovascular disease.

Topics: Adipokines; Adipose Tissue; Cardiovascular Diseases; Humans; Leptin; Obesity; Risk Factors

Chronic sympathetic nervous system overactivity is a hallmark of aging and obesity and contributes to the development of cardiovascular diseases including hypertension and heart failure. The cause of this chronic sympathoexcitation in aging and obesity is multifactorial and centrally mediated. In this mini-review, we have provided an overview of the key and emerging central mechanisms contributing to the pathogenesis of sympathoexcitation in obesity and healthy aging, specifically focusing on hypertension. A clear understanding of these mechanisms will pave way for targeting the sympathetic nervous system for the treatment of cardiovascular diseases in obesity and aging.

Topics: Aging; Animals; Cardiovascular Diseases; Cellular Senescence; Humans; Hypertension; Inflammation; Leptin; Obesity; Oxidative Stress; Renin-Angiotensin System; Sympathetic Nervous System

The systemic inflammatory nature of systemic lupus erythematosus (SLE) is patent not only in the diverse clinical manifestations of the disease but also in the increased risk of premature cardiovascular diseases (CVD). In this review, we discuss the latest findings on the key factors of the innate immune system known to play critical roles in the pathogenesis of accelerated CVD in patients with SLE and discuss the potential that immunometabolism may play a key role in this respect.. Recent studies exploring the association between SLE and premature CVD clearly showed that alterations of specific immune functions play a pivotal role in the increased cardiovascular morbidity and mortality in the SLE patients. Novel molecular factors such as type I interferons (IFN), dysregulated neutrophil function, and changes to cellular metabolism and metabolites are emerging as important regulators of systemic immune dysfunction and as strong risk factors for premature CVD in SLE. Although corticosteroids and cytotoxic agents can be used to effectively manage and control various lupus-related complications, to date, no drug has been proven to prevent the development of premature atherosclerosis in SLE. However, as new mechanisms underlying this complication of SLE are uncovered, such as the role of metabolism and neutrophil-driven inflammation, new avenues for therapeutic intervention are being discovered.

Topics: Atherosclerosis; Cardiovascular Diseases; Chemokine CCL2; Endothelial Cells; Humans; Immunity, Innate; Inflammation; Interferon Type I; Leptin; Lupus Erythematosus, Systemic; Macrophages; Metabolic Syndrome; Neutrophils; Reactive Oxygen Species

Although it has been known for some time that increases in body mass enhance aldosterone secretion, particularly in women, the origin of this elevation in aldosterone production is not well defined. Adipocyte-derived factors have emerged as potential candidates to increase aldosterone production in obesity.. Emerging evidence suggests the presence of a mechanistic link in which the adipocyte-derived hormone leptin stimulates aldosterone production in obesity, thereby creating a positive feedback loop for obesity-associated cardiovascular disease. In addition, recent reports give credence to the concept that this leptin-aldosterone stimulation pathway in obesity is an underlying mechanism for sex-discrepancies in obesity-associated cardiovascular disease.. Leptin appears as a new direct regulator of adrenal aldosterone production and leptin-mediated aldosterone production is a novel candidate mechanism underlying obesity-associated hypertension, particularly in females.

Topics: Adipocytes; Aldosterone; Animals; Cardiovascular Diseases; Humans; Leptin; Obesity; Sex Factors

Sulfur amino acids (SAAs) play numerous critical roles in metabolism and overall health maintenance. Preclinical studies have demonstrated that SAA-restricted diets have many beneficial effects, including extending life span and preventing the development of a variety of diseases. Dietary sulfur amino acid restriction (SAAR) is characterized by chronic restrictions of methionine and cysteine but not calories and is associated with reductions in body weight, adiposity and oxidative stress, and metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure. SAAR-induced changes in blood biomarkers include reductions in insulin, insulin-like growth factor-1, glucose, and leptin and increases in adiponectin and fibroblast growth factor 21. On the basis of these preclinical data, SAAR may also have similar benefits in humans. While little is known of the translational significance of SAAR, its potential feasibility in humans is supported by findings of its effectiveness in rodents, even when initiated in adult animals. To date, there have been no controlled feeding studies of SAAR in humans; however, there have been numerous relevant epidemiologic and disease-based clinical investigations reported. Here, we summarize observations from these clinical investigations to provide insight into the potential effectiveness of SAAR for humans.

Topics: Adiponectin; Adipose Tissue; Amino Acids, Sulfur; Animals; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diet; Energy Metabolism; Fibroblast Growth Factors; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Liver; Models, Animal; Neoplasms

Leptin, an adipokine that is implicated in the control of food intake via appetite suppression, may also stimulate oxidative stress, inflammation, thrombosis, arterial stiffness, angiogenesis and atherogenesis. These leptin-induced effects may predispose to the development of cardiovascular diseases. In the present review we discuss the evidence linking leptin levels with the presence, severity and/or prognosis of both coronary artery disease and non-cardiac vascular diseases such as stroke, carotid artery disease, peripheral artery disease (PAD) and abdominal aortic aneurysms (AAA) as well as with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Leptin levels have been positively associated with the presence, severity, extent and lesion complexity of coronary atherosclerosis as well as with the presence, severity and poor clinical outcomes of both ischemic and hemorrhagic strokes. But conflicting results also exist. Furthermore, leptin was reported to independently predict common carotid intima-media thickness and carotid plaque instability. A link between hyperleptinemia and PAD has been reported, whereas limited data were available on the potential association between leptin and AAA. Elevated leptin concentrations have also been related to CKD incidence and progression as well as with insulin resistance, T2DM, micro- and macrovascular diabetic complications. Statins and antidiabetic drugs (including sitagliptin, metformin, pioglitazone, liraglutide and empagliflozin) may affect leptin levels. Further research is needed to establish the potential use (if any) of leptin as a therapeutic target in these diseases.

Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Leptin

Psoriasis usually combines with metabolic diseases,and the prevalence of cardiovascular disease remarkably increases in psoriatic patients. Adipokines,which play an important role in the cardiovascular diseases,also express abnormally in psoriasis and may induce or exacerbate the skin lesion. The adipokines associated with psoriasis and cardiovascular disease include adiponectin,leptin,resistin,omentin,visfatin,chemerin,and retinoid binding protein 4 (RBP-4). The levels of adiponectin and omentin apparently decrease in psoriatic patients compared to healthy controls,and thus they may play protective roles for psoriasis. Similarly,adiponectin plays a protective role in cardiovascular disease,but the role of retina in cardiovascular disease is still controversial. However,the concentrations of leptin,resistin,visfatin,chemerin,and RBP-4 in patients with psoriasis or cardiovascular disease are significantly higher than those of the controls;therefore,they may serve as the pathogenic factors for both diseases. Low adiponectin,leptin,visfatin,and chemerin levels may induce or aggravate psoriasis by activating plasmacytoid dendritic cells or T cells,as demonstrated in in vitro experiments. However,in vitro experiments also have shown that visfatin may inhibit cardiomyocyte apoptosis.

Topics: Adipokines; Adiponectin; Apoptosis; Cardiovascular Diseases; Chemokines; Cytokines; Dendritic Cells; GPI-Linked Proteins; Humans; Intercellular Signaling Peptides and Proteins; Lectins; Leptin; Myocytes, Cardiac; Nicotinamide Phosphoribosyltransferase; Psoriasis; Resistin; Retinol-Binding Proteins, Plasma; T-Lymphocytes

Epidemiological studies suggest an increased prevalence of cardiovascular disease (CVD) in patients with psoriasis (PS). Therefore, emphasis has lately been laid on the necessity for clinical evaluation of the risk of CVD in these patients. The systemic inflammatory markers C-reactive protein (CRP) and interleukin- (IL-) 6, which have long been used to predict future CVD in the general population, are increased manyfold in patients with PS. Lipid abnormalities characterized by elevated triglycerides, low HDL cholesterol, and higher concentrations of LDL cholesterol and its oxidized form are also prevalent in patients. There is a need for additional laboratory markers for the assessment of cardiovascular status of patients with PS. Due to frequent comorbid overweight and obesity, biologically active compounds produced by adipocytes may have an impact on monitoring the status of the cardiovascular system of patients with PS. For this purpose, two adipokines, adiponectin and leptin, have been most extensively studied. The review focuses on some inflammatory and oxidative stress aspects in patients with PS through the analysis of the impact of prominent adipokines and oxidized low-density lipoprotein (oxLDL) to assess their eligibility for clinical practice as markers of CVD risk in patients with PS.

Topics: Adipokines; Animals; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Humans; Interleukin-6; Leptin; Lipoproteins, LDL; Psoriasis; Risk Factors

Leptin, the adipocyte-derived hormone identified in 1994 for its major role in the control of satiety and body weight regulation, is an adipokine secreted in a sex-specific manner. Although it has clearly been established that females secrete three to four times more leptin than males and that this sexual dimorphism in leptin secretion is exacerbated with overweight and obesity, the origin and the physiological consequences of this sexual dimorphism remain ill-defined. The adipose tissue is the major site of leptin secretion; however, leptin receptors are ubiquitously expressed, conferring to leptin, and indirectly to the adipose tissue, a potential role in the control of numerous physiological functions. Besides its major role in the control of food intake and energy expenditure, leptin has been shown to contribute to the control of immune, bone, reproductive, and cardiovascular functions. The goal of the present chapter is to review and discuss the current knowledge on the contribution of leptin to the control of cardiovascular function while focusing on the impact of the sexual dimorphism in leptin secretion and of the pathological increases in leptin levels induced by overweight and obesity.

Topics: Adipose Tissue; Animals; Biomarkers; Cardiovascular Diseases; Cardiovascular System; Female; Health Status Disparities; Humans; Leptin; Male; Metabolic Diseases; Obesity; Risk Factors; Sex Characteristics; Sex Factors

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality, affecting both developed and developing countries. Whilst it is well recognized that our risk of CVD can be determined by the interaction between our genetics and lifestyle, this only partly explains the variability at the population level. Based on these well-known risk factors, for many years, intervention and primary prevention strategies have focused on modifying lifestyle factors in adulthood. However, research shows that our risk of CVD can be pre-determined by our early life environment and this area of research is known as the Developmental Origins of Health and Disease. The aim of this review is to evaluate our current understanding of mechanisms underlying the programming of CVD. This article is part of a special issue entitled CV Aging.

Topics: Aging; Animals; Cardiovascular Diseases; Disease Models, Animal; Epigenesis, Genetic; Female; Heart; Humans; Insulin; Kidney; Leptin; Obesity; Oxidative Stress; Pregnancy; Renin-Angiotensin System; Risk Factors; Signal Transduction

Obesity is a major health burden with an increased risk of cardiovascular morbidity and mortality. Endothelial dysfunction is pivotal to the development of cardiovascular disease (CVD). In relation to this, adipose tissue secreted factors termed "adipokines" have been reported to modulate endothelial dysfunction. In this review, we focus on two of the most abundant circulating adipokines, that is, leptin and adiponectin, in the development of endothelial dysfunction. Leptin has been documented to influence a multitude of organ systems, that is, central nervous system (appetite regulation, satiety factor) and cardiovascular system (endothelial dysfunction leading to atherosclerosis). Adiponectin, circulating at a much higher concentration, exists in different molecular weight forms, essentially made up of the collagenous fraction and a globular domain, the latter being investigated minimally for its involvement in proinflammatory processes including activation of NF-κβ and endothelial adhesion molecules. The opposing actions of the two forms of adiponectin in endothelial cells have been recently demonstrated. Additionally, a local and systemic change to multimeric forms of adiponectin has gained importance. Thus detailed investigations on the potential interplay between these adipokines would likely result in better understanding of the missing links connecting CVD, adipokines, and obesity.

Topics: Adipokines; Adiponectin; Animals; Atherosclerosis; Cardiovascular Diseases; Endothelium, Vascular; Humans; Ischemia; Leptin; Mice; Neovascularization, Pathologic; Neovascularization, Physiologic; NF-kappa B; Nitric Oxide; Obesity

Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential genetic and racial differences or environmental factors that may protect obese patients against the development of hypertension and other co-morbidities. Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of α-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity. Furthermore, gene-environment interactions may have the potential to modify gene expression and epigenetic mechanisms could also contribute to the heritability of obesity-induced hypertension. Finally, differences in nutrition, gut microbiota, exposure to sun light and exercise may play an important role in the presence or absence of hypertension in obesity.

Topics: Animals; Appetite; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Exercise; Gene-Environment Interaction; Humans; Hypertension; Leptin; Obesity; Potassium, Dietary; Protective Factors; Receptor, Melanocortin, Type 4; Sodium, Dietary; Sympathetic Nervous System

Leptin is a protein hormone produced mainly by obese gene and secreted by adipose tissue and exerts the biological effects through leptin receptors. With the progress in research on the function and receptor signal transduction related leptin and leptin resistance, it has been found that leptin is associated with the development and progression of many cardiovascular diseases, such as hypertension and left ventricular hypertrophy. Some studies have reported that leptin resistance is the pathologic basis for a variety of cardiovascular diseases. This paper will briefly review the advances in the study of correlation between leptin and hypertensive-left ventricular hypertrophy (HLVH), focusing on the relationship between leptin and various factors related to HLVH, such as sympathetic nervous system, renin angiotensin aldosterone system, growth factors, inflammatory factors and insulin resistance.. 瘦素是主要由肥胖基因编码、脂肪组织分泌的一种蛋白质类激素，通过作用于瘦素受体发挥其生物学效应。随着对瘦素功能、瘦素受体信号转导及瘦素抵抗等方面研究的深入，发现瘦素与许多心血管疾病，尤其与高血压的发生、发展密切相关。左心室肥厚(left ventricular hypertrophy，LVH)是高血压最常见的并发症之一。瘦素与促进高血压LVH形成的各种因素如交感神经系统、肾素-血管紧张素-醛固酮系统、生长因子、炎症细胞因子及胰岛素抵抗有密切关系。.

Topics: Adipose Tissue; Cardiovascular Diseases; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin Resistance; Leptin; Receptors, Leptin; Renin-Angiotensin System; Sympathetic Nervous System

Links between short sleep duration and obesity, type 2 diabetes, hypertension, and cardiovascular disease may be mediated through changes in dietary intake. This review provides an overview of recent epidemiologic studies on the relations between habitual short sleep duration and dietary intake in adults from 16 cross-sectional studies. The studies have observed consistent associations between short sleep duration and higher total energy intake and higher total fat intake, and limited evidence for lower fruit intake, and lower quality diets. Evidence also suggests that short sleepers may have irregular eating behavior deviating from the traditional 3 meals/d to fewer main meals and more frequent, smaller, energy-dense, and highly palatable snacks at night. Although the impact of short sleep duration on dietary intake tends to be small, if chronic, it may contribute to an increased risk of obesity and related chronic disease. Mechanisms mediating the associations between sleep duration and dietary intake are likely to be multifactorial and include differences in the appetite-related hormones leptin and ghrelin, hedonic pathways, extended hours for intake, and altered time of intake. Taking into account these epidemiologic relations and the evidence for causal relations between sleep loss and metabolism and cardiovascular function, health promotion strategies should emphasize improved sleep as an additional factor in health and weight management. Moreover, future sleep interventions in controlled studies and sleep extension trials in chronic short sleepers are imperative for establishing whether there is a causal relation between short sleep duration and changes in dietary intake.

Topics: Adult; Aged; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet; Dietary Fats; Dietary Fiber; Energy Intake; Feeding Behavior; Female; Fruit; Ghrelin; Health Promotion; Health Status; Humans; Hypertension; Leptin; Male; Middle Aged; Nutritive Value; Obesity; Sleep; Sleep Deprivation; Snacks; Time Factors

Many experimental and clinical studies have demonstrated that elevated leptin concentration in patients with obesity/metabolic syndrome contributes to the pathogenesis of cardiovascular disorders including arterial hypertension, atherosclerosis, restenosis after coronary angioplasty and myocardial hypertrophy. Receptor tyrosine kinases belonging to the ErbB family, especially ErbB1 (epidermal growth factor receptor) and ErbB2 are abundantly expressed in the blood vessels and the heart. EGFR is activated not only by its multiple peptide ligands but also by many other factors including angiotensin II, endothelin-1, norepinephrine, thrombin and prorenin; the phenomenon referred to as "transactivation". Augmented EGFR signaling contributes to abnormalities of vascular tone and renal sodium handling as well as vascular remodeling and myocardial hypertrophy through various intracellular mechanisms, in particular extracellular signal-regulated kinases (ERK) and phosphoinositide 3-kinase (PI3K). Recent experimental studies indicate that chronically elevated leptin transactivates the EGFR through the mechanisms requiring reactive oxygen species and cytosolic tyrosine kinase, c-Src. In addition, hyperleptinemia increases ErbB2 activity in the arterial wall. Stimulation of EGFR and ErbB2 downstream signaling pathways such as ERK and PI3K in the vascular wall and the kidney may contribute to the increase in vascular tone, enhanced tubular sodium reabsorption as well as vascular and renal lesions in hyperleptinemic obese subjects.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; ErbB Receptors; Humans; Leptin; Receptor, ErbB-2; Receptor, ErbB-3; Receptor, ErbB-4; Signal Transduction; Transcriptional Activation; Up-Regulation

Increased plasma levels of both leptin and C reactive protein (CRP) have been reported in a number of conditions, including obesity, and have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk; interestingly these two biomarkers appear to be able to reciprocally regulate their bioavailability, through complex mechanisms that have not been completely clarified yet. Here we first review clinical evidence suggesting not only that the circulatory levels of CRP and leptin show an independent correlation, but also that assessing them in tandem may result in an increased ability to predict cardiovascular disease. We summarize also molecular studies showing that leptin is able to promote CRP production from hepatocytes and endothelial cells in vitro and discuss the studies addressing the possibility that in vivo leptin administration may be able to modulate plasma CRP levels. Furthermore, we describe two studies demonstrating that CRP directly binds leptin in extra-cellular settings, thus impairing its biological actions. Finally we report genetic evidence that common variations at the leptin receptor locus are associated with CRP blood levels. Overall, the data reviewed here show that the chronic elevation of CRP observed in obese subjects may worsen leptin resistance, contributing to the pathogenesis of cardiovascular disease, and highlight a potential link between conditions, such as leptin resistance and endothelial dysfunction, that may be amenable of pharmacological treatment targeted to the disruption of leptin-CRP interaction.

Topics: Animals; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Evidence-Based Medicine; Humans; Leptin; Models, Cardiovascular; Risk; Up-Regulation

Ghrelin and leptin show opposite effects on energy balance. Ghrelin constitutes a gut hormone that is secreted to the bloodstream in two major forms, acylated and desacyl ghrelin. The isoforms of ghrelin not only promote adiposity by the activation of hypothalamic orexigenic neurons but also directly stimulate the expression of several fat storage-related proteins in adipocytes, including ACC, FAS, LPL and perilipin, thereby stimulating intracytoplasmic lipid accumulation. Moreover, both acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in adipocytes, suggesting an anti-inflammatory role of ghrelin in human adipose tissue. On the other hand, leptin is an adipokine with lipolytic effects. In this sense, leptin modulates via PI3K/Akt/mTOR the expression of aquaglyceroporins such as AQP3 and AQP7 that facilitate glycerol efflux from adipocytes in response to the lipolytic stimuli via its translocation from the cytosolic fraction (AQP3) or lipid droplets (AQP7) to the plasma membrane. Ghrelin and leptin also participate in the homeostasis of the cardiovascular system. Ghrelin operates as a cardioprotective factor with increased circulating acylated ghrelin concentrations in patients with left ventricular hypertrophy (LVH) causally related to LV remodeling during the progression to LVH. Additionally, leptin induces vasodilation by inducible NO synthase expression (iNOS) in the vascular wall. In this sense, leptin inhibits the angiotensin II-induced Ca(2+) increase, contraction and proliferation of VSMC through NO-dependent mechanisms. Together, dysregulation of circulating ghrelin isoforms and leptin resistance associated to obesity, type 2 diabetes, or the metabolic syndrome contribute to cardiometabolic derangements observed in these pathologies.

Topics: Adipose Tissue; Adiposity; Cardiovascular Diseases; Cardiovascular System; Ghrelin; Humans; Inflammation; Leptin; Lipid Metabolism; Obesity

Obesity and excess of adipose tissue are associated with the development of cardiovascular risk factors such as diabetes, hypertension, and hyperlipidemia. At the cardiac level, various morphological adaptations in cardiac structure and function occur in obese individuals. Different mechanisms linking obesity to these modifications have been postulated. Adipose tissue and epicardial fat releases a large number of cytokines and bioactive mediators such as leptin. Leptin circulates in proportion to body fat mass, thus serving as a satiety signal and informing central metabolic control centers as to the status of peripheral energy stores. It participates in numerous other functions both peripherally and centrally, as indicated by the wide distribution of leptin and the different isoforms of its receptor in different tissues including the heart. This hormone has distinct effects on the reproductive, cardiovascular, and immune systems; however, its role in the heart could mediate wide physiological effects observed in obese individuals. Oxidative stress is associated with obesity and may be considered to be a unifying mechanism in the development of obesity-related comorbidities. It has been reported that obesity may induce systemic oxidative stress; in turn, oxidative stress is associated with an irregular production of adipokines. We herein review the current knowledge of cardiac effects of leptin and the possible mechanisms that are involved, including oxidative stress that plays a major role in the development of cardiovascular damage.

Topics: Cardiovascular Diseases; Humans; Leptin; Obesity; Oxidative Stress; Receptors, Leptin

The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and adiposity as its central features. Identifying individuals with metabolic syndrome is important due to its association with an increased risk of coronary heart disease and type 2 diabetes mellitus. Attention has focused on the visceral adipose tissue production of cytokines (adipokines) in metabolic syndrome and type 2 diabetes mellitus, as the levels of the anti-inflammatory adipokine adiponectin are decreased, while proinflammatory cytokines are elevated, creating a proinflammatory state associated with insulin resistance and endothelial dysfunction. In this review, we will give special attention to the role of the leptin/adiponectin ratio. We have previously demonstrated that in individuals with severe coronary artery disease, abdominal obesity was uniquely related to decreased plasma concentrations of adiponectin and increased leptin levels. Leptin/adiponectin imbalance was associated with increased waist circumference and a decreased vascular response to acetylcholine and increased vasoconstriction due to angiotensin II. Leptin and adiponectin have opposite effects on subclinical inflammation and insulin resistance. Leptin upregulates proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6; these are associated with insulin resistance and type 2 diabetes mellitus. In contrast, adiponectin has anti-inflammatory properties and downregulates the expression and release of a number of proinflammatory immune mediators. Therefore, it appears that interactions between angiotensin II and leptin/adiponectin imbalance may be important mediators of the elevated risk of developing type 2 diabetes mellitus and cardiovascular diseases associated with abdominal obesity.

Topics: Adiponectin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Leptin; Metabolic Syndrome; Obesity, Abdominal

Adipose tissue can be considered as a huge gland producing paracrine and endocrine hormones, the adipo(cyto)kines. There is growing evidence that these adipo(cyto)kines may link obesity to cardiovascular diseases. The excessive adipocyte hypertrophy in obesity induces hypoxia in adipose tissue. This leads to adiposopathy, the process that converts "healthy" adipose tissue to "sick" adipose tissue. This is accompanied by a change in profile of adipo(cyto)kines released, with less production of the "healthy" adipo(cyto)kines such as adiponectin and omentin and more release of the "unhealthy" adipo(cyto)kines, ultimately leading to the development of cardiovascular diseases. The present review provides a concise and general overview of the actual concepts of the role of adipo(cyto)kines in endothelial dysfunction, hypertension, atherosclerosis and heart diseases. The knowledge of these concepts may lead to new tools to improve health in the next generations.

Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Animals; Atherosclerosis; Body Mass Index; Cardiovascular Diseases; Cell Hypoxia; Endothelium-Dependent Relaxing Factors; Endothelium, Vascular; Heart Diseases; Humans; Hypertension; Leptin; Obesity; Renin-Angiotensin System; Resistin

The purpose of this study was to determine whether suction-assisted lipectomy (SAL) decreases the incidence of early cardiovascular disease risk factors or its biochemical and clinical risk indicators.. A systematic review of the literature was performed by conducting a predefined, sensitive search in MEDLINE without limiting the year of publication or language. The extracted data included the basal characteristics of the patients, the surgical technique, the amount of fat extracted, the cardiovascular risk factors and the biochemical and clinical markers monitored over time. The data were analysed using pooled curves, risk ratios and standardised means with meta-analytical techniques.. Fifteen studies were identified involving 357 patients. In all of the studies, measurements of predefined variables were recorded before and after the SAL procedure. The median follow-up was 3 months (interquartile range (IQR) 1-6, range 0.5-10.5). The mean amount of extracted fat ranged from 2063 to 16,300 ml, with a mean ± standard deviation (SD) of 6138 ± 4735 ml. After adjusting for time and body mass index (BMI), leptin and fasting insulin were the only markers that were significantly associated with the amount of aspirated fat. No associations were observed for high sensitive C-reactive protein (hCRP), interleukin-6 (IL-6), adiponectin, resistin, tumour necrosis factor-α (TNF-α), Homeostasis Model of Assessment (HOMA), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, free fatty acids or systolic blood pressure.. Based on the results of our analysis, we conclude that there is no evidence to support the hypothesis that subcutaneous fat removal reduces early cardiovascular or metabolic disease, its markers or its risk factors.

Topics: Adiponectin; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Fatty Acids, Nonesterified; Humans; Insulin; Interleukin-1; Leptin; Lipectomy; Lipoproteins, HDL; Lipoproteins, LDL; Metabolic Diseases; Resistin; Risk Factors; Triglycerides; Tumor Necrosis Factor-alpha

The complex mechanisms linking fat excess to metabolic syndrome are not well understood, but several experimental studies have shown that altered production of adipokines plays a main role in development and progression of this disorder. In particular, reduced secretion of adiponectin has a crucial role in inducing insulin resistance but also in determining the clustering of elevated triglycerides and small, dense LDL particles. Increased leptin secretion may be responsible for sympathetic nervous system overactivity and hypertension, while reduced omentin may have an important permissive role in the development of atherogenic processes. Finally, cytokines and other adipokines (resistin, visfatin) determine and modulate the inflammatory process that is an essential component of this condition of cardiovascular risk. Because obesity is prevalent in polycystic ovary syndrome (PCOS), it is not surprising that patients with PCOS present altered adipokine levels and increased prevalence of metabolic syndrome. However, because of the presence of other CV risk factors (androgen excess), in PCOS adipokine dysfunction is particularly severe. Understanding and treating adipokine dysfunction in young women with PCOS is an essential component of any politics of prevention of CV diseases in the general population.

Topics: Abdominal Fat; Adipokines; Adiponectin; Androgens; Cardiovascular Diseases; Female; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Risk Factors

An increase in adiposity is associated with altered levels of biologically active proteins. These include the hormones adiponectin and leptin. The marked change in circulating concentrations of these hormones in obesity has been associated with the development of insulin resistance and metabolic syndrome. Variations in dietary lipid consumption have also been shown to impact obesity. Specifically, omega-3 fatty acids have been correlated with the prevention of obesity and subsequent development of chronic disease sequalae. This review explores animal and human data relating to the effects of omega-3 fatty acids (marine lipids) on adiponectin and leptin, considering plausible mechanisms and potential implications for obesity management. Current evidence suggests a positive, dose-dependent relationship between omega-3 fatty acid intake and circulating levels of adiponectin. In obese subjects, this may translate into a reduced risk of developing cardiovascular disease, metabolic syndrome and diabetes. In non-obese subjects, omega-3 is observed to decrease circulating levels of leptin; however, omega-3-associated increases in leptin levels have been observed in obese subjects. This may pose benefits in the prevention of weight regain in these subjects following calorie restriction.

Topics: Adiponectin; Animals; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Health Promotion; Humans; Inflammation; Leptin; Metabolic Syndrome; Obesity; Randomized Controlled Trials as Topic

Topics: Allylamine; Animals; Blood Glucose; Bromocriptine; Cardiovascular Diseases; Colesevelam Hydrochloride; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Dipeptidyl-Peptidase IV Inhibitors; Gastrins; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Islet Amyloid Polypeptide; Leptin; Metformin; Sodium-Glucose Transporter 1; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds; Thiazolidinediones; United States

Ghrelin is an orexigenic hormone with additional effects on the regulation of inflammation and the cardiovascular system. It may play an important role in the pathogenesis of cachexia/protein-energy wasting (PEW), inflammation and cardiovascular complications in chronic kidney disease (CKD). There are three circulating gene products of ghrelin, namely, acyl ghrelin, des-acyl ghrelin and obestatin, each with individual distinct functions. Perturbations of these circulating ghrelin proteins impact the overall milieu of CKD. Leptin is an anorexigenic hormone which is secreted from the adipocytes and interacts with ghrelin and other appetite-regulating hormones. Leptin also plays a role in regulating inflammation and the cardiovascular system. Indeed, ghrelin and leptin may play yin-and-yang roles in CKD pathophysiology. Clinical trials involving the use of the mimetics or antagonists of these hormones are limited to short-term phase I/II studies. Further understanding of their interactions in CKD pathophysiology is needed for potential large-scale clinical trials, which may impact the quality of life and survival of patients with CKD.

Topics: Animals; Appetite Regulation; Body Weight; Cardiovascular Diseases; Disease Progression; Ghrelin; Humans; Inflammation; Kidney; Leptin; Malnutrition; Prognosis; Renal Insufficiency, Chronic; Signal Transduction

Obesity and diabetes are major causes of CKD and ESRD, and are thus enormous health concerns worldwide. Both obesity and diabetes, along with other elements of the metabolic syndrome including hypertension, are highly interrelated and contribute to the development and progression of renal disease. Studies show that multiple factors act in concert to initially cause renal vasodilation, glomerular hyperfiltration, and albuminuria, leading to the development of glomerulopathy. The coexistence of hypertension contributes to the disease progression, which, if not treated, may lead to ESRD. Although early intervention and management of body weight, hyperglycemia, and hypertension are imperative, novel therapeutic approaches are also necessary to reduce the high morbidity and mortality associated with both obesity-related and diabetes-related renal disease.

Topics: Adiponectin; Animals; Cardiovascular Diseases; Cytokines; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Early Medical Intervention; Glomerular Filtration Rate; Humans; Kidney; Kidney Failure, Chronic; Leptin; Medication Therapy Management; Mice; Models, Animal; Obesity; Risk Reduction Behavior

Obesity is now growing at an alarming rate reaching epidemic proportions worldwide thus increasing morbidity and mortality rates for chronic disease. But although we have ample information on the complications associated with obesity, precisely what causes obesity remains poorly understood. Some evidence attributes a major role to a low-grade chronic inflammatory state (neurogenic inflammation) induced in obesity by inflammatory mediators produced and secreted within the expanded activated adipocyte pool. Adipose tissue is an endocrine organ that secretes numerous adipose tissue-specific or enriched hormones, known as adipokines, cytokine-like molecules thought to play a pathogenic role in cardiovascular diseases. The imbalance between increased inflammatory stimuli and decreased anti-inflammatory mechanisms may depend on chronic stress. Hence the positive correlation found between stress, obesity and cardiovascular diseases. The chronic inflammatory state associated with insulin resistance and endothelial dysfunction is highly deleterious for vascular function. This review focuses on the proposed neuroimmunodulatory mechanisms linking chronic (psychological) stress, obesity and cardiovascular diseases.

Topics: Allostasis; Cardiovascular Diseases; Comorbidity; Extracellular Matrix; Humans; Inflammation; Leptin; Macrophages; Neuroimmunomodulation; Obesity; Risk Factors; Stress, Psychological

For many decades, adipose tissue was considered as an inactive body compartment that was only used as an energy store. During the recent years, an increasing amount of data has revealed that adipose tissue is a major endocrine and paracrine organ producing numerous enzymes, hormones and growth factors which are collectively termed as adipokines. Several experimental and clinical studies showed that adipokines modulate insulin sensitivity and have an influence on glucose/fat metabolism and obesity. Apart from these properties, recent research revealed several direct actions of adipokines on endothelial function, vascular homeostasis and atherogenesis which are independent of their effects on glucose and fat metabolism. The present review focuses on the direct effects of adipokines on vascular/endothelial function and atherosclerosis and summarizes the experimental and clinical data which suggest a role for these molecules as potential diagnostic and prognostic cardiovascular markers as well as potential therapeutic target to reduce cardiovascular risk.

Topics: Adipokines; Adiponectin; Angiotensinogen; Animals; Atherosclerosis; Cardiovascular Diseases; Endothelium, Vascular; Gene Expression Regulation; Humans; Insulin; Leptin; Resistin; Tumor Necrosis Factor-alpha

The incidence of disorders related to the control of energy homeostasis, such as hypertension, diabetes, obesity, and dyslipidemia, has dramatically increased worldwide in the last decades. The central nervous system (CNS) plays a critical role regulating the energy balance, therefore there has been increasing interest in understanding the mechanisms whereby the brain controls peripheral metabolism, in order to develop new potential therapies to treat those disorders. While the involvement of the CNS in development of hypertension, obesity, and diabetes has been thoroughly investigated, less is known about the specific role of the brain in the control of circulating lipids. Here we summarize the evidence linking CNS disorders with dyslipidemia, as well as the central mechanisms that directly influence plasma cholesterol.

Topics: Animals; Cardiovascular Diseases; Central Nervous System; Cholesterol; Energy Metabolism; Homeostasis; Humans; Insulin; Leptin; Liver; Neurosecretory Systems

Cushing's syndrome (CS) is associated with increased cardiovascular morbidity and mortality. Recent evidence also suggests that increased cardiovascular risk may persist even after long-term remission of CS. Increased central obesity, a typical feature of CS, is associated with altered production of adipokines, which contributes to the pathogenesis of several metabolic and cardiovascular complications observed in this condition. In vitro and in vivo studies have shown a relationship between cortisol and adipokines in several experimental settings. In patients with either active or 'cured' CS, an increase in leptin and resistin levels as well as the release of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, may be associated with increased cardiovascular risk. For other adipokines, including adiponectin, results are inconclusive. Studies are needed to further elucidate the interactions between clinical and subclinical increases in cortisol production and altered adipokine release in CS.

Topics: Adipokines; Cardiovascular Diseases; Cushing Syndrome; Humans; Hypothalamo-Hypophyseal System; Leptin; Pituitary-Adrenal System; Risk Factors

Circadian rhythms (approximately 24h) are widely characterized at molecular level and their generation is acknowledged to originate from oscillations in expression of several clock genes and from regulation of their protein products. While general entrainment of organisms to environmental light-dark cycles is mainly achieved through the master clock of the suprachiasmatic nucleus in mammals, this molecular clockwork is functional in several organs and tissues. Some studies have suggested that disruption of the circadian system (chronodisruption (CD)) may be causal for manifestations of the metabolic syndrome. This review summarizes (1) how molecular clocks coordinate metabolism and their specific role in the adipocyte; (2) the genetic aspects of and scientific evidence for obesity as a chronobiological illness; and (3) CD and its causes and pathological consequences. Finally, ideas about use of chronobiology for the treatment of obesity are discussed.

Topics: Adiponectin; Adipose Tissue; Animals; ARNTL Transcription Factors; Cardiovascular Diseases; Chronotherapy; Circadian Rhythm; Cryptochromes; Female; Gene Expression Regulation; Humans; Jet Lag Syndrome; Leptin; Male; Mammals; Metabolic Syndrome; Neoplasms; Obesity; Period Circadian Proteins; PPAR gamma; Receptors, Adiponectin; Receptors, Leptin

It is well established that individuals with the metabolic syndrome have a significantly increased risk of cardiovascular disease and much effort has been expended to elicit the underlying mechanisms. Various studies have proposed that excessive or deficient physiological effects mediated by leptin make an important contribution, yet many paradoxical observations often preclude a clear definition of the role of leptin. This review article will briefly discuss principal and most recent evidence on direct and indirect regulation of the cardiovascular system by leptin, focusing on cardiac structural and functional as well as vascular effects.

Topics: Animals; Blood Vessels; Cardiovascular Diseases; Cardiovascular System; Humans; Leptin; Myocardium

Obesity is now recognised as one of the most important risk factors for heart disease. Obese individuals have high circulating levels of leptin, a hormone secreted by adipose tissue and involved in energy homeostasis. Growing evidence suggests that leptin may contribute to the development of cardiac dysfunction. In a large prospective study leptin has been shown to be an independent risk factor for coronary heart disease. An independent positive association has also been found between plasma leptin levels and heart rate in hypertensive patients and heart transplant recipients. In animal studies chronic leptin infusion increased heart rate and blood pressure. It has also been demonstrated that circulating leptin levels are elevated in patients with heart failure. The level of plasma leptin was associated with increased myocardial wall thickness and correlated with left ventricular mass, suggesting a role for this hormone in mediating left ventricular hypertrophy in humans. Moreover, leptin directly induced hypertrophy and hyperplasia in human and rodent cardiomyocytes, accompanied by cardiac extracellular matrix remodelling. Leptin may also influence energy substrate utilisation in cardiac tissue. These findings suggest that leptin acting directly or through the sympathetic nervous system may have adverse effects on cardiac structure and function, and that chronic hyperleptinaemia may greatly increase the risk of cardiac disorders. Additional studies are needed to define the role of leptin in cardiac physiology and pathophysiology, nevertheless the reduction in plasma leptin levels with caloric restriction and weight loss may prevent cardiac dysfunction in obese patients.

Topics: Adipose Tissue; Cardiovascular Diseases; Coronary Artery Disease; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Myocardium; Myocytes, Cardiac; Obesity; Ventricular Remodeling; Weight Loss

Helicobacter pylori (H. pylori) infection is reported to be associated with many extragastrointestinal manifestations, such as hematological diseases [idiopathic thrombocytopenic purpura (ITP) and unexplained iron deficiency anemia (IDA)], cardiovascular diseases (ischemic heart diseases), neurological disorders (stroke, Parkinson's disease, Alzheimer's disease), obesity and skin disorders. Among these, the best evidence so far is in ITP and unexplained IDA, with high-quality studies showing the improvement of IDA and ITP after H. pylori eradication. The evidence of its association with coronary artery disease is weak and many of the results may be erroneous. The role of H. pylori infection in affecting serum leptin and ghrelin levels has attracted a lot of attention recently and available data to date have been conflicting. There have also been many uncontrolled, small sample studies suggesting an association between H. pylori infection and neurological disorders or chronic urticaria. However, more studies are required to clarify such proposed causal links.

Topics: Anemia, Iron-Deficiency; Cardiovascular Diseases; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Nervous System Diseases; Obesity; Purpura, Thrombocytopenic, Idiopathic

Patients with rheumatic diseases have an increased risk of mortality by cardiovascular events. In fact, several rheumatic diseases such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis are associated with a higher prevalence of cardiovascular diseases (CVDs). Although traditional cardiovascular risk factors have been involved in the pathogenesis of cardiovascular diseases in rheumatic patients, these alterations do not completely explain the enhanced cardiovascular risk in this population. Obesity and its pathologic alteration of fat mass and dysfunction, due to an altered pattern of secretion of proinflammatory adipokines, could be one of the links between cardiovascular and rheumatic diseases. Indeed, the incidence of CVDs is augmented in obese individuals with rheumatic disorders. Thus, in this paper we explore in detail the relationships among adipokines, rheumatic diseases, and cardiovascular complications by giving to the reader a holistic vision and several suggestions for future perspectives and potential clinical implications.

Topics: Adipokines; Adiponectin; Animals; Atherosclerosis; Cardiovascular Diseases; Humans; Leptin; Rheumatic Diseases

It is well known that adverse conditions during intrauterine life, such as intrauterine growth restriction (IUGR), can result in permanent changes in the physiology and metabolism of the newborn, which in turn leads to an increased risk of disease in adulthood (fetal origin of adult disease hypothesis). In the first part of this review the epidemiological studies in which a correlation between low birth weight and chronic pathologies in adulthood was observed are reported. The second part of the review is focused on metabolomics studies that have revealed an altered metabolism in IUGR patients compared to controls. Together with more classic biomarkers of IUGR, such as endothelin-1, leptin, protein S100B and visfatin, the new holistic metabolomics approach has assumed a crescent role in the identification of disorders in the neonatal metabolic profile, determined by the interconnection of the different processes.

Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelin-1; Epigenomics; Female; Fetal Growth Retardation; Fetal Nutrition Disorders; Genotype; Humans; Infant, Low Birth Weight; Infant, Newborn; Leptin; Metabolomics; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors

Elevated blood glucose, obesity, high blood pressure, elevated triglycerides and low high density lipoprotein (HDL) cholesterol are well accepted risk factors in the development of coronary artery disease. Clustering of at least three of these factors in an individual is defined as metabolic syndrome (MetS). Obesity is a central pathological mechanism in the disease and it is expected that the incidence of this condition will increase dramatically within the next years. The visceral adipose tissue is not only an energy depot but also an endocrine organ which produces a large number of bioactive molecules, the so called adipokines. In the setting of obesity, the over-production of proinflammatory and pro-thrombotic adipokines is associated with insulin resistance. This mechanism represents the pathophysiological basis for the development of MetS. Inflammation has a central role in the pathogenesis of MetS and in mediating its impact on the development of cardiovascular disease. Knowledge of these mechanisms has relevance in the context of preventive and therapeutic strategies.

Topics: Adiponectin; Adolescent; Adult; Angiotensinogen; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Endothelium, Vascular; Humans; Inflammation; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Leptin; Life Style; Metabolic Syndrome; Obesity; Plaque, Atherosclerotic; Plasminogen Activator Inhibitor 1; Prognosis; Resistin; Risk; Tumor Necrosis Factor-alpha

Although the state of prediabetes is defined by its role as a diabetes risk factor, it also carries a significant risk of cardiovascular disease, independent of progression to diabetes. Typical diabetic microvascular complications also occur, albeit at low rates, in prediabetes. There is evidence that both glucose-related and glucose-independent mechanisms contribute to these vascular complications. Effective preventive strategies will likely require control of glycemia, as well as other metabolic risk factors. This article reviews some of the proposed mechanisms for the vascular complications of the prediabetic state.

Topics: Adiponectin; Adipose Tissue; Blood Glucose; Cardiovascular Diseases; Diabetes Complications; Endothelium, Vascular; Glucose Intolerance; Humans; Insulin Resistance; Leptin; Obesity; Oxidative Stress; Prediabetic State

Topics: Adipokines; Adiponectin; Adiposity; Cardiovascular Diseases; Humans; Leptin; Rheumatic Diseases

The US is facing an obesity epidemic. Recognizing the biomarkers associated with adipose tissue may impact physicians' management of cardiometabolic disease greatly. EVIDENCE OF ACQUISITION: We searched PubMed for keywords 'obesity', 'leptin', and 'adiponectin', reviewed national surveys, and searched reference articles used in review articles retrieved via the PubMed search. We included articles with multiple relevant citations. Observational data acquired from two sources, not previously published, were also used to support our conclusion.. Literature review and analysis of observational data showed that the level of leptin increases with the increase in weight gain, while adiponectin decreases. The roles of these adipokines in the body have been defined. With the increase in leptin levels, the incidence and prevalence of the components of the metabolic syndrome were seen to be higher, resulting in higher cardiovascular disease, while adiponectin was seen to play a more protective role in the body against developing such disease.. Measuring circulating levels of leptin and adiponectin as a screening tool may help recognize those individuals who do not only have obesity as a major risk factor toward developing cardiometabolic disease but also may have an unfavorable 'biomarker profile', putting them at highest risk. This may encourage the mobilization of resources to help these individuals lose weight rapidly with possibly aggressive measures such as bariatric surgery.

Topics: Adiponectin; Biomarkers; Cardiovascular Diseases; Humans; Leptin; Obesity

1. Leptin is a 16-kDa hormone, synthesized primarily by adipocyte, which acts as a key factor for maintenance of energy homeostasis in central and peripheral tissues. In most obese individuals, serum leptin levels are increased and correlate with the individual's body mass index. 2. Abundant investigations ranging from clinical and animal model studies to in vitro analyses show that leptin plays a pivotal role in obesity-related cardiovascular diseases (CVD). Hyperleptinaemia has been confirmed to be a predictor of acute cardiovascular events. However, some studies have shown that leptin has a cardioprotective effect in leptin-deficient models. These data suggest the influences of leptin on the pathophysiology of cardiovascular diseases are complex and not completely understood. 3. In the present review, we summarize the major leptin signalling pathways, including Janus-activated kinase/signal transducers and activators of transcription (Jak/STAT), mitogen-activated protein kinases (MAPK), and phosphatidylinositol 3-kinase (PI-3K) signalling pathways, and analyse the probable mechanisms of selective leptin resistance. We then provide a detailed review of the effects of leptin on the cardiovascular system, including sympathoactivation, oxidative stress, vascular inflammation, endothelial dysfunction, vascular cell proliferation, cardiomyocytes hypertrophy, as well as fatty acid metabolism, all of which contribute to the pathogenesis of cardiovascular diseases (e.g. ischaemic heart disease). The central premise of this review is to elucidate the mechanisms by which leptin affects the cardiovascular function and provide insight into obesity-related CVD.

Topics: Animals; Cardiomegaly; Cardiovascular Diseases; Endothelium, Vascular; Extracellular Matrix; Female; Humans; Inflammation; Leptin; Male; Mice; Myocardium; Obesity; Rats; Receptors, Leptin; Risk Factors; Signal Transduction; Thrombosis

Obesity in men, particularly when central, is associated with lower total testosterone [TT], free testosterone [FT] and sex hormone-binding globulin [SHBG], and a greater decline in TT and FT with increasing age compared with lean men. Obesity-related conditions such as obstructive sleep apnea, insulin resistance and type 2 diabetes mellitus are independently associated with decreased plasma testosterone. Possible mechanisms include decreased LH pulse amplitude, inhibitory effects of oestrogen at the hypothalamus and pituitary and the effects of leptin and other peptides centrally and on Leydig cells. Obese men have reduced sperm concentration and total sperm count compared to lean men but sperm motility and morphology appear unaffected. The cause and effect relationships between low plasma androgen levels, obesity and the metabolic syndrome, and associated cardiometabolic risk remain unclear. While weight loss normalizes TT and FT in obese men, androgen replacement in the short term does not significantly improve cardiometabolic risk profile despite reducing fat mass.

Topics: Aging; Animals; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Leptin; Luteinizing Hormone; Male; Metabolic Syndrome; Obesity; Risk Factors; Signal Transduction; Sleep Apnea, Obstructive; Spermatogenesis; Testis; Testosterone; Weight Loss

Adipose tissue is now considered to be an active physiologic system operating in concert with multiple other organs. Leptin is a peptide hormone that is primarily synthesized and secreted by adipose tissue whose principal action is the control of appetite and energy balance. However, current information suggests that leptin exerts pleiotropic effects on several organ systems. Herein, we review the potential role of leptin in cardiovascular and renal physiological conditions as well as pathophysiological situations including obesity and hypertension.. Increasing evidence suggests that leptin may function as a pressure and volume-regulating factor under conditions of health; however, in situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for adverse renal, vascular and cardiac remodeling.. Adipose tissue should be regarded as a potentially important mediator of cardiorenal physiology. Further research awaits the characterization of additional mechanisms of action of leptin, including its interface with other important endocrine and hemodynamic sodium-volume regulatory systems, in both health and disease, particularly in obesity and related comorbidities. This information could lead to the development of leptin analogues as well as leptin receptor blockers that given specific circumstances could optimize the beneficial actions of the hormone and minimize its deleterious effects.

Topics: Adipose Tissue; Animals; Blood Pressure; Cardiovascular Diseases; Cardiovascular System; Homeostasis; Humans; Hypertension; Kidney; Leptin; Models, Biological; Models, Cardiovascular; Obesity; Receptors, Leptin; Renal Insufficiency, Chronic; Water-Electrolyte Balance

Obesity is a universal health problem of increasing prevalence and represents a major public health concern. Obesity is associated with a high risk of developing cardiovascular and metabolic diseases such as hypertension, coronary atherosclerosis, myocardial hypertrophy, diabetes, dyslipidemia, and increased cardiovascular morbidity and mortality. There has been an ongoing search for mediators between obesity and cardiovascular disease. Leptin is a novel and very promising molecule of research that may link these pathologic conditions. Since its discovery in 1994, major advances have been made in the understanding of neuroendocrine mechanisms regulating appetite, metabolism, adiposity, sympathetic tone and blood pressure. In this review, we discuss the physiological and pathophysiological roles of leptin in the causation of various cardiovascular diseases.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Homeostasis; Humans; Hypertension; Leptin; Obesity; Risk Factors

A wealth of investigations, ranging from clinical and animal model studies to in vitro analyses, have generated great interest in the cardiovascular effects of leptin. Accordingly, many studies have examined the contribution of leptin to cardiac remodeling in heart failure and whether the effects of leptin on metabolism, apoptosis, extracellular matrix remodeling, and hypertrophy could explain the so-called obesity paradox. Furthermore, obesity and hyperleptinemia have often been associated with hypertension, and regulation of sympathetic tone or direct effects of leptin on contributors such as atherosclerosis, endothelial dysfunction, and thrombosis have been documented. Unfortunately, translating basic research studies in vitro, or in animal models, to human physiology has proven difficult. The degree of leptin resistance in obesity is one intriguing issue that must be resolved. Furthermore, the importance of autocrine and paracrine effects of leptin derived from the heart and perivascular adipose tissue must be further studied. Carefully planned and executed research to conclusively establish distinct effects of leptin on the cardiovascular system in normal and diseased states will be essential to harness any therapeutic potential associated with leptin's effects.

Topics: Adipose Tissue; Animals; Apoptosis; Atherosclerosis; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Endothelium, Vascular; Extracellular Matrix; Humans; Hypertension; Inflammation; Leptin; Myocardium; Obesity

White adipose tissue is a mesenchymal tissue that begins developing in the fetus. Classically known for storing the body's fuel reserves, adipose tissue is now recognized as an endocrine organ. As such, the secretions from adipose tissue are known to affect several systems such as the vascular and immune systems and play major roles in metabolism. Numerous studies have shown nutrient or hormonal manipulations can greatly influence adipose tissue development. In addition, the associations between various disease states, such as insulin resistance and cardiovascular disease, and disregulation of adipose tissue seen in epidemiological and intervention studies are great. Evaluation of known adipokines suggests these factors secreted from adipose tissue play roles in several pathologies. As the identification of more adipokines and determination of their role in biological systems, and the interactions between adipocytes and other cells types continues, there is little doubt that we will gain a greater appreciation for a tissue once thought to simply store excess energy.

Topics: Adipogenesis; Adipokines; Adipose Tissue; Animals; Cardiovascular Diseases; Endocrine System; Gene Expression Regulation, Developmental; Growth Hormone; Humans; Insulin Resistance; Leptin; Mice; Mice, Knockout; Mice, Transgenic; Somatomedins

Body fat distribution is an important metabolic and cardiovascular risk factor, because the proportion of abdominal to gluteofemoral body fat correlates with obesity-associated diseases and mortality. Here, we review the evidence and possible mechanisms that support a specific protective role of gluteofemoral body fat. Population studies show that an increased gluteofemoral fat mass is independently associated with a protective lipid and glucose profile, as well as a decrease in cardiovascular and metabolic risk. Studies of adipose tissue physiology in vitro and in vivo confirm distinct properties of the gluteofemoral fat depot with regards to lipolysis and fatty acid uptake: in day-to-day metabolism it appears to be more passive than the abdominal depot and it exerts its protective properties by long-term fatty acid storage. Further, a beneficial adipokine profile is associated with gluteofemoral fat. Leptin and adiponectin levels are positively associated with gluteofemoral fat while the level of inflammatory cytokines is negatively associated. Finally, loss of gluteofemoral fat, as observed in Cushing's syndrome and lipodystrophy is associated with an increased metabolic and cardiovascular risk. This underlines gluteofemoral fat's role as a determinant of health by the long-term entrapment of excess fatty acids, thus protecting from the adverse effects associated with ectopic fat deposition.

Topics: Adipokines; Adipose Tissue; Adult; Aged; Body Fat Distribution; Buttocks; Cardiovascular Diseases; Female; Health Behavior; Humans; Leptin; Male; Middle Aged; Obesity; Risk Factors; Thigh; Tumor Necrosis Factor-alpha

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

The intrauterine environment supports the development and health of offspring. Perturbations to this environment can have detrimental effects on the fetus that have persistent pathological consequences through adolescence and adulthood. The developmental origins of the health and disease concept, also known as the "Barker Hypothesis", has been put forth to describe the increased incidence of chronic disease such as cardiovascular disease and diabetes in humans and animals exposed to a less than ideal intrauterine environment. Maternal infection, poor or excess nutrition, and stressful events can negatively influence the development of different cell types, tissues and organ systems ultimately predisposing the organism to pathological conditions. Although there are a variety of conditions associated to exposure to altered intrauterine environments, the focus of this review will be on the consequences of stress and high fat diet during the pre- and perinatal periods and associated outcomes related to obesity and other metabolic conditions. We further discuss possible neuroendocrine and epigenetic mechanisms responsible for the metabolic programming of offspring. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.

Topics: Animals; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Disease Models, Animal; Disease Susceptibility; Energy Metabolism; Environment; Epigenesis, Genetic; Female; Glucocorticoids; Humans; Insulin; Leptin; Male; Pregnancy; Prenatal Exposure Delayed Effects; Sex Factors

Obstructive sleep apnea (OSA) is a chronic disease characterized by repetitive partial or complete closure of the upper airway during sleep. OSA tends to be associated with components of metabolic syndrome sharing a common ground of metabolic changes with metabolic syndrome itself. Recent studies showed that subjects with OSA were 6-9 times more likely to have metabolic syndrome than subjects without OSA. Intermittent hypoxia and sleep fragmentation in OSA can initiate intermediary mechanisms (oxidative stress, neurohumoral changes, inflammation) leading to the components of metabolic syndrome. OSA has been suggested to be a novel risk factor, inside the metabolic syndrome, contributing to increased cardiovascular risk. Several studies report that continuous positive airway pressure (CPAP) treatment can reverse pathophysiological changes in OSA, increasing insulin sensitivity and reducing blood pressure. Recent evidences show that CPAP treatment reduces the risk of cardiovascular events and mortality in subjects with OSA. Some subjects with metabolic syndrome can be affected by undiagnosed OSA: CPAP treatment could significantly reduce cardiovascular risk in this subgroup of patients.

Topics: Age Factors; Aged; Blood Glucose; Cardiovascular Diseases; Clinical Trials as Topic; Continuous Positive Airway Pressure; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Humans; Hypertension; Insulin Resistance; Leptin; MEDLINE; Metabolic Syndrome; Obesity; Randomized Controlled Trials as Topic; Risk Factors; Sleep Apnea, Obstructive; Stroke

Several lines of evidence show that metabolic syndrome represents an important therapeutic challenge for the forthcoming years. This is because of the epidemic burden of this multifaceted disease, the adverse impact on cardiovascular risk, as well as the problems posed in its management. This paper will provide an up-to-date report on metabolic syndrome and cardiometabolic risk, focusing in particular on the epidemiological profile of the disease, the impact on risk profile and target organ damage as well as some of the main pathophysiological features of the condition. The general therapeutic recommendations, provided by the 2007 European Society of Hypertension/European Society of Cardiology Guidelines, will be briefly discussed.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Anticholesteremic Agents; Antihypertensive Agents; Cardiovascular Diseases; Cohort Studies; Contraindications; Disease Progression; Female; Humans; Hypertrophy, Left Ventricular; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Practice Guidelines as Topic; Prevalence; Risk Factors; Sympathetic Nervous System

Leptin, a protein containing 167 amino acids, demonstrates structural similarities with cytokine family and is mainly produced by adipocytes. The leptin receptor (OB-R) is a large membrane spanning protein that belongs to the gp 130 family of cytokine class I receptors. Besides the neuroendocrine effects of leptin in the control of food intake and energy expenditure, binding of this hormone has been proven in intestine, liver, kidney, skin, stomach, heart, spleen, lung, and so on. Thus leptin affects maternal, fetal and placental function, it appears to act as an endocrine and paracrine factor for the regulation of reproduction and puberty, prevents ectopic lipid deposition, modifies insulin sensitivity in the muscle or liver, and links the immune and endocrine systems. The LEP gene encodes for leptin. It has been localized in humans on the 7 alpha 31.3 chromosome and consists of three exons separated by two introns. In humans, a mutation in the LEP gene was reported in two children with the same cosanguineous pedigree. Other studies reported a polymorphism in the promoter untranslated exon 1 of the LEP gene (A19G), a polymorphism C(-188)A in the promoter region of the LEP gene (17) and a mutation at codon V110M. The biologic activities of leptin on target tissues are carried out through binding to a specific receptor, LEPR. LEPR maps in humans to the 1p31 chromosome. Variants commonly occur, which cause two nonconservative changes:lysine to asparagine at codon 656 (AAG to AAC) in exon 14 (K656N); lysine to arginine at codon 109 (AAG to AGG) in exon 4 (K109R); a nonconservative change glutamine to arginine at codon 223 (CAG to CGG); a silent TC change at codon 343; and a silent GA transition at codon 1019. Leptin is related with obesity and its metabolic disorders. However, new relation ships have been described; inflammatory bowel disease, cancer, bone formation, asthma and so on. In conclusion, despite the great advances in our knowledge of leptin physiology, many areas of investigation remain. Future research is expected to discover new molecules in the leptin pathway, to treat obesity and its related diseases.

Topics: Animals; Cardiovascular Diseases; Humans; Leptin; Metabolic Syndrome; Mice; Obesity; Receptors, Leptin; Sequence Homology, Amino Acid

The current epidemic of childhood obesity will be a serious threat to population health for at least the next several decades. The biology of childhood obesity was the theme of an international symposium held in November 2007. Speakers discussed monogenic causes of obesity, prenatal epigenetic programming, neurobehavioral aspects of obesity, and hormonal and neuroendocrine abnormalities, and the insights provided by non-murine models for understanding the biology of early-onset obesity. Several new developments have been reported in white and brown adipose tissue biology. They are summarized briefly in this review and include observations about cell lineage of adipocytes, the renewal of adipocytes throughout life and the numerous factors that influence adipocyte fatty acid release. The biological underpinnings of childhood obesity are multiple and complex.

Topics: Adipocytes; Adipose Tissue; Adult; Age of Onset; Cardiovascular Diseases; Child; Fatty Acids; Female; Ghrelin; Homeostasis; Humans; Infant, Newborn; Insulin; Leptin; Lipase; Lipolysis; Maternal Nutritional Physiological Phenomena; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Sterol Esterase

Obesity, especially visceral adiposity, is associated with morbidity and mortality through endocrine and mechanical processes. Clinical manifestations due to effects of obesity on the cardiovascular, respiratory, gastrointestinal, musculoskeletal, immune, and integumentary systems have been described. Further studies are needed to understand the pathologic processes underlying these clinical manifestations to improve disease prevention.

Topics: Adipocytes; Adiponectin; Adiposity; Cardiovascular Diseases; Energy Metabolism; Exercise; Gastrointestinal Diseases; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Musculoskeletal Diseases; Neoplasms; Obesity; Respiratory Tract Diseases

Cardiovascular diseases are currently the most frequent cause of death in Poland and their incidence continually rises. This is related to the high incidence of obesity associated with insulin resistance, which is present in type 2 diabetes mellitus. Adipose tissue produces multiple cytokines(TNF-alpha, IL-6, PAI-1, CRP, angiotensinogen, leptin, adiponectin, visfatin, apelin, resistin)which decrease insulin sensitivity and induce inflammatory processes, endothelial dysfunction,and atherosclerosis. This article presents the link between obesity, insulin resistance, and type 2 diabetes mellitus according to studies conducted in vitro and in animal models. In human studies, the influence of resistin on the development of insulin resistance is controversial. The article underlines the role of resisitin in the development of inflammatory processes and endothelial dysfunction in humans. In clinical studies, resistin was shown to be a predictive factor of coronary artery disease and mortality connected with cardiovascular diseases.

Topics: Adipose Tissue; Animals; Biomarkers; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Inflammation; Inflammation Mediators; Leptin; Metabolic Diseases; Metabolic Syndrome; Obesity; Resistin

Topics: Body Mass Index; Cardiovascular Diseases; Ghrelin; Humans; Leptin; Metabolic Syndrome; Risk Factors

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Mellitus; Drug Therapy, Combination; Humans; Hypertension; Insulin Resistance; Leptin; Obesity

The metabolic syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is a primary risk factor for diabetes and cardiovascular disease. We showed for the first time that the metabolic syndrome is associated with a higher fraction of oxidized LDL and thus with higher levels of circulating oxidized LDL. Hyperinsulinemia and impaired glycaemic control, independent of lipid levels, were associated with increased in vivo LDL oxidation, as reflected by the higher prevalence of high oxidized LDL. High levels of oxidized LDL were associated with increased risk of future myocardial infarction, even after adjustment for LDL-cholesterol and other established cardiovascular risk factors. This association is in agreement with the finding that accumulation of oxidized LDL, which activates/induces subsets of smooth muscle cells and macrophages to gelatinase production, was associated with upstream localization of a vulnerable plaque phenotype. Dyslipidemia and insulin resistance in obese LDL receptor-deficient mice were associated with increased oxidative stress and impaired HDL-associated antioxidant defence associated with accelerated atherosclerosis due to increased macrophage infiltration and accumulation of oxidized LDL in the aorta. The accumulation of oxidized LDL was partly due to an impaired HDL-associated antioxidant defence due to a decrease in PON. Our data in this experimental model are thus the more relevant because a decrease in PON activity was found to be associated with a defective metabolism of oxidized phospholipids by HDL from patients with type 2 diabetes. Weight loss in leptin-deficient, obese, and insulin-resistant mice was associated with expressional changes of key genes regulating adipocyte differentiation, glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. We established an important relationship between PPAR-gamma and SOD1 for the prevention of the oxidation of LDL in the arterial wall. For example we showed that rosuvastatin decreased the oxidized LDL accumulation by increasing the expression of PPAR-gamma and SOD1. In addition, we established a relation between increased PPAR-alpha expression in the adipose tissue and a change in the gene expression pattern, which explains the decrease of free fatty acids, triglycerides and the increase in insulin sensitivity. We demonstrated

Topics: Animals; Cardiovascular Diseases; Comorbidity; Humans; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Lipoproteins, LDL; Metabolic Syndrome; Mice; Obesity; Oxidation-Reduction; Oxidative Stress; Risk Factors; Weight Loss

There is general agreement that central, as opposed to peripheral, adipose tissue confers the most cardiometabolic risk. Although the basis of this differential risk has not been established, the pattern of gene expression and secretory products in visceral fat would be predicted to be more atherogenic compared with that in subcutaneous peripheral fat. Adipose tissue is, in fact, now recognized not simply a store of excess energy but a major endocrine and secretory organ, releasing a wide range of protein factors and signals, termed adipokines, in addition to fatty acids and other lipid moieties. These factors are derived from adipocyte or non-adipocyte fractions, and include proteins, metabolites and hormones. This paper reviews some of the advances in the understanding of biologically active molecules produced by adipose tissue and how dysregulated production of these factors could be implicated in the association between central adiposity, cardiovascular pathology and comorbidities, including metabolic syndrome, type 2 diabetes and systemic inflammation.

Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Animals; Atherosclerosis; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Leptin; Metabolic Syndrome; Obesity; Systemic Inflammatory Response Syndrome

Leptin is an adipocyte-derived hormone and cytokine that regulates energy balance through a wide range of functions, including several that are important to cardiovascular health. Increased circulating leptin, a marker of leptin resistance, is common in obesity and independently associated with insulin resistance and cardiovascular disease (CVD) in humans. The mechanisms of leptin resistance include genetic mutation, leptin self-regulation, limited tissue access, and cellular or circulating molecular regulation. Evidence suggests that central leptin resistance causes obesity and that obesity-induced leptin resistance injures numerous peripheral tissues, including liver, pancreas, platelets, vasculature, and myocardium. This metabolic- and inflammatory-mediated injury may result from either resistance to leptin's action in selective tissues, or excess leptin action from adiposity-associated hyperleptinemia. In this sense, the term "leptin resistance" encompasses a complex pathophysiological phenomenon. The leptin axis has functional interactions with elements of metabolism, such as insulin, and inflammation, including mediators of innate immunity, such as interleukin-6. Leptin is even purported to physically interact with C-reactive protein, resulting in leptin resistance, which is particularly intriguing, given C-reactive protein's well-studied relationship to cardiovascular disease. Given that plasma levels of leptin and inflammatory markers are correlated and also predict cardiovascular risk, it is conceivable that part of this risk may be mediated through leptin resistance-related insulin resistance, chronic inflammation, type II diabetes, hypertension, atherothrombosis, and myocardial injury. Leptin resistance and its interactions with metabolic and inflammatory factors, therefore, represent potential novel diagnostic and therapeutic targets in obesity-related cardiovascular disease.

Topics: Animals; Cardiovascular Diseases; Humans; Inflammation; Leptin; Obesity

Leptin, a product of the obesity gene, is a molecule that has received much attention since its cloning in 1994. Initially, most work centered around the effects of leptin on satiety and energy balance. However, in recent years there has been an intense focus on leptin as it relates to the cardiovascular system. Plasma leptin concentration is markedly elevated in obesity and the metabolic syndrome, both of which are associated with increased incidence of cardiovascular pathologies. In many studies, hyperleptinemia has been linked to endothelial dysfunction (a known precursor to atherosclerotic cardiovascular disease) and activation of the sympathetic nervous system. Additionally, recent evidence suggests that leptin released from perivascular adipose tissue may also have deleterious effects on the underlying vasculature, including the coronary circulation. This report reviews pertinent literature on leptin-mediated endothelial dysfunction, leptin-mediated sympathetic activation, and leptin as a significant perivascular adipose-derived factor.

Topics: Animals; Autonomic Nervous System; Cardiovascular Diseases; Cohort Studies; Disease Models, Animal; Endothelium, Vascular; Female; Humans; Leptin; Male; Mice; Obesity; Receptors, Leptin; Risk Assessment; Sensitivity and Specificity

Cardiovascular disease caused less than 10% of deaths worldwide at the beginning of the 20th century but accounted for nearly 50% toward its end. Obesity has seen a similarly sharp increase in prevalence and is a major contributing factor to the rise in cardiovascular disease incidence. Mechanisms of obesity-induced heart disease are multifaceted and remain largely unknown, but cardiomyocyte programmed cell death, or apoptosis, seems to play a critical role in their development and progression. The heart maintains a delicate balance between cell proliferation and cell death throughout its lifetime. Even a slight increase in the rate of myocyte apoptosis, as seen in various animal models, has devastating consequences for the heart. This article critically reviews studies conducted in animal models of obesity that have expanded our understanding of the mechanisms of cardiomyocyte apoptosis and their role in various obesity-associated cardiovascular diseases.

Topics: Animals; Apoptosis; Cardiovascular Diseases; Disease Models, Animal; Insulin Resistance; Leptin; Male; Myocytes, Cardiac; Obesity; Rats; Rats, Sprague-Dawley; Rats, Zucker; Risk Factors; Sensitivity and Specificity; Signal Transduction; Survival Rate

Increasing evidence supports the role of adipose tissue in the development of a systemic inflammatory state, which contributes to obesity-associated vasculopathy and cardiovascular risk. In addition to storing calories as triglycerides, adipocytes secrete a large variety of proteins, including cytokines, chemokines, and -hormone-like factors (eg, leptin, adiponectin, resistin). This production of pro chemokines by adipose tissue is of particular interest, because their local secretion by perivascular adipose depots may provide a new mechanistic link between obesity and its associated vascular complications. Insulin resistance, in subjects with or without diabetes, is frequently associated with obesity, particularly with an excess of intra-abdominal fat. Recently, the endocannabinoid system, among others, has been shown to be involved in the pathophysiology of visceral obesity and global cardiometabolic risk, as represented by the overall risk of developing type 2 diabetes or cardiovascular diseases.

Topics: Abdominal Fat; Adiponectin; C-Reactive Protein; Cardiovascular Diseases; Humans; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; Resistin; Risk Factors

Leptin and adiponectin are adipokines with respective pro-atherogenic and anti-atherogenic properties, defining the plasma leptin/adiponectin ratio as a novel marker for atherosclerosis. In non-renal patients, both hyperleptinemia and hypoadiponectinemia are associated with cardiovascular complications. In peritoneal dialysis (PD) patients, the leptin/adiponectin ratio is markedly elevated, which is consistent with their increased cardiovascular risk. As glucose metabolism regulates adipokines, we hypothesized that glucose and/or other PD fluid components may affect adipokine production balance. This review summarizes the available data arising from research in this area. In 3T3-L1 adipocytes, glucose-based PD4 1.36% significantly increased leptin secretion vs amino-acid-based (AA) and icodextrin (ICOD)-based PD fluids. In contrast, adiponectin secretion was significantly reduced by PD4 1.36% vs glucose-free dialysates. Glucose concentration in PD fluids was shown to determine leptin secretion. Preliminary data from PD patients showed that a single 6-h dwell with PD4 3.86% glucose acutely increased plasma leptin vs AA (P<0.05). The reduction in glucose load in a standard PD regimen was associated with an improvement in the plasma leptin/adiponectin ratio at 6 months. pH-neutral PD fluids increased leptin secretion in vitro vs acidic PD fluids, without effect on adiponectin. Whether this effect may have an impact on plasma leptin levels in PD patients is unknown. In conclusion, glucose-based PD fluids worsen the adipokine production balance in vitro while glucose-free solutions improve it. In PD patients, hypertonic glucose-based PD fluids may increase plasma leptin levels. Glucose-sparing PD regimens appear to improve the leptin/adiponectin ratio. However, their potential to reduce cardiovascular complications needs to be demonstrated.

Topics: Adiponectin; Biomarkers; Cardiovascular Diseases; Glucose; Humans; Leptin; Peritoneal Dialysis; Risk Factors

With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they have been shown increasingly to affect several aspects of the pathogenesis of obesity-related diseases. Until relatively recently, the role of adipose tissue itself in the development of obesity and its consequences was considered to be a passive one. It is now clear that, in addition to storing energy in the form of triglycerides, adipocytes also secrete a large variety of proteins, including cytokines, chemokines and hormone-like factors. This production of proatherogenic chemokines by adipose tissue is of particular interest, since their local secretion, for example by perivascular adipose depots, may provide a novel mechanistic link between obesity and associated vascular complications.

Topics: Acute-Phase Proteins; Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Cardiovascular Diseases; Humans; Inflammation; Inflammation Mediators; Leptin; Obesity; Resistin

The incidence and prevalence of obesity and the metabolic syndrome have risen markedly in the past decade, representing a serious cardiovascular health hazard with significant morbidity and mortality. The etiology of the metabolic syndrome and its various pathogenic mechanisms are incompletely defined and under intense investigation. Contemporary research suggests that the adipocyte-derived hormone leptin may be an important factor linking obesity, the metabolic syndrome, and cardiovascular disorders. Although recent evidence indicates that under normal conditions leptin may be an important factor in regulating pressure and volume, during situations of chronic hyperleptinemia and leptin resistance, this hormone may function pathophysiologically for the development of hypertension and cardiac and renal diseases. Future research will determine if reduction of circulating leptin and/or blockade of its peripheral actions can confer cardiovascular and renal protection in hyperleptinemic patients with obesity and the metabolic syndrome.

Topics: Appetite Regulation; Blood Pressure; Cardiovascular Diseases; Heart; Humans; Hypertension; Insulin Resistance; Kidney; Leptin; Metabolic Syndrome; Obesity; Receptors, Leptin; Risk Factors; Sympathetic Nervous System

The clustering of cardiovascular risk factors associated with abdominal obesity is well established. Although currently lacking a universal definition, the metabolic syndrome describes a constellation of metabolic abnormalities, including abdominal obesity, and was originally introduced to characterize a population at high cardiovascular risk. Adipose tissue is a dynamic endocrine organ that secretes several inflammatory and immune mediators known as adipokines. Dysregulation of adipokine secretion, free fatty acid toxicity, and the site-specific differences in abdominal (visceral) versus subcutaneous fat support abdominal obesity as a causal factor mediating the insulin resistance, increased risk of diabetes, and cardiovascular disease in the metabolic syndrome.

Topics: Adipokines; Adiponectin; Adiposity; Cardiovascular Diseases; Fatty Acids, Nonesterified; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Metabolic Syndrome; Obesity; Renin-Angiotensin System; Risk Factors; Subcutaneous Fat, Abdominal

Current explanations for obesity center around a predisposition in genotype and phenotype, possibly triggered by an inflammatory process or event, and exacerbated by environmental and psychological factors. It is likely that a variety of physiologic factors may act in combination to produce clinical obesity. Leptin resistance may be an important neurochemical cause of obesity; elevated leptin levels have been correlated with weight gain over extended time periods. Genetic studies support the postulate that a gene originating with our cave-dwelling ancestors, critical to survival when food was scare, has evolved into a trigger for obesity and related diseases. A variety of biochemical markers are prevalent in obesity and obesity-linked disease states. C-reactive protein, interleukin-6, and others are elevated in obesity, supporting the hypothesis that inflammation plays a role in the condition. Tumor necrosis factor-alpha is overexpressed in obesity and diabetes, suggesting that it may be part of the link between the 2 conditions.

Topics: Appetite; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Causality; Cost of Illness; Diabetes Mellitus, Type 2; Dietary Fats; Genetic Predisposition to Disease; Genotype; Humans; Inflammation; Interleukin-6; Leptin; Life Style; Neoplasms; Obesity; Phenotype; Tumor Necrosis Factor-alpha; United States

The increasing national prevalence of obesity is a major public health concern and a substantial burden on the health care resources of Canada. In addition to the direct health impact of obesity, this condition is a well-established risk factor for the development of various prevalent comorbidities including type 2 diabetes, hypertension, and cardiovascular disease. Historically, adipose tissue has been regarded primarily as an organ for energy storage. However, the discovery of leptin in the mid 1990's revolutionized our understanding of this tissue and has focused attention on the endocrine function of adipose tissue as a source of secreted bioactive peptides. These compounds, collectively termed adipokines, regulate a number of biological functions including appetite and energy balance, insulin sensitivity, lipid metabolism, blood pressure, and inflammation. The physiological importance of adipokines has led to the hypothesis that changes in the synthesis and secretion of these compounds in the obese are a causative factor contributing to the development of obesity and obesity-related diseases in these individuals. Following from this it has been proposed that pharmacologic manipulation of adipokine levels may provide novel effective therapeutic strategies to treat and prevent obesity, type 2 diabetes, and cardiovascular disease.

Topics: Adiponectin; Adipose Tissue; Angiotensin II; Animals; Cardiovascular Diseases; Complement Activation; Complement C3a; Complement Factor D; Cytokines; Diabetes Mellitus, Type 2; Fibrinolysis; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Plasminogen Activator Inhibitor 1; Renin-Angiotensin System; Resistin; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Risk Factors; Tumor Necrosis Factor-alpha

Research in the last 10-15 years has shown that fat cells (adipocytes) produce and release proteins with specific biologic activities. These proteins, termed adipokines, include the hormones leptin, adiponectin, and resistin. Adipose tissue is now recognized as an active endocrine organ. With the obesity pandemic swelling in the Western world, ongoing research is aimed at determining the biologic links between obesity and cardiovascular disease. This review presents basic historical background information on the major adipokines, introduces findings from clinical studies associating adipokines with cardiovascular disease, and summarizes results from recent basic science research studies of mechanisms of adipokine-induced cardiovascular dysfunction. Particular emphasis is placed on the action of adipokines in the coronary circulation-especially effects of adipokines on endothelial function, as endothelial damage is likely a critical event initiating atherosclerotic coronary artery disease.

Topics: Adiponectin; Animals; Cardiovascular Diseases; Humans; Leptin; Obesity; Resistin

Leptin, among the best known hormone markers for obesity, exerts pleiotropic actions on multiple organ systems. In this review, we summarize major leptin signaling pathways, namely Janus-activated kinase/signal transducers and activators of transcription and mitogen-activated protein kinase, including possible mechanisms of leptin resistance in obesity. The effects of leptin on the cardiovascular system are discussed in detail, including its contributions to hypertension, atherosclerosis, depressed myocardial contractile function, fatty acid metabolism, hypertrophic remodeling, and reduction of ischemic/reperfusion injury. The overall goal is to summarize current understanding of how altered leptin signaling in obesity contributes to obesity-related cardiovascular disease.

Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Central Nervous System; Hormone Antagonists; Humans; Leptin; Obesity; Risk Factors; Signal Transduction

Obesity is a highly prevalent disease with multiple implications for cardiovascular morbidity and mortality. The traditional view of obesity is that excessive adipose tissue represents a passive storage depot of excess energy. However, obesity has been demonstrated to be a highly active endocrine organ with multiple metabolic pathways that interact with classic cardiac risk factors. The role of inflammation in atherosclerosis has been clarified by the ready availability of a variety of markers, including C-reactive protein, adiponectin, tumor necrosis factor-alpha, hemostatic markers, resistin, and a variety of emerging markers such as interleukins and adhesion molecules. Adipose tissue has been demonstrated to be the site of synthesis of a variety of proteins that are intimately involved in the regulation of inflammation. The concept that obesity represents an inflammatory state has gained credence over the past decade and has provided insights into the mechanisms of atherosclerosis and risk factor interaction.

Topics: Acute-Phase Proteins; Adiponectin; Atherosclerosis; Cardiovascular Diseases; Humans; Inflammation; Inflammation Mediators; Leptin; Obesity; Resistin; Risk Factors; Tumor Necrosis Factor-alpha

A cluster of risk factors associated with obesity defines the metabolic syndrome and identifies cardiometabolic risk. Accumulation of fat in the visceral depot is a more reliable predictor of cardiovascular disease than is total body mass or body mass index. The recent discovery of the endocannabinoid-CB1 receptor system and its impact on the regulation of energy metabolism represents a significant advance that will help target visceral fat and its metabolic implications. As a highly active endocrine organ, visceral fat secretes many bioactive molecules, known as adipokines. Dysregulation of these adipokines contributes to the pathogenesis of the obesity-associated metabolic syndrome, resulting in insulin resistance, type 2 diabetes, hypertension, hyperlipidemia, and vascular disease. Even modest weight reduction leads to reduced cardiometabolic risk by affecting the individual components comprising the metabolic syndrome.

Topics: Adiponectin; Anti-Obesity Agents; Blood Coagulation; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet; Dyslipidemias; Exercise; Fatty Acids; Humans; Hypertension; Inflammation Mediators; Insulin Resistance; Intra-Abdominal Fat; Leptin; Life Style; Metabolic Syndrome; Obesity; Practice Guidelines as Topic; Risk Factors; Weight Loss

Interest in the biology of white adipose tissue has increased dramatically since the discovery of leptin in 1994. The identification of the product of the gene obese (ob) threw light on the role of adipose tissue in the physiopathology of obesity-related diseases and spurred the identification of numerous other adipokines, many of a proinflammatory nature. It has become increasingly evident that white adipose tissue-derived cytokines mediate between obesity-related exogenous factors (nutrition and lifestyle) and the molecular events that lead to metabolic syndrome, inflammation, and cardiovascular diseases. Here we review recent adipokine research, with particular attention to the roles of adiponectin, leptin, resistin, visfatin, apelin, omentin, and chemerin in such conditions.

Topics: Adipokines; Cardiovascular Diseases; Cardiovascular System; Chemokines; Cytokines; Humans; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin

The metabolic syndrome refers to the clustering of upper body obesity, atherogenic dyslipidemia, insulin resistance and elevated blood pressure. Both, obesity and metabolic syndrome, have the potential to influence on the incidence and severity of cardiovascular disease with serious implications for worldwide health care systems. Obesity plays a central role in the development of insulin resistance and dyslipidemia through the mediation of a pro-inflammatory and pro-thrombotic state. Adipose tissue has been shown to exert important endocrine and immune functions. Pathogenesis of obesity associated metabolic syndrome is mediated by disturbed production and release of biologically active molecules by fat cells and other cells infiltrating fat tissue. In obese subjects synthesis of several bioactive compounds--adipokines and cytokines/chemokines by adipose tissue cells is dysregulated. Those bioactive molecules participate in regulation of apetite and energy homeostasis, lipid metabolism (tumour necrosis factor alpha--TNF-alpha), insulin sensitivity (TNF-alpha, adiponectin, resistin, visfatin) immunity (monocyte chemoattractant protein-1--MCP-1, TNF-alpha, IL-6), angiogenesis, blood pressure and hemostasis (plasminogen activator inhibitor--PAI-1). The effects of major pro-/anti-inflammatory and pro-thrombotic adipokines on several physiological processes will be discussed in this review. Also, an evidence-based approach to the laboratory diagnosis and treatment of metabolic syndrome will be presented.

Topics: Adiponectin; Cardiovascular Diseases; Complement Factor D; Humans; Inflammation; Interleukin-6; Leptin; Metabolic Syndrome; Models, Biological; Nicotinamide Phosphoribosyltransferase; Obesity; Plasminogen Activator Inhibitor 1; Resistin; Risk; Thrombosis; Tumor Necrosis Factor-alpha

This review focuses on recent publications concerning medical complications in patients with eating disorders, including anorexia nervosa and bulimia nervosa.. Recent literature continues to reflect that multiple organ systems are frequently affected by eating disorders. The literature underscores the frequently cited risk of premature death in those with anorexia nervosa. A plethora of dermatologic changes have been described, some signaling serious underlying pathophysiology, such as purpura, which indicates a bleeding diathesis. Much of the literature continues to delineate the fact that diabetic patients with eating disorders are at high risk of developing diabetic complications. Gastrointestinal complications can be serious, including gastric dilatation and severe liver dysfunction. Acrocyanosis is common, and patients with anorexia nervosa are at risk of various arrhythmias. Low-weight patients are at high risk for osteopenia/osteoporosis. Nutritional abnormalities are also common, including sodium depletion and hypovolemia, hypophosphatemia and hypomagnesemia. Resting energy expenditure, although very low in low-weight patients, increases dramatically early in refeeding.. Medical complications are common and often serious in patients with eating disorders, particularly those with anorexia nervosa.

Topics: Anorexia Nervosa; Bone Diseases; Bulimia Nervosa; Cardiovascular Diseases; Endocrine System Diseases; Gastrointestinal Diseases; Humans; Leptin; Lung Diseases; Nutrition Disorders; Skin Diseases

The endothelium is responsible for the maintenance of vascular homeostasis. In physiological conditions it acts keeping vascular tonus, laminar blood flow, plasmatic membrane fluidity, the balance between coagulation and fibrinolysis and the inhibition of cellular proliferation, migration and the inflammatory response. Endothelial dysfunction is defined as an alteration of vascular relaxation induced by reduction of endothelium-derived relaxing factors (ERRFs), mainly nitric oxide. These abnormal vasomotor responses occur in the presence of various risk factors for atherosclerosis. The metabolic syndrome is considered a state of chronic inflammation accompanied of endothelial dysfunction causing an increased incidence of ischemic cardiovascular events and high mortality. This revision will encompass the physiological process of vascular function regulation, methods for in vivo assessment of endothelial dysfunction and therapies capable to improve vascular function and consequently minimize the cardiovascular risk due to metabolic syndrome.

Topics: Adiponectin; Atherosclerosis; Cardiovascular Diseases; Endothelium, Vascular; Humans; Leptin; Metabolic Syndrome; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidative Stress; Peroxisome Proliferator-Activated Receptors; Risk Factors

Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.

Topics: Adiponectin; Cardiovascular Diseases; Cytokines; Endothelium, Vascular; Fatty Acids; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin

Topics: Animals; Cardiovascular Diseases; Clinical Trials as Topic; CREB-Binding Protein; Diabetes Mellitus; Dietary Fats; Energy Metabolism; Fatty Acids, Nonesterified; Glucose Transporter Type 4; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; PPAR gamma; Receptors, Adiponectin; Receptors, Cell Surface; Resistin; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Tumor Necrosis Factor-alpha

The discovery of leptin in 1994 led to research into the participation of that hormone in the development of many pathologic states. This article presents current knowledge on the role of leptin, in the pathogenesis of cardiovascular diseases. Leptin is a circulating peptide hormone produced by adipose cells which plays the main role in the regulation of metabolism in humans. Leptin, in the physiological range of plasma levels, is a regulator of cardiovascular function. In fact, higher plasma leptin levels as well as insulin resistance are directly correlated with adiposity. Hyperleptinemia accompanying obesity leads to many pathologic states: stimulation in platelets aggregation, tachycardia, hypertension, increases in plasma levels of pro-thrombotic factors and in levels of CRP and ET-1. In a multicenter study, hyperleptinemia turned out to be the main risk factor responsible for the ischemic disease, especially acute myocardial infarction. Elevated plasma leptin levels play a key role in increased incidence of cardiovascular mortality in obese.

Topics: Adipose Tissue; Cardiovascular Diseases; Humans; Leptin

In previously apparently healthy women, glucose intolerance and high blood pressure during pregnancy are common and frequently occur together. This article reviews the role of these gestational disorders as markers of vascular dysfunction and its pathophysiology. Mechanisms include alterations to function of large arteries and resistance vessels and to capillary blood flow. Much of the vessel pathology is seen in both gestational diabetes and hypertension. In women who have had transient diabetes during pregnancy and later redeveloped overt diabetes, cardiovascular risk is already elevated nearly fourfold before diagnosis, which is almost as high as the average risk after a clinical diagnosis of diabetes is made. This key finding suggests that vascular risk in such women is at least partly independent of overt hyperglycemia.

Topics: Adiponectin; Brachial Artery; Cardiovascular Diseases; Diabetes, Gestational; Endothelium, Vascular; Female; Glucose Intolerance; Humans; Hypertension, Pregnancy-Induced; Leptin; Pregnancy; Risk Factors; Vasodilation

The adipose tissue exerts a double function that is crucial for energy homeostasis. On the one hand, it is the only organ suited to stock triglycerides in highly specialized cells, the adipocytes. On the other hand, the adipose tissue produces biologically active molecules, collectively named "adipokines", which have been implicated in energy balance and glucose and lipid metabolism. Both adipocytes and cells of the stromal fraction participate in this function of secretion. The adipokines acts locally, in an autocrine or paracrine manner, and distantly (endocrine), on various targets, including muscles, the liver and the hypothalamus. Some adipokines, as TNFalpha and IL6, promote insulin resistance and inflammation, whereas others, as leptin and adiponectin, are required for energy and glucose homeostasis. In obesity, adipose cell hypertrophy and the recruitment of macrophages alter the secretory function and induce an inflammatory profile in the adipose tissue. Analyses of gene expression suggest that hypoxia is one of the factors favoring the attraction of the macrophages. The local and systemic consequences of interactions between macrophages and adipocytes are currently actively studied, to understand their potential implication in the metabolic and cardiovascular complications associated with obesity.

Topics: Adipose Tissue; Cardiovascular Diseases; Humans; Leptin; Macrophages; Models, Biological; Obesity

Impairment in the regulation of energy homeostasis and imbalance between energy intake and energy expenditure lead to many metabolic disorders and diseases such as obesity and type 2 diabetes. AMP-activated protein kinase (AMPK) is considered as a "fuel-gauge" in the cell and plays a key role in the regulation of energy metabolism. Activated by an increase in the AMP/ATP ratio, AMPK switches on catabolic pathways such as fatty acid oxidation and switches off anabolic pathways such as lipogenesis or gluconeogenesis. Insulin-sensitizing adipokines (leptin and adiponectin) and anti-diabetic drugs (thiazolidinediones and biguanides) are acting in part through the activation of AMPK. More recent findings indicate that AMPK plays also a major role in the control of whole body energy homeostasis by integrating, at the hypothalamus level, nutrient and hormonal signals that regulate food intake and energy expenditure. AMPK provides therefore a potential target for the treatment of metabolic diseases such as obesity and type II diabetes.

Topics: Adenylate Kinase; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Energy Metabolism; Fatty Acids; Homeostasis; Humans; Insect Hormones; Insulin; Leptin; Models, Biological; Oligopeptides; Prevalence; Pyrrolidonecarboxylic Acid

During the last decade, white adipose tissue was recognized to be an active endocrine organ and a source of many proinflammatory cytokines, chemokines, growth factors and complement proteins. Many of these adipokines seem to play an important role in the pathogenesis of obesity-related diseases including accelerated atherosclerosis, arterial hypertension and some glomerulopathies. As endothelial dysfunction is one of the early stages of atherosclerosis, it is reasonable to consider that substances secreted by adipose tissue may influence directly or indirectly (for instance by induction of microinflammation) the function of endothelial cells. The aim of this review is to summarize the evidences and hypotheses concerning the role of adipokines in the pathogenesis of endothelial dysfunction.

Topics: Adiponectin; Adipose Tissue; Atherosclerosis; Cardiovascular Diseases; Endothelial Cells; Endothelium, Vascular; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Obesity; Plasminogen Activator Inhibitor 1; Renin-Angiotensin System; Tumor Necrosis Factor-alpha

From an evolutionary perspective, Darwinian selection has favored insulin-resistant individuals, ie, those with a trait ensuring brain functioning in situations of extreme fuel deprivation. The ability to mount a powerful inflammatory response to infection was another survival advantage in our ancestors, and we now have solid evidence showing that these 2 traits, insulin resistance and inflammation (as measured by serum C-reactive protein [CRP]), are associated in modern human beings. In an analysis of 192 nondiabetic hemodialysis patients, leptin and adiponectin were related in an opposite fashion with insulin sensitivity in end-stage renal disease (ESRD) and interacted in determining insulin resistance in these patients. The risk of insulin resistance was about 6 times higher in ESRD patients with an unfavorable combination of the 2 adipokines (high leptin and low adiponectin) than in those with a favorable combination (low leptin and high adiponectin). Low adiponectin but not high leptin predicted incident cardiovascular events in this cohort. Neither leptin nor adiponectin were associated with CRP in a cross-sectional analysis, but they were linked in an opposite fashion to CRP in a longitudinal study in 21 patients with acute inflammation secondary to infection. High sympathetic activity predicts adverse cardiovascular outcomes in ESRD. Of note, we found that the risk for cardiovascular events is more than 3 times higher in patients with high sympathetic activity and low adiponectin than in those with high adiponectin and low sympathetic activity. The adipocyte hormones leptin and adiponectin are associated in an opposite fashion to insulin sensitivity and inflammation in ESRD patients. Relatively lower plasma adiponectin levels are associated with a higher rate of incident cardiovascular events. Finally, low adiponectin and high norepinephrine seem to be interacting factors in the dismal cardiovascular outcomes with ESRD.

Topics: Adiponectin; Adipose Tissue; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Cytokines; Energy Metabolism; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Leptin; Renal Dialysis; Risk Factors

An activated inflammatory response is a common feature of end-stage renal disease (ESRD) patients and predicts outcome. Although various factors related to the dialysis procedure may contribute to inflammation in ESRD, a number of nondialysis-related factors also are of importance. Adipose tissue is a complex organ with functions far beyond the mere storage of energy and secretes a number of proinflammatory adipokines, such as leptin, resistin, tumor necrosis factor-alpha and interleukin-6, as well as one anti-inflammatory adipokine, adiponectin. It has been proposed that adipose tissue may be a significant contributor to increased systemic inflammation in nonrenal patients. In this review, we put forward the hypothesis that a reduction of renal mass will contribute to retention of proinflammatory adipokines, thus generating adipokine imbalance. Such an imbalance may, via effects on the central nervous system and the vasculature, contribute to wasting, atherosclerosis, and insulin resistance--all common features of ESRD.

Topics: Adiponectin; Adipose Tissue; Body Composition; Body Mass Index; Cardiovascular Diseases; Cytokines; Humans; Infections; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Obesity; Renal Dialysis; Resistin; Risk Factors; Tumor Necrosis Factor-alpha; Wasting Syndrome

Recently, adipocytes have been shown to be recognized as endocrine cells that secrete a variety of bioactive substances known as adipocytokines. Among adipocytokines, adiponectin, a newly found adipose tissue-specific collagen-like protein, has been noted as an important antiatherogenic and antidiabetic protein. The function of adipocytes might be regulated dynamically by nutritional state. Visceral fat accumulation causes dysfunction of adipocytes and results in the development of a variety of metabolic and circulatory diseases through the abnormal secretion of adipocytokines. In this review, the importance of adipocytokines, including adiponectin, is discussed with respect to atherosclerosis.

Topics: Adipocytes; Adiponectin; Biomarkers; Cardiovascular Diseases; Cytokines; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Plasminogen Activator Inhibitor 1; Resistin

Topics: Adipose Tissue; Biomarkers; Blood Glucose; Cardiovascular Diseases; Cholesterol, HDL; Humans; Insulin Resistance; Leptin; Lipid Metabolism; Metabolic Syndrome; Obesity; Practice Guidelines as Topic; Risk; Triglycerides; Viscera

Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the central control of appetite. More recently, it has become clear that these hormones have a range of effects on the cardiovascular system. Leptin increases sympathetic activity, producing a pressor effect when acting on the central nervous system. However, leptin produces vasodilation by an endothelium-dependent mechanism peripherally. Ghrelin decreases sympathetic activity and has a depressor effect when acting on the central nervous system. Peripherally, ghrelin produces vasodilation by an endothelium-independent mechanism. Ghrelin improves left ventricular function and cardiac cachexia in heart failure. Leptin may contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a variety of mechanisms. Leptin has pro-inflammatory, proliferative and calcification promoting effects in the vasculature. Ghrelin has recently been shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro-thrombotic state through stimulation of platelet aggregation and inhibition of coagulation and fibrinolysis. The evidence for and against these effects as well as their pathophysiological significance in obesity hypertension, heart failure, atherosclerosis and thrombosis are discussed.

Topics: Animals; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Ghrelin; Heart Failure; Humans; Hypertension; Leptin; Obesity; Peptide Hormones; Thrombosis

Atherosclerotic CVD is the most common cause of death in the West. Yet, its pathogenesis and early development are only partially understood. Central to the early atherosclerotic process is impairment of vascular endothelial function. Endothelial dysfunction can be measured non-invasively and is evident in children before clinical manifestations of atherosclerosis in adulthood. Factors in early life, such as conventional cardiovascular risk factors, or programming by perinatal growth and nutrition strongly affect endothelial function and hence the development of atherosclerosis and CVD. For instance, low birth weight and faster growth early in infancy have a detrimental effect on vascular structure and function. Childhood obesity, a key independent risk factor for CVD, also adversely affects early vascular health. Obesity is associated with endothelial dysfunction and greater arterial stiffness from as early as the first decade of life, while weight loss is beneficial. This effect on vascular function is probably mediated in part by low-grade inflammation and insulin resistance associated with obesity or by the production by adipose tissue of cytokine-like molecules, collectively termed adipokines. A high leptin concentration, in particular, is found in obese individuals and is strongly associated with vascular changes related to early atherosclerosis. The present review focuses on the early origins of endothelial dysfunction, emphasising the role of obesity. It also considers the mechanisms by which obesity impairs endothelial function, understanding of which will be important to further scientific knowledge and to improve public health.

Topics: Arteriosclerosis; Cardiovascular Diseases; Endothelium, Vascular; Humans; Leptin; Obesity; Risk Factors

In this review, we attempt to deduce teleologically the physiological mission of leptin. Because overnutrition and diet-induced obesity are the only known causes of hyperleptinemia, we contrast the differences in overnutrition in normally leptinized rodents, in which the added lipids are confined to adipocytes, with those of unleptinized rodents, in which the added lipids are distributed in liver, pancreatic islets, and heart and skeletal muscle, causing organ dysfunction and cell death with a disease cluster resembling metabolic syndrome. We focus here on lipid-induced cardiac dysfunction and the remarkable ability of hyperleptinemia to prevent it. We conclude that the hyperleptinemia of overnutrition prevents the ectopic lipid deposition by: (1) acting on hypothalamic appetite centers to limit the caloric surplus to fit the available adipocyte storage capacity and, (2) upregulating of fatty acid oxidation and downregulating lipogenesis in peripheral tissues to minimize ectopic lipid deposition. The causes of failure of this system and its clinical consequences are discussed.

Topics: Animals; Cardiotonic Agents; Cardiovascular Diseases; Humans; Hyperlipidemias; Leptin; Models, Cardiovascular

Recently, adipocytes have been shown to be endocrine cells that secrete a variety of bioactive substances-the so-called adipocytokines. Among adipocytokines, tumor necrotizing factor alpha, plasminogen activator inhibitor 1, and heparin-binding epidermal growth factor-like growth factor are produced in adipocytes as well as already known organs, and they contribute to the development of vascular diseases. Visfatin is a very recently discovered visceral fat-specific protein that may be related to the development of obesity-related diseases such as diabetes mellitus and cardiovascular disease. In contrast to these adipocytokines, adiponectin, also a newfound adipose tissue-specific collagen-like protein, has been noted recently as an important antiatherogenic as well as antidiabetic protein. The function of adipocytokine secretion might be regulated dynamically by nutritional state. Visceral fat accumulation causes dysfunction of adipocytes including oversecretion of tumor necrotizing factor alpha, plasminogen activator inhibitor 1, and heparin-binding epidermal growth factor-like growth factor, as well as hyposecretion of adiponectin, which results in the development of a variety of metabolic and circulatory diseases. In this review, the importance of adipocytokines, including adiponectin, is discussed with respect to atherosclerosis.

Topics: Adipocytes; Adiponectin; Animals; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Obesity; Prognosis; Prospective Studies; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, diabetes and dyslipidemia. Recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome itself has been shown to be associated with endothelial dysfunction, one of the initial steps in the process of atherosclerosis. In the present article we review the molecular mechanisms by which the metabolic syndrome causes endothelial dysfunction and subsequently promotes atherosclerosis. We also discuss promising therapeutic strategies that specifically target the mechanisms responsible for vascular alterations in the metabolic syndrome.

Topics: Animals; Cardiovascular Diseases; Humans; Leptin; Metabolic Syndrome; Renin-Angiotensin System; Tumor Necrosis Factor-alpha

COPD is a major cause of death and disability worldwide. Treatment of COPD improves lung function but is unlikely to slow the steady downhill course of the disease or reduce mortality. In COPD, numerous abnormalities can be found outside the lung. These include systemic inflammation, cachexia, and skeletal muscle dysfunction. Thus, COPD has been called a systemic disease. Convincing data demonstrate that COPD causes neurohumoral activation. By precedents derived from chronic heart failure and other diseases characterized by neurohumoral activation, we propose that the negative consequences of neurohumoral activation, namely inflammation, cachexia, effects on ventilation, and skeletal muscle dysfunction, give rise to a self-perpetuating cycle that contributes to the pathogenesis of COPD, and which may involve respiratory muscle dysfunction as well as systemic inflammation. This concept may further help explain the increased cardiovascular morbidity and mortality in COPD patients. Currently, little is known about the effect of treatments directed at neurohumoral activation and COPD. As this aspect of COPD becomes better understood, new insights may direct novel therapeutic approaches.

Topics: Aldosterone; Animals; Bronchoconstriction; Cachexia; Cardiovascular Diseases; Comorbidity; Heart Rate; Humans; Leptin; Nordefrin; Pulmonary Disease, Chronic Obstructive; Renin; Respiratory Muscles; Risk Factors; Sympathetic Nervous System

With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they are increasingly shown to affect several aspects in the pathogenesis of obesity-related diseases. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centred in the hypothalamus. In recent years, a number of additional signalling molecules secreted by adipose tissue have been discovered, commonly referred to as 'adipocytokines'. Among these, adiponectin is perhaps the most interesting and promising compound for the clinician since it has profound protective actions in the pathogenesis of diabetes and cardiovascular disease. Adiponectin is low in obese subjects and, in particular, insulin-resistant patients. In contrast, resistin seems to be of greater relevance in relation to the immune stress response than in the regulation of glucose homeostasis. However, inflammatory processes have recently been connected with the development of atherosclerosis. Finally, little is known regarding the clinical relevance of visfatin. Recent research has revealed many functions of adipocytokines extending far beyond metabolism, such as immunity, cancer and bone formation. This report aims to review some of the recent topics of adipocytokine research that may be of particular importance.

Topics: Adiponectin; Adipose Tissue; Animals; Cardiovascular Diseases; Cytokines; Diabetes Mellitus; Humans; Insulin Resistance; Leptin; Mice; Nicotinamide Phosphoribosyltransferase; Resistin

Although obesity is strongly associated with cardiovascular disease (CVD), the endogenous relationship between obesity and CVD is still not fully clear. Emerging evidence from both animal and human studies indicates that leptin may play an important role in obesity-related CVD. Besides modulating appetite and metabolism, leptin has also been shown to increase sympathetic nerve activity, stimulate generation of reactive oxygen species, upregulate endothelin-1 production and potentiate platelet aggregation. These effects of leptin may contribute to hypertension, endothelial dysfunction and atherosclerosis in obese individuals. Better understanding the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance. These recent discoveries could lead to novel strategies for treatment of obesity-associated CVD.

Topics: Adult; Animals; Cardiovascular Diseases; Endothelin-1; Humans; Leptin; Obesity; Reactive Oxygen Species; Sympathetic Nervous System; Ventricular Remodeling

Topics: Adrenal Glands; Adult; Androgens; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hydrocortisone; Insulin Resistance; Leptin; Luteinizing Hormone; Ovary; Pituitary Gland; Polycystic Ovary Syndrome

Obesity is associated with increased cardiovascular morbidity and mortality, in part through development of hypertension. Recent observations suggest that the cardiovascular actions of leptin may help explain the link between excess fat mass and cardiovascular diseases. Leptin is an adipocyte-derived hormone that acts in the central nervous system to promote weight loss by decreasing food intake and increasing metabolic rate. Leptin causes a significant increase in overall sympathetic nervous activity, which appears to be due to direct hypothalamic effects and is mediated by neuropeptide systems such as the melanocortin system and corticotropin-releasing hormone. Renal sympathoactivation to leptin is preserved in the presence of obesity, despite resistance to the metabolic effects of leptin. Such selective leptin resistance, in the context of circulating hyperleptinemia, could predispose to obesity-related hypertension. Some in vitro studies have suggested that leptin may have peripheral actions such as endothelium-mediated vasodilation that might oppose sympathetically induced vasoconstriction. However, we and others have shown that leptin does not have direct vasodilator effects in vivo. The fact that chronic leptin administration or overexpression of leptin produces hypertension supports the concept that the hemodynamic actions of leptin are due predominantly to sympathetic activation. Exploration of the sites and mechanisms of leptin resistance should provide novel therapeutic strategies for obesity, insulin resistance, and hypertension.

Topics: Animals; Blood Pressure; Cardiovascular Diseases; Cardiovascular System; Humans; Kidney; Leptin; Obesity; Receptors, Cell Surface; Receptors, Leptin; Signal Transduction; Sympathetic Nervous System

The obese gene product, leptin, plays a central role in food intake and energy metabolism. The physiological roles of leptin in human bodily function have been broadened over the past decade since leptin was first discovered in 1994. Evidence has suggested that leptin plays a specific role in the intricate cascade of cardiovascular events, in addition to its well-established metabolic effects. Leptin, a hormone linking adiposity and central nervous circuits to reduce appetite and enhance energy expenditure, has been shown to increase overall sympathetic nerve activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin is capable of regulating cardiac and vascular contractility through a local nitric oxide-dependent mechanism. However, elevated plasma leptin levels or hyperleptinemia, have been demonstrated to correlate with hyperphagia, insulin resistance and other markers of the metabolic syndrome including obesity, hyperlipidemia and hypertension, independent of total adiposity. Elevated plasma leptin levels may be an independent risk factor for the development of cardiovascular disease. Although mechanisms leading to hyperleptinemia have not been well described, factors such as increased food intake and insulin resistance have been shown to rapidly enhance plasma leptin levels and subsequently tissue leptin resistance. These findings have prompted the speculation that leptin in the physiological range may serve as a physiological regulator of cardiovascular function whereas elevated plasma leptin levels may act as a pathophysiological trigger and/or marker for cardiovascular diseases due to tissue leptin resistance.

Topics: Appetite Regulation; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Energy Metabolism; Heart Rate; Humans; Insulin; Leptin; Obesity; Receptors, Cell Surface; Receptors, Leptin; Signal Transduction; Sympathetic Nervous System

In addition to its direct effects on energy metabolism and caloric intake, leptin exerts several circulatory effects that appear to be mediated by an interaction with the sympathetic nervous system and the major reflexogenic area involved in cardiovascular homeostatic control--that is, the arterial baroreflex. In this paper, the relationships between the adipocyte hormone and the neuroadrenergic function are reviewed, taking into account data collected in experimental animal models as well as in human cardiovascular (hypertension and heart failure) and noncardiovascular (obesity) diseases that are characterized by a hyperadrenergic state coupled with a hyperleptinemia.

Topics: Animals; Baroreflex; Blood Pressure; Cardiovascular Diseases; Humans; Leptin; Metabolic Diseases; Sympathetic Nervous System

Obesity is a risk factor for cardiovascular diseases. Leptin levels are increased in obesity and leptin exhibits cardiovascular actions that may contribute to increased cardiovascular risk. We review the sympathetic, renal and vascular actions of leptin and their relevance to cardiovascular disease.. Leptin possesses cardio-renal actions potentially contributing to obesity-related hypertension including generalized sympathoactivation. However, given that leptin resistance occurs in obesity, it has been difficult to link hyperleptinemia with hypertension. One possibility is that leptin resistance is confined to the metabolic effects of leptin, with preservation of its sympathoexcitatory actions. Other mechanisms may contribute to the pressor effects of leptin. For instance, angiotensin II induces leptin generation. Leptin also potentiates the pressor effect of insulin. Therefore, interactions between angiotensin II and insulin with leptin could have deleterious cardiovascular effects in obesity. Additionally, leptin appears to stimulate vascular inflammation, oxidative stress and hypertophy. These actions may contribute to the pathogenesis of hypertension, atherosclerosis, and left ventricular hypertrophy.. The potential actions of leptin in the pathophysiology of cardiovascular complications of obesity are diverse, despite evidence of leptin resistance to its metabolic actions. However, most information about cardiovascular actions of leptin derives from in-vitro and animal studies. Future research in humans is widely awaited.

Topics: Autonomic Nervous System Diseases; Cardiovascular Diseases; Humans; Kidney Diseases; Leptin; Obesity

Leptin was originally discovered as an adipocyte-derived hormone involved in the central control of body weight and energy homeostasis. It is now clear that leptin is a pleiotropic cytokine, with activities on many peripheral cell types. These findings may help explain the surprising role of leptin in pathophysiological processes. Recent evidence suggests that leptin contributes to atherosclerosis and to the increased risk of cardiovascular disease in obese people. Leptin also appears to be involved in T-cell-dependent immunity and possibly in the development and maintenance of certain autoimmune diseases. Here, we review the role of leptin in cardiovascular and autoimmune diseases, and also briefly address the potential therapeutic use of leptin antagonists.

Topics: Adipocytes; Arteriosclerosis; Autoimmune Diseases; Cardiovascular Diseases; Humans; Immunity, Cellular; Insulin Resistance; Leptin; Receptors, Leptin; Receptors, Mitogen; Signal Transduction

The development of obesity is caused by a disturbance of energy balance, with energy intake exceeding energy expenditure. As the autonomic nervous system (ANS) has a role in the regulation of both these variables, it has become a major focus of investigation in the fields of obesity pathogenesis. The enhanced cardiac sympathetic drive shown in most of the studies in obese persons might be due to an increase in their levels of circulating insulin. The role of leptin needs further investigation with studies in humans. There is a blunted response of the cardiac sympathetic nervous system (SNS) activity in obese subjects after consumption of a carbohydrate-rich meal as well as after insulin administration. This might be due to insulin resistance. It is speculated that increased SNS activity in obesity may contribute to the development of hypertension in genetically susceptible individuals. It is also speculated that the increase in cardiac SNS activity under fasting conditions in obesity may be associated with high cardiovascular morbidity and mortality.

Topics: Autonomic Nervous System; Cardiovascular Diseases; Heart; Humans; Insulin; Leptin; Norepinephrine; Obesity; Risk Factors

In the last few years, there has been increasing interest in the physiological role of acylation-stimulating protein (ASP). Recent studies in rats and mice, in particular in C3 (-/-) mice that are ASP deficient, have advanced our understanding of the role of ASP. Of note, the background strain of the mice influences the phenotype of delayed postprandial triglyceride clearance in ASP-deficient mice. Administration of ASP in all types of lean and obese mice studied to date, however, enhances postprandial triglyceride clearance. On the other hand, regardless of the background strain, ASP-deficient mice demonstrate reduced body weight, reduced leptin and reduced adipose tissue mass, suggesting that ASP deficiency results in protection against development of obesity. In humans, a number of studies have examined the relationship between ASP, obesity, diabetes and dyslipidemia as well as the influence of diet, exercise and pharmacological therapy. While many of these studies have small subject numbers, interesting observations may help us to better understand the parameters that may influence ASP production and ASP action. The aim of the present review is to provide a comprehensive overview of the recent literature on ASP, with particular emphasis on those studies carried out in rodents and humans.

Topics: Adipose Tissue; Animals; Blood Proteins; Body Weight; Cardiovascular Diseases; Complement C3; Complement C3a; Complement Factor B; Complement Factor D; Diabetes Mellitus; Humans; Hyperlipidemias; Insulin Resistance; Leptin; Mice; Mice, Knockout; Models, Animal; Obesity; Postprandial Period; Rats; Serine Endopeptidases; Triglycerides

In health, growth hormone (GH) is secreted in a circadian rhythm with superimposed pulsatility. Temporal fluctuations of hormone concentrations are essential for physiological action, and loss of diurnal rhythm is important in the development of disease. GH feedback occurs through the hypothalamus and involves neuropeptides such as somatostatin, GH-releasing hormone, GH-releasing peptides and neuropeptide Y. In addition, the same neuropeptides are involved in the regulation of other hormone axes and biological systems, thus, establishing a link through which regulation by GH may occur. Clinical features of adult growth hormone deficiency (AGHD) include abnormal body composition, reduction in quality of life, osteoporosis and increased risk of cardiovascular mortality. In health, many of the factors which regulate these features demonstrate circadian rhythmicity and pulsatility. Furthermore, AGHD is associated with abnormalities in the periodic variation of such controlling factors. GH replacement therapy, administered in the form of timed, intermittent subcutaneous injections, results in improvement of many of the clinical effects of AGHD, and is associated with normalization of the temporal fluctuations. Currently, there remains scope for further investigation of the effects of AGHD and subsequent GHR on the circadian rhythmicity of many hormones and systems; and additional studies are required to understand the physiological significance of the changes observed to date.

Topics: Adult; Blood Pressure; Cardiovascular Diseases; Circadian Rhythm; Drug Administration Schedule; Feedback, Physiological; Female; Growth Hormone; Human Growth Hormone; Humans; Hypopituitarism; Hypothalamo-Hypophyseal System; Injections, Subcutaneous; Insulin-Like Growth Factor I; Leptin; Male; Osteoporosis; Parathyroid Hormone; Pulsatile Flow; Quality of Life; Receptors, Somatotropin; Syndrome

Obesity is a problem of epidemic proportions that is associated with adverse cardiovascular outcomes. The long-term efficacy of currently available treatments is limited, and therapeutic benefits might paradoxically be achieved only at the expense of other serious adverse cardiovascular consequences. Owing to these limitations, new paradigms in the management of obesity are being explored, including expanded surgical and pharmacologic therapies. Recent discoveries in the pathogenesis of obesity, including the discovery of leptin, might lead to new treatment options. Leptin dysregulation within the central nervous system or in peripheral adipose tissue has a putative role in the pathogenesis of obesity. Furthermore, important differences exist between men and women in regard to leptin levels; these discrepancies might ultimately impact the therapeutic approach in a gender-specific manner. The goals of obesity therapy and the appropriate therapeutic endpoints are being evaluated to maximize the efficacy of therapy and improve cardiovascular outcomes, while diminishing the risk of adverse cardiovascular complications.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Diet, Reducing; Exercise; Female; Humans; Leptin; Male; Obesity; Sex Factors; United States

The obesity epidemic is driving metabolic (insulin resistance) syndrome-related health problems including an approximately threefold increased coronary heart disease risk. Sympathetic hyperfunction may participate in the pathogenesis and complications of the metabolic syndrome including higher blood pressure, a more active renin-angiotensin system, insulin resistance, faster heart rates, and excess cardiovascular disease including sudden death. Possible factors augmenting sympathetic activation in the metabolic syndrome include alterations of insulin, leptin, nonesterified fatty acids (NEFAs), cytokines, tri-iodothyronine, eicosanoids, sleep apnea, nitric oxide, endorphins, and neuropeptide Y. Of note, high plasma NEFAs are a risk factor for hypertension and sudden death. In short-term human studies, NEFAs can raise blood pressure, heart rate, and a(1)-adrenoceptor vasoreactivity, while reducing baroreflex sensitivity, endothelium-dependent vasodilatation, and vascular compliance. Efforts to further identify the mechanisms and consequences of sympathetic dysfunction in the metabolic syndrome may provide insights for therapeutic advances to ameliorate the excess cardiovascular risk and adverse outcomes.

Topics: Cardiovascular Diseases; Fatty Acids, Nonesterified; Humans; Hypertension; Insulin Resistance; Leptin; Metabolic Syndrome; Muscle, Skeletal; Obesity; Risk Factors; Sleep Apnea Syndromes; Sympathetic Nervous System

Obesity, the most common nutritional disorder in industrial countries, is associated with increased cardiovascular mortality and morbidity. Nevertheless, the molecular basis linking obesity with cardiovascular disturbances have not yet been fully clarified. Recent advances in the biology of adipose tissue indicate that it is not simply an energy storage organ, but also a secretory organ, producing a variety of bioactive substances, including leptin and adiponectin, that may influence the function as well as the structural integrity of the cardiovascular system. Leptin, besides being a satiety signal for the central nervous system and to be related to insulin and glucose metabolism, may also play an important role in regulating vascular tone because of the widespread distribution of functional receptors in the vascular cells. On the other hand, the more recently discovered protein, adiponectin, seems to play a protective role in experimental models of vascular injury, in probable relation to its ability to suppress the attachment of monocytes to endothelial cells, which is an early event in the atherosclerotic process. There is already considerable evidence linking altered production of some adipocyte hormones with the cardiovascular complications of obesity. Therefore, the knowledge of alterations in the endocrine function of adipose tissue may help to further understand the high cardiovascular risk associated with obesity.

Topics: Adiponectin; Adipose Tissue; Angiotensin II; Animals; Calcium; Cardiovascular Diseases; Cations, Divalent; Endocrine Glands; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Potassium Chloride; Proteins; Rats; Rats, Wistar

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

Obstructive sleep apnoea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension. Although the association between OSA and the metabolic syndrome tends to confound studies of the independent effects of OSA on vascular disease, recent evidences from basic science to epidemiological and clinical studies suggest that OSA may add worsening pathophysiological conditions to obesity. OSA contributes to the imbalance between vasodilators and vasoconstrictors, in particular through oxidative stress-dependent catabolism of nitric oxide, increased sympathetic nerve activity, enhanced renin-angiotensin system activity and endothelin synthesis. Additionally, several recent studies suggest that OSA may be a circumstance favouring central and vascular resistance to leptin. The beneficial effects of this hormone in normal subjects, are lost during endothelial dysfunction and OSA. Moreover, high leptin concentrations, within a range observed during OSA, display adverse effects on endothelial function and vascular physiology. Through of a yet unknown mechanism, OSA per se accounts for part of the elevated serum leptin concentration reported in patients. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnoea and the ensuing acute hemodynamic changes during sleep. Accordingly, vasopressor mediators and leptin concentration are shifted toward normal values by CPAP. Thus, in addition to this effective therapy, evaluation of specific strategies targeting leptin sensitivity and vasopressor mediators may open novel perspectives for treatment of OSA and its associated end-organ damages.

Topics: Adolescent; Adult; Animals; Cardiovascular Diseases; Comorbidity; Endothelium, Vascular; Humans; Leptin; Oxidative Stress; Rats; Sleep Apnea, Obstructive; Sympathetic Nervous System

There is a very high prevalence of OSA in obese individuals and a high prevalence of obesity in patients with OSA. The pathophysiology of OSA is intimately linked to obesity. Anatomic and functional considerations of the pharyngeal airway, the CNS, central obesity, and leptin likely interact in the development of OSA in obese individuals. OSA may itself predispose individuals to worsening obesity because of sleep deprivation, daytime somnolence, and disrupted metabolism. The diagnosis of OSA requires the clinician's awareness of its potential to cause a spectrum of acute and chronic neurocognitive, psychiatric, and nonspecific symptoms in patients who may be unaware that their sleep is disturbed. Symptoms and examination findings help predict which obese individuals have OSA, and polysomnography is the gold standard by which to make the diagnosis and assess the effects of treatment. Numerous disease states are associated with both OSA and obesity, and it is becoming clear that the relationships are mediated by complex interrelated mechanisms. Common diseases and disease mechanisms in OSA and obesity suggest that conditions related to obesity may be better managed if patients, particularly those who are morbidly obese, are evaluated and treated for previously undiagnosed OSA. OSA is cured in only specific cases with craniofacial or upper airway surgery, and the general application of UVP is not efficacious. OSA also can be cured with sufficient lifestyle-mediated or surgical weight loss; however, in the absence of long-term weight maintenance, OSA returns with weight gain. Although not curative, nasal CPAP is the initial treatment of choice for most patients because of its noninvasive approach and technical efficacy. It is limited, however, by patient acceptance and long-term compliance. Advances in mask comfort and use of humidified air should increase its acceptance. Future management strategies include newer generations of positive airway devices that automatically titrate pressures (which are not yet recommended by expert organizations) and multidisciplinary approaches to managing the care of patients with OSA.

Topics: Blood Coagulation Disorders; Cardiovascular Diseases; Drug Therapy; Genetic Predisposition to Disease; Humans; Inflammation; Leptin; Life Style; Obesity; Sleep Apnea, Obstructive; Surgical Procedures, Operative

Topics: Adipose Tissue; Cardiovascular Diseases; Complement Factor D; Hormones, Ectopic; Humans; Hyperlipidemias; Hypertension; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Renin-Angiotensin System; Resistin; Serine Endopeptidases; Tumor Necrosis Factor-alpha

Obesity is the most common nutritional disorder in the United States. Growing evidence suggests that obesity initiates a cascade of disorders including hypertension, diabetes, atherosclerosis, and chronic renal disease, many of which are interdependent. Abnormal kidney function, caused by increased renal tubular reabsorption, initiates volume expansion and increased blood pressure during excess weight gain, and the hypertension and metabolic abnormalities associated with obesity, in turn, contribute to chronic renal disease. Obesity causes cardiac and vascular disease through well-known mediators such as hypertension, type II diabetes, and dyslipidemia, but there is evidence for less well-characterized mediators such as chronic inflammation and hypercoagulation. Although obesity is increasingly recognized as a serious health problem, there are still many unanswered questions about how the multiple disorders associated with excess weight gain interact to cause cardiovascular and renal disease. Also, there are few studies that have examined whether sustained weight loss in obese subjects can reverse these changes. In view of the "epidemic" of obesity in our country and the excess burden of cardiovascular and renal disease in minority populations, addressing these issues is of paramount importance for the Jackson Heart Study, as well as for other national health initiatives.

Topics: Animals; Blood Pressure; Cardiovascular Diseases; Humans; Hypertension; Kidney Diseases; Leptin; Models, Biological; Obesity

Patients with sleep disordered breathing (SDB) are at increased risk for cardiovascular disease including hypertension, angina, myocardial infarction, and stroke. Neurohumoral and hemodynamic responses to untreated sleep apnea are likely mechanisms that produce functional and structural changes within the cardiovascular system. Obesity, higher blood pressure, and advancing age, which are common characteristics of patients with SDB, contribute to the overall risk for cardiovascular disease. Recent studies indicate that OSA is associated with or aggravates other risk markers for cardiovascular disease. These factors include leptin, C-reactive protein, homocysteine, and insulin resistance syndrome. Elevations in C-reactive protein and glucose intolerance may be correlated with the severity of SDB. The impact of alleviating SDB on these cardiovascular risk factors has not been fully elucidated. Regardless, assessment of overall cardiovascular risk in patients with sleep apnea is warranted to identify those individuals that are high-risk who require immediate attention and intervention or in those that should be treated more aggressively.

Topics: Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Homocysteine; Humans; Leptin; Metabolic Syndrome; Positive-Pressure Respiration; Risk Factors; Severity of Illness Index; Sleep Apnea Syndromes

The debate on metformin use in polycystic ovary syndrome (PCOS) has mainly focused on its treatment for infertility in ovulation induction and menstrual cyclicity. Here we will summarize the data supporting the effect of metformin on improving hyperandrogenaemia and hyperinsulinaemia in PCOS patients. We propose that metformin benefits PCOS patients undergoing gonadotrophin therapy and IVF as well as ovulation induction. We also advocate the use of insulin sensitizing drugs to reduce miscarriage rates, and risks associated with coronary artery disease, gestational diabetes and obesity.

Topics: Androgens; Cardiovascular Diseases; Female; Fertilization in Vitro; Gonadotropins; Humans; Hypoglycemic Agents; Infertility, Female; Insulin; Insulin Resistance; Leptin; Menstrual Cycle; Metformin; Ovulation Induction; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome

Topics: Adipocytes; Animals; Cardiovascular Diseases; Carrier Proteins; Humans; Ion Channels; Leptin; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Uncoupling Protein 1

Topics: Animals; Cardiovascular Diseases; Humans; Leptin; Mice; Mice, Transgenic

The deposition of excess amounts of energy in adipose tissue is enhanced by high-fat diets and lack of physical activity. Furthermore, the existence of a specific genetic predisposition towards the development of obesity becomes evident by marked interindividual differences in the response to caloric oversupply.. In recent years, numerous genes and genetic defects with importance for human obesity were identified, especially through studies in animal models. The adipocyte-derived hormone leptin and its hypothalamic receptor play a premier role, as they interact with a network of proteins and neuropeptides within the regulation of food intake and energy expenditure.. The search for the key molecular mechanisms in the pathogenesis of obesity will not only improve our understanding of energy metabolism, but may ultimately also lead to the development of new treatment strategies for obese patients.

Topics: Adipose Tissue; Animals; Cardiovascular Diseases; Carrier Proteins; Energy Intake; Energy Metabolism; Gene Expression Regulation; Humans; Hypothalamus; Leptin; Obesity; Receptors, Cell Surface; Receptors, Leptin; Risk Factors

Human obesity is associated with leptin resistance, elevated leptin levels in the circulation, and increased risk of arterial and venous thrombotic disease. Our studies suggest that elevated leptin levels may directly promote arterial thrombosis in vivo. We found that leptin-deficient ob/ob mice had prolonged times to thrombosis after arterial injury with ferric chloride and that exogenously administered leptin corrected their phenotype in a dose-dependent manner. These effects appear to result from a direct, receptor-mediated effect of leptin on platelets, because leptin stimulated the aggregation of murine (wild-type and ob/ob) and human platelets, but it had no effect on platelets from leptin receptor-deficient db/db mice. Moreover, db/db mice had an attenuated thrombotic response to ferric chloride injury (indistinguishable from that of the ob/ob mice), which was unaffected by exogenous leptin. Our results raise the possibility that elevated plasma levels of leptin may contribute to the risk of atherothrombotic complications in human obesity.

Topics: Animals; Body Weight; Cardiovascular Diseases; Homeostasis; Humans; Leptin; Mice; Mice, Obese; Obesity; Platelet Aggregation; Risk Assessment; Thrombosis

Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Insulin Resistance; Leptin; Male; Proteins; Research

It has been increasingly recognised in recent years that type 2 (non-insulin-dependent) diabetes is part of a cluster of cardiovascular risk factors known as the metabolic syndrome, but also endorsed with such names as the deadly quartet, syndrome X and the insulin resistance syndrome. Atherosclerosis is the most common complication of type 2 diabetes among Europeans, and coronary artery, cerebrovascular and peripheral vascular disease are 2 to 5 times more common in people with this condition than in those without diabetes. These observations indicate that the treatment of type 2 diabetes requires agents that do more than simply lower blood glucose levels, and a therapy with both antihyperglycaemic effects and beneficial effects on dyslipidaemia, hypertension, obesity, hyperinsulinaemia and insulin resistance is likely to be most useful. In this respect, metformin has an important and established role: this drug has been shown to lower blood glucose and triglyceride levels, and to assist with weight reduction and to reduce hyperinsulinaemia and insulin resistance. Studies in the Israeli sand rat, Psammomys obesus, have indicated hyperinsulinaemia/insulin resistance to be the initial and underlying metabolic disorder in obesity and type 2 diabetes. Thus, the well established effect of metformin in reducing insulin resistance makes this drug an excellent candidate for the prevention of progression of impaired glucose tolerance to type 2 diabetes, and for the reduction of mortality associated with cardiovascular disease.

Topics: Animals; Blood Glucose; Cardiovascular Diseases; Chromans; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Male; Metformin; Rats; Risk Factors; Thiazoles; Thiazolidinediones; Troglitazone

The combination of obesity with arterial hypertension is frequent finding in clinical practice. In 70% of the males and 61% of the females the high blood pressure is directly connected with obesity. The assumed mechanisms by which obesity leads to arterial hypertension are: insuline resistance; genetic factors (hypothesis for the sparing gene); correlations leptin-neuropeptide Y; fatty tissue as origin of local pressor and depressor humoral factors. The arterial hypertension in obesity is salt-sensible, associated with increased intraglomerular pressure, microalbuminuria and increased risk for cardiovascular complications. The reduction of the body weight is the principal nonmedical mean for treatment of the arterial hypertension. Of the antihypertensive drugs those which are neutral with respect to the carbohydrat and fat metabolism are preferred inhibitors of the converting enzyme, calcium antagonists, selective alpha-1 blockers, central alpha-2 agonist.

Topics: Adipose Tissue; Cardiovascular Diseases; Humans; Hypertension; Insulin Resistance; Leptin; Obesity; Risk Factors

This review considers recent findings and ideas on the impact of dietary carbohydrates on insulin sensitivity in the context of the prevention of diabetes and cardiovascular disease. We assess the evidence for benefits in insulin sensitivity following high starch as distinct from high sucrose intakes when the diet is low in fat. We consider relationships between obesity, leptin and carbohydrate intake. We conclude that reducing the rate of carbohydrate digestion in the small bowel may be the key stage at which to intervene to reduce insulinaemia and so prevent downregulation of insulin receptors and insulin resistance.

Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Humans; Insulin Resistance; Leptin; Obesity; Rats; Starch

Non-alcoholic fatty liver disease (NAFLD) is one of the metabolic disturbances associated with liver cell inflammation. Nigella sativa (N.sativa) is a widely used medicinal plant known for its anti-inflammatory, antimicrobial, antioxidant, and hepato-protective properties. This study aimed to assess the effect of supplementation of N. sativa oil on plasma levels of adiponectin, leptin, and blood pressure (BP) in patients diagnosed with NAFLD.. This randomized, double-blind, placebo-controlled clinical trial was conducted on 44 NAFLD patients. Participants were randomly assigned to two groups (n = 22/group); the experimental group received 1000 mg of N. sativa oil per day, while the control group received a placebo for eight weeks. The primary outcome measures were serum levels of adiponectin, leptin, and systolic and diastolic blood pressure measured at the baseline and the end of the intervention.. After eight weeks of supplementation with N. sativa oil, no statistically significant differences were found in serum levels of adiponectin (p = 0.40), leptin (p = 0.89), systolic BP (p = 0.13), and diastolic BP (p = 0.09) between the two groups. Furthermore, after supplementation with N. sativa, no significant changes were observed in leptin (p = 0.07), adiponectin (p = 0.13), systolic BP (p = 0.82), and diastolic BP (p = 0.38) within the two groups.. These results indicate that administration of N. sativa oil 1000 mg/day for 8 weeks has no favorable effect on cardiometabolic measures in NAFLD patients. Further studies with higher dosage over a longer period are needed to investigate whether this effect is dose- and time-dependent.

Topics: Adiponectin; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Humans; Leptin; Nigella sativa; Non-alcoholic Fatty Liver Disease; Plant Extracts

Excess adiposity is characterized by alterations in adipokine secretion such that circulating leptin concentrations are increased with reductions in adiponectin. An emerging biomarker for the assessment of this adipose tissue (AT) dysfunction is the adiponectin:leptin (AL) ratio. A low AL ratio may be suggestive of dysfunctional AT and, consequently, a heightened cardiometabolic disease risk. This ancillary study investigated the relationship between the AL ratio and cardiometabolic health among community-dwelling older adults with obesity, as well as the effects of a 12-month exercise and diet intervention on changes in the AL ratio.. Participants (n = 163, 70.2 ± 4.7 years, 38.0% male) were randomized to the exercise only group, exercise + nutrient-dense weight maintenance group (exercise + weight maintenance), or exercise + nutrient-dense caloric restriction of 500 kcal/d group (exercise + intentional weight loss) (clinicaltrials.gov #NCT00955903). Total and regional adiposity as determined by magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA), anthropometrics, and cardiometabolic biomarkers were assessed at baseline and 12 months.. The AL ratio was significantly (p < 0.05) inversely correlated with body mass index, waist circumference, measures of adiposity, and insulin among all participants at baseline. Among females only, significant positive and inverse correlations were also observed between this ratio and high-density lipoprotein cholesterol and the inflammatory biomarkers high sensitivity C-reactive protein and interleukin-6, respectively. While controlling for biological sex, a significant time by intervention group interaction effect (p < 0.05) was observed such that the AL ratio significantly increased from baseline to study completion among participants in the exercise + weight maintenance group and exercise + intentional weight loss group. Post hoc analysis revealed that the exercise + intentional weight loss group exhibited a significantly greater AL ratio at study completion compared to other groups (p < 0.05 all).. Results are in support of the AL ratio as a measure of AT dysfunction among older adults. Furthermore, results suggest that a 12-month exercise and diet intervention with intentional weight loss assists in improving the AL ratio in this population.

Topics: Adiponectin; Aged; Biomarkers; Cardiovascular Diseases; Diet, Reducing; Female; Humans; Leptin; Male; Obesity; Weight Loss

High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation.

Topics: Adiponectin; Adult; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Carbohydrate-Restricted; Dietary Carbohydrates; Dietary Fats; Glucose; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Metabolome

olive pomace oil (OPO) is a nutritionally relevant fat due to its high oleic acid content (C18:1) and the presence of a wide range of minor bioactive components. Although numerous in vitro and preclinical studies have been developed to study some of its characteristic components, the health effect of prolonged OPO consumption is unknown.. a randomised, blinded, cross-over, controlled clinical trial was carried out in 31 normocholesterolemic and 37 hypercholesterolemic subjects. Participants consumed 45 g/day of OPO or sunflower oil (SO) for 4 weeks, each preceded by a 3-week run-in/wash-out phase with corn oil (CO).. regular consumption of OPO and SO had no statistically significant effect on any of the markers related to lipid profile, blood pressure, and endothelial function in both groups, except for eNOS levels, which were close to statistical significance due to the effect of oil (OPO and SO) (. reducing visceral fat after prolonged OPO intake might contribute to improve cardiometabolic status, with a potentially positive effect on the vascular tone. Further clinical trials are needed to confirm the present results.

Topics: Cardiovascular Diseases; Cardiovascular System; Corn Oil; Humans; Leptin; Oleic Acid; Olive Oil; Plant Oils; Sunflower Oil

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; 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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

To comparatively investigate the differential effect of second-line tumour necrosis factor inhibitors (TNFis) versus other biological agents on cardiovascular disease (CVD) risk-associated biomarkers in patients with rheumatoid arthritis (RA).. We evaluated the serum levels of lipoprotein-associated apoproteins ApoA1 and ApoB100 and lipoprotein(a) (Lp(a)) and the leptin/adiponectin ratio (LAR) as an insulin resistance proxy in patients with RA from the Rotation Or Change (ROC) trial treated with either a second-line TNFi or another biologic (tocilizumab (TCZ), rituximab or abatacept) at baseline and week 24. We compared the changes in biomarker levels in each group and according to the EULAR response.. Of the 300 patients enrolled in the ROC trial, 203 were included in the study, including 96 in the second-line TNFi group and 107 in the other biological group. The measured biomarkers did not deteriorate between baseline and week 24 regardless of the group. A greater improvement in the LAR was noted in the other biological group (median (IQR) -0.12 ng/µg (-0.58 to 0.31) vs 0.04 (-0.19 to 0.43), p=0.033), and a greater improvement in the Lp(a) level was observed following treatment with TCZ than with a TNFi (-0.05 g/L (-0.11 to -0.01) vs -0.01 g/L (-0.02 to 0.01), p<0.001). When considering the patients' responses to treatment, improved biomarkers were mainly observed in the EULAR responders in each treatment group.. TNFis and non-TNFis were neutral on improved CVD risk-associated biomarkers in patients with RA insufficiently controlled by TNFis. TCZ could be associated with a better improvement concerning Lp(a) and LAR than TNFis. This improvement could be related to a good therapeutic response, thereby supporting the need of good control of RA.. ClinicalTrials.gov Identifier NCT01000441, registered on 22 October 2009.

Topics: Abatacept; Adiponectin; Aged; Antibodies, Monoclonal, Humanized; Apolipoprotein A-I; Apolipoprotein B-100; Arthritis, Rheumatoid; Biological Factors; Biomarkers; Cardiovascular Diseases; Female; Humans; Insulin Resistance; Leptin; Lipoprotein(a); Male; Middle Aged; Risk Factors; Rituximab; Tumor Necrosis Factor Inhibitors

The present study examined the effect of a 12-week combined resistance and aerobic exercise training program on cardiometabolic biomarkers and red blood cell (RBC) hemorheological function in 20 obese older men (mean age: 68.8 ± 0.9 years). Subjects were randomly divided into two groups (exercise intervention [EXP;

Topics: Aged; Biomarkers; Blood Glucose; Body Composition; Cardiovascular Diseases; Erythrocytes; Exercise; Exercise Therapy; Hemorheology; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity

The relatively recent advent of polyphenol supplement for exercise studies has been tested in a variety of forms and doses. However, the dose-response on adipokines and oxidative stress biomarker effect remains unknown. The aim of the present study was to assess the effect of intense, long-duration (48-h) exercise, and a single dose of proanthocyanidin, on plasma leptin, adiponectin, and electronegative low-density lipoprotein (LDL(-)) concentrations.. Fifty-four healthy male army cadets (22 ± 2 years) participated in a double-blind, randomized, placebo-controlled study and were distributed between control (CG; n = 27) and supplemented groups (SG; n = 27). Immediately before the start of the exercise, both CG and SG groups received a capsule containing starch (200 mg) or proanthocyanidin (dry Vitis vinifera extract, 200 mg), respectively. Following a 12-h fasting period, the plasma adiponectin, leptin, and LDL(-) concentrations were measured prior to the start of the exercise after 24 and 48 h of military training, and after 24 h of rest. The effects of the proanthocyanidin (supplement), exercise (time), and their interaction were investigated using factorial two-way ANOVA.. Plasma leptin concentration was only influenced by exercise (p = 0.001). Plasma adiponectin concentration was influenced by exercise (p = 0.037), and by the exercise x supplement interaction (p = 0.033). LDL(-) was influenced by the supplement (p = 0.001), exercise (p = 0.001), and their interaction (p = 0.001).. A single dose of proanthocyanidin (200 mg) was able to reduce LDL(-) concentration and increase plasma adiponectin concentration after 24 h of rest in SG group, indicating its potential protective action.

Topics: Adiponectin; Adult; Antioxidants; Biomarkers; Brazil; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Exercise; Fruit; Humans; Hypolipidemic Agents; Leptin; Lipoproteins, LDL; Male; Military Personnel; Oxidative Stress; Plant Extracts; Proanthocyanidins; Risk; Vitis; Young Adult

The aim of this study was to analyze whether ω-3 supplementation improves cardiometabolic profile in individuals with cardiovascular risk factors and to determine the effect of adiponectin levels on these changes.. In this double-blind, placebo-controlled, 2-mo clinical trial, we randomized 80 individuals of both sexes (mean age 52 y) with at least one cardiovascular risk factor (excess weight, hypertension, dyslipidemia, diabetes, or smoking) into two groups: ω-3 (supplemented with 3 g/d of fish oil containing 37% eicosapentaenoic acid and 23% docosahexaenoic acid) and placebo (3 g/d of sunflower oil containing 65% linoleic acid). At baseline and after the intervention, we evaluated serum adiponectin, leptin, lipid profile, apolipoproteins (apo), electronegative low-density lipoprotein (LDL[-]), and glucose metabolism (glucose and insulin).. After supplementation, the ω-3 group showed an increase in serum adiponectin. After stratifying the ω-3 group by adiponectin concentration at baseline, participants with lower adiponectin concentration showed a higher reduction of total cholesterol, LDL, LDL/high-density lipoprotein ratio, LDL/apo B, and LDL(-). Individuals with a higher variation of adiponectin concentration after ω-3 supplementation presented with reduced blood glucose. The variation of serum adiponectin induced by ω-3 supplementation was negatively correlated with the Framingham and Adult Treatment Panel IV scores (r = -0.4 and P < 0.05 for both).. Adiponectin is shown as one of the mechanisms by which ω-3 improves cardiometabolic profile in persons with cardiovascular risk. Moreover, the benefit varies according to the adiponectin basal level and adiponectin variation after supplementation.

Topics: Adiponectin; Adult; Aged; Blood Glucose; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Risk Factors; Triglycerides

The aim of the present study was to determine the effect of combined aerobic and resistance exercise training on body weight and cutaneous microvascular reactivity in overweight individuals.. A total of 41 overweight women aged 30-45 years (BMI 25-29.9 kg/m²) were randomized into sedentary time control (CON; N.=15), traditional aerobic dance (AD; N.=11), and step aerobic dance combined with upper-body resistance training (SAR; N.=15) groups. Exercise programs were 50 minutes/session, 3 times/week for 12 weeks.. Maximal oxygen consumption and 1-RM strength of lower body increased (P<0.05) in the AD and SAR groups. Body mass and BMI decreased (P<0.05) in the SAR group. Plasma concentration of adiponectin increased (P<0.05) whereas leptin concentration did not change. Peak postocclusive reactive hyperemia measured by laser-Doppler fluxmeter improved (P<0.05) in the SAR group. These changes were not observed in the CON or AD groups. Peak occlusive reactive hyperemia was positively and significantly correlated with adiponectin level (r=0.23).. The present findings suggest that simultaneously performed step aerobic dance and resistance training exerts more favorable effects on weight loss and improving cutaneous microvascular reactivity in overweight women.

Topics: Adiponectin; Adult; Body Weight; Cardiovascular Diseases; Exercise; Female; Hemodynamics; Humans; Leptin; Microcirculation; Middle Aged; Overweight; Oxygen Consumption; Physical Endurance; Physical Fitness; Regional Blood Flow; Resistance Training; Skin; Time Factors

Being overweight or obese is associated with a greater risk of coronary heart disease and stroke compared with normal weight. The role of the specific adipose tissue-derived substances, called adipocytokines, in overweight- and obesity-related cardiovascular disease (CVD) is still unclear.. To investigate the associations of three adipose tissue-derived substances: adiponectin, leptin, and interleukin-6 with incident CVD in a longitudinal population-based study, including extensive adjustments for traditional and metabolic risk factors closely associated with overweight and obesity. C-reactive protein (CRP) was used as a proxy for interleukin-6.. Prospective population-based study of 6.502 participants, 51.9% women, aged 30-60 years, free of CVD at baseline, with a mean follow-up time of 11.4 years, equivalent to 74,123 person-years of follow-up. As outcome, we defined a composite outcome comprising of the first event of fatal and nonfatal coronary heart disease and fatal and nonfatal stroke.. During the follow-up period, 453 composite CV outcomes occurred among participants with complete datasets. In models, including gender, age, smoking status, systolic blood pressure, treatment for hypertension, diabetes, body mass index (BMI), total cholesterol, high-density-lipoprotein cholesterol, homeostasis model assessment of insulin resistance, estimated glomerular filtration rate, adiponectin, leptin, and CRP, neither adiponectin (hazard ratio [HR] with 95% confidence interval [CI]: 0.97 [0.87-1.08] per SD increase, P = 0.60) nor leptin (0.97 [0.85-1.12] per SD increase, P = 0.70) predicted the composite outcome, whereas CRP was significantly associated with the composite outcome (1.19 [1.07-1.35] per SD increase, P = 0.002). Furthermore, in mediation analysis, adjusted for age and sex, CRP decreased the BMI-associated CV risk by 43% (95%CI 29-72).. In this study, neither adiponectin nor leptin were independently associated with CVD, raising questions over their role in CVD. The finding that CRP was significantly associated with an increased risk of CVD and decreased the BMI-associated CVD risk substantially, could imply that interleukin-6-related pathways may play a role in mediating overweight- and obesity-related CVD.

Topics: Adipokines; Adult; Aged; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Denmark; Early Medical Intervention; Female; Humans; Incidence; Insulin Resistance; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Prognosis; Prospective Studies; Risk Factors

It has been found that the expression of fatty acid-binding protein 2 gene mRNA is under dietary control. The polymorphism Ala54Thr of this protein was associated with high insulin resistance.. The aim of our study was to investigate the influence of Thr54 polymorphism on metabolic response, weight loss and serum adipokine levels secondary to high-protein/low-carbohydrate vs. standard hypocaloric diets during 9 months.. A population of 193 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high-protein/low-carbohydrate vs. diet S: standard diet).. With both diets and in both genotype groups, body mass index, weight, fat mass, waist circumference, systolic blood pressure and leptin levels decreased. With both diets and only in wild genotype (diet HP vs. diet S), glucose (-6.2 ± 2.1 vs. -4.9 ± 2.0 mg/dl; p < 0.05), insulin levels (-5.0 ± 3.9 vs. -2.0 ± 2.1 UI/l; p < 0.05), homeostasis model assessment for insulin resistance (HOMA-R) (-1.1 ± 0.9 vs. -0.7 ± 1.0 units; p < 0.05) decreased. The improvement in these parameters was higher with diet HP than HS. With both diets and only in the wild genotype, total cholesterol and LDL-total cholesterol levels decreased.. Carriers of Thr54 allele have a different metabolic response after weight loss than wild type non-A carriers obese, with a lack of decrease of LDL-cholesterol, glucose, insulin levels and HOMA-R.

Topics: Adipokines; Adult; Blood Pressure; Body Mass Index; Body Weight; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diet, Carbohydrate-Restricted; Diet, Reducing; Dietary Carbohydrates; Dietary Proteins; Fatty Acid-Binding Proteins; Female; Genotype; Genotyping Techniques; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Risk Factors; Waist Circumference; Weight Loss

Elevated levels of serum leptin are associated with increased adiposity and production of pro-inflammatory cytokines. Both cytokines and body adiposity have been shown to predict cardiovascular events and mortality. The primary objective of the present study is to explore the associations between serum leptin and all-cause mortality and mortality from cardiovascular disease (CVD) over a span of 10 years, controlling for body adiposity and proinflammatory cytokines.. The Health, Aging and Body Composition (Health ABC) study is a prospective cohort of 3,075 older adults aged 70 to 79 years. This analysis includes 2,919 men and women with complete serum leptin and vital status data. Data on all-cause mortality and incident cardiovascular events (including Coronary Heart Disease and Congestive Heart Failure) were collected over 10 years of follow-up (mean 8.4 years).. Women with leptin in quartile 2 and 3 were at lower risk of all-cause mortality, and those with leptin in quartile 2 were at lower risk of mortality from CVD as compared to women with lowest leptin values when adjusted for age, race, site, years of education, alcohol use, smoking, and physical activity. When these associations were additionally adjusted for body fat, C-reactive protein and pro-inflammatory cytokines, women with leptin values in quartile 3 were at lower risk of all-cause mortality and women with leptin in quartile 2 and 3 were at lower risk of mortality from CVD than women with lowest leptin values. These associations were not significant among men after adjusting for body fat and cytokines.. The present study suggests that moderately elevated concentrations of serum leptin are independently associated with lower risk of all-cause mortality and CVD-related mortality among older women. Among men, serum leptin is not associated with reduced risk of all-cause and CVD mortality after controlling for body fat and cytokines.

Topics: Adiposity; Aged; Aged, 80 and over; C-Reactive Protein; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Leptin; Male; Risk Factors; Sex Characteristics

The purpose of this study was to determine whether aerobic plus resistance training (AT + RT) is more effective than aerobic training (AT) at reducing inflammatory markers and cardiovascular risk in obese adolescents. A total of 139 obese adolescents were enrolled, aged 15-19 years, body mass index (BMI) ≥ 95th percentile and participated in 1 year of interdisciplinary intervention. They were randomised into two groups: AT (n = 55), AT + RT (n = 61). Blood samples were collected to analyse glycaemia, insulin, the lipid profile, leptin and adiponectin concentrations. Insulin resistance was measured by homeostasis model assessment of insulin resistance index (HOMA-IR). The AT + RT group showed better results with regard to decreased body fat mass, low-density lipoprotein concentration (LDL-c) levels, subcutaneous and visceral fat and increased body lean mass. Indeed, a reduction of hyperleptinaemia and an increase in adiponectin concentrations, promoting an improvement in the leptin/adiponectin ratio, was observed. Important clinical parameters were improved in both types of exercise; however, AT + RT was more effective in improving the visceral adiposity, metabolic profile and inflammatory markers than AT alone, suggesting clinical applications for the control of intra-abdominal obesity and cardiovascular risk in the paediatric population.

Topics: Abdominal Fat; Adiponectin; Adiposity; Adolescent; Biomarkers; Body Fluid Compartments; Body Mass Index; Cardiovascular Diseases; Cholesterol, LDL; Exercise; Humans; Inflammation; Intra-Abdominal Fat; Leptin; Obesity, Abdominal; Pediatric Obesity; Resistance Training; Subcutaneous Fat; Young Adult

Some of the health advantages of breast-fed as compared to formula-fed infants have been suggested to be due to metabolic programming effects resulting from early nutrition.. In a prospective double-blinded randomized trial, 160 infants <2 mo of age were randomized to experimental formula (EF) with added milk fat globule membrane (MFGM) or standard formula (SF) until 6 mo of age. A breast-fed reference (BFR) group consisted of 80 infants. Measurements were made at inclusion and at 4, 6, and 12 mo of age.. During the intervention, the EF group had higher total serum cholesterol concentration than the SF group, reaching the level of the BFR group. The EF group had a low-density lipoprotein to high-density lipoprotein ratio not significantly different from the SF group but lower than the BFR group.. Supplementation of infant formula with MFGM modified the fat composition of the formula and narrowed the gap between breast-fed and formula-fed infants with regard to serum lipid status at 12 mo.

Topics: Adiponectin; Animals; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cattle; Glycolipids; Glycoproteins; Homocysteine; Humans; Infant; Infant Food; Leptin; Leukocyte L1 Antigen Complex; Lipid Droplets; Lipids; Risk Factors

The visceral fat is linked to insulin resistance, the metabolic syndrome, type 2 diabetes and an increased cardiovascular risk, but it is not clear whether it has a causative role.. Surgical resection of this fat depot is a research model to address this issue. Twenty premenopausal women with metabolic syndrome and grade III obesity were randomized to undergo Roux-en-Y gastric bypass (RYGBP) either alone or combined with omentectomy. Insulin sensitivity (IS; euglycemic-hyperinsulinemic clamp), acute insulin response to glucose (AIR; intravenous glucose tolerance test), disposition index (DI = AIR × IS measured by clamp), lipid profile, adipokine profile (leptin, adiponectin, resistin, visfatin, interleukin-6, TNF-α, MCP-1), ultra-sensitive C-reactive protein (CRP), body composition, and abdominal fat echography were assessed prior to surgery and 1, 6, and 12 months post-surgery.. Omentectomy was associated with greater weight loss at all time points. IS improved similarly in both groups. Omentectomy was associated to lower CRP after 12 months, but it did not influence adipokines and other metabolic parameters. Among non-diabetic subjects, omentectomy was associated with a preservation of baseline AIR after 12 months (as opposed to deterioration in the control group) and a greater DI after 6 and 12 months.. Although omentectomy did not enhance the effect of RYGBP on insulin sensitivity and adipokines, it was associated with a preservation of insulin secretion, a greater weight loss, and lower CRP.

Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Chemokine CCL2; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucose Tolerance Test; Humans; Inflammation; Insulin Resistance; Insulin-Secreting Cells; Interleukin-6; Intra-Abdominal Fat; Leptin; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Obesity; Premenopause; Prospective Studies; Resistin; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss; Young Adult

Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by BMI and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study).. Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules, and hemostatic factors were determined at baseline and after 12 weeks of four dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA), and two low fat high complex carbohydrate (LFHCC) diets, one supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs)).. About 39 and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (≥ 30 kg/m(2)) and BF% (≥ 25% (men) and ≥ 35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as nonobese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more proinflammatory (higher C reactive protein (CRP) and leptin), prothrombotic (higher plasminogen activator inhibitor-1 (PAI-1)), proatherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA-IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumor necrosis factor-α (TNF-α) concentrations were lower post-intervention in NOO individuals compared with OO subjects (P < 0.001).. In conclusion, assessing BF% and BMI as part of a metabotype may help to identify individuals at greater cardiometabolic risk than BMI alone.

Topics: Adiponectin; Adipose Tissue; Body Composition; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Diet Therapy; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Plasminogen Activator Inhibitor 1; Reference Values; Risk Factors; Tumor Necrosis Factor-alpha

It is unclear why despite a comparable cardiometabolic risk profile, "metabolically benign" overweight/obese individuals show an elevated risk of cardiovascular disease compared to normal weight individuals.. In cross-sectional analyses, we compared levels of ectopic fat (epicardial, pericardial, and hepatic fat) and adipokines (leptin, soluble leptin receptor, and high molecular weight [HMW] adiponectin) among metabolically benign (MBO) and at-risk overweight/obese (ARO), and metabolically benign normal weight (MBNW) women, screened for the Kronos Early Estrogen Prevention Study. We defined "metabolically benign" with ≤ 1, and "at-risk" with ≥2 components of the metabolic syndrome.. Compared to MBO women, ARO women had significantly elevated odds of being in the top tertile of epicardial fat (OR: 1.76, 95% CI: 1.04-2.99), hepatic fat (OR: 1.90, 95% CI:1.12-3.24) and leptin (OR: 2.15, 95% CI: 1.23-3.76), and the bottom tertile of HMW-adiponectin (OR: 2.90, 95% CI: 1.62-5.19). Compared to MBNW women, MBO women had significantly higher odds of being in the top tertile of epicardial fat (OR: 5.17, 95% CI: 3.22-8.29), pericardial fat (OR: 9.27, 95% CI: 5.52-15.56) and hepatic fat (OR: 2.72, 95% CI: 1.77-4.19) and the bottom tertile of HMW adiponectin levels (OR: 2.51, 95% CI: 1.60-3.94).. Levels of ectopic fat and the adverse adipokine profile increase on a continuum of BMI, suggesting that the metabolically benign phenotype may be a transient state.

Topics: Adiponectin; Adipose Tissue; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Double-Blind Method; Female; Humans; Leptin; Life Style; Logistic Models; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Pericardium; Postmenopause; Prospective Studies; Receptors, Leptin

A deficit in adiponectin plays an important causal role in insulin resistance and metabolic syndrome. We hypothesized that as seen during the fasting state, the intake of a walnut-enriched meal increased postprandial adiponectin. Twenty-one healthy white men followed a 4-week baseline diet and then consumed 3 fat-loaded meals that included 1 g fat/kg body weight (65% fat) according to a randomized crossover design: olive oil-enriched meal (22% saturated fatty acids [SFA], 38% monounsaturated fatty acids [MUFA], 4% polyunsaturated fatty acids [PUFA]), butter-enriched meal (35% SFA, 22% MUFA, 4% PUFA), and walnut-enriched meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Leptin, resistin, adiponectin, and free fatty acids were determined at 0, 3, 6, and 8.5 hours after the fat load. After the walnut-enriched meal, plasma adiponectin concentrations were higher at 3 and 6 hours (P = .011, P = .046, respectively) compared with the butter-enriched meal and higher at 6 hours compared with the olive oil-enriched meal (P = .036). Free fatty acid levels decreased from baseline at 3 hours after the walnut-enriched meal (P = .001). No differences were observed between the 3 meals for leptin and resistin responses. Our data confirmed a beneficial profile in the postprandial response to walnuts, source of omega-3 PUFA with an increased postprandial adiponectin and lower postprandial free fatty acid responses. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with omega-3 PUFA dietary fat.

Topics: Adiponectin; Adolescent; Adult; Butter; Cardiovascular Diseases; Cross-Over Studies; Diet; Dietary Fats; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Humans; Juglans; Leptin; Male; Meals; Nuts; Olive Oil; Plant Oils; Plant Preparations; Postprandial Period; Reference Values; Resistin; Young Adult

Epidemiological and clinical studies suggest that low-glycemic index diets could protect against weight gain. However, the relationship between these diets and adipokines or inflammatory markers is unclear. In the present study we examine how the dietary glycemic index (GI) and dietary glycemic load (GL) are associated with several adipokines and related metabolic risk markers of obesity and diabetes in a cross-sectional and longitudinal manner.. 511 elderly community-dwelling men and women at high cardiovascular risk were recruited for the PREDIMED trial. Dietary data were collected at baseline and after 1 year of follow-up. The GI and GL were calculated. Plasma leptin, adiponectin and other metabolic risk markers were measured at baseline and after 1 year. At baseline, subjects in the highest quartiles of GI showed significantly higher levels of TNF and IL-6 than those in the lowest quartiles. Dietary GI index was negatively related to plasma leptin and adiponectin levels. After 1 year of follow-up, subjects with a higher increase in dietary GI or GL showed a greater reduction in leptin and adiponectin plasma levels. There was no association between GI or GL and the other metabolic markers measured.. Our results suggest that the consumption of high-GI or high-GL diets may modulate plasma concentrations of leptin and adiponectin, both adipostatic molecules implicated in energy balance and cardiometabolic risk.

Topics: Adipokines; Adiponectin; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet, Mediterranean; Dietary Carbohydrates; Female; Follow-Up Studies; Glycemic Index; Humans; Interleukin-6; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Nutrition Assessment; Obesity; Resistin; Risk Factors; Spain; Tumor Necrosis Factor-alpha

The purpose of the present secondary analysis study was to investigate the ability of the body adiposity index (BAI) to detect changes in % body fat levels before and after a weight loss intervention when compared to % body fat levels measured using dual-energy X-ray absorptiometry (DXA) and to examine the relationship between the BAI with cardiometabolic risk factors.. The study population for this secondary analysis included 132 non-diabetic obese sedentary postmenopausal women (age: 57.2 ± 4.7 years, BMI: 35.0 ± 3.7 kg/m(2)) participating in a weight loss intervention that consisted of a calorie-restricted diet with or without resistance training. We measured: (1) visceral fat using CT-scan, (2) body composition using DXA, (3) hip circumference and height from which the BAI was calculated, and (4) cardiometabolic risk factors such as insulin sensitivity (using the hyperinsulinemic-euglycemic clamp), blood pressure as well as fasting plasma lipids, hsC-reactive protein (CRP), leptin, and glucose.. Percent body fat levels for both methods significantly decreased after the weight loss intervention. In addition, the percent change in % body fat levels after the weight loss intervention was significantly different between % body fat measured using the DXA and the BAI (-4.5 ± 6.6 vs. -5.8 ± 5.9%; p = 0.03, respectively). However, we observed a good overall agreement between the two methods, as shown by the Bland-Altman analysis, for percent change in % body fat. Furthermore, similar correlations were observed between both measures of % body fat with cardiometabolic risk factors. However, results from the multiple linear regression analysis showed that % body fat using the BAI appeared to predict cardiometabolic risk factors differently than % body fat using the DXA in our cohort.. Estimating % body fat using the BAI seems to accurately trace variations of % body fat after weight loss. However, this index showed differences in predicting cardiometabolic risk factors when compared to % body fat measured using DXA.

Topics: Absorptiometry, Photon; Adiposity; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Caloric Restriction; Cardiovascular Diseases; Cohort Studies; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Linear Models; Middle Aged; Obesity; Postmenopause; Risk Factors; Triglycerides; Weight Loss

Obesity is a chronic disease defined by an excess amount of adipose tissue and presents a low-grade inflammatory state, increasing cardiovascular risk.. To assess the effect of weight loss magnitude on the inflammatory profile and carotid intima-media thickness (cIMT) in obese adolescents engaged in interdisciplinary therapy.. Seventy-seven postpubertal obese adolescents with a BMI greater than the 95th percentile (37·18 ± 5·14), of both genders and between the ages of 14 and 19 years (16·74 ± 1·59) were subjected to a 1-year period of interdisciplinary intervention (nutrition, psychology, physical exercise and clinical support).. Blood samples were collected to analyse glucose, lipid and adipokine concentrations. Body composition, anthropometric profiles and cIMT were measured. The results are presented according to quartiles of weight loss: 1st (≤5·80 kg) = low; 2nd (5·80-10·90 kg) = low to moderate; 3rd (10·90-15·90 kg) = moderate; and 4th (>15·90 kg) = massive.. Leptin, the leptin/adiponectin ratio and plasminogen activator inhibitor 1 (PAI-1) were decreased significantly in the low-to-moderate weight loss. The cIMT was reduced in the moderate weight loss. Moreover, adiponectin was increased only in the massive weight loss. Additionally, weight loss was an independent predictor of changes in leptin level, the adiponectin/leptin ratio (A/L ratio) and PAI-1 when the data were adjusted for age and gender. BMI changes were predictors of changes in leptin and PAI-1 levels. A/L ratio was associated with lean body mass (%), independent of gender and age. In addition, changes in A/L ratio were independent predictors of cIMT alterations.. Interdisciplinary therapy may reduce cardiovascular risk factors among adolescents depending on their degree of weight loss (moderate to massive) and when correlated with their inflammatory profile, metabolic state and cIMT.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adolescent; Blood Glucose; Body Composition; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cholesterol, VLDL; Exercise; Female; Humans; Leptin; Male; Obesity; Plasminogen Activator Inhibitor 1; Regression Analysis; Risk Factors; Time Factors; Treatment Outcome; Triglycerides; Weight Loss

This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth.. Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measured at randomization, 36 weeks' gestation, and 6-8 weeks postpartum as well as in cord plasma. Women with available cord blood samples (metformin n = 236, insulin n = 242) were included.. Maternal plasma triglycerides increased more from randomization to 36 weeks' gestation in women treated with metformin (21.93%) versus insulin (9.69%, P < 0.001). Maternal and cord plasma lipids, CRP, and neonatal anthropometry did not differ between treatments. In logistic regression analyses adjusted for confounders, the strongest associations with birth weight >90th centile were maternal triglycerides and measures of glucose control at 36 weeks.. There were few differences in circulating maternal and neonatal markers of metabolic status and no differences in measures of anthropometry between the offspring of women treated with metformin and the offspring of women treated with insulin. There may be subtle effects of metformin on maternal lipid function, but the findings suggest that treating gestational diabetes mellitus with metformin does not adversely affect lipids or CRP in cord plasma or neonatal anthropometric measures.

Topics: Adult; Blood Glucose; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Diabetes, Gestational; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Leptin; Metformin; Pregnancy; Risk Factors; Triglycerides

Cardiovascular disease (CVD) is the leading cause of death in the United States and the world. Clinical trials have suggested that soybean protein lowers lipids and blood pressure. The effect of soybean protein on novel CVD risk factors has not been well studied. The objective of this study was to examine the effect of soybean protein on biomarkers of inflammation, endothelial dysfunction and adipocytokines.. The effect of 8 weeks of 40 g of soybean protein supplement (89.3 mg isoflavones), 40 g of milk protein supplement and 40 g of complex carbohydrate placebo was examined in a randomized, placebo-controlled, double-blind, three-phase crossover trial among adults in New Orleans, Louisiana and Jackson, Mississippi. Plasma levels of inflammation biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-α), endothelial dysfunction biomarkers (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, thrombomodulin) and adipocytokines (high-molecular weight adiponectin, leptin, resistin) were measured at baseline and at the end of each intervention using immunoturbidimetric and enzyme-linked immunosorbent assay techniques.. Soy protein supplementation resulted in a significant mean net change (95% confidence interval) in plasma E-selectin of -3.93 ng/ml (-7.05 to -0.81 ng/ml; P=0.014) compared with milk protein, and in plasma leptin of -2089.8 pg/ml (-3689.3 to -490.3 pg/ml; P=0.011) compared with carbohydrate. There were no significant changes in any other risk factors.. Soy protein supplementation may reduce levels of E-selectin and leptin. Further research is warranted to investigate the mechanisms through which protein may confer protective effects on novel CVD risk factors.

Topics: Adipokines; Adult; Biomarkers; Cardiovascular Diseases; Cross-Over Studies; Dietary Supplements; Double-Blind Method; E-Selectin; Endothelium, Vascular; Female; Humans; Inflammation Mediators; Leptin; Louisiana; Male; Middle Aged; Milk Proteins; Mississippi; Risk Factors; Soybean Proteins

The purpose of this study was to investigate the effects of 12-week exercise training on circulating retinol-binding protein 4 (RBP4) concentration and cardiovascular disease (CVD) risk factors in obese men.. 29 obese men (age 48 ± 2 years; BMI 29.6 ± 0.7 kg/m(2)) participated in a 12-week exercise program (50-70% maximal heart rates; 3 times/week) without calorie restriction. Anthropometric parameters, CVD risk factors (total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, triglycerides (TG), and quantitative insulin sensitivity check index), and circulating RBP4 and adipokine (adiponectin, leptin, and interleukin-6 (IL-6)) concentrations were measured.. Exercise training significantly improved in absolute peak oxygen consumption (p < 0.05), and CVD risk factors (p < 0.05), with the exception of HDLC. There was a significant decrease in circulating RBP4, leptin, and IL-6 concentrations (p < 0.05). Stepwise regression analysis revealed that changes in RBP4 concentration were independently related to the changes in TG concentration (β = 0.46, p < 0.05).. These results demonstrate that exercise training without calorie restriction improves several CVD risk factors and circulating RBP4 and adipokine concentrations. Moreover, the change in circulating RBP4 may be more associated with the improvements in TG concentration in obese men.

Topics: Body Mass Index; Cardiovascular Diseases; Cholesterol; Exercise; Heart Rate; Humans; Interleukin-6; Leptin; Lipids; Male; Middle Aged; Obesity; Oxygen Consumption; Regression Analysis; Retinol-Binding Proteins, Plasma; Risk Factors; Triglycerides

Low-fat (LF) and high-fat (HF) weight loss diets improve brachial artery flow-mediated dilation (FMD) in obese individuals, although results are conflicting. Moreover, the role that adipose tissue plays in mediating these diet-related effects are unknown.. This study examined how modulations in FMD by HF and LF diets relate to changes in adipocyte parameters.. Obese subjects (n = 17) were randomized to a HF diet (60% kcal as fat) or a LF diet (25% kcal as fat) for 6 weeks. Both groups were restricted by 25% of energy needs.. Body weight decreased (P <0.05) in both groups (HF: -6.6 ± 0.5 kg, LF: -4.7 ± 0.6 kg). Fat mass and waist circumference were reduced (P <0.05) in the LF group only (-4.4 ± 0.3 kg; -3.6 ± 0.8 cm, respectively). FMD improved (P <0.05) in the LF group (7.4 ± 0.8% to 9.8 ± 0.8; 32% increase) and was impaired in the HF group (8.5 ± 0.6% to 6.9 ± 0.7; 19% reduction). Increases in plasma adiponectin (P <0.05, 16 ± 5%), and decreases in resistin (P <0.05, -26 ± 11%), were shown by the LF diet only. Greater decreases in leptin were observed with LF (-48 ± 9%) versus HF (-28 ± 12%) (P <0.05, diet × time). Increased FMD by the LF diet was associated with increased adiponectin, and decreased fat mass, waist circumference, leptin, and resistin.. Beneficial modulations in vascular health by LF diets may be mediated by improvements in adipocyte parameters.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Adult; Analysis of Variance; Body Composition; Body Weight; Cardiovascular Diseases; Diet, Fat-Restricted; Dietary Fats; Female; Humans; Leptin; Male; Obesity; Random Allocation; Risk Factors; Weight Loss

Patients with moderate-to-severe plaque-type psoriasis exhibit increased cardiovascular mortality. Recent publications point towards psoriasis-induced insulin resistance as an important pathomechanism driving cardiovascular comorbidity in these patients. As the hormonal status in general and sex hormone-binding globulin (SHBG) in particular serve as sensitive indicators for insulin resistance, we analysed these parameters in the context of a set of multiple additional clinical and laboratory measurements in a cohort of male patients. Of 33 consecutively enrolled male patients receiving continuous systemic therapy for their moderate-to-severe plaque-type psoriasis, 23 male patients for whom all parameters could be collected over a 24-week treatment period were included in this analysis. At baseline, testosterone levels varied between 212 and 660 ng/ml (median: 377.0), and SHBG between 11.9 and 46.0 nmol/l (median: 29.2), thus documenting lack of hypogonadism among these patients. Clinically, 19/23 patients experienced at least a 50% reduction in their PASI under therapy. Using a multivariate regression model to further analyse the sub-group of patients responding to treatment, hs-CRP, PASI, leptin and resistin all improved under effective systemic anti-inflammatory therapy, thus losing their significant influence on SHBG. SHBG performed well as a sensitive biomarker for insulin resistance and systemic inflammation in these patients. Its improvement, as well as the reduction of resistin serum levels, most likely reflects a state of reduced cardiovascular risk in patients undergoing effective continuous systemic therapy. Long-term safety data, generated e.g. from psoriasis registries, are needed to assess whether this effect translates into reduced cardiovascular mortality.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Disease Progression; Follow-Up Studies; Humans; Inflammation; Insulin Resistance; Leptin; Male; Middle Aged; Pilot Projects; Prospective Studies; Psoriasis; Resistin; Risk; Sex Hormone-Binding Globulin; Testosterone

The intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies, although the mechanisms of this association are unclear. Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form.. Fifteen healthy individuals (12 M/3 F), mean age 54.5+/-7.6 years, BMI 27.4+/-3.0 kg/m(2) (mean+/-SD), participated in a randomized sequential crossover study. After 2 weeks run-in, participants were randomly assigned to two isoenergetic diets with similar macronutrient composition, one rich in wholemeal wheat foods and the other with the same foods but in refined form (cereal fibre 23.1 vs. 9.8 g/day). After the two treatment periods (each lasting 3 weeks) plasma glucose and lipid metabolism, antioxidant activity, acetic acid, magnesium, adipokines, incretins and high-sensitivity C-reactive protein (hs-CRP) were measured at fasting and for 4h after a standard test meal (kcal 1103, protein 12%, CHO 53%, fat 35%) based on wholemeal or refined wheat foods, respectively. After the two diets there were no differences in fasting nor in postprandial plasma parameter responses; only glucose was slightly but significantly lower at 240 min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (-4.3%; p<0.03) and LDL (-4.9%; p<0.04) cholesterol levels were lower than after the refined wheat diet at fasting.. Consumption of wholemeal wheat foods for 3 weeks reduces significantly fasting plasma cholesterol as well as LDL cholesterol levels in healthy individuals without major effects on glucose and insulin metabolism, antioxidant status and sub-clinical inflammation markers.

Topics: Blood Glucose; Blood Pressure; Body Weight; C-Peptide; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Diet; Fasting; Female; Food Handling; Gastric Inhibitory Polypeptide; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Risk Factors; Triticum

The aims of this study are to examine in children: (i) obesity-related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity-based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 +/- 0.6 for 15 obese and 56.2 +/- 1.1 for 6 lean). The obese subjects underwent a 3-month randomized controlled physical activity-based lifestyle intervention. Leptin, soluble leptin receptor (sOB-R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual-energy X-ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB-R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB-R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity-based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk.

Topics: Adolescent; Biomarkers; Body Weight; Cardiovascular Diseases; Exercise; Female; Ghrelin; Humans; Inflammation; Insulin Resistance; Leptin; Life Style; Male; Motor Activity; Obesity; Receptors, Leptin; Satiation

Obesity is an escalating global health problem associated with both an increased risk of death and an increased risk of cardiovascular events. Our goal was to use magnetic resonance imaging (MRI) to determine the effect of obesity and weight loss, in the absence of the traditional cardiovascular risk factors, on aortic pulse wave velocity (PWV) a reliable, reproducible, and accurate clinical measure of aortic stiffness linked to increased mortality. Fifty obese (BMI 38.3 ± 6.8 kg/m(2)) and eighteen normal-weight controls (BMI 22.0 ± 1.7 kg/m(2)) with no identifiable cardiovascular risk factors underwent vascular MRI to assess PWV between the ascending aorta at the level of the pulmonary artery and the abdominal aorta (AA). Twenty-eight subjects underwent repeat imaging after a 1-year period of weight loss. Both groups were well matched for age, systolic blood pressure, fasting glucose, and total cholesterol. Obesity was associated with a 14% increase in PWV (P = 0.021), and with elevated C-reactive protein (CRP) (P < 0.01) and leptin levels (P < 0.001) factors known to cause increase arterial stiffness. Weight loss (average 50% excess weight) was associated with a 14% improvement in PWV (P = 0.03), and with reductions in serum leptin levels (P < 0.01). Obesity, in the absence of the traditional cardiovascular risk factors, is associated with increased aortic PWV, a noninvasive clinical measure of aortic stiffness independently predictive of cardiovascular mortality. Significant weight loss results in improvements in aortic PWV. This may provide a potential link between both obesity and increased mortality, and the reduction in mortality that occurs with weight loss.

Topics: Adult; Aorta; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Leptin; Magnetic Resonance Angiography; Male; Middle Aged; Obesity; Pulsatile Flow; Pulse; Risk Factors; Vascular Resistance; Weight Loss

Clinical trials designed to examine the effects of calcium supplementation on abdominal obesity have had ambiguous results.. This study aimed to evaluate, during energy restriction, the effects of a high-calcium diet (HCD) on measures of abdominal obesity and cardiometabolic risk factors in Brazilian obese subjects of multiethnic origin.. We conducted a randomised clinical trial. Fifty obese subjects of both sexes, aged 22-55 years, with stable body weight and a low calcium intake were randomised into the following outpatient dietary regimens: (i) a low-calcium diet (LCD; < 500 mg/day) or (ii) a HCD [1200-1300 mg/day, supplemented with non-fat powdered milk (60 g/day)]. Both groups followed an energy-restricted diet (-800 kcal/day) throughout the study (16 weeks).. Thirty-nine participants completed the study. After 16 weeks of energy restriction, a significant reduction was observed in all anthropometric parameters, metabolic variables (except for high-density lipoprotein cholesterol) and blood pressure levels in both the groups. Insulin was significantly reduced only in the HCD group. Subjects on the HCD compared with those on the LCD exhibited a greater reduction in waist circumference (p = 0.002), waist-to-hip ratio (p = 0.0001), diastolic blood pressure (p = 0.04) and mean blood pressure (p = 0.03).. Our study suggests that increased calcium intake may enhance the beneficial effects of energy restriction on abdominal obesity and blood pressure.

Topics: Adult; Blood Glucose; Blood Pressure; Calcium, Dietary; Cardiovascular Diseases; Diet, Reducing; Female; Humans; Leptin; Lipid Metabolism; Male; Metabolic Diseases; Middle Aged; Obesity, Abdominal; Risk Factors; Young Adult

To investigate the relationships between plasma leptin and adiponectin levels and recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes.. A nested case-control study examined circulating leptin and adiponectin levels in plasma obtained 4-6 years after entry into the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial. Plasma was assayed from 184 men who suffered recurrent events within 4.4 years after blood collection and 184 matched controls who remained free of further events. The association between cardiovascular events and the explanatory variables was examined by conditional logistic regression analysis.. Relative risk (RR) increased across increasing leptin quartiles; the highest quartile compared with the lowest quartile was related to the highest risk (P for trend=0.002); the increased risk remained after adjustment for risk factors (P=0.018) or for obesity (P=0.038), but in the final model (adjusted for randomized treatment, other drugs, LIPID risk score, age and body mass index), the risk was attenuated (RR=1.61, 95% CI: 0.72-3.57, P for trend=0.34). Adiponectin did not predict cardiovascular events. Subjects randomly allocated to pravastatin had 6% lower leptin levels (P=0.04) than those allocated to placebo.. Plasma leptin was a significant and independent predictor of recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes.

Topics: Adiponectin; Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Coronary Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Pravastatin; Recurrence; Risk; Stroke

The purpose of this study was to determine the effects of consuming raisins, increasing steps walked, or a combination of these interventions on lipoprotein metabolism and appetite hormones by assessing plasma apolipoprotein concentrations, cholesterol ester transfer protein activity, low-density lipoprotein (LDL) receptor messenger RNA (mRNA) abundance, and plasma ghrelin and leptin concentrations. Thirty-four subjects (17 men and 17 postmenopausal women) were matched for weight and sex and randomly assigned to consume 1 cup raisins per day (RAISIN), increase the amount of steps walked per day (WALK), or a combination of both interventions (RAISIN + WALK). The subjects completed a 2-week run-in period, followed by a 6-week intervention. Ribonucleic acid was extracted from mononuclear cells, and LDL receptor mRNA abundance was quantified by use of reverse transcriptase polymerase chain reaction. Plasma apolipoproteins were measured by Luminex (Austin, TX) technology. Apoproteins A-1, B, C-II, and E and cholesterol ester transfer protein activity were not altered for any of the groups. In contrast, apolipoprotein C-III was significantly decreased by 12.3% only in the WALK group (P < .05). Low-density lipoprotein receptor mRNA abundance was increased for all groups after the intervention (P < .001). There was a significant group effect for plasma leptin (P = .026). Plasma concentrations increased for RAISIN and RAISIN + WALK. Similarly, plasma ghrelin concentrations were elevated postintervention for both groups consuming raisins (P < .05). These data suggest that walking and raisin consumption decrease plasma LDL cholesterol by up-regulating the LDL receptor and that raisin consumption may reduce hunger and affect dietary intake by altering hormones influencing satiety.

Topics: Aged; Apolipoproteins; Cardiovascular Diseases; Cholesterol Ester Transfer Proteins; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Lipoproteins; Male; Middle Aged; Peptide YY; Receptors, LDL; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Up-Regulation; Vitis; Walking

The authors compared effects of macronutrients on self-reported appetite and selected fasting hormone levels. The Optimal Macronutrient Intake Trial to Prevent Heart Disease (OMNI-Heart) (2003-2005) was a randomized, 3-period, crossover feeding trial (n = 164) comparing the effects of 3 diets, each rich in a different macronutrient. Percentages of kilocalories of carbohydrate, fat, and protein were 48, 27, and 25, respectively, for the protein-rich diet; 58, 27, and 15, for the carbohydrate-rich diet; and 48, 37, and 15 for the diet rich in unsaturated fat. Food and drink were provided for each isocaloric 6-week period. Appetite was measured by visual analog scales. Pairwise differences between diets were estimated using generalized estimating equations. Compared with the protein diet, premeal appetite was 14% higher on the carbohydrate (P = 0.01) and unsaturated-fat (P = 0.003) diets. Geometric mean leptin was 8% lower on the protein diet than on the carbohydrate diet (P = 0.003). Obestatin levels were 7% and 6% lower on the protein diet than on the carbohydrate (P = 0.02) and unsaturated-fat (P = 0.004) diets, respectively. There were no between-diet differences for ghrelin. A diet rich in protein from lean meat and vegetables reduces self-reported appetite compared with diets rich in carbohydrate and unsaturated fat and can be recommended in a weight-stable setting. The observed pattern of hormone changes does not explain the inverse association between protein intake and appetite.

Topics: Appetite; Cardiovascular Diseases; Cross-Over Studies; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Eating; Energy Intake; Fasting; Female; Ghrelin; Humans; Leptin; Male; Middle Aged

The objective of this study was to investigate the effect of long-term exercise training on concentrations of five hormones related to appetite and insulin resistance in overweight adolescents. In addition, we were interested in the relationships of these hormones with each other and with anthropometric and/or cardiovascular disease marker changes. Participants were >or=the 85th percentile for BMI for age and sex and participated in an 8-month supervised aerobic training program. Anthropometrics, cardiovascular fitness assessment, and fasting blood samples were taken pre- and post-training. Glucose, insulin, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, leptin, active ghrelin, total peptide YY (PYY), adiponectin, and resistin concentrations were measured. The participants increased their time to exhaustion on an incremental treadmill test and decreased both percent body fat and blood triglyceride concentrations. Total PYY concentration increased and resistin concentration decreased after long-term exercise training, which are favorable outcomes. Leptin concentrations were related to weight, percent body fat, waist circumference, and triglyceride concentrations pre- and post-training. The changes in resistin concentrations were related to the changes in triglyceride concentrations. We conclude that long-term exercise training has beneficial effects for overweight adolescents with respect to PYY and resistin, hormones related to appetite and insulin sensitivity.

Topics: Adiponectin; Adiposity; Adolescent; Appetite; Biomarkers; Blood Glucose; Cardiovascular Diseases; Exercise Therapy; Exercise Tolerance; Female; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Overweight; Peptide YY; Resistin; Time Factors; Treatment Outcome; Triglycerides

Insulin resistance, a key component of the metabolic syndrome, is a risk factor for diabetes mellitus and cardiovascular disease. Acetyl-L-carnitine infusion acutely ameliorated insulin sensitivity in type 2 diabetics with insulin resistance. In this sequential off-on-off pilot study, we prospectively evaluated the effects of 24-week oral acetyl-L-carnitine (1 g twice daily) therapy on the glucose disposal rate (GDR), assessed by hyperinsulinemic euglycemic clamps, and components of the metabolic syndrome in nondiabetic subjects at increased cardiovascular risk a priori segregated into 2 groups with GDR < or =7.9 (n=16) or >7.9 (n=16) mg/kg per minute, respectively. Baseline GDR and systolic blood pressure were negatively correlated (n=32; P=0.001; r=-0.545), and patients with GDR < or =7.9 mg/kg per minute had higher systolic/diastolic blood pressure than those with higher GDR. Acetyl-L-carnitine increased GDR from 4.89+/-1.47 to 6.72+/-3.12 mg/kg per minute (P=0.003, Bonferroni-adjusted) and improved glucose tolerance in patients with GDR < or =7.9 mg/kg per minute, whereas it had no effects in those with higher GDRs. Changes in GDR were significantly different between groups (P=0.017, ANCOVA). Systolic blood pressure decreased from 144.0+/-13.6 to 135.1+/-8.4 mm Hg and from 130.8+/-12.4 to 123.8+/-10.8 mm Hg in the lower and higher GDR groups, respectively (P<0.05 for both; P<0.001 overall) and progressively recovered toward baseline over 8 weeks posttreatment. Total and high molecular weight adiponectin levels followed specular trends. Diastolic blood pressure significantly decreased only in those with higher GDRs. Treatment was well tolerated in all of the patients. Acetyl-L-carnitine safely ameliorated arterial hypertension, insulin resistance, impaired glucose tolerance, and hypoadiponectinemia in subjects at increased cardiovascular risk. Whether these effects may translate into long-term cardioprotection is worth investigating.

Topics: Acetylcarnitine; Adiponectin; Administration, Oral; Adult; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Double-Blind Method; Drug Administration Schedule; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Prospective Studies; Treatment Outcome; Vitamin B Complex; Young Adult

To examine prospective changes in cardiovascular disease (CVD) and type-2 diabetes risk factors in young adult first episode psychotic (FEP) patients treated with second generation antipsychotic medications.. At baseline, fasting serum and anthropometric measures were obtained from 45 FEP patients and 41 healthy adults (controls) of similar age, ethnicity and sex; sixteen of the FEP patients remained on the same antipsychotic medication and were available for a second blood draw at 24 weeks of treatment. Serum was assayed for glucose, insulin, triglycerides, total cholesterol and high and low density lipoproteins (HDL, LDL), adiponectin, leptin, interleukin 6, E-selectin and VCAM-1. Wilcoxon nonparametric tests were used to compare risk markers between the FEP and control group at baseline and to evaluate pre-post treatment changes within the FEP group.. At baseline, the distributions of risk marker values were similar between the two groups and the percentages of FEP patients and healthy controls who were overweight/obese, dyslipidemic, hyperglycemic, and hyperinsulinemic did not differ. At 24 weeks, compared to baseline, FEP patients showed significant increases in BMI (p=0.0002), glucose (p=0.0449), insulin (p=0.0161), cholesterol (p=0.0129), leptin (p=0.0215), and E-selectin (p=0.0195), and a decrease in adiponectin (p=0.0371).. Among patients with first episode psychosis, 6-month treatment with second generation antipsychotics is associated with the exacerbation of pre-existing and emergence of new CVD and diabetes risk factors.

Topics: Adolescent; Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Insulin; Leptin; Male; Psychotic Disorders; Retrospective Studies; Risk Factors; Statistics, Nonparametric; Triglycerides

We have reported that, compared with glucose-sweetened beverages, consuming fructose-sweetened beverages with meals results in lower 24-h circulating glucose, insulin, and leptin concentrations and elevated triacylglycerol (TG). However, pure fructose and glucose are not commonly used as sweeteners. High-fructose corn syrup (HFCS) has replaced sucrose as the predominant sweetener in beverages in the United States.. We compared the metabolic/endocrine effects of HFCS with sucrose and, in a subset of subjects, with pure fructose and glucose.. Thirty-four men and women consumed 3 isocaloric meals with either sucrose- or HFCS-sweetened beverages, and blood samples were collected over 24 h. Eight of the male subjects were also studied when fructose- or glucose-sweetened beverages were consumed.. In 34 subjects, 24-h glucose, insulin, leptin, ghrelin, and TG profiles were similar between days that sucrose or HFCS was consumed. Postprandial TG excursions after HFCS or sucrose were larger in men than in women. In the men in whom the effects of 4 sweeteners were compared, the 24-h glucose and insulin responses induced by HFCS and sucrose were intermediate between the lower responses during consumption of fructose and the higher responses during glucose. Unexpectedly, postprandial TG profiles after HFCS or sucrose were not intermediate but comparably high as after pure fructose.. Sucrose and HFCS do not have substantially different short-term endocrine/metabolic effects. In male subjects, short-term consumption of sucrose and HFCS resulted in postprandial TG responses comparable to those induced by fructose.

Topics: Adult; Area Under Curve; Beverages; Blood Glucose; Cardiovascular Diseases; Cross-Over Studies; Dietary Carbohydrates; Fatty Acids, Nonesterified; Female; Fructose; Ghrelin; Glucose; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Postprandial Period; Sex Factors; Sucrose; Time Factors; Triglycerides; Zea mays

To verify whether platelet responsiveness to leptin is associated with metabolic syndrome risk factors.. Cross-sectional study.. We studied 169 consecutive patients, mean age=43.6+/-9.9 years, with overweight (N=57) or obesity (N=112).. Cluster analysis was used to generate three clusters based on platelet responsiveness to increasing doses of leptin. Profiles of metabolic syndrome risk factors of the three clusters were compared by discriminant analysis.. Platelet responsiveness to leptin was absent in cluster 1, whereas cluster 3 had the greatest platelet aggregation response to leptin pre-incubation. Plasma leptin levels significantly decreased from cluster 1 to cluster 3 in both gender. Patients in cluster 2 had an intermediate profile of leptin responsiveness. Highest body mass index (BMI) values were more frequent in non-responders, whereas the prevalence of high waist circumference, as well as hypertriglyceridemia and hypertension, increased with increasing responsiveness to leptin from cluster 1 to cluster 3. Pattern of metabolic syndrome risk factors qualified as group specific in 69.0% of the cluster 1, 54.9% of the cluster 2 and 55.8% of the cluster 3. Circulating leptin, waist circumference, plasma triglycerides and BMI defined distinctive patterns of metabolic syndrome risk factors in the clusters.. In overweight and obese outpatients, metabolic syndrome risk factors parallel to some extent platelet responsiveness to leptin. Such a correlation involves plasma leptin levels, waist circumference, plasma triglycerides and BMI, and may contribute to the excess risk of cardiovascular events in overweight and obese patients.

Topics: Adult; Cardiovascular Diseases; Female; Humans; Leptin; Male; Metabolic Syndrome; Obesity; Overweight; Platelet Aggregation; Risk Factors; Triglycerides

In addition to lipid-lowering and cardiovascular protective actions, statins may have beneficial effects on insulin sensitivity. The objective of the present study was to evaluate the effect of simvastatin therapy on insulin resistance and on leptin, adiponectin, and C-reactive protein (CRP) levels, as compared to metformin, in overweight pre-diabetic subjects. Forty-one subjects with BMI >25 kg/m(2) and impaired fasting glucose or impaired glucose tolerance were randomized to take simvastatin, 20 mg/day (N = 20) or metformin, 1.7 g/day (N = 21) for 16 weeks. Blood samples for the determination of metabolic, hormonal, and inflammatory parameters were obtained at baseline and after each treatment. After metformin therapy, significant reductions in mean BMI and waist circumference were observed, and after simvastatin treatment LDL and triglyceride levels were significantly reduced. Insulin resistance determined by the homeostasis model assessment decreased only with metformin. Independently of the type of medication, a significant decrease in CRP levels was detected from baseline to the end of the study. CRP showed a mean reduction of 0.12 +/- 0.04 mg/dL (P = 0.002) over time. No change in leptin or adiponectin levels was induced by any therapy. The data suggest that a low dose of simvastatin does not affect insulin resistance in overweight pre-diabetic subjects and has no effect on leptin or adiponectin levels. Further studies including a larger sample size, higher doses of statins, and a placebo control group are necessary to confirm the present data.

Topics: Adiponectin; Adolescent; Adult; Aged; Anticholesteremic Agents; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Hypoglycemic Agents; Leptin; Male; Metabolic Syndrome; Metformin; Middle Aged; Simvastatin

To compare the effects of standard and low dose of 17beta-estradiol/norethisterone acetate (E2/NETA) on body composition and leptin in postmenopausal women at risk of body mass index (BMI) -and waist girth (WG) related cardiovascular and metabolic disease.. Ninety postmenopausal women aged 45-55 years with BMI >or= 25 kg/m2 participated in this 6-month prospective, randomized, single-blinded and controlled study, conducted between September 2004 and April 2006 at Adnan Menderes University Hospital. According to their WG, the subjects were divided into 2 risk groups: WG <88 cm (Group increased risk [IR], n=48) or WG >or= 88 cm (Group high risk [HR], n=42). The subjects in each group were equally assigned to receive standard or low dose of E2/NETA (2 mg E2/1 mg NETA, or 1 mg E2/0.5 mg NETA). Accordingly, the 2 groups were divided into 4 subgroups. Serum leptin levels (SLLs), body weight/height, waist/hip girth, BMI and waist-to-hip ratio were evaluated before and after therapy.. In the Group IR, WG decreased significantly only in low dose subgroup. In the Group HR, both standard and low dose subgroups had a significant reduction in WG. Those who had WG >or= 88 cm showed more reduction than those who had WG <88 cm in response to both doses of E2/NETA, insignificantly. Basal SLLs had a significant correlation with body weight, BMI and WG.. Oral standard and low dose E2/NETA reduce WG and attenuate the BMI- and waist girth- related risk of cardiovascular and metabolic diseases in postmenopausal women.

Topics: Body Composition; Body Mass Index; Cardiovascular Diseases; Estradiol; Female; Hormone Replacement Therapy; Humans; Leptin; Metabolic Diseases; Middle Aged; Norethindrone; Norethindrone Acetate; Postmenopause; Prospective Studies; Single-Blind Method; Waist-Hip Ratio

One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease (CHD) risk. A cross-sectional study was designed to randomly assign 79 morbidly obese subjects (27 men and 52 women; age: 30-45 years) either to a diet protocol (20 kcal per kg fat-free mass (FFM); 55% carbohydrates, 30% fat, and 15% proteins) or to malabsorptive surgery (biliopancreatic diversion). Fatness parameters, measured by dual-energy X-ray absorptiometry, lipid profile, insulin, leptin, sex steroid hormones and sex hormone-binding globulin (SHBG) levels were compared at baseline and 1 year after the beginning of the study. The data showed that plasma SHBG levels, but not testosterone levels, correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women. Total leptin levels were significantly lower (P<0.0001) in post-BPD subjects of both sexes compared to dietary treated obese subjects. The logarithm of plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG, but not insulin levels, were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients. The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness. Finally, in obese patients, SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis.

Topics: Adult; Biomarkers; Body Composition; Cardiovascular Diseases; Cholesterol, HDL; Cohort Studies; Cross-Sectional Studies; Diet, Fat-Restricted; Female; Gastroplasty; Humans; Incidence; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity, Morbid; Probability; Regression Analysis; Risk Factors; Sensitivity and Specificity; Sex Hormone-Binding Globulin; Weight Loss

Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body, little information is available on the long-term effects on leptin concentrations of changes in diet and exercise.. We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure, alone or in combination, affect plasma leptin concentrations.. In a randomized, 2 x 2 factorial trial, 186 men with metabolic syndrome were divided into 4 groups: diet, exercise, a combination of diet and exercise, and control. Data on dietary intake, physical fitness, and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period.. Plasma leptin concentrations, body mass index, and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity. By adjusting for either body mass index or fat mass, we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions. There was no interaction between the interventions, suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations.. Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass.

Topics: Adipose Tissue; Adult; Body Mass Index; Cardiovascular Diseases; Diet; Dietary Fats; Exercise; Health Behavior; Humans; Insulin Resistance; Leptin; Longitudinal Studies; Male; Middle Aged; Risk Factors; Smoking; Weight Loss

To assess whether circulating levels of adiponectin, leptin, and fibroblast growth factor 21 (FGF-21) are associated with incident cardiovascular disease (CVD) in rheumatoid arthritis (RA).. Adipokines were measured using banked enrollment serum from patients with RA and dichotomized above/below the median value. Incident CVD events (coronary artery disease [CAD], stroke, heart failure [HF] hospitalization, venous thromboembolism, CVD-related deaths) were identified using administrative data and the National Death Index. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox models were generated to quantify associations between adipokine concentrations and CVD incidence. Five-year incidence rates were predicted.. Among 2,598 participants, 639 (25%) had at least 1 CVD event over 19,585 patient-years of follow-up. High adiponectin levels were independently associated with HF hospitalization (hazard ratio [HR] 1.39 [95% confidence interval (95% CI) 1.07-1.79], P = 0.01) and CVD-related death (HR 1.49 [95% CI 1.16-1.92], P = 0.002) but not with other CVD events. High leptin was independently associated with CVD-related death (HR 1.44 [95% CI 1.05-1.97], P = 0.02). High FGF-21 levels were independently associated with lower rates of CAD (HR 0.75 [95% CI 0.58-0.97], P = 0.03). In subgroup analyses, associations between high adiponectin and leptin levels with CVD-related death were driven by strong associations in nonobese patients.. Adipokines are associated with HF hospitalization and CVD-related death in patients with RA, with stronger associations in nonobese participants. These findings suggest that adipokines effectively predict clinically important outcomes in RA perhaps through an association with body composition and metabolic health. Further study is needed to determine whether adipokine measures might augment existing tools to identify RA patients at increased risk of CVD.

Topics: Adipokines; Adiponectin; Arthritis, Rheumatoid; Cardiovascular Diseases; Coronary Artery Disease; Humans; Leptin; Risk Factors

Visceral adipose tissue (VAT) is a metabolic organ known to regulate fat mass, and glucose and nutrient homeostasis. VAT is an active endocrine gland that synthesizes and secretes numerous bioactive mediators called 'adipocytokines/adipokines' into systemic circulation. These adipocytokines act on organs of metabolic importance like the liver and skeletal muscle. Multiple preclinical and in vitro studies showed strong evidence of the roles of adipocytokines in the regulation of metabolic disorders like diabetes, obesity and insulin resistance. Adipocytokines, such as adiponectin and omentin, are anti-inflammatory and have been shown to prevent atherogenesis by increasing nitric oxide (NO) production by the endothelium, suppressing endothelium-derived inflammation and decreasing foam cell formation. By inhibiting differentiation of vascular smooth muscle cells (VSMC) into osteoblasts, adiponectin and omentin prevent vascular calcification. On the other hand, adipocytokines like leptin and resistin induce inflammation and endothelial dysfunction that leads to vasoconstriction. By promoting VSMC migration and proliferation, extracellular matrix degradation and inflammatory polarization of macrophages, leptin and resistin increase the risk of atherosclerotic plaque vulnerability and rupture. Additionally, the plasma concentrations of these adipocytokines alter in ageing, rendering older humans vulnerable to cardiovascular disease. The disturbances in the normal physiological concentrations of these adipocytokines secreted by VAT under pathological conditions impede the normal functions of various organs and affect cardiovascular health. These adipokines could be used for both diagnostic and therapeutic purposes in cardiovascular disease.

Topics: Adipokines; Adiponectin; Adipose Tissue; Cardiovascular Diseases; Humans; Inflammation; Intra-Abdominal Fat; Leptin; Resistin

Puberty has been described as a life stage of considerable metabolic risk specially for those with obesity. The low-grade systemic inflammatory status associated with obesity could be one of the connections with metabolic syndrome (MetS). Thus, we aimed to assess the relationship between inflammatory and cardiovascular biomarkers and the development of MetS during puberty. Seventy-five children from the PUBMEP study (33 females), aged 4-18 years, were included. Cardiovascular and inflammatory biomarkers were measured in the prepubertal and pubertal stage, including high-sensitivity C-reactive protein (CRP), leptin, tumor necrosis factor-alpha (TNFα), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP-1), total plasminogen activator inhibitor-1 (tPAI), resistin, adiponectin, myeloperoxidase (MPO), and soluble intercellular adhesion molecule-1 (sICAM-1). MetS was diagnosed at each measurement point. Mixed-effects and logistic regressions were performed. Those children with MetS in puberty presented higher prepubertal values of several cardiometabolic biomarkers in comparison to those without MetS (z-score body mass index (zBMI), waist circumference, insulin, HOMA-IR, leptin, and tPAI (p < 0.05)). For prepubertal children with obesity, the odds of developing MetS in puberty were significantly higher in those having high zBMI (OR = 4.27; CI: 1.39-22.59) or high concentrations of tPAI (OR = 1.19; CI: 1.06-1.43).. Those with obesity with higher prepubertal tPAI plasma levels had 19% higher odds of having MetS at puberty highlighting the existence of association between MetS, obesity, and inflammation already in puberty. Thus, assessing cardiometabolic and inflammatory status in children with obesity already at prepuberty is key to avoiding future comorbidities.. • Inflammation, metabolic syndrome, and obesity may have their onset in childhood. • Puberty is a life stage characterized for an increased cardiovascular risk.. • Prepuberty state could be an early indicator of future cardiometabolic risk. • Children with obesity and high total plasminogen have higher odds of future metabolic syndrome.

Topics: Adiponectin; Adolescent; Biomarkers; Body Mass Index; Cardiovascular Diseases; Child; Child, Preschool; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Puberty

Sedentary life style separated during COVID-19 pandemic. Patients with cardiovascular diseases (CVD) are vulnerable with sedentary life style. Therefore, the aim of this study was to investigate the effect of 8 weeks of combined and high intensity interval training (HIIT) on C Reactive protein, galectin-3, leptin, fibrinogen and insulin resistance index in coronary heart disease after COVID-19.. Thirty-six cardiovascular patients (55.14 ± 1.4 years, 78.6 ± 5.1 kg) were divided into three groups of combined exercise (n=13), HIIT (n=12) and control group (n=11). Combined exercise consisted of aerobic (4 weeks) and aerobic + HIIT exercise (4 weeks), three sessions per weeks. The protocol of the HIIT group included performing high intensity interval training, three sessions per weeks for 8 weeks. Blood samples were taken 24 h before the first training session and 48 h after the last training. C Reactive protein (CRP), galectin-3, leptin, fibrinogen measured with ELISA kit.. CRP, galectin-3 and fibrinogen decreased significantly after 8 weeks of combined training and HIIT (compare to pre-test). Also, insulin resistance index after 8 weeks of combined exercise showed a significant decrease compare to pre-test (p<0.05). After 8 weeks, CRP, galectin-3 and insulin resistance significantly decreased compare to control group (p<0.05).. In the patient with CVD, combined exercise training may be more effective than HIIT in reducing metabolic and heart risk factors after an epidemic such as COVID-19. However, change of leptin need to more studies.

Topics: C-Reactive Protein; Cardiovascular Diseases; Coronary Disease; COVID-19; Exercise; Fibrinogen; Galectin 3; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Pandemics; Risk Factors

Childhood adversity is a major risk factor for cardiometabolic health problems. Stress-related changes in diet suggest a role for endocrine factors that influence dietary intake, such as leptin and ghrelin. These hormones influence metabolism and may contribute to the relationship of early adversity, mental, and cardiometabolic health. This study examined levels of leptin and ghrelin in a sample of young adults with and without early life stress (ELS).. Young adults ages 18-40 (N = 200; 68.5% female) were recruited from the community. Participants with ELS (N = 118) had childhood maltreatment, and a subset, n = 92 (78.0%) also had parental loss, and n = 65 (55.1%) also had a current psychiatric disorder. Control participants (N = 82) had no maltreatment, parental loss, or psychiatric disorders. Standardized interviews and self-reports assessed demographics, adversity, medical/psychiatric history, and health behaviors. Exclusion criteria included medical conditions and current medications other than hormonal contraceptives. Body Mass Index (BMI) and other anthropometrics were measured, and fasting plasma was assayed for total ghrelin and leptin with the Bio-Plex Pro Human Diabetes Panel.. While ELS was significantly associated with greater leptin (r = .16, p = .025), a finding which held when adjusted for age and sex (F(3196)= 28.32, p = .011), this relationship was abolished when accounting for BMI (p = .44). Participants with ELS also had significantly lower total ghrelin (r = .21, p = .004), which held adjusting for age and sex (p = .002) and was attenuated (p = .045) when the model included BMI (F=46.82, p < .001). Current psychiatric disorder was also a significant predictor of greater leptin (r = .28, p < .001) and lower ghrelin (r = .29, p = .003). In the model with ELS and covariates, psychiatric disorder remained significant (F=7.26, p = .008) and ELS was no longer significant (p = .87). Associations with severity and recent perceived stress were also examined.. The relationship of ELS and leptin was no longer significant when accounting for BMI, suggesting potential avenues for intervention. Ghrelin findings persisted after correction for BMI, which may be secondary to physiological differences in the regulation of these hormones (leptin is produced by adipocytes, whereas ghrelin is produced primarily in the GI tract). Lastly, these findings suggest that psychiatric functioning may be a key component contributing to the relationship of lower total ghrelin and childhood adversity.

Topics: Adolescent; Adult; Adverse Childhood Experiences; Body Mass Index; Cardiovascular Diseases; Female; Ghrelin; Humans; Leptin; Male; Parental Death; Young Adult

To investigate the associations of milk intake (non-fermented and fermented milk), lactase persistence (LCT-13910 C/T) genotype (a proxy for long-term non-fermented milk intake), and gene-milk interaction with risks of cardiovascular disease (CVD) and CVD mortality. Also, to identify the CVD-related plasma proteins and lipoprotein subfractions associated with milk intake and LCT-13910 C/T genotype. The prospective cohort study included 20,499 participants who were followed up for a mean of 21 years. Dietary intake was assessed using a modified diet history method. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After adjusting for sociodemographic and lifestyle factors, higher non-fermented milk intake was significantly associated with higher risks of coronary heart disease (CHD) and CVD mortality, whereas higher fermented milk intake was significantly associated with lower risks of CVD and CVD mortality. The genotype associated with higher milk (mainly non-fermented) intake was positively associated with CHD (CT/TT vs. CC HR = 1.27; 95% CI: 1.03, 1.55) and CVD (HR = 1.22; 95% CI: 1.05, 1.42). The association between rs4988235 genotype and CVD mortality was stronger in participants with higher milk intake than among participants with lower intake (P for interaction < 0.05). Furthermore, leptin, HDL, and large HDL were associated with non-fermented milk intake, while no plasma proteins or lipoprotein subfractions associated with fermented milk intake and LCT-13910 C/T genotype were identified. In conclusion, non-fermented milk intake was associated with higher risks of CHD and CVD mortality, as well as leptin and HDL, whereas fermented milk intake was associated with lower risks of CVD and CVD mortality.

Topics: Animals; Cardiovascular Diseases; Diet; Genotype; Humans; Lactase; Leptin; Milk; Prospective Studies; Risk Factors; Sweden

A complex relationship of adipokines and cytokines with cardiovascular risk motivates the use of an integrated approach to identify early signs of adiposity-related inflammation. We compared the inflammatory profiles, including an integrated inflammatory score, and cardiovascular profiles of young adults who are living with overweight and/or obesity (OW/OB).. This cross-sectional study included 1194 men and women with a median age of 24.5 ± 3.12 years from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT). Participants were divided into approximate quartiles based on adiposity measures (body mass index, waist circumference, and waist-to-height ratio). We compared an integrated inflammatory score (including leptin, adiponectin, interleukin-6, interleukin-8, interleukin-10, and tumour necrosis factor-α) as well as the individual inflammatory markers, between extreme quartiles. We also compared blood pressure measures, left ventricular mass index, carotid-femoral pulse wave velocity, and carotid intima-media thickness between these groups.. Individuals in the top quartile had worse inflammatory- and cardiovascular profiles as the integrated inflammatory score, leptin, interleukin-6, blood pressure measures, and left ventricular mass index were higher, while adiponectin was lower (all p ≤ 0.003). Unexpectedly, carotid-femoral pulse wave velocity was also lower (p < 0.001) in the top quartile. Exclusively in the top quartile, all adiposity measures related positively with the integrated inflammatory score and central systolic blood pressure (both r ≥ 0.24; p < 0.001), and negatively with interleukin-10 (all r ≤ -0.13; p < 0.03). Of these relationships, the correlations with the integrated inflammatory score were the strongest (p < 0.001). The percentage difference of being in the top quartile of all adiposity measures were higher for the inflammatory score (all ≥ 263 %), leptin (all ≥ 175 %), interleukin-6 (all ≥ 134 %), and tumour necrosis factor-α (all ≥ 26 %), and lower for adiponectin (all ≥ 57 %), interleukin-10 (all ≥ 9 %), and interleukin-8 (all ≥ 15 %) compared to being in the bottom quartile.. The inflammatory score, as a comprehensive marker of adiposity-related inflammation, is strongly related to adiposity and may be an indication of early cardiovascular risk in young adults; however, further work is required to establish the clinical use thereof.

Topics: Adiponectin; Adiposity; Adult; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Female; Heart Disease Risk Factors; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Leptin; Male; Obesity; Overweight; Prospective Studies; Pulse Wave Analysis; Risk Factors; Tumor Necrosis Factor-alpha; Young Adult

Leptin has been associated with adverse effects on cardiovascular disease, but the effect of confounding by body fat in these associations remains unclear. To investigate associations between leptin and heart function and subclinical cardiovascular disease adjusted for total body fat, and to investigate the causal relation between leptin and cardiovascular disease using Mendelian randomisation.. Leptin concentrations, total body fat and diverse measures of subclinical cardiovascular disease were determined in participants of the Netherlands Epidemiology of Obesity study. Linear regression between leptin concentration and measures of heart function, ECG measures, and carotid intima media thickness as a measure of subclinical atherosclerosis was adjusted for potential confounding factors, and additionally including total body fat. We analysed the combined effects of genetic variants from a GWAS on leptin concentrations in publicly-available summary statistics of coronary heart disease GWAS (CARDIoGRAMplusC4D, n = 184,305). As many as 6107 men and women, mean (SD) age 56 (6) years, BMI 26 (4) kg/m. Observational associations between leptin and subclinical measures of cardiovascular disease were largely explained by differences in total body fat. Results of analyses of genetically-determined leptin and coronary heart disease risk were inconclusive due to a large confidence interval.

Topics: Adipose Tissue; Cardiovascular Diseases; Carotid Intima-Media Thickness; Coronary Disease; Female; Humans; Leptin; Male; Mendelian Randomization Analysis; Middle Aged; Risk Factors

Adipokines are associated with cardiovascular disease; in chronic kidney disease (CKD) patients adipokines could be useful prognostic factors.. To explore whether leptin and adiponectin in kidney replacement therapy (KRT) children could have a role on their cardiac function, in the long-term.. Prospective cohort study was performed with pediatric KRT patients, aged 8 to 17 years who were undergoing hemodialysis or peritoneal dialysis. At enrollment, lipid profile, adipokines (leptin, leptin receptor, free leptin, and adiponectin), anthropometric measurements and cardiological evaluation were determined. At two-year follow-up, a new cardiological evaluation was performed.. We included 56 patients, with a median age of 12.5 years. In the first cardiological evaluation, median LVEF was 70.0% (IQR 61%, 76%), 20 patients (35.7%) had some cardiovascular condition, and 10 (17.8%) altered LVEF. At 24-month follow-up, the median LVEF was 70.5% (IQR 65.1%, 77%), while the delta-LVEF values was 3% (IQR -6.5%, 7%). Delta-LVEF were correlated with baseline adipokines serum levels, and the only positive correlation found was with free leptin (r=0.303, p=0.025). In multivariate analysis, levels of free leptin (Coef. 0.12, p<0.036) and leptin (coef. 1.72, p=0.049), as well as baseline LVEF (Coef. -0.65, p<0.001) were associated with delta-LVEF.. Free leptin, leptin and LVEF at the beginning of follow-up were associated with the LVEF decrease at the 24-month follow-up in KRT children.

Topics: Adipokines; Adiponectin; Cardiovascular Diseases; Child; Humans; Leptin; Prospective Studies; Renal Insufficiency, Chronic

To evaluate the association between ideal cardiovascular health (CVH) and adipokine levels. Adipokines are hormones implicated in obesity and its cardiometabolic consequences. The concept of ideal CVH was introduced to promote 7 key health factors and behaviors in the general population. Previous studies have found strong associations between obesity and ideal CVH. However, existing literature on the link between CVH and adipokines is scarce.. We studied 1842 Multi-Ethnic Study of Atherosclerosis participants free of cardiovascular disease who had 7 CVH metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) measured at baseline and serum adipokine levels measured at a median of 2.4 years later. Each CVH metric was assigned a score of 0 (poor), 1 (intermediate), or 2 (ideal), and all scores were summed for a total CVH score (0-14). The total CVH scores of 0 to 8, 9 to 10, and 11 to 14 were considered inadequate, average, and optimal, respectively. We used multivariable linear regression models to assess the nonconcurrent associations between the CVH score and log-transformed adipokine levels.. The mean age was 62.1 ± 9.8 years; 50.2% of participants were men. After adjusting for sociodemographic factors, a 1-unit higher CVH score was significantly associated with 4% higher adiponectin and 15% and 1% lower leptin and resistin levels. Individuals with optimal CVH scores had 27% higher adiponectin and 56% lower leptin levels than those with inadequate CVH scores. Similar trends were observed for those with average versus inadequate CVH scores.. In a multi-ethnic cohort free of cardiovascular disease at baseline, individuals with average and optimal CVH scores had a more favorable adipokine profile than those with inadequate CVH scores.

Topics: Adipokines; Adiponectin; Aged; Atherosclerosis; Blood Pressure; Cardiovascular Diseases; Female; Health Status; Humans; Leptin; Male; Middle Aged; Obesity; Risk Factors

Adiponectin/leptin ratio (ALR) is a promising novel marker of cardio-metabolic risk in patients with metabolic syndrome. Our aim was to study the association of adiponectin-leptin ratio with markers of obesity and adiposity and also to assess its usefulness as a marker of increased cardiometabolic risk (CMR) in Indian children and youth with type 1 diabetes mellitus.. This observational study included 79 children and youth with type 1 diabetes (T1DM) (10-21 years) having disease duration>6 months. Demographic data and laboratory findings were obtained from patients' records. Patients with ALR<1 were categorised as having increased CMR and those with ALR>1 were categorised as having no CMR.. ALR showed a significant negative correlation with body mass index (BMI), waist and hip circumference and body fat percentage (p<0.05). Body fat percentage was the single most important predictor of ALR. Children and youth with increased CMR had higher weight, BMI, waist and hip circumferences and body fat percentage as compared to those with no CMR (p<0.05). In T1DM children with dyslipidemia, ALR was significantly lower as compared to those without dyslipidemia (p<0.05).. ALR may be a useful marker for adiposity and increased cardiometabolic risk in Indian children and youth with type 1 diabetes mellitus.

Topics: Adiponectin; Adolescent; Body Mass Index; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 1; Humans; Leptin; Obesity; Waist Circumference

Type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) have a significant impact on the expression of genes in peripheral blood mononuclear cells (PBMCs). The primary objective of this study was to investigate the role of two signaling pathways, STAT1/6, and two important modulators of immunometabolism, leptin and PPARs, in the development of T2DM with and without CVD. Furthermore, the study aimed to assess the correlation between these factors and the dynamics of CD14 in PBMCs. This research was conducted within the context of a growing body of literature on the complex pathophysiology of T2DM and its association with CVD. Prior studies have indicated that T2DM is characterized by an imbalance in immunometabolism and the involvement of various signaling pathways.. Blood samples were collected from a total of 47 subjects, including 7 healthy volunteers, 20 individuals diagnosed with diabetes and cardiovascular disease (D.CVD) and another 20 individuals diagnosed with diabetes only (D). PBMCs were isolated from these samples, and the expression levels of leptin, PPARγ, PPARα, and CD14 genes were measured using Real-Time PCR.. The most relevant result showed that diabetic patients with CVD had significantly higher levels of leptin expression, which was positively correlated with STAT1 (r = 0.7497, p = 0.0001). On the other hand, diabetic patients without CVD had elevated PPARγ expression, which was strongly correlated with STAT6 (r = 0.8437, p = 0.0001). Interestingly, we found a significant increase in the PPARγ/ PPARα ratio in the D.CVD group compared to the D group (4.273 ± 0.9531; 7.52 ± 3.556, p = 0.0479). Moreover, CD14 expression was significantly reduced in this group compared to diabetic patients without CVD.. These findings suggested that the immunometabolic imbalance in T2DM was driven by a STAT1/Leptin phenotype in diabetic patients with CVD and by a STAT6/PPARγ phenotype in diabetic patients without CVD. Taking into account STAT1/Leptin and STAT6/PPARγ profiling could help clinicians identify novel therapeutic targets for T2DM and other related diseases.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Leptin; Leukocytes, Mononuclear; Phenotype; PPAR alpha; PPAR gamma; RNA, Messenger

Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood.. Cross-sectional study.. We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH.. Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = -0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (-0.15 normalized protein expression [NPX], P = .0001, and -0.25 NPX, P = .0003, respectively).. We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small.

Topics: Addison Disease; Biomarkers; Cardiovascular Diseases; Cosyntropin; Cross-Sectional Studies; Extracellular Matrix Proteins; Female; Glucocorticoids; Humans; Inflammation; Leptin; Male; Neoplasm Proteins; Quality of Life

Hepatic insulin resistance (HIR) is considered to be an independent predictor of metabolic disorders and plays an important role in systemic inflammation, which contributes to abnormalities in cardiovascular disease (CVD) risk factors. The aim of this study was to investigate the relationship between HIR and new markers of cardiovascular risks, including leptin/adiponectin ratio (L/A), lipoprotein(a) [Lp(a)], and tumor necrosis factor alpha (TNF-α), at comparable whole body insulin sensitivity in non-diabetic individuals with or without CVD and at high risk of developing type 2 diabetes.. The HIR index, L/A, Lp(a), and TNF-α were measured in 50 participants with CVD and in 200 without CVD (1:4 ratio). These were also matched for the homeostatic model assessment for insulin resistance (HOMA-IR) and Matsuda-insulin sensitivity index (ISI) in an observational study design.. The HIR index (1.52 ± 0.14 vs. 1.45 ± 0.17, p < 0.02), L/A (3.22 ± 3.10 vs. 2.09 ± 2.27, p < 0.004), and levels of Lp(a) (66.6 ± 49.5 vs. 37.9 ± 3 6.8 mg/dL, p < 0.0001) and TNF-α (18.9 ± 21.8 vs. 5.4 ± 7.1 pg/mL, p < 0.0001) were higher in those with CVD than those without CVD. HOMA-IR and ISI were not significantly different (p = 0.88 and p = 0.35, respectively). The HIR index was directly correlated with L/A (r = 0.41, p < 0.0001), Lp(a) (r = 0.20, p < 0.002), TNF- α (r = 0.14, p < 0.03), and diastolic blood pressure (DBP) (r = 0.13, p < 0.03). The stepwise model analysis showed that L/A, Lp(a), and TNF-α explained about 20% of the variation in the HIR indices of all the participants (p < 0.02).. Our results suggest a positive association between HIR and new markers of cardiovascular risk [L/A, Lp(a), and TNF- α] at comparable whole body insulin sensitivity in those with or without CVD and at high risk of developing type 2 diabetes.

Topics: Adiponectin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Heart Disease Risk Factors; Humans; Insulin Resistance; Leptin; Lipoprotein(a); Tumor Necrosis Factor-alpha

Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors.. We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling.. We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels.. The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers.. This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.

Topics: Adiponectin; Adolescent; Biomarkers; Cardiovascular Diseases; Ghrelin; Hispanic or Latino; Humans; Insulin; Insulin Resistance; Leptin; Longitudinal Studies; Orexins

Childhood obesity has been related to metabolic syndrome and low-grade chronic inflammation. This study aimed to evaluate the impact of physical activity intensities and practice on inflammation, endothelial damage, and cardiometabolic risk factors in children. There were 513 participants, aged 6-14 years, recruited for the study. Physical activity was measured by accelerometry, and the children were classified into four groups according to quartiles of moderate to vigorous physical activity (MVPA) practice as very low active, low active, moderate active, and high active. Anthropometric measures, blood pressure, and plasma metabolic and proinflammatory parameters were analyzed. Very low active group presented a worse lipid profile and higher insulin, leptin, adiponectin, resistin, matrix metallopeptidase-9, and tissue plasminogen activator inhibitor-1, while lower levels of tumor necrosis factor-alpha, Type 1 macrophages, and interleukin 8 than high-active children. Regression analyses showed that a higher MVPA practice was associated with lower levels of triacylglycerols (β: -0.118; p = .008), resistin (β: -0.151; p = .005), tPAI (β: -0.105; p = .046), and P-selectin (β: -0.160; p = .006), independently of sex, age, and body mass index (BMI). In contrast, a higher BMI was associated with higher levels of insulin (β: 0.370; p < .001), Homeostasis Model Assessment (β: 0.352; p < .001), triacylglycerols (β: 0.209; p < .001), leptin (β: 0.654; p < .001), tumor necrosis factor-alpha (β: 0.182; p < .001), Type 1macrophages (β: 0.181; p < .001), and tissue plasminogen activator inhibitor (β: 0.240; p < .001), independently of sex, age, and MVPA. A better anthropometric, metabolic, and inflammatory profile was detected in the most active children; however, these differences were partly due to BMI. These results suggest that a higher MVPA practice and a lower BMI in children may lead to a better cardiometabolic status.

Topics: Body Mass Index; Cardiovascular Diseases; Child; Exercise; Humans; Inflammation; Insulin; Leptin; Pediatric Obesity; Resistin; Risk Factors; Tissue Plasminogen Activator; Triglycerides; Tumor Necrosis Factor-alpha

Topics: Adiponectin; Adolescent; Body Composition; Breast Feeding; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Glucose; Humans; Infant; Insulin; Leptin; Students; Universities; Young Adult

Adverse effects of antipsychotics (AP) contribute to cardiovascular disease (CVD) risk in patients with severe mental disorders (SMD). We investigated sex differences in AP-related CVD risk factors and the role of metabolic hormones.. Patients with SMD (N = 1791) receiving AP with different CVD risk were recruited and grouped into olanzapine and/or clozapine (N = 532), other APs (N = 744) or no use of APs (N = 515). Associations between CVD risk factor (total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), body mass index (BMI), glucose, blood pressure), sex and AP groups were tested in multiple linear regression with interactions, controlling for diagnostic group, lifestyle factors, polypharmacy, age and ethnicity. Next, we tested associations between sex differences in AP-related CVD risk factors and metabolic regulatory hormones.. AP groups and male sex were significantly associated with higher levels of LDL-C, TG and BMI, and lower levels of HDL-C. Significant interaction between AP groups and sex were found for TG (p = 0.017), with larger increase in males. Serum adiponectin, insulin, cortisol, leptin, testosterone, free thyroxine and thyroid-stimulating hormone (TSH) were associated with TG levels (all p ≤ 0.001), and a significant interaction with sex for insulin (p = 0.005), cortisol (p = 0.016), leptin (p < 0.001) and TSH (p = 0.001).. We found more severe AP-related CVD risk factors in male patients with SMD. The male-dependent increase in TG levels was associated with leptin, insulin, cortisol and TSH levels. Clinicians treating patients with SMD should be aware of increased vulnerability for AP-related lipid abnormalities in males.

Topics: Antipsychotic Agents; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Female; Heart Disease Risk Factors; Humans; Hydrocortisone; Insulin; Leptin; Male; Mental Disorders; Sex Factors; Thyrotropin; Triglycerides

Premature pubarche (PP) is a risk factor for metabolic syndrome (MS). The aim was to evaluate if glucose-insulin metabolism, cardiovascular risk factors, familial cardiovascular risk factors (FCVRF) created a risk for insulin resistance (IR) and if PP was a risk factor alone for MS in normal weight prepubertal girls with PP.. Thirty-five prepubertal, non-obese girls with PP with normal birth weight and 35 age-matched control girls were evaluated for FCVRF, anthropometric measurements, blood pressure, lipid profile, fasting blood glucose-insulin, hemoglobin A1c (HbA1c), sex hormone binding globulin (SHBG), leptin, adiponectin, tumor necrosis factor-alpha (TNF-α), androgen levels, and bone age. Oral glucose tolerance test was performed in PP participants. Homeostasis model of assessment of IR (HOMA-IR), fasting glucose/insulin ratio, atherogenic index (AI), and free androgen index (FAI) were calculated. PP participants were further stratified by FCVRF.. HbA1c, lipid profile, testosterone, leptin, adiponectin, TNF-α, HOMA-IR, glucose/insulin ratio, AI, and fasting glucose-insulin levels were similar. In the PP group FAI was significantly higher (p=0.001), whereas SHBG was significantly lower (p=0.010) than the control group. Leptin levels of FCVRF+ and FCVRF- subgroups were 15.2±9.1 and 9.7±7.2 ng/mL, respectively and the difference was significant (p=0.016).. As PP does not appear to be a risk factor alone for impaired glucose metabolism and IR in prepubertal non-obese girls with normal birth weight, it is our opinion that it is unnecessary to examine in detail such cases before puberty. Low SHBG levels in the PP group and high leptin levels in FCVRF+ subgroup might suggest that these may be predictive for MS in the future.

Topics: Adiponectin; Androgens; Birth Weight; Blood Glucose; Cardiovascular Diseases; Female; Glucose; Glycated Hemoglobin; Heart Disease Risk Factors; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Puberty, Precocious; Risk Factors; Tumor Necrosis Factor-alpha

Adipokines have been associated with increased risk of cardiovascular disease. Our aim was to determine if adipokine levels are associated with coronary artery calcification (CAC) as well as all-cause mortality in incident dialysis patients.. In patients new to dialysis, we prospectively investigated the association of adiponectin, leptin and resistin with coronary artery calcification measured by ECG-gated computer tomography. Participants were recruited a median of two months after starting dialysis.. The mean age was 50.0 (12.6) years and 31.1% were women. About 42% percent had BMI > 30. Higher adiponectin levels were inversely associated with CAC progression as change in Agatston score [-155.1 (-267.9, -42.2), p = 0.008] or change in CAC volumes between scans [-2.8 (-4.9, -0.6), p = 0.01]. Higher leptin levels were associated with CAC progression [110.4 (34.3-186.6), p = 0.005]. Decreased leptin [HR 0.5 (0.3-0.9), p = 0.05] was associated with all-cause mortality in adjusted models. There was no significant association between all-cause mortality and adiponectin [1.4 (0.6-3.4), p = 0.4] or resistin [HR 1.7 (0.5-5.0), p = 0.4].. High adiponectin protects against CAC progression, but is not associated with increased all-cause mortality. Higher leptin, as well as higher leptin to adiponectin ratio, is associated with CAC progression. Lower leptin levels were associated with all-cause mortality. The association of adipokines and cardiovascular disease in individuals on dialysis is complex and requires further study.

Topics: Adipokines; Adiponectin; Cardiovascular Diseases; Coronary Artery Disease; Female; Humans; Leptin; Male; Middle Aged; Renal Dialysis; Resistin; Risk Factors; Vascular Calcification

Topics: Angiopoietin-1; Biomarkers; Cardiovascular Diseases; Cystatins; Diabetes Mellitus; E-Selectin; Endoglin; Endothelium; Humans; Interleukin-8; Leptin; Lipocalin-2; P-Selectin; Vascular Endothelial Growth Factor A; von Willebrand Factor

Material and methods: a retrospective study of childhood acute leukemia survivors. Survivors with a diagnosis of leukemia before 16 years of age in a tertiary hospital, during the period of 1998-2018, were selected, who had completed their treatment at least two years earlier. We examined: blood adipokine levels and carbohydrate metabolism, body composition by bioimpedance, and carotid status by ultrasound. Somatometric measures were also taken. Results: the registry showed 82 children diagnosed with acute leukemia, aged between 6 and 16 years. Only 22 met the criteria to be included in the study. Results reveled that 32 % of the sample met the criteria for overweight-obesity, and 36 % had high insulin resistance indexes (IR). Leptin levels were higher in women (15.45 vs. 3.25; p = 0.044) and in obese and overweight subjects, as was the leptin/adiponectin ratio, which rises in the presence of IR (2.52 vs. 0.45; p = 0.037). We observed an increase in carotid intima-media thickness in relation to BMI (0.008; CI, -0.002 to 0.013; p = 0.007) without any association with an increase in fat mass in these patients (0.204; CI, -0.043 to 0.451; p = 0.101). Conclusions: childhood leukemia survivors have a high cardiovascular risk, characterized by an increase in IR, not associated with an increase in fat mass. This risk could justify the implementation of preventive actions in these long-lived patients.. Material y métodos: estudio retrospectivo de supervivientes de leucemia aguda en edad infantil. Se seleccionaron aquellos supervivientes con diagnóstico de leucemia antes de los 16 años de edad, en un hospital de tercer nivel y durante el período 1998-2018, que hubieran finalizado su tratamiento como mínimo dos años antes. Se analizaron: niveles de adipokinas y metabolismo hidrocarbonado en sangre, composición corporal mediante bioimpedancia y evaluación ecográfica carotídea. Se tomaron además datos somatométricos. Resultados: de 82 niños con diagnóstico de leucemia aguda, con edades comprendidas entre 6 y 16 años, incluidos en el registro, solamente 22 cumplieron los criterios para ser incluídos en el estudio. Entre los resultados destaca que el 32 % de la muestra cumplían los criterios de sobrepeso-obesidad y el 36 % presentaban índices de resistencia insulínica (RI) elevados. Los niveles de leptina fueron más elevados en las mujeres (15,45 vs. 3,25; p = 0,044) y en los individuos con obesidad o sobrepeso, así como la ratio leptina/adiponectina, que se eleva en presencia de RI (2,52 vs. 0,45; p = 0,037). Se observó un incremento del grosor mediointimal carotídeo en relación con el IMC (0,008; IC: -0,002 a 0,013; p = 0,007) sin asociarse a un aumento de masa grasa en estos pacientes (0,204; IC: -0,043 a 0,451; p = 0,101). Conclusiones: los pacientes supervivientes de leucemia en la edad infantil tienen un riesgo cardiovascular elevado, caracterizado por un aumento de la RI no asociado a aumento de la masa grasa. Este riesgo podría justificar la implementación de medidas preventivas en estos pacientes, cada vez más longevos.

Topics: Adipokines; Adiponectin; Adolescent; Cardiovascular Diseases; Carotid Intima-Media Thickness; Child; Cross-Sectional Studies; Female; Heart Disease Risk Factors; Humans; Insulin Resistance; Leptin; Leukemia; Male; Obesity; Overweight; Retrospective Studies; Risk Factors; Survivors

The aim of this study was to cross-sectionally and longitudinally examine whether higher hemoglobin (Hb) levels within the normal variation associate with key components of metabolic syndrome and total and cardiovascular mortality. The study included 967 Finnish subjects (age 40-59 years) followed for ≥ 20 years. The focus was on Hb levels, cardiovascular diseases (CVDs) and mortality rates. Higher Hb levels associated positively with key anthropometric and metabolic parameters at baseline. At the follow-up similar associations were seen in men. The highest Hb quartile showed higher leptin levels and lower adiponectin levels at baseline and follow-up (p < 0.05) and lower plasma ghrelin levels at baseline (p < 0.05). Higher baseline Hb levels associated independently with prevalence of type 2 diabetes at follow-up (p < 0.01). The highest Hb quartile associated with higher serum alanine aminotransferase levels (p < 0.001) and independently with increased risk for liver fat accumulation (OR 1.63 [1.03; 2.57]) at baseline. The highest Hb quartile showed increased risk for total (HR = 1.48 [1.01; 2.16]) and CVD-related mortality (HR = 2.08 [1.01; 4.29]). Higher Hb levels associated with an adverse metabolic profile, increased prevalence of key components of metabolic syndrome and higher risk for CVD-related and total mortality.

Topics: Adiponectin; Adult; Aged; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus, Type 2; Female; Finland; Follow-Up Studies; Ghrelin; Hemoglobins; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Risk Factors

Topics: Body Mass Index; Cardiovascular Diseases; Humans; Leptin; Risk Factors

Cardiovascular diseases (CVDs) are important complications for patients with rheumatoid arthritis (RA). The study aimed to explore whether serum leptin is associated with a increased risk of cardiovascular (CV) events in patients with RA.. Two hundred twenty-three patients with RA were followed for a mean of 40 (range = 8-42) months. Serum leptin levels were measured at baseline. Cox regression analysis was performed to assess the association between leptin levels and the risk of CV events.. The univariate analysis showed that patients with RA with higher serum leptin levels had higher rates of CV events and CV mortality, respectively (P <.001). The logistic regression model showed that leptin was independently related to CVD history (odds ratio = 1.603, 95% confidence interval [CI], 1.329-2.195; P =.005) after adjusting for confounding factors in patients with RA at baseline. The multivariate Cox proportional hazard model suggested that leptin was an independent prognostic factor for CV events in patients with RA after adjustments were made for clinical confounding factors (hazard ratio = 2.467, 95% CI, 2.019-4.495; P <.001). The Kaplan-Meier analysis showed that compared with patients with RA with leptin levels below the median value (≤15.4 mg/L), patients with leptin above the median value (>15.4 μg/L) had a higher rate of CV events (P <.001).. Leptin was significantly associated with CV events in patients with RA. Elevated serum leptin levels may be a reliable prognostic factor for predicting CV complications in patients with RA.

Topics: Aged; Arthritis, Rheumatoid; Cardiovascular Diseases; Female; Humans; Leptin; Male; Middle Aged; Proportional Hazards Models

Literature reports that insults, such as hormonal disturbances, during critical periods of development may modulate organism physiology and metabolism favoring cardiovascular diseases (CVDs) later in life. Studies show that leptin administration during lactation leads to cardiovascular dysfunction in young and adult male Wistar rats. However, there are sex differences regarding CVD. Thus, the present work aimed to investigate neonatal leptin administration's consequences on different outcomes in female rats at prepubertal and adult age. Newborn Wistar female rats were divided into two groups, Leptin and Control, receiving daily subcutaneous injections of this adipokine (8 μg/100 g) or saline for the first 10 of 21 d of lactation. Nutritional, biometric, hemodynamic, and echocardiographic parameters, as well as maximal effort ergometer performance, were determined at postnatal days (PND) 30 and 150. Leptin group presented lower food intake (p = 0.0003) and higher feed efficiency (p = 0.0058) between PND 21 and 30. Differences concerning echocardiographic parameters revealed higher left ventricle internal diameter (LVID) in systole (p = 0.0051), as well as lower left ventricle ejection fraction (LVEF) (p = 0.0111) and fractional shortening (FS) (p = 0.0405) for this group at PND 30. Older rats treated with leptin during lactation presented only higher LVID in systole (p = 0.0270). Systolic blood pressure and maximum effort ergometer test performance was similar between groups at both ages. These data suggest that nutritional, biometric, and cardiac outcomes due to neonatal leptin administration in female rats are age-dependent.

Topics: Animals; Cardiovascular Diseases; Disease Models, Animal; Female; Lactation; Leptin; Rats; Rats, Wistar; Sex Characteristics; Stroke Volume

Pro- and anti-inflammatory adipokines have been regarded as potential markers of obesity and cardiometabolic comorbidities. However, few studies have evaluated this association in children. We aimed to evaluate the relationship between adipokine concentrations and cardiometabolic risk markers in Brazilian schoolchildren. This was a cross-sectional study with 378 children aged 8-9 years from Viçosa, Minas Gerais, Brazil. We measured adipokines (leptin, retinol-binding protein 4, adiponectin, and chemerin) and cardiometabolic risk markers (fasting glucose, HOMA-IR, lipid profile, and blood pressure). Cardiometabolic risk markers were compared by quintiles of adipokines with linear regression adjusted for potential confounders. Leptin was positively associated with diastolic blood pressure (P = 0.03) and HOMA-IR (P = 0.01), and retinol-binding protein 4 was positively associated with total cholesterol (P = 0.04). Each standard deviation of leptin and retinol-binding protein 4 was associated to, respectively, a 0.1 (95%CI: 0.1; 0.2), 0.3 (95%CI: 0.1; 0.6), and 2.5 (95%CI: 0.1; 4.9) units increase in diastolic blood pressure, HOMA-IR, and total cholesterol. Adiponectin was negatively associated with diastolic blood pressure (P = 0.01) and HOMA-IR (P = 0.01), and chemerin was negatively associated with glucose (P = 0.001). Each standard deviation of adiponectin and chemerin was associated to, respectively, a -0.1 (95%CI: -0.2; -0.1), -0.2 (95%CI: -0.3; -0.1), and -1.2 (95%CI: -1.9; -0.5) units decrease in diastolic blood pressure, HOMA-IR, and glucose.Conclusion: Pro- and anti-inflammatory adipokines were positively and negatively associated with cardiometabolic risk markers, respectively, among schoolchildren, indicating this relationship may be identified at earlier ages. What is Known: • Although leptin, retinol-binding protein 4, and adiponectin are well-known adipokines, a consensus regarding their relationship with cardiometabolic risk markers, especially in schoolchildren, has not yet been reached. • Chemerin is an adipokine that has been studied recently. Yet, due to its dependence on the target cell type, its functions are still a controversial topic. What is New: • Leptin was positively associated with diastolic blood pressure and HOMA-IR, and retinol-binding protein 4 was positively associated with total cholesterol. • Adiponectin was negatively associated with diastolic blood pressure and HOMA-IR, and chemerin was negatively associated with glucose.

Topics: Adipokines; Adiponectin; Anti-Inflammatory Agents; Body Mass Index; Brazil; Cardiovascular Diseases; Chemokines; Child; Cross-Sectional Studies; Humans; Insulin Resistance; Leptin

This study aimed to establish standard reference values for soluble thrombomodulin in healthy prepubertal school-aged children and elucidate the relationship between soluble thrombomodulin levels and obesity, metabolic syndrome-associated indices, and other markers of vascular endothelial damage. The participants in this study were healthy Japanese children aged 9-10 years (315 boys and 267 girls). Blood tests for soluble thrombomodulin, leptin, fibrinogen, and general biochemical markers were performed, and the mean and 10th, 50th, and 90th percentiles for each marker were determined. Participants were divided into two groups based on their waist circumference (≥75 vs. <75 cm), and each parameter was compared between the two groups. Analyses were performed to compare subgroups with different numbers of risk factors for cardiovascular disease (CVD). We found that as CVD risk factors accumulated, the levels of total cholesterol, alanine aminotransferase, uric acid, soluble thrombomodulin, fibrinogen, and leptin were significantly elevated, whereas the level of high-density lipoprotein cholesterol significantly decreased. We determined reference values for soluble thrombomodulin in prepubertal children, and our results suggest that soluble thrombomodulin levels contribute to the latent progress of arteriosclerosis from childhood.

Topics: Cardiovascular Diseases; Child; Cholesterol, HDL; Female; Fibrinogen; Heart Disease Risk Factors; Humans; Japan; Leptin; Male; Obesity; Thrombomodulin; Waist Circumference

This study was aimed to analyze the mediation role of cardiorespiratory fitness (CRF) on the association between fatness and cardiometabolic risk scores (CMRs) in European adolescents.. A cross-sectional study was conducted in adolescents (n = 525; 46% boys; 14.1 ± 1.1 years old, mean ± SD) from 10 European cities involved in the Healthy Lifestyle in Europe by Nutrition in Adolescence study. CRF was measured by means of the shuttle run test, while fatness measures included body mass index (BMI), waist to height ratio, and fat mass index estimated from skinfold thicknesses. A clustered CMRs was computed by summing the standardized values of homeostasis model assessment, systolic blood pressure, triglycerides, total cholesterol/high-density lipoprotein cholesterol ratio, and leptin.. Linear regression models indicated that CRF acted as an important and partial mediator in the association between fatness and CMRs in 12-17-year-old adolescents (for BMI: coefficients of the indirect role β = 0.058 (95% confidence interval (95%CI): 0.023-0.101), Sobel test z = 3.11 (10.0% mediation); for waist to height ratio: β = 4.279 (95%CI: 2.242-7.059), z =3.86 (11.5% mediation); and for fat mass index: β = 0.060 (95%CI: 0.020-0.106), z = 2.85 (9.4% mediation); all p < 0.01).. In adolescents, the association between fatness and CMRs could be partially decreased with improvements to fitness levels; therefore, CRF contribution both in the clinical field and public health could be important to consider and promote in adolescents independently of their fatness levels.

Topics: Adiposity; Adolescent; Blood Pressure; Body Mass Index; Cardiometabolic Risk Factors; Cardiorespiratory Fitness; Cardiovascular Diseases; Cholesterol; Europe; Female; Healthy Lifestyle; Humans; Leptin; Linear Models; Lipoproteins, HDL; Male; Physical Examination; Skinfold Thickness; Triglycerides; Waist-Height Ratio

We explored the associations between serum leptin concentration and cardiovascular prognosis in maintenance hemodialysis patients.. In our prospective study with no intervention, demographics data at baseline were collected from electronic medical records. Serum leptin concentration was determined by ELISA. Patients underwent body composition assessment and echocardiographic measurements after hemodialysis. The primary endpoints were defined as cardiovascular events (CVEs), cardiovascular death (CVD) and all-cause death.. A total of 165 eligible patients aged 51(43-65) y were enrolled and the mean serum leptin concentration was 35.49 (29.98) ng/ml. During a median follow-up of 18 (12-22) months, CVEs occurred in 37 (22.42%) patients and the cardiovascular and all-cause mortality was 10.91% and 21.82%. Serum leptin concentration was associated with CVEs (HR = 0.982, p = 0.003), CVD (HR = 0.934, p = 0.002) and all-cause death (HR = 0.943, p < 0.001). Decreased serum leptin concentration was an independent risk factor for the development of left ventricular hypertrophy (LVH, OR = 0.98, p = 0.007) and peripheral vascular disease (PVD, OR = 0.974, p = 0.007).. Serum leptin concentration can independently predict cardiovascular outcomes and all-cause death in MHD patients. The effects that serum leptin concentration on development of LVH and PVD maybe the potential mechanism.

Topics: Cardiovascular Diseases; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Leptin; Prospective Studies; Renal Dialysis

Cardiovascular disease (CVD) is a leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship of leptin-to-adiponectin (L/A) ratio with hepatic steatosis and arterial stiffness in NAFLD.. The subjects were 871 Japanese adults who participated in a health survey. Dietary intake, body composition, lipid profile, serum interleukin-6 (IL-6), leptin, and adiponectin were analyzed. NAFLD was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. Arterial stiffness was evaluated by the brachial-ankle pulse wave velocity (baPWV).. The subjects with NAFLD had a greater body mass index (BMI) and body fat percentage (BFP); a higher intake of daily energy (kcal) and carbohydrates; and a higher prevalence of hypertension, diabetes, and hyperlipidemia. The subjects with NAFLD had higher serum leptin and lower serum adiponectin concentrations and a higher L/A ratio than subjects without NAFLD. The L/A ratio increased with increasing severity of steatosis. The L/A ratio showed positive correlations with BMI and BFP, and a negative correlation with age. Women had higher L/A ratio and BFP levels than men regardless of the presence or absence of NAFLD. There was a weak positive correlation between baPWV and severity of steatosis. BaPWV was strongly correlated with age, while no relation was found between baPWV and L/A ratio. IL-6 level was correlated with baPVW and age, while the correlation between Il and 6 level and L/A ratio was very weak. The L/A ratio was correlated with triglycerides and the ratio of total cholesterol to high-density lipoprotein-cholesterol.. L/A ratio and arterial stiffness were associated with the severity of steatosis, whereas there was no correlation between L/A ratio and arterial stiffness in NAFLD. These findings suggest that not only leptin and adiponectin but also other factors might be involved in the pathogenesis for atherosclerosis in NAFLD.

Topics: Adiponectin; Ankle Brachial Index; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Diet; Female; Humans; Hypertension; Interleukin-6; Japan; Leptin; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Surveys and Questionnaires; Vascular Stiffness

Cardiovascular diseases (CVDs) are responsible for 31% of all deaths worldwide. Genetic predisposition to CVDs in adolescents remains largely unknown. The aim of this study was to examine the association of UCP1, UCP2 and UCP3 gene polymorphisms with CVD risk factors in European adolescents.. A cross-sectional study that involves 1.057 European adolescents (12-18 years old) from the HELENA study. A total of 18 polymorphisms of UCP1, UCP2 and UCP3 genes were genotyped. We measured serum total cholesterol, high-density lipoprotein,low-density lipoprotein, ApoA1, ApoB, leptin, triglycerides, glucose, insulin and blood pressure, and calculated HOMA (homeostatic model assessment), Quantitative Insulin Sensitivity Check Index (QUICKI) and a CVD risk score.. The G allele of UCP2 rs2735572 and T allele of UCP2 rs17132534 were associated with higher diastolic blood pressure (P = 0.001; false discovery rate [FDR] = 0.009 and P = 8e-04; FDR = 0.009, respectively). We observed that the AATAG haplotype of UCP1 was associated with higher serum ApoB/ApoA1 (P = 0.008; FDR = 0.031) and ApoB levels (P = 0.008; FDR = 0.031). Moreover, the ACC haplotype of UCP3 was associated with a higher CVD risk score (P = 0.0036; FDR = 0.01).. Two UCP2 polymorphisms and haplotypes of UCP1 and UCP3 were associated with CVD risk factors. These findings suggest that UCPs may have a role in the development of CVD already in adolescents.

Topics: Adolescent; Alleles; Apolipoprotein A-I; Apolipoprotein B-100; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Child; Cross-Sectional Studies; Europe; Female; Genotype; Homeostasis; Humans; Leptin; Lipoproteins, HDL; Lipoproteins, LDL; Male; Polymorphism, Single Nucleotide; Risk Factors; Triglycerides; Uncoupling Protein 1; Uncoupling Protein 2; Uncoupling Protein 3

The occurrence of cardiovascular diseases and metabolic disorders steadily increases with the body mass index (BMI). Since the latter is not the best and earliest indicator of obesity and cardiovascular risk, the aim of the study was to evaluate some potential biological markers that would allow us to detect children and adolescents at higher risk at an early stage.. A sample of 330 children and adolescents were included in the study and divided into four groups: obese patients with hypertension, normal-weight patients with hypertension, patients with mildly elevated lipids and a control group of healthy children and adolescents. Some clinical parameters (age, body weight, body height, BMI, waist circumference, hip circumference, blood pressure), biochemical parameters (glucose, total cholesterol, triglycerides, HDL, LDL, apolipoprotein A1, homocysteine) and biological markers of obesity (ghrelin, adiponectin, leptin) were evaluated.. Ghrelin and adiponectin were found to have a strong negative statistically significant correlation with BMI in all three observed groups (p < 0.001), but not in the control group (p = 0.053 and p = 0.316, respectively). In addition, leptin had a strong positive statistically significant correlation with BMI in all four groups (p < 0.001 for the research groups, p = 0.009 for the controls). In the group of obese patients with hypertension, statistically significant differences in all three markers of obesity were found in comparison to the control group (p < 0.001 for all markers). In the group of patients with mildly elevated lipids, ghrelin and leptin were significantly different (p = 0.002 and p < 0.001, respectively). In the group of normal-weight hypertensive patients, only values of ghrelin were different compared to the control group (p = 0.001).. In the research groups, significant differences were found in clinical, biochemical and biological parameters compared to the control group. The observed biological markers of obesity are useful early markers for identifying groups of patients that are at cardiovascular risk.

Topics: Adolescent; Biomarkers; Body Mass Index; Cardiovascular Diseases; Child; Heart Disease Risk Factors; Humans; Leptin; Obesity; Risk Factors; Slovenia

Survivors of Childhood Brain Tumors (SCBT) are at a higher risk of developing cardiovascular disease and type 2 diabetes compared to the general population. Adiposity is an important risk factor for the development of these outcomes, and identifying biomarkers of adiposity may help the stratification of survivors based on their cardiovascular risk or allow for early screening and interventions to improve cardiometabolic outcomes. Leptin is an adipokine that positively correlates with the adipose mass in the general population and is a predictor of adverse cardiometabolic outcomes, yet its association with adiposity in SCBT has not been studied. The aim of this study was to determine if leptin levels are associated with the adipose mass in SCBT, and to define its predictors. This cross-sectional study included 74 SCBT (n = 32 females) with 126 non-cancer controls (n = 59 females). Total adiposity was measured using Bioelectrical Impendence Analysis (BIA) and central adiposity was measured using waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). We used multivariable linear regression analysis to determine if leptin predicts adiposity in SCBT and adjusted for age, sex, puberty, and cancer status. Leptin correlated strongly with total (p < 0.001) and central (WHR p = 0.001; WHtR p < 0.001) adiposity in SCBT and non-cancer controls. In conclusion, leptin is a potential biomarker for adiposity in SCBT, and further investigation is needed to clarify if leptin is a predictor of future cardiometabolic risk in SCBT.

Topics: Adiposity; Adolescent; Biomarkers; Brain Neoplasms; Cancer Survivors; Cardiovascular Diseases; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Early Diagnosis; Female; Humans; Leptin; Male; Predictive Value of Tests; Risk Factors; Waist-Height Ratio; Waist-Hip Ratio

Previous studies have shown that red blood cell distribution width (RDW) is an independent predictor of poor prognosis in type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). The mechanisms underlying increased anisocytosis in patients with T2D and confirmed ASCVD remain poorly understood.. We sought to evaluate the relationship among the leptin-to-adiponectin ratio, systemic low -grade inflammation, and RDW in optimally treated patients with T2D and established ASCVD.. A total of 68 patients, aged 47 to 85 years (mean [SD], 65.3 [6.8] years) and including 21 women (30.9%), were enrolled and grouped according to median RDW into those with RDW <13.5% (n = 33) and those with RDW ≥13.5% (n = 35).. Patients with RDW ≥13.5% had a significantly higher median (interquartile range [IQR]) serum leptin-to-adiponectin ratio (1.7 [0.49-2.3] ng/μg vs 0.66 [0.31-1.25] ng/μg; P = 0.04) and median (IQR) tumor necrosis factor α levels (1.58 [1.42-1.97] pg/ml vs 1.39 [1.18-1.57] pg/ml; P = 0.02). There were no significant differences in the concentrations of other inflammatory markers. The leptin-to-adiponectin ratio (r = 0.25; P = 0.04) and levels of tumor necrosis factor α (r = 0.32; P = 0.01) and soluble intercellular adhesion molecule 1 (r = 0.31; P = 0.01) were positively correlated with RDW, which was confirmed by univariate linear regression analysis. A multivariable regression model, which included demographic, clinical, and laboratory data, showed that white blood cell count (β = 0.25; 95% CI, 0.05-0.45; P = 0.01), soluble intercellular adhesion molecule 1 levels (β = 0.21; 95% CI, 0.02-0.41; P = 0.03), and mean corpuscular hemoglobin concentration (MCHC), (β = -0.48; 95% CI, 0.67 to -0.28; P < 0.001) were independent predictors of RDW in our patients.. In well-controlled patients with T2D and ASCVD, the RDW values are associated with leptin-to-adiponectin imbalance and selected inflammatory markers.

Topics: Adiponectin; Aged; Aged, 80 and over; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Erythrocyte Indices; Female; Humans; Inflammation; Leptin; Male; Middle Aged

Phosphorus is a common additive used in food processing that is typically consumed in excess of the recommended daily allowance; however, our knowledge of its effects on health, in the context of normal renal function, is limited. Unlike phosphorus, calcium intake is generally less than recommended, and it has been hypothesized that the calcium to phosphorus ratio may be partly responsible for the proposed negative health consequences. Therefore, this study sought to determine the effects of increased phosphorus additive intake, in the context of high calcium consumption, on endocrine markers of mineral metabolism and cardiometabolic health. An outpatient feeding study was performed in which healthy adults were fed a run-in control diet for 2 weeks followed by a phosphorus additive enhanced diet with supplemental calcium to an approximate ratio of 1 (experimental diet) for 2 weeks. Blood and urine samples were collected, and participants had brachial flow-mediated dilatation measured, with analyses comparing follow-up measures to baseline. Two weeks of experimental diet increased serum fibroblast growth factor 23 concentrations but lowered body weight and serum leptin; however, other phosphorus responsive factors such as osteopontin and osteocalcin did not increase. A complementary study in male mice also demonstrated that the regulation of known dietary phosphorus responsive factors was mostly abrogated when dietary calcium was raised in parallel with phosphorus. In conclusion, the study identifies weight, leptin and insulin as responsive to dietary phosphorus and that certain aspects of the systemic phosphorus response are attenuated by a corresponding high calcium intake.

Topics: Adult; Animals; Biomarkers; Body Weight; Calcium; Calcium, Dietary; Cardiovascular Diseases; Diet; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Food Additives; Humans; Insulin; Leptin; Male; Mice; Minerals; Osteocalcin; Osteopontin; Phosphorus; Phosphorus, Dietary

Waist-to-height ratio has been shown to be an important indicator of cardiometabolic risk. There are few studies evaluating this measure against existing measures of adiposity and cardiometabolic markers in early childhood. The objectives were: (i) to determine in young children the ability of waist-to-height ratio, BMI z-score, weight for length, and sum of skin fold thickness to predict cardiometabolic risk and (ii) to examine this association at ages 1, 3 and 5 years.. Prospective cohort study.. A university hospital in Toronto, Ontario.. Infants at 1 (n 406), 3 (n 112) and 5 years of age (n 94) born to mothers with and without gestational diabetes mellitus.. Weight for length and BMI z-score demonstrated the strongest correlations with biochemical measures compared to waist-to-height ratio, including leptin (at 5 years, weight for length z-score: ρ = 0·65, P < 0·001; BMI z-score: ρ = 0·67, P < 0·001) and measures of insulin resistance (at 3 years, weight for length z-score: ρ = 0·25, P = 0·02; BMI z-score: ρ = 0·24, P = 0·02). The magnitude of associations between anthropometric measures and biochemical measures strengthened over time. Weight for length and BMI z-scores were moderately correlated with overall measures of fat mass as measured by dual-energy X-ray absorptiometry (ρ = 0·65, P = 0·00; ρ = 0·61, P = 0·01).. Waist-to-height ratio was not superior to existing measures in predicting cardiometabolic risk in young children. BMI z-score is a preferred measure of adiposity between birth and 5 years of age.

Topics: Adiposity; Body Mass Index; Cardiovascular Diseases; Child, Preschool; Humans; Infant; Insulin Resistance; Leptin; Ontario; Prospective Studies; Risk Factors; Waist Circumference; Waist-Height Ratio

Topics: Adiponectin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Inflammation; Leptin; Risk Factors

Leptin is a vasoactive peptide that has been linked to diseases associated with macrovascular deterioration. What is still uncertain is its involvement in the microvasculature. Since microvascular changes are presumed to precede macrovascular deterioration, we examined whether measures of the retinal microvasculature are associated with leptin in healthy, young Black and White individuals.. We included 283 Black and 289 White men and women (aged 20-30 years). We determined serum leptin, calculated central retinal artery and vein equivalents and arterio-venous ratio. We also measured retinal vessel responses to light flicker provocation.. Black men were leaner and had lower leptin than White men, whereas Black women had increased adiposity and leptin compared to White women (all p<0.001). Black groups had narrower retinal arteries, and greater maximum arteriolar and venular dilations in response to light flicker than the White groups (p<0.001). Arterio-venous ratio associated negatively with leptin (all p≤0.044) in all groups (except Black women), but was lost upon adjustment for body mass index and other covariates. We found an inverse association between maximal venular dilation and leptin only in Black men in single and multiple regression analyses (Std β= -0.22; R. We found an independent, negative association between retinal vein dilation with leptin in healthy, young Black men, suggesting a potential detrimental role for leptin in regulating microvascular responses in a population group known to be at greater risk of cardiovascular disease development.

Topics: Adult; Black People; Blood Pressure; Cardiovascular Diseases; Cross-Sectional Studies; Electrocardiography; Female; Follow-Up Studies; Humans; Incidence; Leptin; Male; Microvessels; Prognosis; Prospective Studies; Retinal Vessels; South Africa; Time Factors; White People; Young Adult

Topics: Adiponectin; Aged; Aged, 80 and over; Ankle Brachial Index; Aorta, Abdominal; Cardiovascular Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Case-Control Studies; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Leptin; Male; Middle Aged; Overweight; Peripheral Arterial Disease; Polymyalgia Rheumatica; Resistin; Risk Factors; Smoking; Ultrasonography, Doppler, Color; Vascular Stiffness

Obesity and being overweight among adolescents pose a significant problem and are known to cause several physical and biochemical disorders during adulthood. This study was designed to identify the biomarkers of obesity and describe associations with selected metabolic disorders of obesity among Sri Lankan adolescents.. The present study compared the characteristics of obese (n = 121) and normal weight (n = 263) adolescents, including sociodemographic, anthropometric, and selected biochemical parameters (e.g., lipid profile, serum leptin, adiponectin, and high-sensitivity C-reactive protein [hs-CRP]). An enzyme-linked immunosorbent assay technique and fully automated clinical chemistry analyzer were used to analyze the biochemical parameters among adolescents ages 10 to 16.. The mean age of the sample was 13.1 y [standard deviation (SD): 1.9 y], and the male-to-female ratio 1:1. The mean weight of obese children was 55.70 kg (SD: 14.82 kg), which was significantly higher than that of children of normal weight [41.63 kg (SD: 7.88 kg)]. Total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels were significantly higher (P = 0.000) among obese adolescents compared with those of normal weight. High-density lipoprotein cholesterol was significantly lower among obese adolescents. Serum leptin and hs-CRP were higher among obese adolescents, but adiponectin was lower. In the multivariate analysis, owing to confounding effects among the tested adipokines, serum leptin was the only predictor of an abnormal lipid profile.. Serum leptin, adiponectin, and hs-CRP were found to be reliable biomarkers of predicting adiposity related metabolic disorders in adolescents. Obese adolescents showed disorders in the lipid metabolism with abnormal lipid profiles compared with children of normal weight.

Topics: Adipokines; Adolescent; Adult; Body Mass Index; Cardiovascular Diseases; Child; Female; Heart Disease Risk Factors; Humans; Leptin; Lipids; Male; Obesity; Risk Factors

Topics: Adipose Tissue; Animals; Body Weight; Cardiovascular Diseases; Endothelial Cells; HIV Protease Inhibitors; Inflammation; Leptin; Mice; NADPH Oxidase 1; Oxidative Stress; Receptors, CCR5; Receptors, Leptin; Ritonavir; Signal Transduction

Survivors of childhood acute lymphoblastic leukemia (cALL) are at higher risk of developing cardiometabolic complications. We aimed at exploring the associations between biomarkers of inflammation, oxidative stress, endothelial function, endotoxemia and cardiometabolic risk factors. We conducted a cross-sectional analysis in 246 cALL survivors (mean age, 22.1 ± 6.3 years; mean time since diagnosis, 15.5 ± 5.2 years) and evaluated the associations using a series of logistic regressions. Using structural equation models, we also tested if the relationship between endotoxemia and cardiometabolic complications was mediated by the latent (unobserved) variable inflammation inferred from the observed biomarkers CRP, TNF-α and IL-6. High leptin-adiponectin ratio was associated with obesity [adjusted OR = 15.7; 95% CI (6.2-39.7)], insulin resistance [20.6 (5.2-82.1)] and the metabolic syndrome [11.2 (2.6-48.7)]. Higher levels of plasminogen activator inhibitor-1 and tumor necrosis factor-α were associated with obesity [3.37 (1.6-7.1) and 2.34 (1.3-4.2), respectively] whereas high C-reactive protein levels were associated with insulin resistance [3.3 (1.6-6.8)], dyslipidemia [2.6 (1.4-4.9)] and MetS [6.5 (2.4-17.9)]. Our analyses provided evidence for a directional relationship between lipopolysaccharide binding protein, related to metabolic endotoxemia, inflammation and cardiometabolic outcomes. Identification of biomarkers and biological mechanisms could open new avenues for prevention strategies to minimize the long-term sequelae, improve follow-up and optimize the quality of life of this high-risk population.

Topics: Adiponectin; Adolescent; Adult; Biomarkers; Cancer Survivors; Cardiovascular Diseases; Cross-Sectional Studies; Dyslipidemias; Female; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Obesity; Oxidative Stress; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Quality of Life; Risk Factors; Young Adult

The aim of this study was to evaluate the relationship between adipokines and arterial stiffness in a group of 85 elderly subjects and the role of leptin and adiponectin on subclinical vascular damage, defined by a PWV>10 m/s.. In each subject, we evaluated anthropometry, body composition by DXA (fat mass, fat mass%, lean mass), metabolic variables, leptin, adiponectin, systolic, diastolic, mean arterial pressure and pulse pressure (SBP, DBP, MAP, PP), carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV).. In the study population, significant associations were observed between cfPWV and crPWV, age, SBP, MAP, waist circumference, fat body mass and leptin. The study population was subdivided in 2 subgroups according to adipokine patterns: group 1 included patients with high adiponectin and low leptin, and group 2 patients had high leptin and low adiponectin. SBP, PP, cfPWV were significantly higher in subjects with high leptin and low adiponectin (group 2). Even after adjustment for gender, fat mass%, MAP, HDL cholesterol and triglycerides, cfPWV was higher in group 2 than group 1. In a logistic binary regression on the entire population, considering subclinical vascular damage as a dependent variable and age, gender, MAP, fat mass%, triglycerides, HDL cholesterol and category of subjects with high leptin and low adiponectin as independent variables, MAP and category of subjects with high leptin and low adiponectin were significant predictors (OR, respectively, 1.09 and 3.61).. In conclusion, in the elderly, the presence at the same time of high leptin levels and low adiponectin levels seems to have synergic effects on arterial stiffness.

Topics: Adiponectin; Age Factors; Aged; Aged, 80 and over; Aging; Biomarkers; Body Composition; Cardiovascular Diseases; Female; Humans; Leptin; Male; Risk Factors; Vascular Stiffness

Metabolic syndrome (MetS) characteristics include chronic inflammation and elevated oxidative stress. This study assessed associations between circulating concentrations of micronutrients/phytochemicals and inflammatory/oxidative stress markers with MetS and MetS components. Adults (N = 606) from the European Health Examination Survey in Luxembourg (2013-2015) were randomly selected. We performed a multivariable logistic regression model using the least absolute shrinkage and selection operator to identify MetS-associated variables. Participants with MetS had higher concentrations of C-reactive protein (CRP), 8-iso-prostaglandin F2α, leptin, insulin, and vitamins E/A, but lower concentrations of adiponectin, beta-carotene, and oxidized low-density lipoprotein. A one-unit increase in log-CRP was associated with 51% greater odds of MetS (OR = 1.51 (95% CI: 1.16, 1.98)). Adults with a one-unit increase in log-leptin were 3.1 times more likely to have MetS (3.10 (2.10, 4.72)). Women with a one-unit increase in vitamin A were associated with 3% increased odds of MetS (1.03 (1.01, 1.05)), while those with a one-unit increase in log-adiponectin were associated with 82% decreased odds (0.18 (0.07, 0.46)). Chronic inflammation best characterized adults with MetS, as CRP, adiponectin, and leptin were selected as the main MetS determinants. Micronutrients did not seem to affect MetS, except for vitamin A in women.

Topics: Adipokines; Adiponectin; Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Insulin; Leptin; Logistic Models; Luxembourg; Male; Metabolic Syndrome; Micronutrients; Middle Aged; Oxidative Stress; Prostaglandins; Surveys and Questionnaires

Background The incidence and clinical manifestations of cardiovascular disease (CVD) differ between blacks and whites. Biomarkers that reflect important pathophysiological pathways may provide a window to allow deeper understanding of racial differences in CVD. Methods and Results The study included 2635 white and black participants from the Dallas Heart Study who were free from existing CVD. Cross-sectional associations between race and 32 biomarkers were evaluated using multivariable linear regression adjusting for age, traditional CVD risk factors, imaging measures of body composition, renal function, insulin resistance, left ventricular mass, and socioeconomic factors. In fully adjusted models, black women had higher lipoprotein(a), leptin, d-dimer, osteoprotegerin, antinuclear antibody, homoarginine, suppression of tumorigenicity-2, and urinary microalbumin, and lower adiponectin, soluble receptor for advanced glycation end products and N-terminal pro-B-type natriuretic peptide versus white women. Black men had higher lipoprotein(a), leptin, d-dimer, high-sensitivity C-reactive protein, antinuclear antibody, symmetrical dimethylarginine, homoarginine, high-sensitivity cardiac troponin T, suppression of tumorigenicity-2, and lower adiponectin, soluble receptor for advanced glycation end products, and N-terminal pro-B-type natriuretic peptide versus white men. Adjustment for biomarkers that were associated with higher CVD risk, and that differed between blacks and whites, attenuated the risk for CVD events in black women (unadjusted hazard ratio 2.05, 95% CI 1.32, 3.17 and adjusted hazard ratio 1.15, 95% CI 0.69, 1.92) and black men (unadjusted hazard ratio 2.39, 95% CI 1.64, 3.46, and adjusted hazard ratio 1.21, 95% CI 0.76, 1.95). Conclusions Significant racial differences were seen in biomarkers reflecting lipids, adipokines, and biomarkers of endothelial function, inflammation, myocyte injury, and neurohormonal stress, which may contribute to racial differences in the development and complications of CVD.

Topics: Adiponectin; Adult; Albuminuria; Antibodies, Antinuclear; Arginine; Biomarkers; Black or African American; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products; Homoarginine; Humans; Interleukin-1 Receptor-Like 1 Protein; Leptin; Linear Models; Lipoprotein(a); Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Proportional Hazards Models; Receptor for Advanced Glycation End Products; Troponin T; White People

This study is designed to investigate the effects of obstructive sleep apnea/hypopnea syndrome (OSA) surgery on serum leptin levels and metabolic disturbances, both of which contribute to the risk of cardiovascular diseases.. Case series with planned data collection.. Tertiary referral medical center.. A retrospective chart review of 101 consecutive patients with OSA who refused or failed conservative therapy and who then underwent upper airway surgery for OSA treatment was conducted. The personal medical history, anthropometric measurements, subjective symptoms, and objective polysomnographic parameters and fasting morning blood samples for leptin and metabolic biomarkers measurements were collected preoperatively and at a minimum of 3 months postoperatively.. Eighty patients with OSA (69 men and 11 women; mean [SD] age of 42.2 [10.2] years) with complete data were included in the final analysis. At least 3 months after surgery, serum leptin, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels and the mean systolic blood pressure (SBP) (night and morning) significantly decreased. According to the classical definition of surgical success, 40 subjects had successful surgery and were categorized as surgical responders, and the other 40 patients who failed surgery were categorized as surgical nonresponders. Significant reductions in serum leptin, total cholesterol, LDL-C, and triglyceride levels and improvement of mean SBP (morning) occurred in surgical responders but not in nonresponders.. Effective OSA surgery improves serum leptin, lipid profiles, and SBP. Further studies are needed to investigate the role of serial measurements of these biomarkers in monitoring surgical outcome of OSA treatment.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Female; Humans; Leptin; Male; Middle Aged; Polysomnography; Retrospective Studies; Risk Factors; Sleep Apnea, Obstructive

The objective of this study was to evaluate the association of genetically determined leptin with lipids.. We conducted a Mendelian randomisation study to assess a potential causal relationship between serum leptin and lipid levels. We also evaluated whether alcohol drinking modified the associations of genetically determined leptin with blood lipids.. 3860 participants of the Framingham Heart Study third generation cohort.. Both genetic risk scores (GRSs), the GRS generated using leptin loci independent of body mass index (BMI) and GRS generated using leptin loci dependent of BMI, were positively associated with log-transformed leptin (log-leptin). The BMI-independent leptin GRS was associated with log-transformed triglycerides (log-TG, β=-0.66, p=0.01), but not low-density lipoprotein cholesterol (LDL-C, p=0.99), high-density lipoprotein cholesterol (HDL-C, p=0.44) or total cholesterol (TC, p=0.49). Instrumental variable estimation showed that per unit increase in genetically determined log-leptin was associated with 0.55 (95% CI: 0.05 to 1.00) units decrease in log-TG. Besides significant association with log-TG (β=-0.59, p=0.009), the BMI-dependent GRS was nominally associated with HDL-C (β=-10.67, p=0.09) and TC (β=-28.05, p=0.08). When stratified by drinking status, the BMI-dependent GRS was associated with reduced levels of LDL-C (p=0.03), log-TG (p=0.004) and TC (p=0.003) among non-current drinkers only. Significant interactions between the BMI-dependent GRS and alcohol drinking were identified for LDL-C (p=0.03), log-TG (p=0.03) and TC (p=0.02).. These findings together indicated that genetically determined leptin was negatively associated with lipid levels and the association may be modified by alcohol consumption.

Topics: Adult; Alcohol Drinking; Biomarkers; Cardiovascular Diseases; DNA; Female; Follow-Up Studies; Genotype; Humans; Leptin; Lipids; Male; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Prognosis

Leptin and adiponectin are important regulators of energy metabolism and body composition. Leptin exerts cardiodepressive effects, whereas adiponectin has cardioprotective effects, but several conflicting findings have been reported. The aim of the present study was to assess the relationship between serum leptin and adiponectin levels and echocardiographic parameters and pathophysiological states in patients with cardiovascular disease (CVD) receiving cardiovascular surgery. A total of 128 patients (79 males, average age 69.6 years) that had surgery for CVD including coronary artery bypass graft (CABG) and valve replacement were recruited in this study. Preoperative serum adiponectin and leptin concentrations were measured by enzyme-linked immunosorbent assay and compared with preoperative echocardiographic findings. Body fat volume and skeletal muscle volume index (SMI) were estimated using bioelectrical impedance analysis. We also measured grip strength and gait speed. Sarcopenia was diagnosed based on the recommendations of the Asian Working Group on Sarcopenia. Positive correlations were found between adiponectin and brain natriuretic peptide (BNP), age, left atrial diameter (LAD), E/e' (early-diastolic left ventricular inflow velocity / early-diastolic mitral annular velocity), and left atrial volume index (LAVI). Negative correlations were observed between adiponectin and body mass index (BMI), estimated glomerular filtration rate (eGFR), triglyceride, hemoglobin, and albumin. Serum leptin was positively correlated with BMI, total cholesterol, triglyceride, albumin, body fat volume, and LV ejection fraction (LVEF), whereas it was negatively correlated with BNP and echocardiographic parameters (LAD, LV mass index (LVMI), and LAVI). Multiple regression analysis showed associations between log (leptin) and log (adiponectin) and echocardiographic parameters after adjusting for age, sex, and BMI. Serum adiponectin was negatively correlated with leptin, but positively correlated with tumor necrosis factor α (TNFα), an inflammatory cytokine. In males, serum leptin level had a positive correlation with skeletal muscle volume and SMI. However, adiponectin had a negative correlation with anterior mid-thigh muscle thickness, skeletal muscle volume and SMI. And, it was an independent predictive factor in males for sarcopenia even after adjusted by age. These results suggest that leptin and adiponectin may play a role in cardiac remodeling in CVD patients recei

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Comorbidity; Echocardiography; Female; Humans; Leptin; Male; Middle Aged; Models, Biological; ROC Curve; Young Adult

Leptin is a hormone crucial in the regulation of food intake and body-weight maintenance. However, the genes and gene variants that influence its plasma levels are still not well known. Results of studies investigating polymorphisms in candidate genes have been inconsistent, and, in addition, very few genome-wide association studies (GWAS) have been undertaken. Our aim was to investigate the genes and gene variants most associated with plasma leptin concentrations in a high-cardiovascular-risk Mediterranean population. We measured plasma leptin in 1011 men and women, and analyzed the genetic factors associated using three approaches: (1) Analyzing the single nucleotide polymorphisms (SNPs) reported in a GWAS meta-analysis in other populations (including an SNP in/near each of these LEP, SLC32A1, GCKR, CCNL, COBLL1, and FTO genes); (2) Investigating additional SNPs in/near those genes, also including the RLEP gene; and (3) Undertaking a GWAS to discover new genes. We did not find any statistically significant associations between the previously published SNPs and plasma leptin (Ln) in the whole population adjusting for sex and age. However, on undertaking an extensive screening of other gene variants in those genes to capture a more complete set of SNPs, we found more associations. Outstanding among the findings was the heterogeneity per sex. We detected several statistically significant interaction terms with sex for these SNPs in the candidate genes. The gene most associated with plasma leptin levels was the FTO gene in men (specifically the rs1075440 SNP) and the LEPR in women (specifically the rs12145690 SNP). In the GWAS on the whole population, we found several new associations at the

Topics: Aged; Cardiovascular Diseases; Cross-Sectional Studies; Female; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Leptin; Male; Mediterranean Region; Polymorphism, Single Nucleotide; Sex Factors; Spain

Trace metal concentrations may affect cardiometabolic risk, but the role of prenatal exposure is unclear. We examined (1) the relation between blood metal concentrations during pregnancy and child cardiometabolic risk factors; (2) overall effects of metals mixture (essential vs. nonessential); and (3) interactions between metals.. We measured 11 metals in maternal second-trimester whole blood in a prospective birth cohort in Mexico City. In children 4-6 years old, we measured body mass index (BMI), percent body fat, and blood pressure (N = 609); and plasma hemoglobin A1C (HbA1c), non-high-density lipoprotein (HDL) cholesterol, triglycerides, leptin, and adiponectin (N = 411). We constructed cardiometabolic component scores using age- and sex-adjusted z scores and averaged five scores to create a global risk score. We estimated linear associations of each metal with individual z scores and used Bayesian Kernel Machine Regression to assess metal mixtures and interactions.. Higher total metals were associated with lower HbA1c, leptin, and systolic blood pressure, and with higher adiponectin and non-HDL cholesterol. We observed no interactions between metals. Higher selenium was associated with lower triglycerides in linear (β = -1.01 z score units per 1 unit ln(Se), 95% CI = -1.84, -0.18) and Bayesian Kernel Machine Regression models. Manganese was associated with decreased HbA1c in linear models (β = -0.32 and 95% CI = -0.61, -0.03). Antimony and arsenic were associated with lower leptin in Bayesian Kernel Machine Regression models. Essential metals were more strongly associated with cardiometabolic risk than were nonessential metals.. Low essential metals during pregnancy were associated with increased cardiometabolic risk factors in childhood.

Topics: Adiponectin; Adipose Tissue; Adolescent; Adult; Bayes Theorem; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Child; Child, Preschool; Cholesterol; Female; Glycated Hemoglobin; Humans; Leptin; Metals; Mexico; Pregnancy; Pregnancy Trimester, Second; Prospective Studies; Risk Factors; Triglycerides; Young Adult

Topics: Adult; Aged; Aged, 80 and over; Asian People; Cardiovascular Diseases; Case-Control Studies; Chemokine CXCL12; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Linear Models; Logistic Models; Male; Mexico; Middle Aged; Obesity; Polymorphism, Genetic; White People

"Accelerated aging," assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age.. DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA; preserved across cell types) and extrinsic (EEAA; dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors [lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers] were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development.. In 995 participants (49.6% female; age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ-inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors.. Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction.

Topics: Absorptiometry, Photon; Adiponectin; Adolescent; Aging; Aging, Premature; Algorithms; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Chemokine CXCL10; Cholesterol, HDL; Cholesterol, LDL; DNA Methylation; Epigenesis, Genetic; Female; Humans; Inflammation; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-18; Leptin; Male; Middle Aged; Receptors, Tumor Necrosis Factor, Type II; Risk Assessment; Risk Factors; Western Australia; Young Adult

To assess the differences in the parameters that are metabolically related to cardiovascular diseases after weight loss in obese people with coronary artery diseases (CADs).. This study was conducted on 184 patients who were diagnosed with CADs in Istanbul University Cardiology Institute Hospital, Istanbul, Turkey. The levels of leptin, fibrinogen, homocysteine, high-sensitivity C-reactive protein (hs-CRP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), fasting blood glucose and insulin, glycated hemoglobin, and uric acid of the obese patients who were put on calorie restricted diet were evaluated retrospectively and compared before and after weight loss. For comparison, non-obese control patients were also studied. Student's t-test and Chi-square test were used for the statistical analysis. Results: Levels of homocysteine, glycated hemoglobin, and leptin were significantly higher in the obese patients than in the non-obese patients. Diabetic obese patients with CADs lost (11.1%) and non-diabetic obese patients with CADs lost (10.5%) of their body weight in 6 months. The levels of cholesterol, LDL-C, and fibrinogen were significantly improved in both groups. Conclusion: The obese patients lost weight after being on calorie-restricted diets and showed significant improvement in the levels of cholesterol, LDL-C, fibrinogen. There was no significant difference in the levels of homocysteine, hs-CRP, and leptin before and after weight loss in both diabetic and non-diabetic obese patients.

Topics: Adult; Aged; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, Reducing; Female; Fibrinogen; Glycated Hemoglobin; Homocysteine; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Triglycerides; Uric Acid; Weight Loss

Topics: Cardiovascular Diseases; Humans; Leptin; Liver; Non-alcoholic Fatty Liver Disease

To identify the age-dependent effect of diets containing elevated amounts of either saturated or unsaturated fatty acids on cardiac steatosis in mice.. Five- and eight-week-old C57BL/6J mice cohorts are given free access to either a saturated or an unsaturated fatty-acid-enriched diet during 8 weeks. Body weight (BW) and food intake are monitored during this period. Cardiac lipid content, carnitine palmitoyltransferase-I (CPT-I) activity, and the amount of uncoupling proteins 2 and 3 (UCP2 and UCP3) are analyzed and correlated with blood leptin concentration. Leptin and PPARγ gene expression is quantified in white adipose tissue (WAT). Both diets have a similar effect on food intake, BW, and adiposity, independently of the age. Nevertheless, cardiac steatosis is specifically identified in adolescent mice consuming the saturated diet. These animals also display lower activity of cardiac CPT-I, a down-regulation of cardiac UCP2, together with lower concentration of plasma leptin. Accordingly, leptin gene expression is reduced in the visceral WAT.. Consumption of diets containing elevated amounts of saturated fat during adolescence and early adult life promotes cardiac steatosis in mice. An insufficient endocrine activity of WAT, in terms of leptin production, may account for such an effect.

Topics: Adipose Tissue, White; Age Factors; Aging; Animals; Cardiovascular Diseases; Carnitine O-Palmitoyltransferase; Dietary Fats; Dietary Fats, Unsaturated; Down-Regulation; Fatty Acids; Leptin; Lipids; Male; Mice; Mice, Inbred C57BL; Myocardium; Palm Oil; PPAR gamma; Uncoupling Protein 2

Recent body composition studies on the island of Mauritius in young adults belonging to the two main ethnicities-Indians (South Asian descent) and Creoles (African/Malagasy descent)-have shown gender-specific ethnic differences in their body mass index (BMI)-Fat% relationships. We investigated here whether potential gender and ethnic differences in blood leptin would persist beyond that explained by differences in body composition. In healthy young adult Mauritian Indians and Creoles (79 men and 80 women; BMI range: 15-41 kg m

Topics: Adiposity; Adult; Africa; Analysis of Variance; Asia; Asian People; Black People; Body Composition; Body Mass Index; Cardiovascular Diseases; Ethnicity; Fasting; Female; Health Surveys; Humans; Leptin; Male; Mauritius; Metabolic Diseases; Sex Characteristics; Young Adult

Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.. We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418).. In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.. Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10. The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Chitinase-3-Like Protein 1; Coffee; Fas Ligand Protein; Female; Humans; Leptin; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Proteomics; Risk Factors; Surveys and Questionnaires; TNF-Related Apoptosis-Inducing Ligand

Spexin, a novel peptide, has potential implications in obesity, satiety and energy homeostasis. The current study examined the relationship of spexin with various biomarkers of cardiovascular disease and endothelial function in adolescents with obesity.. Nineteen adolescents with obesity (age, 15.8 ± 1.7 years) were studied. Spexin, leptin and various cardiovascular disease biomarkers were measured. Endothelial function was assessed by high-resolution Doppler ultrasonography of the right brachial artery.. Spexin concentration (median [interquartile range] 0.38 ng/mL [0.29-0.59 ng/mL]) was inversely correlated (r = -0.50, P = 0.03) with leptin. When participants were clustered into two groups ('high spexin and low leptin' vs. 'low spexin and high leptin'), the odds of having 'low spexin and high leptin' in participants with higher hs-CRP (≥ 3 mg/L) were 12.25 times (95 per cent CI -1 to139, P = 0.026) higher than those of participants with lower hs-CRP (<3 mg/L). Spexin levels, however, were not associated with measures of endothelial function.. The inverse association between spexin and leptin and the presence of higher concentrations of hs-CRP in adolescents with obesity in the setting of 'low spexin and high leptin' suggest a potential role for spexin in the regulation of satiety and certain cardiovascular risk factors in children with obesity.

Topics: Adolescent; Biomarkers; Brachial Artery; C-Reactive Protein; Cardiovascular Diseases; Child; Cross-Sectional Studies; Endothelium, Vascular; Female; Humans; Leptin; Male; Pediatric Obesity; Peptide Hormones; Pilot Projects; Ultrasonography, Doppler

Pro-inflammatory cytokines such as leptin and IL-6 play an important role in the development of cardiovascular risk. Determine the relationship between leptin and IL-6 concentrations with cardiovascular risk in patients with rheumatoid arthritis. We determined IL-6 and leptin levels in 77 patients with the diagnosis of rheumatoid arthritis. The cardiovascular risk was calculated using the modified Framingham scale. Statistical analysis was performed using SPSS 22 considering a significant p < 0.05. Serum leptin concentrations and cardiovascular risk (CVR) factors were compared and found that there was a significant difference between higher leptin values and disease activity (p 0.047), obesity (p 0.038), positive rheumatoid factor (p 0.009), tobacco (p 0.009), and metabolic syndrome (p 0.001). Likewise, a significant relationship was found between lower leptin concentrations and hydroxychloroquine consumption (p = 0.023). We found significant difference between IL-6 concentrations and disease activity (p 0.028), hypertriglyceridemia (p 0.023), LDL-C (p 0.029), and smoking (0.005). Similarly, an association between hydroxychloroquine consumption and low concentrations of IL-6 was found (p 0.005). Framingham CVR was calculated and the result obtained was multiplied by 1.5. The 35.2% of the population studied had a low Framingham CVR, 38.9% moderate, and 25.9% presented a high risk. We compared the level of CVR and serum leptin and IL-6 concentrations, finding that the highest CVR was the leptin and IL-6 values. There is a positive association between CVR and serum leptin concentrations. It is also significantly associated with traditional and non-traditional risk factors.

Topics: Adult; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Female; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors

Then objective of this study was to evaluate the ability of several nontraditional cardiometabolic and inflammatory biomarkers in identifying high cardiometabolic risk in adolescents.. A cross-sectional study was conducted with 529 Portuguese adolescents (267 girls) aged 14.3 ± 1.7 years. A clustered cardiometabolic risk score (body fat percentage, systolic blood pressure, ratio of total cholesterol to high-density lipoprotein cholesterol, triglycerides, homeostatic model assessment of insulin resistance, and negative values of cardiorespiratory fitness) was computed. The nontraditional cardiometabolic biomarkers assessed were complement factors (C3 and C4), C-reactive protein (CRP), fibrinogen, leptin, white blood cells (WBCs), albumin, interleukin-6, and a clustered score of inflammatory biomarkers (InflaScore) (C3, C4, CRP, fibrinogen, and leptin).. Receiver operating characteristic curves analyses showed that C3, C4, CRP, fibrinogen, leptin, and the InflaScore were able to present discriminatory ability in identifying an unfavorable cardiometabolic profile in both girls and boys (p <.01 for all). Logistic regression analyses showed that C3, C4, CRP, fibrinogen, leptin, the InflaScore (in both sexes), and WBC (boys) were associated with high cardiometabolic risk, independent of age, pubertal stage, socioeconomic status, or adherence to a Mediterranean diet (p <.05 for all).. C3, C4, CRP, fibrinogen, and leptin were associated with high cardiometabolic risk in both sexes and WBC in boys. In addition, the clustered inflammatory biomarkers seem to have a better diagnostic accuracy in identifying an unfavorable cardiometabolic profile than single biomarkers. Such biomarkers may have utility in motivating health professionals, public health workers, and adolescents' families toward lifestyle changes, improving prevention efforts early in life.

Topics: Adolescent; Biomarkers; C-Reactive Protein; Cardiorespiratory Fitness; Cardiovascular Diseases; Cross-Sectional Studies; Exercise; Female; Fibrinogen; Humans; Inflammation; Leptin; Male; Portugal; Risk Factors

We investigated whether cardiometabolic risk factors measured in serum (total cholesterol [TC], high-density lipoprotein [HDL], triglyceride, leptin, insulin, glucose and insulin resistance) are associated with the retinal microvasculature, a marker of cardiovascular aging, in healthy children and adolescents. Moreover, we tested whether these associations are due to direct biological effects or more indirectly due to adiposity-related side effects.. We recruited 168 healthy Flemish children (7-16 years old, 54.8% boys). Blood samples and retinal photographs were taken during clinical examinations. Arteriolar and venular vessel calibers were calculated using a semi-automated computer program. Multivariable regression models were used and adjusted for age, sex, mean arterial pressure (MAP) and alternate retinal caliber. In a second step, we adjusted for body mass index z-score (zBMI).. Only continuous serum leptin was associated with retinal parameters, i.e. wider arterioles; however, this disappeared after adjustment for zBMI. Children with high cardiometabolic risk factors (>90th percentile for serum leptin, insulin and insulin resistance) had wider arterioles compared to children with lower concentrations, even after additional adjustment for zBMI. No significant associations were found with lipids.. In this healthy population of children and adolescents, the hormones insulin and leptin and insulin resistance were associated with retinal microvasculature alterations, mainly in children with high cardiometabolic factors (>90th percentile), while lipids were not. These associations were independent of zBMI.

Topics: Adiposity; Adolescent; Belgium; Biomarkers; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Health Surveys; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Longitudinal Studies; Male; Microvessels; Ophthalmoscopy; Retinal Vessels; Risk Factors

Metabolic abnormalities in congenital generalized lipodystrophy (CGL) are associated with microvascular complications. However, the evaluation of different types of neuropathy in these patients, including the commitment of cardiovascular autonomic modulation, is scarce. The objective of the present study was to determine the prevalence of cardiovascular autonomic neuropathy (CAN) in patients with CGL compared with individuals with type 1 diabetes and healthy subjects.. Ten patients with CGL, 20 patients with type 1 diabetes and 20 healthy subjects were included in the study. Controls were paired 1:2 for age, gender, BMI and pubertal stage. Heart rate variability (HRV) was analyzed using cardiovascular autonomic reflex tests, including postural hypotension test, Valsalva (VAL), respiratory (E/I) and orthostatic (30/15) coefficients, and spectral analysis of the HRV, determining very low (VLF), low (LF) and high (HF) frequencies components. The diagnosis of CAN was defined as the presence of at least two altered tests.. CAN was detected in 40% of the CGL patients, 5% in type 1 diabetes patients and was absent in healthy individuals (p < 0.05). We observed a significant reduction in the E/I, VLF, LF and HF in CGL cases vs. type 1 diabetes and healthy individuals and lower levels of 30/15 and VAL in CGL vs. healthy individuals. A significant positive correlation was observed between leptin and 30/15 coefficient (r = 0.396; p = 0.036) after adjusting for insulin resistance and triglycerides. Autonomic cardiovascular tests were associated with HbA1c, HOMA-IR, triglycerides and albumin/creatinine ratio in CGL cases.. We observed a high prevalence of CAN in young patients with CGL, suggesting that insulin resistance, hypertriglyceridemia and hypoleptinemia, may have been involved in early CAN development. Additional studies are needed to evaluate the role of leptinemia in the physiopathogenesis of the condition.

Topics: Adolescent; Adult; Autonomic Nervous System; Autonomic Nervous System Diseases; Biomarkers; Blood Glucose; Brazil; Cardiovascular Diseases; Cardiovascular System; Case-Control Studies; Child; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glycated Hemoglobin; Heart Rate; Humans; Insulin; Insulin Resistance; Leptin; Lipodystrophy, Congenital Generalized; Male; Prevalence; Serum Albumin, Human; Triglycerides

Soda intake is associated with an increased risk of cardiovascular disease. Consumption of diet sodas, often considered healthy alternatives to sodas, could also increase the likelihood of cardiovascular outcomes.. This study aims to evaluate the relation between soda and diet soda and biomarkers of cardiovascular risk.. We conducted a cross-sectional analysis among 825 Mexican women free of diabetes, cardiovascular disease, and cancer, and for whom serum concentrations of C-reactive protein (CRP), C-peptide, adiponectin, and leptin were available. Mean ± SD age was 45.9 ± 6.6 y, the majority of women were premenopausal (60.4%), and the prevalence of obesity was 35%. We estimated the adjusted percentage differences in biomarkers and 95% CIs by performing multiple linear regression models comparing categories of consumption for soda and diet soda adjusting for age, family history of heart disease, menopause, menopausal hormone therapy, socioeconomic status, region, smoking, physical activity, alcohol intake, and dietary patterns.. In the entire study sample we observed a 50% higher serum CRP concentration in women in the highest soda intake quartile (median intake: 202.9 mL/d, IQR: 101.4, 304.3 mL/d) compared to those in the lowest (median intake: 11.8 mL/d, IQR: 0.0, 152.1 mL/d). After stratification by menopausal status, results remained significant only for premenopausal women. Premenopausal women in the highest quartile of soda intake had 56% higher CRP concentration relative to women in the lowest quartile. We observed no significant association with the other biomarkers. After further adjustment for body mass index, a potential mediator, results remained significant only for CRP. Diet soda consumption was not associated with any of the biomarkers.. Consumption of soda was associated with adverse levels in a biomarker of inflammation and cardiovascular risk, serum CRP, in Mexican women. These results add to the accumulating evidence on soda and cardiovascular risk. More research is necessary to understand the potential impact of artificially sweetened sodas.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Peptide; C-Reactive Protein; Carbonated Beverages; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Exercise; Female; Humans; Inflammation; Leptin; Mexico; Middle Aged; Nutritive Sweeteners; Obesity; Risk Factors; Socioeconomic Factors

BACKGROUND The postoperative adverse cardiovascular events (PACE) after surgery can result in prolonged length of stay and poorer prognosis. The purpose of this Asian single-center study was to investigate the potential predicative role of leptin for PACE in elderly patients undergoing major non-cardiac surgery. MATERIAL AND METHODS The patients in the study were prospectively recruited from a series of elderly patients (≥60 years) undergoing elective major non-cardiac surgery (≥2 hours) in our hospital from June 2013 to June, 2016. The demographic and clinical data and the preoperative serum biomarkers of each participant were recorded in details. Suspected PACE were assessed by the same experienced expert based on clinical, blood, and other accessory tests. The univariate and multiple logistic regression analyses were plotted to evaluate the potential independent predictive factors for PACE. RESULTS A total of 270 elderly patients (145 males and 125 females), undergoing major elective non-cardiac surgery, were finally enrolled in this study. Older age, higher revised cardiac risk index score, higher levels of systolic blood pressure, B-type natriuretic peptide and leptin, the preoperative medication of beta blocker and lipid-lowering agents were positive predictors of PACE by univariate analyses (p<0.05). Our results indicated that preoperative leptin level (OR 1.84, 95% CI 1.08-3.42; p=0.015) and advanced age (OR 0.24, 95% CI 0.09-0.94; p=0.041) were significantly associated with the occurrence of PACE by multiple logistic regression analyses. CONCLUSIONS Preoperative serum leptin level and advanced age were two independent risk factors for PACE among elderly patients undergoing elective major non-cardiac surgery.

Topics: Age Factors; Aged; Aged, 80 and over; Asian People; Biomarkers; Cardiovascular Diseases; China; Elective Surgical Procedures; Female; Humans; Leptin; Male; Middle Aged; Postoperative Complications; Postoperative Period; Predictive Value of Tests; Prospective Studies; Risk Assessment

The relationship among inadequate vitamin D status, obesity, and cardiometabolic risk and the potential impact of physical activity-based interventions on vitamin D status are poorly characterized in children. This study aimed to address these issues.. We studied a total of 21 adolescents (15 obese and 6 normal weight; age: 14-18 years; Tanner stage>IV). Adolescents with obesity (n = 15) underwent a randomized controlled (8 in the intervention group and 7 in the control group) 3-month physical activity-based lifestyle intervention. 25-Hydroxy vitamin D [25(OH)D] by mass spectrometry, adiponectin, leptin, high-sensitivity C-reactive protein (CRP), insulin, and glucose were measured and body composition was assessed by dual-energy x-ray absorptiometry (DXA). Analysis of covariance and mixed-effects model were used to compare mean change in 25(OH)D between intervention and nonintervention groups. Bootstrap method was used to validate the estimates and principle component analysis reduced the variables in the data for adjustment.. 25(OH)D was lower (P < 0.001) in the obese versus lean adolescents. Homeostasis model assessment-insulin resistance, CRP, fat mass (FM), and body mass index z-score were negatively correlated with baseline 25(OH)D, while adiponectin showed a positive correlation. After adjustment for baseline biomarkers of cardiometabolic risk, the concentration of 25(OH)D increased in the obese intervention group (P = 0.06), but not in the nonintervention group. Fat-free mass increased and FM decreased (P < 0.05 for both) in the intervention group. The magnitudes of increase in 25(OH)D and decrease in FM directly correlated (P < 0.05).. The increase in circulating 25(OH)D concentration by physical activity-based lifestyle-only intervention in adolescents with obesity, who did not receive vitamin D supplementation, suggests a putative independent role of physical activity-based interventions in the regulation of vitamin D status and potentially in the mitigation of risk factors of cardiovascular disease.

Topics: Adiponectin; Adolescent; Blood Glucose; Body Composition; Body Mass Index; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Exercise; Female; Homeostasis; Humans; Insulin; Leptin; Life Style; Male; Mass Spectrometry; Pediatric Obesity; Risk Factors; Vitamin D

To evaluate markers of cardiovascular disease in women with normal insulin sensitivity who had recently initiated use of depot medroxyprogesterone acetate (DMPA) as a contraceptive.. A prospective, non-randomised, comparative study. Data of 30 women of 18-40 years of age, with normal hyperinsulinaemic-euglycaemic clamp at baseline and body mass index (BMI) < 30, who opted to use DMPA or a copper intrauterine device (IUD) as a contraceptive, were analysed. Serum samples were collected for evaluation of the lipid and hepatic profile, C-reactive protein, TNF-α, interleukin-6, leptin/adiponectin ratio and free fatty acids; body composition was evaluated using DXA, blood pressure and carotid intima-media thickness were measured. Evaluations were performed at baseline and 12 months later. The groups were compared using repeated measures analysis of variance (ANOVA). Significance level was 5%.. The mean age of the women in the DMPA and IUD group was 28.7 ± 6.5 and 28.3 ± 5.8 years, respectively; the BMI was 23.0 ± 3.4 and 24.3 ± 2.7 kg/m. No clinical cardiovascular effect was found but deterioration in CV markers was observed in the first year of use of DMPA.

Topics: Adiponectin; Adolescent; Adult; Body Composition; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Contraceptive Agents, Female; Female; Humans; Interleukin-6; Intrauterine Devices, Copper; Leptin; Lipids; Liver Function Tests; Medroxyprogesterone Acetate; Prospective Studies; Tumor Necrosis Factor-alpha; Young Adult

Prior research has indicated that as an important biomarker of chronic low-grade inflammation, high-sensitivity C-reactive protein (hs-CRP) can play important roles on the onset of metabolic syndrome and cardiovascular diseases (CVD). We conducted an integrative approach, which combines biological wet-lab experiments, statistical analysis, and semantics-oriented bioinformatics & computational analysis, to investigate the association among hs-CRP, body fat mass (FM) distribution, and other cardiometabolic risk factors in young healthy women. Research outcomes in this study resulted in two novel discoveries. Discovery 1: There are four primary determinants for hs-CRP, i.e., central/abdominal FM (a.k.a. trunk FM) accumulation, leptin, high density lipoprotein cholesterol (HDL-C), and plasminogen activator inhibitior-1 (PAI-1). Discovery 2: Chronic inflammation may involve in adipocyte-cytokine interaction underlying the metabolic derangement in healthy young women.

Topics: Adolescent; Body Fat Distribution; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Computational Biology; Female; Humans; Leptin; Models, Biological; Plasminogen Activator Inhibitor 1; Risk Factors; Young Adult

Helicobacter pylori (H. pylori) is a common gastric infection associated with extragastric conditions. The association between H. pylori infection and obesity is unclear. H. pylori may affect gut hormones involved in food intake and energy expenditure. The aim of this study is to evaluate ghrelin/obestatin balance and leptin in obese subjects with H. pylori infection.. Sixty healthy volunteers were divided into: obese and non-obese groups. Each group was divided into H. Pylori positive or H. pylori negative. Anthropometric parameters, H. pylori status, serum glucose, insulin level, and lipid profile were estimated with calculation of Homeostasis Model Assessment Insulin Resistance (HOMA-IR). Serum levels of ghrelin, obestatin, and leptin were evaluated.. Significant increase was found in serum glucose, insulin and HOMA-IR ratio in obese subjects with positive H. pylori as compared to other groups. H. pylori positive obese subjects showed significantly increased ghrelin, ghrelin/obestatin balance, and leptin with a significant decrease in obestatin as compared to negative subjects. Ghrelin/obestatin ratio positively correlated with weight, body mass index, waist, glucose, insulin, HOMA-IR, leptin, cholesterol, triglycerides, low density cholesterol and also with H. pylori antigen in the same group.. It can be concluded that ghrelin, obestatin, and leptin are affected by presence of H. pylori seropositivity in obese subjects. The higher ghrelin levels and ghrelin/obestatin ratio with lowered obestatin could be considered as a gastro-protective effect against inflammation induced by H. pylori.

Topics: Adult; Cardiovascular Diseases; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Metabolic Diseases; Middle Aged; Obesity; Risk

This study examined the associations of muscle area and radiodensity with adiponectin and leptin.. A total of 1,944 participants who enrolled in the Multi-Ethnic Study of Atherosclerosis underwent computed tomography to quantify body composition and measurements of adiponectin, leptin, interleukin-6, C-reactive protein, and resistin.. The data suggest that increases in muscle area and radiodensity may have positive impacts on chronic inflammation and, in turn, reduce the risk of cardiometabolic disease.

Topics: Abdominal Muscles; Adiponectin; Adult; Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Body Composition; Cardiovascular Diseases; Cohort Studies; Female; Humans; Intra-Abdominal Fat; Leptin; Longitudinal Studies; Male; Middle Aged; Risk Factors; Tomography, X-Ray Computed

Several observational studies have shown that low serum vitamin B-12 is associated with increased body mass index (BMI) and adverse cardiometabolic outcomes. However, it is unclear if these associations reflect a causal effect of vitamin B-12 on cardiometabolic risk factors and diseases, latent confounding, or reverse causality.. The aims of this study were to investigate 1) the possible causal relation between vitamin B-12 and indicators of body fat, lipid, and glucose variables; type 2 diabetes (T2D); and cardiovascular disease by using a 2-sample Mendelian randomization (MR) method and 2) the possible pleiotropic role of fucosyltransferase 2 (FUT2).. We selected 11 single nucleotide polymorphisms (SNPs) robustly associated with serum concentrations of vitamin B-12 in a previous genomewide association study (GWAS) in 45,576 individuals. We performed 2-sample MR analyses of the relation between vitamin B-12 and cardiometabolic risk factors and diseases with the use of publicly available GWAS summary statistics for 15 outcomes in ≤339,224 individuals. The robustness of results was tested with sensitivity analyses by using MR Egger regression and weighted-median estimation, and by performing additional analyses excluding a variant in the FUT2 gene, which may be pleiotropic.. We found a suggestive causal relation between vitamin B-12 and fasting glucose and β cell function [homeostatic model assessment (HOMA) of β cell function (HOMA-B)]. However, we found no evidence that serum concentrations of vitamin B-12 were causally related to BMI, waist-to-hip ratio, plasma leptin, body fat, fasting insulin, insulin resistance (from HOMA of insulin resistance), glycated hemoglobin, triglycerides, T2D, coronary artery disease, or HDL, LDL, or total cholesterol.. We found no evidence that serum concentrations of vitamin B-12 are causally related to body weight or the majority of cardiometabolic outcomes investigated. However, vitamin B-12 may have a causal effect on fasting glucose and HOMA-B, although these results will require replication in large independent data sets. This trialwas registered at http://www.isrctn.com/ISRCTN47414943 as ISRCTN47414943.

Topics: Blood Glucose; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fucosyltransferases; Galactoside 2-alpha-L-fucosyltransferase; Genome-Wide Association Study; Humans; Insulin Resistance; Leptin; Lipids; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; Vitamin B 12

Metabolic syndrome (MetS) or prediabetes is a complex disorder that is defined by a clustering of cardiometabolic risk factors, including obesity, hypertriglyceridemia, reduced high-density lipoprotein (HDL) cholesterol, hypertension, and insulin resistance. Among cardiometabolic risk factors, central obesity plays a key role in the development of MetS through alterations in the secretion of adipokines and interacts with other MetS risk factors to unfavorably influence overall cardiometabolic risk. Obesity has grasped epidemic proportions in Asia, which has the highest number of people with diabetes in the world. But, the importance of central obesity in the clustering of all four MetS risk factors or vice versa in predicting severity of MetS has not yet been investigated in Asian population. Therefore, the present study examined the influence of central obesity on circulating levels of adipokines through its interaction with the clustering of cardiometabolic risk factors of MetS including hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension in Hong Kong Chinese adults.. Blood samples from 83 Hong Kong Chinese adults, who were previously screened for MetS according to the guideline of the United States National Cholesterol Education Program Expert Panel Adult Treatment Panel III criteria were selected. Insulin and adipokines, including visfatin, chemerin, plasminogen activator inhibitor-1 (PAI-1), resistin, C-C motif chemokine ligand 2 (CCL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), leptin and adiponectin were assessed.. The interacting effect of central obesity with all of the other four MetS risk factors increased the proinflammatory status of adipokines (TNF-α, leptin) and decreased the anti-inflammatory status of adipokine (adiponectin).. Our results indicate that the inflammatory status of MetS may be more severe in the presence of central obesity. Adipokines, as biomarkers for pathophysiological changes, may help to improve early patient identification and to predict MetS-associated morbidity and mortality.

Topics: Adipokines; Adiponectin; Aged; Cardiovascular Diseases; Female; Hong Kong; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity, Abdominal; Risk Factors; Tumor Necrosis Factor-alpha

Background We examined associations of objectively measured physical activity ( PA ) and sedentary time with cardiovascular disease biomarkers at age 60 to 64 years. This included investigation of sex differences and the extent to which associations may be mediated by adiposity. Methods and Results Participants were 795 men and 827 women aged 60 to 64 years from the Medical Research Council National Survey of Health and Development. Combined heart rate and movement sensors worn for 5 consecutive days were used to derive overall PA energy expenditure, kJ /kg per day) and time spent sedentary (<1.5 metabolic equivalent of tasks), in light PA (1.5-3 metabolic equivalent of tasks) and moderate-to-vigorous intensity PA (>3 metabolic equivalent of tasks). Linear regression models were used to relate each PA parameter to inflammatory (C-reactive protein, interleukin-6), endothelial (tissue-plasminogen activator, E-selectin) and adipokine (leptin, adiponectin) markers extracted from fasting blood samples. Greater time in light PA and moderate-to-vigorous intensity PA and less sedentary time were associated with more favorable biomarker levels. For C-reactive protein, interleukin-6, and leptin, these differences were greater among women than men. For example, % differences (95% confidence intervals) in leptin for men and women per SD increases in sedentary time: 7.9 (2.7, 13.0) and 20.6 (15.3, 25.8); light intensity PA : -3.8 (-8.9, 12.7) and -17.7 (-23.1, -12.4), moderate-to-vigorous intensity PA : -12.9 (-17.9, -8.0) and -18.3 (-23.4, -13.1). Fat mass mediated a greater proportion of these associations in women than men. Conclusions Greater light PA and moderate-to-vigorous intensity PA and less sedentary time in early old age were associated with more favorable cardiovascular biomarker profiles. Fat mass partially mediated these associations but more strongly in women than men, which explained sex differences.

Topics: Adiponectin; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; E-Selectin; Energy Metabolism; Exercise; Female; Humans; Interleukin-6; Leptin; Linear Models; Male; Middle Aged; Sedentary Behavior; Time Factors; Tissue Plasminogen Activator

The pericardial fluid may be representative of the interstitium of the heart. The aim of this study was to discriminate in cardiovascular disease patients between adipocytokines that are produced locally by the heart and those supplied by the circulation.. Enzyme-linked immunosorbent assays (ELISA) were used to determine levels of N-terminal pro-brain natriuretic peptide (NT-pBNP), fatty acid-binding protein 4 (FABP4), leptin, lipocalin-2, neutrophil elastase, proteinase-3, high sensitivity C-reactive protein (hsCRP) and adiponectin in venous plasma and pericardial fluid harvested during elective cardio-thoracic surgery (n = 132-152).. In pericardial fluid compared to plasma, the levels were significantly smaller (p < 0.001) for leptin, lipocalin-2, neutrophil elastase, proteinase-3, hsCRP and adiponectin. For these biomarkers, the ratio of pericardial fluid-to-plasma level ([PF]/[P], median (interquartile range)) was 0.65 (0.47-1.01), 0.78 (0.56-1.09), 0.23 (0.11-0.60), 0.17 (0.09-0.36), 0.14 (0.08-0.35), and 0.25 (0.15-0.34), respectively. In contrast, pericardial fluid was significantly enriched (p < 0.001) in NT-pBNP ([PF]/[P]: 1.9 (1.06-2.73)) and even more so for FABP4 ([PF]/[P]: 3.90 (1.47-9.77)). Moreover, in pericardial fluid, the adipocytokines interrelated all significantly positive and correlated negative to hsCRP, whereas for NT-pBNP only a significantly positive correlation with adiponectin was found. These interrelations were distinct from those in the plasma, as were the correlations of the pericardial biomarkers with patient characteristics compared to plasma.. In cardiovascular disease patients, the pericardial cavity is a distinct adipocytokine microenvironment in which especially FABP4 is mainly derived from the heart.

Topics: Adipokines; Adiponectin; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Fatty Acid-Binding Proteins; Female; Humans; Leptin; Leukocyte Elastase; Lipocalin-2; Male; Middle Aged; Myeloblastin; Natriuretic Peptide, Brain; Peptide Fragments; Pericardium

To evaluate the additional discriminatory performance of adiponectin, leptin, and their ratio in the identification of impaired glucose tolerance (IGT) in men and women without diabetes on top of conventional risk factors.. A total of 698 subjects underwent an oral glucose tolerance test (oGTT) and adipocytokine measurements. A comprehensive stepwise selection procedure was performed, followed by c-statistics and integrated discrimination improvement (IDI) analysis. In males, adiponectin levels were significantly lower in the IGT group compared to the non-IGT group (Whitney U test, p < 10-4), whereas leptin levels were significantly higher (p = 0.009) in IGT group. In females, adiponectin and leptin levels were not significantly different between groups (Mann-Whitney U test, p = 0.073 and p = 0.08, respectively). Adjusting for the most informative, sex-specific, clinical and biochemical factors, adiponectin, leptin and their ratio were not found to be significant predictors of the response to the glucose load, when modelled as continuous terms or tertiles. In males, the area-under-the-curve (AUC) for adiponectin was estimated at 0.620 (95% CI: 0.558-0.682) and the addition of adiponectin into the basic model provided a ΔAUC benefit of 0.004, showing no additional discriminatory benefit on top of conventional risk factors (IDI p-value: 0.27), nor did the addition of leptin or their ratio. The results were similar in females.. In Chinese individuals without diabetes, no significant evidence for the potential discriminatory value of adiponectin, leptin or their ratio in the identification of IGT on top of conventional risk factors was observed.

Topics: Adiponectin; Area Under Curve; Biological Specimen Banks; Biomarkers; Blood Glucose; Cardiovascular Diseases; Cross-Sectional Studies; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Leptin; Male; Odds Ratio; ROC Curve

Cardiovascular (CVS) morbidity and mortality in the peritoneal dialysis patients (PD) is 10-30-fold higher than in the general population. A relatively low level of adiponectin and a higher level of leptin are important predictors of vascular complications as well as CVS events in PD patients. The asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is an important risk factor of CVS morbidity and mortality. It is very important to establish all CVS risk factors in the PD patients to prevent CVS morbidity and mortality in this population. The aim of the study was to determine the plasma concentration of ADMA and adipokines in relation to the protein-energy wasting (PEW) in PD patients. The study was performed in 30 PD patients and in the control group which consisted of 23 healthy volunteers. Plasma levels of hsC-reactive protein, TNF, IL-6, leptin, adiponectin, oxyLDL and ADMA were measured by ELISA method in both groups. The nutritional status was determined by measuring the albumin, body mass index (BMI), the percentage of body fat (%F), lean body mass (LBM) and Subjective Global Assessment Score (SGA). The adequacy of dialysis was estimated by weekly Kt/V. In all PD patients, significantly higher levels of ADMA, leptin, oxyLDL, hsCRP and TNF in comparison to controls were observed. In contrast to well-nourished subjects, patients with PEW, in addition to increased hsCRP, showed significantly higher ADMA. PEW was associated with high levels of ADMA and hsCRP and this could probably be responsible for increased CVS risk in PD patients.

Topics: Adiponectin; Adult; Aged; Arginine; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Energy Metabolism; Humans; Interleukin-6; Kidney Failure, Chronic; Leptin; Lipoproteins, LDL; Middle Aged; Peritoneal Dialysis; Risk Factors; Tumor Necrosis Factor-alpha

Topics: Adolescent; Antioxidants; Body Mass Index; Brazil; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Humans; Leptin; Male; Risk Factors; Vitamins

To assess the associations between sleep duration and cardiometabolic risk factors in Chinese school-aged children and to explore the possible mediating role of adipokines.. Sleep duration was collected in 3166 children from the Beijing Child and Adolescent Metabolic Syndrome study. Glucose homeostasis and other cardiometabolic risk factors were assessed. Serum adipokines including leptin, total and high-molecular-weight (HMW) adiponectin, resistin, fibroblast growth factor 21 (FGF21), and retinol binding protein 4 (RBP4) were determined.. Among the 6- to 12-year-old children, after adjusting for covariates including puberty, short sleep duration was associated with increased body mass index (BMI), waist circumference, fasting glucose, insulin and homeostasis model assessment of insulin resistance (all p < .0001), higher triglyceride and lower high-density lipoprotein cholesterol (p < .05), along with increased leptin (p < .0001), FGF21 (p < .05) and decreased HMW-adiponectin (p ≤ .01); the association with leptin remained significant after further adjustment for BMI. However, these associations, except for glucose (p < .0001), disappeared after further adjusted for leptin. For the 13-18 years old group, short sleep duration was associated with higher BMI, waist circumference, and RBP4 (all p < .05), but the association with RBP4 was attenuated after adjusting for BMI (p = .067).. Short sleep duration is strongly associated with obesity and hyperglycemia (in 6-12 years old), along with adverse adipokine secretion patterns among Chinese children. The associations with cardiometabolic risk factors appear to be more pronounced in younger children, and could be explained, at least partially, by leptin levels.

Topics: Adipokines; Adiponectin; Adolescent; Asian People; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Child; China; Cholesterol, HDL; Female; Fibroblast Growth Factors; Humans; Hyperglycemia; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Resistin; Retinol-Binding Proteins, Plasma; Risk Factors; Sleep; Time Factors; Triglycerides; Waist Circumference

Although physical activity is an established risk factor for chronic disease prevention, the specific mechanisms underlying these relationships are poorly understood. We examined the associations between total activity counts and moderate-vigorous physical activity (MVPA) measured by accelerometer, and physical activity energy expenditure measured by doubly labeled water, with plasma levels of proinsulin, insulin, c-peptide, insulin growth factor binding protein-3, insulin growth factor-1, adiponectin, leptin, and leptin-sR.. We conducted a cross-sectional analysis of 526 healthy US women in the Women's Lifestyle Validation Study, 2010 to 2012. We performed multiple linear regression models adjusting for potential lifestyle and health-related confounders to assess the associations between physical activity, measured in quartiles (Q) and biomarkers.. Participants in Q4 versus Q1 of total activity counts had lower proinsulin (-20%), c-peptide (-7%), insulin (-31%), and leptin (-46%) levels, and higher adiponectin (55%), leptin-sR (25%), and insulin growth factor-1 (9.6%) levels (all P trend ≤ 0.05). Participants in Q4 versus Q1 of MVPA had lower proinsulin (-26%), c-peptide (-7%), insulin (-32%), and leptin (-40%) levels, and higher adiponectin (31%) and leptin-sR (22%) levels (all P trend ≤ 0.05). Further adjustment for body mass index (BMI) attenuated these associations, but the associations with adipokines remained significant. Those in Q4 versus Q1 of physical activity energy expenditure had lower leptin (-21%) and higher leptin-sR (10%) levels (all P trend ≤ 0.05), after additional adjustment for BMI. In the sensitivity analysis, the associations were similar but attenuated when physical activity was measured using the subjective physical activity questionnaire.. Our data suggest that greater physical activity is modestly associated with favorable levels of cardiometabolic and endocrine biomarkers, where the strongest associations were found with accelerometer-measured physical activity. These associations may be only partially mediated through BMI, further supporting the role of physical activity in the reduction of cardiometabolic and endocrine disease risk, independent of adiposity.

Topics: Accelerometry; Adiponectin; Aged; Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cross-Sectional Studies; Endocrine System Diseases; Energy Metabolism; Exercise; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Middle Aged; Proinsulin; Risk Factors

Inflammation plays a key role in atherosclerosis and this process seems to appear in childhood. The ideal cardiovascular health index (ICHI) has been inversely related to atherosclerotic plaque in adults. However, evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to assess the association between ICHI and inflammation in European adolescents.. As many as 543 adolescents (251 boys and 292 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional multi-center study including 9 European countries, were measured. C-reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell counts were used to compute an inflammatory score. Multilevel linear models and multilevel logistic regression were used to assess the association between ICHI and inflammation controlling by covariates. Higher ICHI was associated with a lower inflammatory score, as well as with several individual components, both in boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal components of the ICHI had significantly lower inflammatory score and lower levels of the study biomarkers, except CRP. Finally, the multilevel logistic regression showed that for every unit increase in the ICHI, the probability of having an inflammatory profile decreased by 28.1% in girls.. Results from this study suggest that a better ICHI is associated with a lower inflammatory profile already in adolescence. Improving these health behaviors, and health factors included in the ICHI, could play an important role in CVD prevention.

Topics: Adolescent; Age Factors; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Complement C3; Complement C4; Cross-Sectional Studies; Diet; Europe; Female; Health Status; Humans; Inflammation; Inflammation Mediators; Leptin; Leukocyte Count; Life Style; Linear Models; Logistic Models; Male; Multivariate Analysis; Nutrition Surveys; Odds Ratio; Risk Assessment; Risk Factors; Risk Reduction Behavior

Gestational diabetes mellitus is a significant risk factor for metabolic syndrome and cardiovascular disease.. To assess the relationships between components of the metabolic syndrome and cytokine and adhesion molecule levels in women with GDM during pregnancy and after delivery.. A prospective case-control study on a sample of 126 pregnant women (63 with and 63 without gestational diabetes mellitus). In an intra-subject analysis, 41 women with history of gestational diabetes mellitus and 21 controls were re-assessed in the postpartum period. Clinical data and levels of cytokines and adhesion molecules were recorded during weeks 24-29 of pregnancy and 12 months after delivery.. In the postpartum period, there were significantly higher levels of tumor necrosis factor alpha in both cases and controls, and of adiponectin in controls. Cases showed higher leptin levels, with no significant differences during and after pregnancy. No significant differences were seen in adhesion molecules and interleukin-6 between cases and controls during pregnancy and in the postpartum period, but levels of both were higher in cases. During pregnancy and after delivery, adiponectin decreased in cases and increased in controls. Significant positive correlations were seen between adiponectin and fasting blood glucose levels and vascular cell adhesion molecule-1, and also between leptin and tumor necrosis factor alpha levels.. The results suggest that increased inflammation and transient hyperglycemia during pregnancy would represent a latent form of metabolic syndrome, with an increased risk for type 2 diabetes mellitus and future cardiovascular disease.

Topics: Adiponectin; Adult; Blood Glucose; Cardiovascular Diseases; Case-Control Studies; Cell Adhesion Molecules; Cytokines; Diabetes, Gestational; Disease Susceptibility; Female; Humans; Hyperglycemia; Inflammation; Leptin; Metabolic Syndrome; Postpartum Period; Prediabetic State; Pregnancy; Prospective Studies; Tumor Necrosis Factor-alpha; Young Adult

Topics: Adiponectin; Adult; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Interleukin-6; Leptin; Metabolic Syndrome; MicroRNAs; Obesity; Risk Factors

Eating habits formed during childhood may contribute to the increasing prevalence of cardiometabolic disorders. Assessing nutritional risk in young children may help to prevent later cardiometabolic disease. The objective of this study was to determine whether parent-reported nutritional risk in preschool-aged children was associated with laboratory indices of cardiometabolic risk, namely leptin and insulin.. In this cross-sectional study, the relationship between nutritional risk as determined by the parent-completed NutriSTEP® questionnaire was assessed and compared to the serum leptin and insulin concentrations, hormones involved in regulation of food intake and biomarkers of adiposity and cardiometabolic risk. The community-based primary care research network for children in Toronto, Canada (TARGet Kids!) was used. The participants were children aged 3-5 years recruited from TARGet Kids! A total of 1856 children were recruited from seven primary care practices. Of these, 1086 children completed laboratory testing. Laboratory data for leptin and insulin were available for 714 and 1054 of those individuals, respectively.. The total NutriSTEP® score was significantly associated with serum leptin concentrations (p=0.003); for each unit increase in the total NutriSTEP® score, there was an increase of 0.01 ng/mL (95% confidence interval [CI] 0.004-0.018) in serum leptin concentrations after adjusting for potential confounders. The total NutriSTEP® score was not significantly associated with serum insulin concentration.. Parent reported nutritional risk is associated with serum leptin, but not insulin, concentrations in preschool-aged children. The NutriSTEP® questionnaire may be an effective tool for predicting future cardiometabolic risk in preschool-aged children.

Topics: Cardiovascular Diseases; Child, Preschool; Cross-Sectional Studies; Feeding Behavior; Female; Humans; Insulin; Leptin; Male; Nutritional Status; Risk Assessment; Risk Factors; Surveys and Questionnaires

Predictors of subclinical inflammatory obesity (SIO) can be important tools for early therapeutic interventions in obesity-related comorbidities. Waist circumference (WC) and BMI have different SIO sensitivity. We aimed to i) identify SIO predictors and ii) investigate whether CD16+ monocytes are associated with BMI- (generally) or WC-defined (centrally) obesity.. Anthropometric and metabolic/endocrine (namely catecholamines, adrenaline and noradrenaline) parameters were evaluated, and CD16+ monocytes were studied by flow cytometry in the peripheral blood from 63 blood donors, and compared and correlated to each other. Multiple linear regression analysis was performed to identify variables that best predict SIO.. CD16+ monocyte counts were similar in BMI and WC groups. CD16+ monocytes from centrally obese (CO) showed a more inflammatory pattern, as compared to non-CO subjects. WC was sensitive to lipidemia and, in CO subjects, lipidemia was associated with a more inflammatory phenotype of CD16+ monocytes. These differences were not noticed between BMI groups. Adrenaline was correlated with CD16+ monocyte expansion with a lower inflammatory pattern. Leptin, very low-density lipoprotein cholesterol (VLDL-C), and CD14 expression of CD16+ monocytes were found to be CO predictors.. WC-, but not BMI-defined obesity, was associated with a more inflammatory pattern of CD16+ monocytes, without monocyte expansion, suggesting that a monocyte maturation process rather than an independent arise of CD16+ monocytes occurs in CO. Thus, in a population with low cardiovascular risk, leptin, VLDL-C, and CD14 expression of CD16+ monocytes predict CO, constituting a putative tool for screening of SIO.

Topics: Anthropometry; Antigens, CD; Body Mass Index; Cardiovascular Diseases; Cholesterol, VLDL; Female; GPI-Linked Proteins; Humans; Inflammation; Leptin; Leukocyte Count; Lipopolysaccharide Receptors; Male; Monocytes; Obesity; Receptors, Immunologic; Risk Factors; Waist Circumference

Recent data indicates that adults with Down syndrome (DS) are at increased risk for cardiovascular disease (CVD) that significantly contributes to their morbidity and mortality. Although identification of cardiometabolic risk factors during childhood is desirable to design preventive interventions, the data on such risk factors in children with DS is scarce. The aim of this study was to study the cardiometabolic risk factors such as insulin resistance (IR), leptin and adiponectin concentrations, lipid abnormalities and leptin resistance in non-obese children with DS.. This cross-sectional case control study included karyotype confirmed trisomy-21 DS children aged 2-12 years and their matched healthy controls. After detailed anthropometry, weight, height and body mass index (BMI) standard deviation scores (SDSs) were calculated with reference data. Laboratory evaluation included determination of fasting lipid parameters, insulin, glucose, leptin and adiponectin concentrations. The homeostasis model assessment method (HOMA-IR) was used to assess IR and the ratio of leptin to BMI was used as an index of leptin resistance.. Seventy-seven children (39 with DS and 38 controls) comprised the study cohort. The anthropometric parameters were similar in the two groups. Children with DS showed significantly higher mean leptin concentrations (2.098±1.68 ng/mL vs. 1.44±0.52 ng/mL, p-value: 0.00) and higher indices of leptin resistance (0.127±0.085 vs. 0.09±0.03, p-value: 0.001) as compared to controls. Fasting adiponectin concentrations were lower (20.64±19.87 ng/mL vs. 32.58±34.25 ng/mL, p-value: 0.21) and fasting glucose higher (89.25±8.12 mg/dL vs. 85.71±5.52 mg/dL, p-value: 0.06) in the DS group as compared to the controls but the differences did not reach statistical significance. The concentrations of insulin, various lipid parameters and calculated HOMA-IR values were similar in the two groups. In the DS group, five children were identified to have high (>75th centile) leptin levels and four as impaired fasting glucose as compared to none in the controls.. Alterations of several cardiometabolic risk factors, in particular, leptin concentrations and leptin resistance are present in children with DS. The presence of hyperleptinemia without hyperinsulinemia suggests a probable inherent genetic basis for increased leptin resistance in patients with DS. There is a need for larger studies to further understand increased leptin resistance in DS that may contribute to increased CVD related morbidity and mortality in these patients.

Topics: Adiponectin; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Down Syndrome; Female; Humans; Insulin Resistance; Leptin; Male; Risk Factors

Topics: Adipose Tissue, White; Body Composition; Cardiovascular Diseases; Diabetes Mellitus; Humans; Leptin; Lipolysis; Metabolic Syndrome; Obesity

A number of clinical studies have demonstrated that leptin concentrations are related to the metabolic disturbances that constitute the metabolic syndrome (MetS) and to diabetes mellitus (DM).. To investigate possible determinants of leptin concentrations in a sample of patients at high cardiovascular (CV) risk carrying two or more features of the MetS and to investigate if any difference exist between at risk patients with or without DM.. Serum leptin concentrations were measured in 60 consecutive male patients affected by at least two CV risk factors which belong to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) definition of MetS: 30 patients affected by type 2 DM (T2DM) and 30 nondiabetic patients (non-T2DM). Nineteen healthy subjects were included in the study as a control group (HC).. Leptin was significantly higher in patients carrying two or more features of the MetS compared with HC (P = 0.02). Stratifying MetS patients for DM, we found that leptin level was higher in non-T2DM patients (7.8 ng/ml), intermediate in T2DM (6.2 ng/ml), and lower in HC (4.6 ng/ml). In MetS patients, a positive correlation was found between leptin and waist, triglycerides, and number of MetS criteria. After stratification for T2DM, the correlations were still significant in the non-T2DM but not in the T2DM group.. In our sample of moderate-to-high-risk patients, leptin level is positively associated with waist circumference and triglycerides but only in non-T2DM patients. Our data suggest that diabetic subjects could modulate leptin production in a different way compared with patients carrying other MetS-related anomalies.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors; Triglycerides; Waist Circumference

Adipokines contribute to the inflammatory process which can lead to obesity-associated cardiometabolic complications. Metabolically healthy obese individuals seem to be protected or more resistant to develop these complications and it is intriguing why some individuals develop comorbidities and others do not. Thus, we questioned whether the differences between metabolically healthy and unhealthy obese relied on the alterations in metabolic profile, characterized by serum leptin and adiponectin. A total of 142 obese adults were divided into 2 groups - metabolically healthy obese (MHO) or unhealthy obese (MUO) - and they were evaluated for anthropometric measures, body composition, blood pressure, dietary intakes and plasma levels of leptin and adiponectin. Leptin/adiponectin ratio (L/A) was calculated. Age, BMI and blood pressure were higher in the MUO. No differences in anthropometric measurements, body composition, dietary intake and dietary quality were observed between groups. Leptin were significantly higher in the MUO (53.07 ± 34.56 versus 36.27 ± 24.02 ng/ml in the MHO, r < 0.04). The logistic regression analysis demonstrated that leptin was an important factor associated with not being healthy, independent of age, body weight and BMI. There were no differences between groups for adiponectin and L/A. Leptin correlated positively with body weight (r = 0.25, r < 0.05), BMI (r = 0.38, r < 0.05) and BF (r = 0.74, r < 0.05), and negatively with FFM (r = -0.74, r < 0.05). Our findings suggest that leptin is an important cardiovascular disease marker to obese population and can contribute to evaluate metabolic risks in these individuals.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Female; Humans; Leptin; Logistic Models; Male; Middle Aged; Nutrition Assessment; Obesity; Risk Factors

Healthful dietary patterns have been associated with lower risks of type 2 diabetes and coronary artery disease, but their relations with intermediate markers of cardiometabolic and endocrine health are less established.. We evaluated the Dietary Approaches to Stop Hypertension (DASH), the alternate Mediterranean diet (aMED), and the Alternate Healthy Eating Index (aHEI) diet-quality scores with cardiometabolic and endocrine plasma biomarkers in US women.. The trial was a cross-sectional analysis of 775 healthy women in the Women's Lifestyle Validation Study that was conducted within the NHS (Nurses' Health Study) and NHS II longitudinal cohorts. Multiple linear regression models adjusted for potential confounders were used to estimate associations between quartiles of dietary pattern-adherence scores that were derived from a food-frequency questionnaire and plasma biomarker concentrations that were collected simultaneously.. In multivariable models in which highest and lowest quartiles of dietary pattern scores were compared, 1) DASH was significantly associated with higher concentrations of high-density lipoprotein (9%) and sex-hormone binding globulin (SHBG) (21%), and lower concentrations of leptin (28%), triglycerides (19%), and C-peptide (4%) (all P-trend ≤ 0.04); 2) the aMED was associated with 19% higher SHBG and 16% lower triglycerides (P-trend = 0.02 and 0.003, respectively); and 3) the aHEI was associated with significantly higher concentrations of insulin (16%) and SHBG (19%) and lower concentrations of leptin (18%) (all P-trend ≤ 0.02). Further adjustment for body mass index (BMI) attenuated these associations but remained significant for 1) DASH with leptin and triglycerides and 2) the aMED with triglycerides (all P-trend ≤ 0.03).. Adherence to healthful dietary patterns is associated with favorable concentrations of many cardiometabolic and endocrine biomarkers. These relations are mediated in part by BMI.

Topics: Adiponectin; Aged; Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cholesterol, HDL; Cross-Sectional Studies; Diet, Mediterranean; Female; Folic Acid; Follow-Up Studies; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Metabolic Syndrome; Middle Aged; Receptors, Leptin; Reproducibility of Results; Risk Factors; Sex Hormone-Binding Globulin; Surveys and Questionnaires; Triglycerides; United States

The effects of grape-seed polyphenols against the development of hypertension and other cardiometabolic conditions associated with the metabolic syndrome (MetS) were studied in rats fed a high-fat, high-carbohydrate diet, known as the cafeteria (CAF) diet. Two groups of Wistar rats were fed standard (STD) or CAF diets for 12 weeks. The CAF diet-fed rats were administered different doses of a low-molecular-weight grape-seed polyphenol extract (LM-GSPE) (25, 100 and 200 mg/kg per d) or vehicle daily, and the STD diet-fed rats were administered LM-GSPE (100 mg/kg per d) or vehicle using ten animals per group. Body weight (BW), waist perimeter (WP) and systolic and diastolic blood pressures (BP) by the tail-cuff method were recorded weekly. The animals were housed in metabolic chambers every 2 weeks to estimate daily food and liquid intakes and to collect faeces and urine samples. The plasma lipid profile was analysed at time 0 and on the 4th, 7th, 10th and 12th weeks of the experiment. Moreover, plasma leptin was measured at the end of the experiment. Results demonstrated that LM-GSPE, when administered with the CAF diet, attenuated the increase in BP, BW, WP and improved lipid metabolism in these animals. However, although the 25- and 100-mg/kg per d doses were sufficient to produce beneficial effects on BP and lipid metabolism, a 200-mg/kg per d dose was necessary to have an effect on BW and WP. The present findings suggest that LM-GSPE is a good candidate for a BP-lowering agent that can also ameliorate other conditions associated with the MetS.

Topics: Animals; Blood Pressure; Body Weight; Cardiovascular Diseases; Diet; Grape Seed Extract; Hypertension; Leptin; Lipids; Male; Metabolic Syndrome; Phytotherapy; Polyphenols; Rats, Wistar; Risk Factors; Time Factors; Waist Circumference

Patients with congenital adrenal hyperplasia (CAH) appear to have adverse cardiovascular risk profile and other long-term health problems in adult life, but there are limited data in young CAH patients. We aim to evaluate the cardio-metabolic risk factors in adolescents and young adults with classical 21-hydroxylase deficiency (21-OHD). We performed a cross-sectional study of 21 patients (17 females) with classic CAH detected clinically and not through newborn screening, aged 15.2 ± 5.8 years, and 21 healthy matched controls. Anthropometric, biochemical, inflammatory markers, and body composition using dual-energy X-ray absorptiometry were measured. Obesity was observed in 33% of the CAH patients. The waist/hip ratio and waist/height ratio were significantly higher in CAH patients. Five out of 21 patients (24%) had elevated blood pressure. Silent diabetes was diagnosed in one patient (4.8%), but none in the control group. Serum leptin and interleukin-6 levels were not different between groups, but hs-CRP levels tended to be higher in CAH patients. Other metabolic profiles and body composition were similar in CAH and controls.. Adolescents and young adults with CAH appear to have an increased risk of obesity and cardio-metabolic risk factors. Close monitoring, early identification, and secondary prevention should be implemented during pediatric care to improve the long-term health outcomes in CAH patients. What is Known: • Lifelong glucocorticoid (GC) replacement is the main treatment modality in patients with congenital adrenal hyperplasia which predispose to an adverse metabolic profile. • Adult CAH patients have adverse cardiovascular risk profile and other long-term health problems. What is New: • Adolescents and young adults with CAH appear to have an increased risk of obesity and cardio-metabolic risk factors.

Topics: Adolescent; Adrenal Hyperplasia, Congenital; Body Composition; Cardiovascular Diseases; Case-Control Studies; Child; Cross-Sectional Studies; Female; Humans; Leptin; Male; Metabolic Syndrome; Obesity; Risk Factors; Young Adult

During the transition from premenopause to postmenopause, many women experience weight gain and central fat deposition; therefore, we hypothesized that circulating growth factors can play a role in the pathogenesis of hypertension, metabolic syndrome, and subclinical organ damage in perimenopausal women.. The study included 192 women aged 40 to 60years; 152 had newly diagnosed essential hypertension that had never been treated, and 40 were normotensive age-matched controls. For all subjects, 24-h ambulatory blood pressure monitoring (ABPM), echocardiographic examination with assessment of left ventricular mass (LVM) and systolic and diastolic functions (GE Vivid 7.0, General Electric Vingmed Ultrasound, Horten, Norway), carotid ultrasound with measurement of intima-media thickness, and carotid-femoral pulse wave velocity (PWV) measurement (SphygmoCor, AtCor Medical, Sydney, Australia) were performed. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 2 (IGFBP-2), and insulin-like growth factor-binding protein 3 (IGFBP-3) were measured using an immunochemical assay.. Hypertensive women had significantly lower IGFBP-2 levels than did normotensive controls (162.9±83.7 vs. 273.1±103.0μg/L, p<0.001); the groups did not differ regarding IGF and IGFBP-3 concentrations. After adjusting the covariates, multivariate analysis showed that IGFBP2 was significantly negatively correlated with 24-h systolic blood pressure (β=-0.31, p=0.02). The adjusted odds ratio for hypertension per standard deviation decrease in IGFBP-2 was 3.43 (95% confidence interval [CI] 1.65-7.13). IGFBP-2 showed a negative correlation with the number of metabolic syndrome components. Independent of body composition, IGFBP-2 was significantly related to left ventricular relative wall thickness and the ratio of mitral inflow velocities as parameter of diastolic function.. In perimenopausal women, decreased IGFBP-2 levels may play a role in blood pressure regulation and the development of subclinical left ventricular diastolic dysfunction. Whether IGFBP-2 is a marker or a mediator of cardiovascular disease in this population merits further investigation.

Topics: Adult; Blood Pressure; Cardiovascular Diseases; Carotid Intima-Media Thickness; Echocardiography; Essential Hypertension; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Menopause; Metabolic Diseases; Metabolic Syndrome; Middle Aged; Pulse Wave Analysis; Risk Assessment

We examined the effects of diet quality and dietary patterns in relation to biomarkers of risk including leptin, soluble intracellular adhesion molecule 1 (sICAM-1), C-reactive protein (CRP), and irisin.. We analyzed data from 196 adults cross-sectionally. Dietary patterns were identified by factor analysis and diet quality scores were generated using a validated food-frequency questionnaire.. Both the alternate healthy eating index-2010 (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) scores were negatively related to CRP, even after controlling for body mass index and total energy intake. Similarly, the prudent diet pattern was negatively related to leptin, sICAM-1, and CRP, whereas the Western diet pattern showed positive associations with these markers; however, after adjusting for all confounders, the associations only remained significant for leptin and sICAM-1. Irisin was positively associated with DASH and the prudent diet after controlling for all confounders (standardized β = 0.23, P = 0.030; standardized β = 0.25, P = 0.021, respectively). Irisin showed positive associations with increasing fruit consumption, whereas the levels of irisin decreased as meat consumption increased.. Irisin was directly associated with healthy diet types and patterns. Further studies regarding these mechanisms are warranted. This trial is registered at http://www.clinicaltrials.gov. Identifier: NCT01853332.

Topics: Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Dairy Products; Diet, Healthy; Eggs; Energy Intake; Ethnicity; Female; Fibronectins; Fruit; Humans; Intercellular Adhesion Molecule-1; Leptin; Male; Meat; Metabolic Syndrome; Middle Aged; Nutrition Assessment; Surveys and Questionnaires; Vegetables; Whole Grains

As the earliest atherosclerotic lesions begin during childhood, our aim was to correlate gender-related adiposity to classical cardiovascular risk factors in a group of children.An observational and transversal analysis was carried out in a cohort consisting of 161 children of both sexes, aged 6 to 17 years of age. Waist circumference was correlated to leptin, high-sensitivity C-reactive protein, systolic and diastolic blood pressure, plasma lipids, homeostasis model assessment-insulin resistance, and the left ventricular mass index. After adjusting for age, waist circumference in boys, compared to girls, correlated more strongly and directly to systolic (r = 0.538; p < 0.001) and diastolic blood pressure (ρ = 0.401; p < 0.01), ApoB/ApoA ratio (ρ = 0.515; p < 0.01), high-density lipoprotein cholesterol (r = -0.441; p < 0.001), low-density lipoprotein cholesterol (ρ = 0.280; p < 0.01), triglycerides (ρ = 0.420; p < 0.001), homeostasis model assessment-insulin resistance (ρ = 0.463; p < 0.001), and the left ventricular mass index (ρ = 0.286; p < 0.01). A similar pattern was observed regarding the correlations between leptin, high-sensitivity C-reactive protein, and the above parameters (except between high-sensitivity C-reactive protein and diastolic blood pressure), and also, particularly in boys.. Although increased childhood adiposity is related to a more adverse metabolic and clinical profile in both genders, males appear to have a potentially greater cardiovascular risk.. Obesity is characterized by a chronic low-grade inflammatory process.. Increased adiposity is related to a more pronounced pro-inflammatory response in boys. Childhood male adiposity is a potentially greater cardiovascular risk factor. Arterial hypertension, insulin resistance, and dyslipidemia is more strongly correlated to waist circumference in boys.

Topics: Adiposity; Adolescent; Apolipoproteins; Blood Pressure; Cardiovascular Diseases; Child; Female; Heart Ventricles; Homeostasis; Humans; Insulin Resistance; Leptin; Lipids; Male; Risk Factors; Sex Factors; Waist Circumference

The association between dietary patterns and metabolic cardiovascular risk factors has long been addressed but there is a lack of evidence towards the effects of the overall diet on the complex net of biological inter-relationships between risk factors. This study aimed to derive dietary patterns and examine their associations with metabolic cardiovascular risk factors following a theoretic model for the relationship between them. Participants included 417 adults of both sexes, enrolled to the cross-sectional population-based study performed in Brazil. Body weight, waist circumference, high-sensitivity C-reactive protein, blood pressure, total cholesterol:HDL-cholesterol ratio, TAG:HDL-cholesterol ratio, fasting plasma glucose and serum leptin were evaluated. Food consumption was assessed by two non-consecutive 24-h dietary recalls adjusted for the within-person variation of intake. A total of three dietary patterns were derived by exploratory structural equation modelling: 'Traditional', 'Prudent' and 'Modern'. The 'Traditional' pattern had a negative and direct effect on obesity indicators (serum LEP, body weight and waist circumference) and negative indirect effects on total cholesterol:HDL-cholesterol ratio, TAG:HDL-cholesterol ratio and fasting plasma glucose. The 'Prudent' pattern had a negative and direct effect on systolic blood pressure. No association was observed for the 'Modern' pattern and metabolic risk factors. In conclusion, the 'Traditional' and 'Prudent' dietary patterns were negatively associated with metabolic cardiovascular risk factors among Brazilian adults. Their apparent protective effects against obesity and high blood pressure may be important non-pharmacological strategies for the prevention and control of obesity-related metabolic disorders and CVD.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Brazil; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Feeding Behavior; Female; Humans; Leptin; Lipids; Male; Middle Aged; Models, Biological; Obesity; Risk Factors; Waist Circumference

Obesity is a major risk factor for cardiovascular disease in males and females. Whether obesity triggers cardiovascular disease via similar mechanisms in both the sexes is, however, unknown. In males, the adipokine leptin highly contributes to obesity-related cardiovascular disease by increasing sympathetic activity. Females secrete 3× to 4× more leptin than males, but do not exhibit high sympathetic tone with obesity. Nevertheless, females show inappropriately high aldosterone levels that positively correlate with adiposity and blood pressure (BP). We hypothesized that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in females. Leptin control of the cardiovascular function was analyzed in female mice sensitized to leptin via the deletion of protein tyrosine phosphatase 1b (knockout) and in agouti yellow obese hyperleptinemic mice (Ay). Hypersensitivity to leptin (wild-type, 115 ± 2; protein tyrosine phosphatase 1b knockout, 124 ± 2 mm Hg; P<0.05) and obesity elevated BP (a/a, 113 ± 1; Ay, 128 ± 7 mm Hg; P<0.05) and impaired endothelial function. Chronic leptin receptor antagonism restored BP and endothelial function in protein tyrosine phosphatase 1b knockout and Ay mice. Hypersensitivity to leptin and obesity reduced BP response to ganglionic blockade in both strains and plasma catecholamine levels in protein tyrosine phosphatase 1b knockout mice. Hypersensitivity to leptin and obesity significantly increased plasma aldosterone levels and adrenal CYP11B2 expression. Chronic leptin receptor antagonism reduced aldosterone levels. Furthermore, chronic leptin and mineralocorticoid receptor blockade reduced BP and improved endothelial function in both leptin-sensitized and obese hyperleptinemic female mice. Together, these data demonstrate that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in female mice and suggest that obesity leads to cardiovascular disease via sex-specific mechanisms.

Topics: Aldosterone; Analysis of Variance; Animals; Cardiovascular Diseases; Disease Models, Animal; Endothelium, Vascular; Female; Hypertension; Leptin; Male; Mice; Mice, Knockout; Mice, Obese; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Random Allocation; Renin-Angiotensin System; Sensitivity and Specificity; Sex Factors; Statistics, Nonparametric

Obesity and especially hypertrophy of epicardial adipose tissue accelerate coronary atherogenesis. We aimed at comparing levels of inflammatory and atherogenic hormones from adipose tissue in the pericardial fluid and circulation of cardiovascular disease patients.. Venous plasma (P) and pericardial fluid (PF) were obtained from elective cardiothoracic surgery patients (n = 37). Concentrations of leptin, adipocyte fatty acid-binding protein (A-FABP) and adiponectin (APN) were determined by enzyme-linked immunosorbent assays (ELISA). The median concentration of leptin in PF (4.3 (interquartile range: 2.8-9.1) μg/L) was comparable to that in P (5.9 (2.2-11) μg/L) and these were significantly correlated to most of the same patient characteristics. The concentration of A-FABP was markedly higher (73 (28-124) versus 8.4 (5.2-14) μg/L) and that of APN was markedly lower (2.8 (1.7-4.2) versus 13 (7.2-19) mg/L) in PF compared to P. APN in PF was unlike in P not significantly related to age, body mass index, plasma triglycerides or coronary artery disease. PF levels of APN, but not A-FABP, were related to the size of paracardial adipocytes. PF levels of APN and A-FABP were not related to the immunoreactivity of paracardial adipocytes for these proteins.. In cardiac and vascular disease patients, PF is enriched in A-FABP and poor in APN. This adipokine microenvironment is more likely determined by the heart than by the circulation or paracardial adipose tissue.

Topics: Adipokines; Adiponectin; Adipose Tissue; Aged; Cardiovascular Diseases; Fatty Acid-Binding Proteins; Female; Humans; Leptin; Male; Pericardial Fluid; Pericardium

Visceral adipose tissue (VAT) and fatty liver differ in their associations with cardiovascular risk compared with subcutaneous adipose tissue (SAT). Several biomarkers have been linked to metabolic derangements and may contribute to the pathogenicity of fat depots. We examined the association between fat depots on multidetector computed tomography and metabolic regulatory biomarkers.. Participants from the Framingham Heart Study (n=1583, 47% women) underwent assessment of SAT, VAT, and liver attenuation. We measured circulating biomarkers secreted by adipose tissue or liver (adiponectin, leptin, leptin receptor, fatty acid binding protein 4, fetuin-A, and retinol binding protein 4). Using multivariable linear regression models, we examined relations of fat depots with biomarkers. Higher levels of fat depots were positively associated with leptin and fatty acid binding protein 4 but negatively associated with adiponectin (all P<0.001). Associations with leptin receptor, fetuin-A, and retinol binding protein 4 varied according to fat depot type or sex. When comparing the associations of SAT and VAT with biomarkers, VAT was the stronger correlate of adiponectin (β=-0.28 [women]; β=-0.30 [men]; both P<0.001), whereas SAT was the stronger correlate of leptin (β=0.62 [women]; β=0.49 [men]; both P<0.001; P<0.001 for comparing VAT versus SAT). Although fetuin-A and retinol binding protein 4 are secreted by the liver in addition to adipose tissue, associations of liver attenuation with these biomarkers was not stronger than that of SAT or VAT.. SAT, VAT, and liver attenuation are associated with metabolic regulatory biomarkers with differences in the associations by fat depot type and sex. These findings support the possibility of biological differences between fat depots.

Topics: Adiponectin; Adipose Tissue; Adult; Alanine Transaminase; alpha-2-HS-Glycoprotein; Aspartate Aminotransferases; Biomarkers; Cardiovascular Diseases; Cohort Studies; Fatty Acid-Binding Proteins; Female; Humans; Intra-Abdominal Fat; Leptin; Linear Models; Liver; Male; Middle Aged; Multidetector Computed Tomography; Multivariate Analysis; Receptors, Leptin; Retinol-Binding Proteins, Plasma; Subcutaneous Fat

Low birthweight (LBW) increases the risk of developing cardiovascular diseases (CVD). Few studies have established its impact at early ages.. To study endothelial function (EF) and arterial stiffness (AS) and their relationship to early markers of CVD risk in children with LBW.. In children with LBW (4-6 years; n = 53), anthropometric, haemodynamic and laboratory parameters, including HOMA-IR, hs-CRP, adiponectin and leptin, were determined. EF and AS were evaluated by digital pulse plethysmography. Data were compared with a control group (n = 33).. In both groups, anthropometric parameters remained within normal limits. Insulin and HOMA-IR had normal values, but they were significantly augmented in LBW children. LBW children showed higher leptin and hs-CRP levels than the control group. The LBW group had decreased EF (37.5 ± 5.6%) compared with the control group (75.0 ± 11.9%; p < 0.01), however without differences in AS. In LBW children, EF was negatively correlated with waist circumference, leptin, hs-CRP and with a cumulative score of risk factors.. LBW children display altered EF that is related to early changes in CVD risk factors. The differences found in the metabolic parameters might indicate a pro-inflammatory state. This hypothesis is also supported by the laboratory findings and the correlation between EF and the number of CVD risk factors, suggesting that very early lifestyle interventions may be needed.

Topics: C-Reactive Protein; Cardiovascular Diseases; Child; Child, Preschool; Endothelium, Vascular; Female; Follow-Up Studies; Hemodynamics; Humans; Infant, Low Birth Weight; Leptin; Male; Risk Factors; Vascular Stiffness

Excess body weight leads to a variety of metabolic changes and increases the risk for cardiovascular diseases (CVD) in adulthood. The objective of this study was to investigate the presence of risk markers for CVD among Brazilian adolescents of normal weight and with excess body weight. The markers included blood pressure, C-reactive protein, homocysteine, tumor necrosis factor alpha, fibrinogen, fasting insulin and glucose, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triglycerides. We calculated odds ratios (OR) using logistic regression and adjusted for potential confounders such as age, sex, physical activity, and socioeconomic background. Compared with normal weight subjects, overweight/obese adolescents were more likely to have higher systolic blood pressure (OR = 3.49, p < 0.001), fasting insulin (OR = 8.03, p < 0.001), HOMA-IR (OR = 8.03, p < 0.001), leptin (OR = 5.55, p < 0.001), and LDL-c (OR = 5.50, p < 0.001) and lower serum HDL-c concentrations (OR = 2.76, p = 0.004). After adjustment for confounders, the estimates did not change substantially, except for leptin for which the risk associated with overweight increased to 11.09 (95% CI: 4.05-30.35). In conclusion, excess body weight in adolescents exhibits strong associations with several markers that are established as causes of CVD in adults. This observation stresses the importance of primary prevention and of maintaining a healthy body weight throughout adolescence to reduce the global burden of CVD.

Topics: Adolescent; Biomarkers; Blood Glucose; Blood Pressure; Body Weight; Brazil; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Exercise; Female; Fibrinogen; Homocysteine; Humans; Insulin; Insulin Resistance; Leptin; Logistic Models; Male; Metabolic Syndrome; Overweight; Risk Factors; Socioeconomic Factors; Triglycerides; Tumor Necrosis Factor-alpha

Fatigue induced by complex dysfunctions of the central nervous system is frequently complained by patients with cardiovascular risk factors. Although leptin is considered to regulate the central nervous system, there are no reports regarding its association with fatigue in those patients. This cross-sectional study included 347 patients with cardiovascular risk factors. Fatigue score and plasma leptin concentration were measured. In addition, abdominal fat accumulation, systemic inflammation, sleep condition, and functions of hypothalamus-pituitary axis and autonomic system were estimated. Plasma leptin concentration (natural logarithm transformed) was significantly and positively (r=0.222, p<0.001) associated with fatigue score, and significantly (p<0.001) higher in the moderately-fatigued group (2.32±0.75ng/ml, mean±SD, n=52) than in the normally-fatigued group (1.85±1.02ng/ml, mean±SD, n=295). Multiple logistic regression analysis showed that plasma leptin concentration was significantly and independently associated with a moderately-fatigued condition independent of other factors, including age, gender, presence of diabetes, hypertension, dyslipidemia, alcohol consumption habit, urinary free cortisol, serum high-sensitive CRP concentration, visceral and subcutaneous fat area, apnea/hypopnea index, sleep efficiency, and heart rate variability. Hyperleptinemia may contribute to fatigue severity in patients with cardiovascular risk factors.

Topics: Adult; Aged; Cardiovascular Diseases; Cross-Sectional Studies; Fatigue; Female; Humans; Japan; Leptin; Male; Middle Aged; Risk Factors; Severity of Illness Index

Individuals with insulin resistance (IR) are at greater risk for cardiovascular disease (CVD). Psychological stress may contribute to develop CVD in IR, although mechanisms are poorly understood. Our aim was to test the hypothesis that individuals with IR have enhanced emotional and physiological responses to acute psychological stress, leading to increased CVD risk. Sixty participants were enrolled into the study, and classified into IR group (n = 31) and insulin sensitive group (n = 29) according to the Quantitative insulin sensitivity check index, which was calculated based on an oral glucose tolerance test. The Trier social stress test, a standardized experimental stress paradigm, was performed on each participant, and emotional and physiological responses were examined. Blood was collected from each subject for insulin, cytokines, and cortisol measurements. Compared with the insulin-sensitive group, individuals with IR had significantly lower ratings of energy and calm, but higher fatigue levels in response to acute stressors. Individuals with IR also showed blunted heart rate reactivity following stress. In addition, the IR status was worsened by acute psychological stress as demonstrated by further increased insulin secretion. Furthermore, individuals with IR showed significantly increased levels of leptin and interleukin-6, but decreased levels of adiponectin, at baseline, stress test, and post-stress period. Our findings in individuals with IR under acute stress would allow a better understanding of the risks for developing CVD and to tailor the interventions for better outcomes.

Topics: Adiponectin; Adult; Cardiovascular Diseases; Cytokines; Fatigue; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Risk Factors; Social Environment; Stress, Psychological

This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population.. A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m² and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m²) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer.. Vitamin B12 was negatively associated with TNF-α (r = -0.14, p < 0.05), insulin (r = -0.230, p < 0.01) and HOMA-IR (r = -0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = -0.160, p < 0.01), insulin (r = -0.248, p < 0.01), HOMA-IR (r = -0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = -0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r² = -0.17, p < 0.05) and in children (r² = -0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r² = -0.78, p < 0.05).. Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population.

Topics: Adiponectin; Adolescent; Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Humans; Inflammation; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Resistin; Risk Factors; Saudi Arabia; Tumor Necrosis Factor-alpha; Vitamin B 12; Waist Circumference

What is the central question of this study? This study addresses the relative impact of obesity and intermittent hypoxia in the pathophysiological process of obstructive sleep apnoea by investigating the metabolic, inflammatory and cardiovascular consequences of intermittent hypoxia in lean and obese Zucker rats. What is the main finding and its importance? We found that obesity and intermittent hypoxia have mainly distinct consequences on the investigated inflammatory and cardiometabolic parameters in Zucker rats. This suggests that, for a given severity of sleep apnea, the association of obesity and obstructive sleep apnoea may not necessarily be deleterious. Obstructive sleep apnoea is associated with obesity with a high prevalence, and both co-morbidities are independent cardiovascular risk factors. Intermittent hypoxia (IH) is thought to be the main factor responsible for the obstructive sleep apnoea-related cardiometabolic alterations. The aim of this study was to assess the respective impact of obesity and IH on the inflammatory and cardiometabolic state in rats. Lean and obese Zucker rats were exposed to normoxia or chronic IH, and we assessed metabolic and inflammatory parameters, such as plasma lipids and glucose, serum leptin and adiponectin, liver cytokines, nuclear factor-κB activity and cardiac endothelin-1 levels. Myocardial infarct size was also evaluated following in vitro ischaemia-reperfusion. Circulating lipids, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin and adiponectin levels were higher in obese versus lean rats. Chronic IH did not have a significant impact on metabolic parameters in lean rats. In obese rats, IH increased glycaemia and HOMA-IR. Liver interleukin-6 and tumour necrosis factor-α levels were elevated in lean rats exposed to IH; obesity prevented the increase in interleukin-6 but not in tumour necrosis factor-α. Finally, IH exposure enhanced myocardial sensitivity to infarction in both lean and obese rats and increased cardiac endothelin-1 in lean but not obese rats. In conclusion, this study shows that the dyslipidaemia and insulin resistance induced by obesity of genetic origin does not enhance the deleterious cardiovascular response to IH and may even partly protect against IH-induced inflammation.

Topics: Adiponectin; Animals; Blood Glucose; Cardiovascular Diseases; Cytokines; Disease Models, Animal; Endothelin-1; Hypoxia; Inflammation; Insulin; Interleukin-6; Leptin; Lipids; Liver; Male; Myocardium; NF-kappa B; Obesity; Rats; Rats, Zucker; Tumor Necrosis Factor-alpha

Traditional evaluations of metabolic health may overlook underlying dysfunction in individuals who show no signs of insulin resistance or dyslipidemia. The purpose of this study was to characterize metabolic health in overweight and obese adults using traditional and non-traditional cardiometabolic variables. A secondary purpose was to evaluate differences between overweight/obese and male/female cohorts, respectively.. Forty-nine overweight and obese adults (Mean ± SD; Age = 35.0 ± 8.9 yrs; Body mass index = 33.6 ± 5.2 kg·m. The prevalence of individuals with two or more cardiometabolic risk factors increased from 13%, using traditional risk factors (GLUC, TRG, HDL), to 80% when non-traditional metabolic factors (VAT, LM, RMR, RER, TC, LDL, HOMA-IR) were considered. Between overweight/obese, there were no significant differences in %fat (p = 0.152), VAT (p = 0.959), RER (p = 0.493), lipids/GLUC (p > 0.05), insulin (p = 0.143), leptin (p = 0.053), or cortisol (p = 0.063); obese had higher FM, LM, RMR, and estradiol (p < 0.01). Males had greater LM, RMR, and TRG (p < 0.01); females had greater %fat, and leptin (p < 0.001). There were no significant sex differences in RER, estradiol, insulin, or cortisol (p > 0.05).. Evaluating metabolic health beyond BMI and traditional cardiometabolic risk factors can give significant insights into metabolic status. Due to high variability in metabolic health in overweight and obese adults and inherent sex differences, implementation of body composition and visceral fat measures in the clinical setting can improve early identification and approaches to disease prevention.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Composition; Body Mass Index; Calorimetry, Indirect; Cardiovascular Diseases; Estradiol; Female; Hormones; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipids; Male; Obesity; Overweight; Risk Factors; Sex Factors

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with chronic kidney disease (CKD) including kidney transplant recipients (KTR). Secondary lipid metabolism disorders, endothelial dysfunction, and inflammation enhance the risk of CVD development in these patients. The aim of the present study was to investigate the lipid profile, adiponectin, leptin, nitric oxide (NO), and high sensitivity C-reactive protein (hs-CRP) levels in KTR and to compare these parameters with those of the patients with chronic renal failure (CRF), hemodialysis (HD) patients, and healthy controls.. Serum adiponectin and leptin levels were measured by radioimmunoassay; hs-CRP was determined immunoturbidimetrically. Determination of NO was based on the Griess reaction.. Compared with the control group, serum NO and adiponectin levels were significantly higher in the KTR, CRF, and HD groups; hs-CRP levels were significantly higher in the KTR and HD groups; leptin levels were significantly higher in the KTR. In addition, serum NO level was significantly higher in the KTR compared to CRF cases. Adiponectin correlated positively with high density lipoprotein-cholesterol in the control and patient groups. A positive correlation was observed between hs-CRP and NO in the KTR and the patients with CRF. Serum adiponectin levels were inversely correlated with hs-CRP and leptin in the HD group.. KTR suffer from inflammation and accompanying changes in levels of adipocytokines and NO which contribute to the increased risk of CVD in these patients.

Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Inflammation; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Middle Aged; Nitric Oxide; Renal Dialysis; Transplant Recipients; Turkey

Obesity is an important health problem worldwide and many studies have suggested a relationship between obesity and thyroid function, with controversial results. Interestingly, high TSH levels have been involved with the presence of inflammatory state and risk for developing cardiovascular diseases in hypothyroid and obese patients. The aim in this work was to determine the prevalence of hypothyroidism in patients with extreme obesity and to determine whether their TSH levels were related to increased serum levels of inflammatory and cardiovascular markers.. A cross-sectional study in 101 patients with extreme obesity (BMI ≥40) was performed. Anthropometric (weight, height and waist circumference) and biochemical (fasting glucose, glycosylated hemoglobin, triglycerides, total cholesterol, LDL-C, HDL-C and insulin) parameters were measured. TSH and FT4 levels as well as clinical exploration for diagnosis of hypothyroidism were carried out. Serum concentration of IL-10, IL-6, adiponectin, resistin, leptin, ICAM-1, VCAM-1 and E-selectin were determined.. A high prevalence for diabetes (37.6%), prediabetes (50.5%), dyslipidemia (74.3%), hypertension (61.4%) and hypothyroidism (48.5%) was observed in patients with extreme obesity. The presence of hypothyroidism increased serum concentration of proinflammatory cytokines IL-6 and leptin and decreased the antiinflammatory cytokine adiponectin. In addition, serum TSH levels showed a correlation for waist circumference, weight, BMI, A1c, insulin, IL-6, leptin, ICAM-1 and E-selectin.. There is a high prevalence for hypothyroidism in patients with extreme obesity. High levels of TSH contribute to elevate proinflammatory and cardiovascular risk markers, increasing the risk for development of cardiovascular diseases.

Topics: Adiponectin; Adult; Biomarkers; Body Weight; Cardiovascular Diseases; Cross-Sectional Studies; E-Selectin; Female; Humans; Hypothyroidism; Inflammation; Insulin; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-6; Leptin; Male; Middle Aged; Obesity, Morbid; Prevalence; Resistin; Risk Factors; Thyrotropin; Triglycerides; Vascular Cell Adhesion Molecule-1; Waist Circumference

Studies of the glucagon-like peptide 1 (GLP-1) receptor have been directed at identifying polymorphisms in the GLP-1 receptor gene that may be a contributing factor in the pathogenesis of diabetes mellitus and cardiovascular risk factors. Nevertheless, the role of GLP-1 variants on body weight, cardiovascular risk factors, and adipokines remains unclear in obese patients.. Our aim was to analyze the effects of rs6923761 GLP-1 receptor polymorphism on body weight, cardiovascular risk factors, and serum adipokine levels in nondiabetic obese females.. A sample of 645 obese nondiabetic Caucasian females was enrolled in a prospective way. Basal fasting glucose, c-reactive protein (CRP), insulin, insulin resistance (homeostasis model assessment (HOMA)), total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides concentration, and adipokines were measured. Weights, body mass index (BMI), waist circumference, fat mass by bioimpedance, and blood pressure measures were measured.. Three hundred and twenty-seven participants (50.7%) had the genotype GG and 318 (49.3%) study subjects had the next genotypes; GA (270 study subjects, 41.9%) or AA (48 study subjects, 7.4%) (second group). In wild group (GG genotype), BMI (1.8 ± 2.3 kg/m(2) ; P < 0.05), weight (3.1 ± 1.3 kg; P < 0.05), fat mass (2.4 ± 1.1 kg; P < 0.05), waist circumference (2.7 ± 1.9 cm; P < 0.05), triglyceride levels (10.4 ± 5.3 mg/dl; P < 0.05), interleukin 6 (IL-6) (1.5 ± 0.9 ng/dl; P < 0.05), resistin (1.1 ± 0.3 ng/dl; P < 0.05), and leptin (30.1 ± 10.3 ng/dl; P < 0.05) levels were higher than mutant group (GA + AA).. Data from our study revealed an association with decreased metabolic and cardiovascular markers in obese females. BMI weight, fat mass, waist circumference, triglycerides, leptin, resistin, and IL-6 serum levels were lower in subjects with A allele than non-A allele subjects.

Topics: Adipokines; Adult; Body Composition; Body Mass Index; Body Weight; Cardiovascular Diseases; Female; Genotype; Glucagon-Like Peptide-1 Receptor; Humans; Interleukin-6; Leptin; Middle Aged; Obesity; Polymorphism, Genetic; Prospective Studies; Receptors, Glucagon; Resistin; Risk Factors; Triglycerides; Waist Circumference; White People

Human obesity is characterized by high levels of leptin, and leptin levels may change with weight loss and dietary restriction. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on cardiovascular risk factors, weight loss, and serum leptin levels to a high polyunsaturated fatty acid (PUFA) hypocaloric diet in obese patients.. A sample of 132 obese patients was analyzed in a prospective way with a dietary intervention. The enriched PUFAs hypocaloric intervention consisted in a diet of 1,459 kcal, 45.7% of carbohydrates, 34.4% of lipids, and 19.9% of proteins.. In wild-type group, BMI (-1.9 ± 1.4 kg/m(2) ), weight (-4.4 ± 3.2 kg), fat mass (-4.2 ± 3.8 kg), waist circumference (-4.1 ± 3.1 cm), systolic blood pressure (-7.0 ± 12.1 mmHg), diastolic blood pressure (-3.9 ± 6.8 mmHg), insulin (-1.8 ± 5.6 MUI/l) and HOMA-IR (-0.5 ± 1.5 Units) decreased. In mutant genotype group, BMI (-2.0 ± 2.1 kg/m(2) ), weight (-3.6 ± 4.1 kg), waist circumference (-3.1 ± 4.1 cm), total cholesterol (-25.2 ± 19.6 mg/dl), LDL cholesterol (-16.6 ± 25.6 mg/dl), and tryglicerides (-26.6 ± 39.1 mg/dl) decreased. Only leptin levels have a significant decrease in wild genotype group (-6.6 ± 10.2 ng/ml) (25.1%).. Carriers of ASn656 allele have a different response than wild-type obese, with a lack of decrease in insulin levels, leptin levels, and HOMA-IR. However, obese patients with this mutant allele have a better lipid profile after weight loss.

Topics: Adipokines; Body Mass Index; Cardiovascular Diseases; Diet, Reducing; Female; Follow-Up Studies; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Polymorphism, Genetic; Prognosis; Prospective Studies; Receptors, Leptin; Risk Factors

This study aimed to evaluate the associated cardiovascular risk in Egyptian healthy consumers of different types of combined oral contraceptives pills (COCPs) via determination of lipids profiles, Castelli index I, leptin, adiponectin, and resistin concentrations as cardiovascular risk factors. In this cross-sectional study, the study groups consisted of control group that represented by 30 healthy married women who were not on any contraceptive mean or any hormonal therapy and had normal menstrual cycles, group two consisted of 30 women who were users of Levonorgesterl 0.15 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, group three consisted of 30 women who were users of Gestodene 0.075 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, and group four consisted of 30 women who were users of Drospirenone 3 mg plus Ethinylestradiol 0.03 mg as 21 days cycle. One-way analysis of variance followed by LSD post hoc test was used for comparison of variables. P value <0.05 was considered to be significant. The comparison of the studied groups revealed that COCPs containing levonorgestrel plus ethinylestradiol resulted in significantly lower adiponectin level, and significantly higher leptin and resistin levels with more atherogenic lipid profile presented by significantly higher LDL-C, significantly lower HDL-C concentrations, and significantly higher atherogenic index. Formulation containing ethinylestradiol combined with gestodene neither altered adipose tissue function nor showed deleterious effect on lipid panel. Formulation containing ethinylestradiol combined with drospirenone resulted in significantly higher HDL-C and adiponectin concentrations. In conclusion, the uptake of COCPs containing levonorgestrel plus ethinylestradiol is associated with high cardiovascular risk since this formulation showed significantly lower adiponectin concentration, significantly higher leptin, resistin, and atherogenic index as compared to other studied groups. By contrast, the formulations containing ethinylestradiol combined with third generation progestin gestodene or fourth generation progestin drospirenone are associated with low cardiovascular risk since they neither altered adipose tissue function nor impaired lipoprotein metabolism as experienced by their favorable effect on leptin, adiponectin, and resistin, with non-changed atherogenic index, higher HDL-C levels and lower LDL-C levels as compared to levonorgestrel plus ethinylestradiol formulation.

Topics: Adiponectin; Adipose Tissue; Adult; Androstenes; Anthropometry; Cardiovascular Diseases; Chemistry, Pharmaceutical; Cholesterol, HDL; Cholesterol, LDL; Contraceptives, Oral, Combined; Cross-Sectional Studies; Drug Combinations; Egypt; Ethinyl Estradiol; Female; Humans; Leptin; Levonorgestrel; Norpregnenes; Resistin; Risk Factors

Higher serum leptin levels have been associated with a modestly higher incidence of cardiovascular disease in studies involving mostly Caucasian men. We aimed to assess the hypothesis that higher baseline levels of serum leptin are associated with higher risk of future cardiovascular disease in a diverse cohort.. The Multi-Ethnic Study of Atherosclerosis (MESA) is a modern, community-based, ethnically-diverse, and sex-balanced prospective cohort study of US adults free from cardiovascular disease. Serum leptin was measured in an ancillary study in 2002-2005. This analysis included 1905 MESA participants with baseline leptin and incident cardiovascular event data. Leptin levels were modeled as a log-transformed continuous variable and multivariable-adjusted Cox regression was performed for the primary outcome of hard cardiovascular disease, including coronary heart disease and stroke.. The median follow-up was 7.6 years (25th-75th 7.1-8.3) with 7051 and 6738 person-years of follow-up in women and men. A hard cardiovascular disease event occurred in 47 women and 63 men. The age- and ethnicity-adjusted hazard ratio estimates for a 1 standard deviation increase in ln(leptin) were 1.16 in women (95% CI 0.78-1.73, p = 0.46) and 0.91 (95% CI 0.69-1.20, p = 0.51) in men. Pooling sexes, and adjusting for sex in addition to age and ethnicity, estimates were 0.98 (95% CI 0.78-1.23, p = 0.89). With additional adjustment for cardiovascular risk factors, the results remained nonsignificant: 0.87 (95% CI 0.68-1.11, p = 0.26).. In conclusion, in a modern, US prospective cohort study of multi-ethnic women and men of multi-ethnic backgrounds, leptin levels are not associated with incident cardiovascular events.

Topics: Aged; Anthropometry; Atherosclerosis; Cardiovascular Diseases; Cohort Studies; Ethnicity; Female; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Research Design; Risk Factors; Sex Factors; United States

Estimate leptin reference values and calculate leptinemia cutoff values for identifying cardiometabolic abnormalities in Spain.. Cross-sectional study carried out between 2008 and 2010 in 11 540 individuals representing the Spanish population aged ≥ 18 years. Data were obtained by standardized physical examination and analyses were performed at a central laboratory. Leptinemia was measured using ELISA. Cardiometabolic abnormality was defined as the presence of at least two of the following: high blood pressure, high triglycerides, reduced high density lipoprotein cholesterol, high insulin resistance values, and elevated C-reactive protein and glucose.. Leptin values were higher in women than men (geometric mean, 21.9 and 6.6 ng/mL; P<.001). The median [interquartile range] was 24.5 [14.1-37.0] ng/mL in women, and 7.2 [3.3-14.3] ng/mL in men. In the multivariate analysis, leptin was significantly associated with anthropometric measures, insulin, and C-reactive protein, and inversely associated with age, smoking, and physical activity in women (r(2)=0.53; P<.001) and in men (r(2)=0.61; P<.001). The leptin values that identified cardiometabolic abnormality were 23.75 ng/mL in women (area under the curve, 0.722; sensitivity, 72.3%; specificity, 58.7%) and 6.45 ng/mL in men (area under the curve, 0.716; sensitivity, 71.4%; specificity, 60.2%).. These results facilitate the interpretation of leptin values in clinical and population studies. Leptin has moderate sensitivity and specificity for identifying cardiometabolic abnormalities.

Topics: Adolescent; Adult; Cardiovascular Diseases; Cross-Sectional Studies; Exercise; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Morbidity; Obesity; Reference Values; Retrospective Studies; Risk Factors; Spain; Young Adult

Our purpose was to analyse if catecholamine responses to exercise would be different in Down syndrome (DS) with or without chronotropic incompetence.. Twenty five men with DS (mean age 22.2 ± 3.2) and twenty six controls (CONT, mean age 22.5 ± 1.4) participated in the study, and are divided into 3 groups: CONT, DS with chronotropic incompetence (DS+) and DS without chronotropic incompetence (DS-). During two treadmill incremental tests, blood samples were collected for the determination of hormonal and metabolic variables.. Ten out of 25 DS had chronotropic incompetence whereas no CONT. At rest, compared to CONT, despite similar physical activity, DS with chronotropic incompetence had significantly higher subcutaneous fat mass (p<0.001), lower epinephrine concentration (p<0.01), and higher leptin (p<0.01) and insulin concentrations (p<0.05). At peak exercise, all DS had lower heart rate, oxygen uptake and blood lactate concentrations than controls (p<0.001). During a 'Submaximal incremental test', DS with chronotropic incompetence had lower HR and lactate values (p<0.001) compared to CONT and DS without chronotropic incompetence (p<0.01). They also had blunted epinephrine and impaired norepinephrine responses to exercise compared to DS without chronotropic incompetence and CONT (p<0.01 and p<0.05 respectively).. Our results indicate that catecholamine adaptations to exercise are not adequate in DS+ and are associated with exercise intolerance. Thus, this endocrine profile at rest and during exercise may limit endurance performance of DS.

Topics: Cardiovascular Diseases; Down Syndrome; Epinephrine; Exercise; Exercise Test; Heart Rate; Humans; Insulin; Lactic Acid; Leptin; Male; Norepinephrine; Oxygen Consumption; Subcutaneous Fat; Young Adult

There is growing evidence that early development of obesity increases cardiovascular risk later in life, but less is known about whether there are effects of long-term excess body weight on the biological drivers associated with the atherosclerotic pathway, particularly adipokines, inflammatory and endothelial markers. This paper therefore investigates the influence of overweight across the life course on levels of these markers at retirement age.. Data from the Medical Research Council National Survey of Health and Development (n=1784) were used to examine the associations between overweight status at 2, 4, 6, 7, 11, 15, 20, 26, 36, 43, 53 and 60-64 years (body mass index (BMI)⩾25 kg m(-2) for adult ages and gender-specific cut-points for childhood ages equivalent to BMI⩾25 kg m(-2)) and measurements of adipokines (leptin and adiponectin), inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6)) and endothelial markers (E-selectin, tissue plasminogen activator (t-PA) and von Willebrand factor) at 60-64 years. In addition, the fit of different life course models (sensitive periods/accumulation) were compared using partial F-tests.. In age- and sex-adjusted models, overweight at 11 years and onwards was associated with higher leptin, CRP and IL-6 and lower adiponectin; overweight at 15 years and onwards was associated with higher E-selectin and t-PA. Associations between overweight at all ages earlier than 60-64 with leptin, adiponectin, CRP and IL-6 were reduced but remained apparent after adjustment for overweight at 60-64 years; whereas those with E-selectin and t-PA were entirely explained. An accumulation model best described the associations between overweight across the life course with adipokines and inflammatory markers, whereas for the endothelial markers, the sensitive period model for 60-64 years provided a slightly better fit than the accumulation model.. Overweight across the life course has a cumulative influence on adipokines, inflammatory and possibly endothelial markers. Avoidance of overweight from adolescence onwards is likely important for cardiovascular disease prevention.

Topics: Adiponectin; Adolescent; Adult; Age of Onset; Aging; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Child; Child, Preschool; Diabetes Mellitus, Type 2; E-Selectin; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Risk Factors; United Kingdom; von Willebrand Factor

At elevated concentrations, circulating leptin has been associated with metabolic disturbances, namely insulin resistance, elevated blood pressure, inflammation, and endothelial dysfunction. Because women have higher leptin concentrations than men, it is possible that the effects of leptin on the metabolic profile are different between the sexes. The aim of this study was to investigate whether leptin is one of the key hormones to sex affect differences in the pathophysiology of cardiometabolic risk.. Participants were 178 men and 284 women (average age: 53.9 y), evaluated in a cross-sectional, population-based study performed in Brazil. A structural equation model was used to test a theoretic pathway for the relationship between serum leptin, obesity indicators (body weight and waist circumference), and cardiometabolic risk factors (high-sensitivity C-reactive protein; blood pressure; atherogenic dyslipidemia-total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio and triacylglycerol /HDL-C ratio; and fasting plasma glucose) stratified by sex.. In men, increasing 1 SD in serum leptin predicted an increase in 0.731 SD in body weight and in 0.123 SD in C-reactive protein. Serum leptin had positive and significant indirect effects on men's ratios of total cholesterol to HDL-C (β = 0.215) and triacylglycerol to HDL-C (β = 0.209), as well as fasting glucose (β = 0.173). In women, serum leptin predicted an increase of 0.675 SD in body weight and had positive indirect effects on all cardiometabolic risk factors evaluated.. Serum leptin was indirectly related to cardiometabolic risk factors and its relation was modest and different between sexes. The effects of leptin through mediation of body weight and waist circumference highlight the importance of weight control to prevent cardiometabolic disorders in middle-aged adults.

Topics: Aged; Biomarkers; Blood Glucose; Body Weight; Brazil; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cross-Sectional Studies; Female; Humans; Leptin; Lipids; Male; Middle Aged; Obesity; Sex Factors; Triglycerides

The identification of genetic, early childhood and lifestyle factors related to cardiometabolic risk factors in childhood is important for the development of preventive strategies against cardiovascular diseases. Intrafamilial associations of cardiometabolic risk factors are rarely studied and the few existing results are inconsistent.. To study the relationship of cardiometabolic risk factors in parent-offspring pairs (trios) of the prospective Ulm Birth Cohort Study (UBCS).. At the 8-yr follow-up examination of the UBCS weights, heights, waist circumferences (WC), systolic (sysBP) and diastolic blood pressure (diasBP) of n=304 8 yrs old children and their parents were measured. Fasting plasma samples were collected and concentrations of insulin, glucose, retinol-binding-protein 4 (RBP4), adiponectin, leptin, apolipoprotein A and B (ApoA, ApoB) were analyzed.. BMI values and WC were stronger related in father-offspring than in mother-offspring pairs. Adjustment for potential confounders did not change these results. Fasting plasma concentrations of insulin, glucose, RBP4, ApoB, sysBP and diastBP were stronger correlated in mother-offspring than in father-offspring pairs also after adjusting for potential confounders. Offsprings of fathers that have ≥3 cardiometabolic risk factors had 0.74 kg/m2 higher BMI values and 2.34 cm higher WC compared to offsprings of the reference group (both parents having <3 cardiometabolic risk factors). There was a trend for higher fasting plasma insulin concentrations in offsprings where the mother had ≥3 cardiometabolic risk factors compared to offsprings of the reference group.. These results might be explained by gender-specific genetic factors as well as by early life programming.

Topics: Adiponectin; Adult; Age Factors; Apolipoprotein B-100; Apolipoproteins A; Biomarkers; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Child; Fathers; Follow-Up Studies; Genetic Predisposition to Disease; Germany; Heredity; Humans; Insulin; Leptin; Life Style; Metabolic Diseases; Middle Aged; Mothers; Pedigree; Phenotype; Prognosis; Prospective Studies; Retinol-Binding Proteins, Plasma; Risk Factors; Sex Factors; Time Factors; Waist Circumference

Polyphenols from fruits have been implied in the prevention of risk factors for cardiometabolic disorders and cardiovascular disease. The purpose of this study was to investigate if the consumption of peach and plum juice has a protective effect against obesity and metabolic disorders that promote the development of cardiovascular diseases. Obese Zucker and lean rats were fed with peach, plum juice ad libitum or placebo. Body weight gain, biochemical markers and molecular markers for inflammation and cardiovascular disease in heart tissue were quantified. Results show that peach and plum juice consumption protected against a combination of obesity-induced metabolic disorders including hyperglycemia, insulin and leptin resistance, dyslipidemia and low-density lipoprotein oxidation. This was accompanied by a decreased expression of pro-atherogenic and pro-inflammatory biomarkers in plasma and heart tissues including intercellular cell adhesion molecule-1, monocyte chemotactic protein-1, NF-κB and foam cell adherence to aortic arches. In addition, peach and plum juice consumption decreased the levels of angiotensin II in plasma and its receptor Agtr1 in heart tissues, suggesting a role of peach and plum polyphenols as peroxisome proliferator-activated receptor-γ agonists. Furthermore, only plum juice significantly prevented body weight gain and increased the ratio high-density lipoprotein cholesterol/total cholesterol in plasma. This effect is most likely attributed to the plum's higher content of polyphenols (three times that of peach). Altogether, these results imply that cardioprotective effects can be achieved by replacing drinks high in sugar content with fruit juice rich in polyphenols in a diet.

Topics: Angiotensin II; Animals; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Fruit and Vegetable Juices; Insulin; Intercellular Adhesion Molecule-1; Leptin; Male; Metabolic Syndrome; NF-kappa B; Obesity; Polyphenols; PPAR gamma; Prunus domestica; Prunus persica; Rats; Rats, Zucker; Receptor, Angiotensin, Type 1; Risk Factors; RNA, Messenger; Weight Gain

Topics: Arthritis, Rheumatoid; Atherosclerosis; Cardiovascular Diseases; Humans; Leptin

Topics: Arthritis, Rheumatoid; Atherosclerosis; Cardiovascular Diseases; Humans; Leptin

To determine whether leptin is related to all-cause and cardiovascular (CV) mortality in older adults.. Participants 60 years and older with plasma leptin level measurements from the National Health and Nutrition Examination Survey III (1988-1994) and mortality data linked to the National Death Index were included. We created sex-specific tertiles of leptin (men: 4.2-7.7 μg/L; women: 11.5-21.4 μg/L) to identify the effect of leptin on all-cause and CV mortality. We also determined whether leptin predicted mortality in patients with obesity. We classified obesity using 4 possible definitions: body mass index 30 kg/m(2) or greater; body fat 25% or more in men and 35% or more in women; waist circumference 102 cm or greater in men and 88 cm or greater in women; and waist-hip ratio 0.85 or higher in women and 0.95 or higher in men. Sex-specific proportional hazard models were used to assess the effect of leptin on all-cause and CV mortality.. Of 1794 participants, 51.6% were women; the mean age was 70.3±0.4 years, and the follow-up period was 12.5 years with 994 deaths (469 were CV deaths). All-cause mortality in the highest leptin tertile was significant neither in men (hazard ratio [HR], 1.23; 95% CI, 0.93-1.63) nor in women (HR, 0.97; 95% CI, 0.68-1.40). CV mortality was the highest in the highest leptin tertile in men (HR, 1.69; 95% CI, 1.06-2.70) but not in women (HR, 1.21; 95% CI, 0.73-1.98). Evaluating the effect of leptin in subgroups of different obesity definitions, we found that high leptin levels as predict CV mortality in men as measured by waist circumference or body fat.. Elevated leptin level is predictive of CV mortality only in men. Leptin may provide additional mortality discrimination in obese men.

Topics: Adiposity; Aged; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Female; Humans; Leptin; Male; Middle Aged; Nutrition Surveys; Obesity; Proportional Hazards Models; Sex Factors; United States; Waist Circumference; Waist-Hip Ratio

Obesity is characterised by low-grade inflammation, which increases the metabolic syndrome (MetS) and cardiovascular risks. The aim of the present study was to verify the role of multicomponent therapy in controlling the MetS, inflammation and carotid intima-media thickness (cIMT) in obese adolescents. The second aim was to investigate the relationships between adipokines, the MetS parameters and cIMT. A total of sixty-nine obese adolescents participated in the present study and completed 1 year of multicomponent therapy (a combination of strategies involving nutrition, psychology, physical exercise and clinical therapy), and were divided according to their MetS diagnosis as follows: MetS (n 19); non-MetS (n 50). Blood analyses of glucose, lipid and adipokine concentrations (adiponectin, leptin, plasminogen activator inhibitor 1 (PAI-1) and C-reactive protein) were collected. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance, quantitative insulin sensitivity check index and homeostasis model assessment-adiponectin. cIMT and visceral and subcutaneous fat were estimated using ultrasonography. At baseline, the MetS group presented higher waist circumference, glucose and insulin levels, and systolic and median blood pressures compared with the non-MetS group. After therapy, both groups showed improvements in the anthropometric profile, body composition, insulin level, insulin resistance, insulin sensibility, TAG and VLDL-cholesterol, adiponectin, leptin and PAI-1 levels, blood pressure and cIMT. The prevalence of the MetS was reduced from 27·5 to 13·0 %. Metabolic syndrome patients showed resistance in the attenuation of total cholesterol and LDL-cholesterol (LDL-C) levels and leptin:adiponectin and adiponectin:leptin ratios. In the MetS group, the variation in the adiponectin:leptin ratio was correlated with variations in glucose, insulin sensibility, total cholesterol, LDL-c and systolic blood pressure. Additionally, the number of MetS parameters was correlated with the carotid measurement. Moreover, the variation in cIMT was correlated with the variations in insulin sensibility, total cholesterol and LDL-c. For the entire group, the number of MetS alterations was correlated with the leptin level and leptin:adiponectin ratio and adiponectin:leptin ratio after therapy. In conclusion, multicomponent therapy was effective in controlling the MetS, inflammation and cIMT in the obese adolescents. However, the MetS patie

Topics: Adipokines; Adiponectin; Adiposity; Adolescent; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; Brazil; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Combined Modality Therapy; Diet; Exercise; Female; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Nutrition Therapy; Obesity; Plasminogen Activator Inhibitor 1; Psychotherapy; Risk Factors; Treatment Outcome; Waist Circumference

Obesity-related comorbidities are present in young obese children, providing a platform for early adult cardiovascular disorders.. To compare and correlate markers of adiposity to metabolic disturbances, vascular and cardiac morphology in a European pediatric obese cohort.. We carried out an observational and transversal analysis in a cohort consisting of 121 obese children of both sexes, between the ages of 6 and 17 years. The control group consisted of 40 children with normal body mass index within the same age range. Markers of adiposity, plasma lipids and lipoproteins, homeostasis model assessment-insulin resistance, common carotid artery intima-media thickness and left ventricular diameters were analyzed.. There were statistically significant differences between the control and obese groups for the variables analyzed, all higher in the obese group, except for age, high-density lipoprotein cholesterol and adiponectin, higher in the control group. In the obese group, body mass index was directly correlated to left ventricular mass (r=0.542; p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001) and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In that same group, insulin resistance was present in 38.1%, 12.5% had a combined dyslipidemic pattern, and eccentric hypertrophy was the most common left ventricular geometric pattern.. These results suggest that these markers may be used in clinical practice to stratify cardiovascular risk, as well as to assess the impact of weight control programs.

Topics: Acanthosis Nigricans; Adiponectin; Adiposity; Adolescent; Age Factors; Biomarkers; Body Mass Index; Cardiovascular Diseases; Carotid Intima-Media Thickness; Case-Control Studies; Child; Cross-Sectional Studies; Dyslipidemias; Female; Humans; Hypertrophy, Left Ventricular; Insulin Resistance; Leptin; Lipoproteins; Male; Pediatric Obesity; Risk Factors; Sex Factors; Waist Circumference

Maternal obesity increases adult offspring risk for cardiovascular disease; however, the role of offspring adiposity in mediating this association remains poorly characterized.. To investigate the associations of maternal pre-pregnant body mass index (maternal BMI) and gestational weight gain (GWG) with neonatal cardiometabolic markers independent of fetal growth and neonatal adiposity.. A total of 753 maternal-infant pairs from the Healthy Start study, a large multiethnic pre-birth observational cohort were used. Neonatal cardiometabolic markers included cord blood glucose, insulin, glucose-to-insulin ratio (Glu/Ins), total and high-density lipoprotein cholesterol (HDL-c), triglycerides, free fatty acids and leptin. Maternal BMI was abstracted from medical records or self-reported. GWG was calculated as the difference between the first pre-pregnant weight and the last weight measurement before delivery. Neonatal adiposity (percent fat mass) was measured within 72 h of delivery using whole-body air-displacement plethysmography.. In covariate adjusted models, maternal BMI was positively associated with cord blood insulin (P=0.01) and leptin (P<0.001) levels, and inversely associated with cord blood HDL-c (P=0.05) and Glu/Ins (P=0.003). Adjustment for fetal growth or neonatal adiposity attenuated the effect of maternal BMI on neonatal insulin, rendering the association nonsignificant. However, maternal BMI remained associated with higher leptin (P<0.0011), lower HDL-c (P=0.02) and Glu/Ins (P=0.05), independent of neonatal adiposity. GWG was positively associated with neonatal insulin (P=0.02), glucose (P=0.03) and leptin levels (P<0.001) and negatively associated with Glu/Ins (P=0.006). After adjusting for neonatal adiposity, GWG remained associated with higher neonatal glucose (P=0.02) and leptin levels (P=0.02) and lower Glu/Ins (P=0.048).. Maternal weight prior and/or during pregnancy is associated with neonatal cardiometabolic makers including leptin, glucose and HDL-c at delivery, independent of neonatal adiposity. Our results suggest that intrauterine exposure to maternal obesity influences metabolic processes beyond fetal growth and fat accretion.

Topics: Adiposity; Adult; Birth Weight; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Colorado; Female; Fetal Development; Humans; Infant, Newborn; Insulin; Leptin; Lipoproteins, HDL; Longitudinal Studies; Obesity; Plethysmography; Pregnancy; Risk Factors; Triglycerides; Weight Gain

Adipokines released by adipose tissue have been recognised as important players in the development of cardiovascular disease. Leptin is a well-studied adipokine with an important role in body metabolism and energy expenditure and leptin-deficiency or deficient leptin signalling results in excessive obesity and type 2 diabetes. Studies in cells and animal models support that leptin has a pro-atherogenic potential and exerts pro-hypertrophic effects on the heart. However, recent basic and clinical evidence suggests that leptin may also have a beneficial role in cardiovascular physiology. Notably, clinical studies have failed to convincingly link leptin with increased cardiovascular disease risk. We herein summarise the role of leptin in cardiovascular disease as another example of the 'adipokine paradox' and discuss the complexity in using serum adipokine levels as biomarkers in cardiovascular disease.

Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Humans; Leptin

Adiposity is an inflammatory condition contributing to the morbidity and mortality of several disorders, including type 2 diabetes mellitus (T2D) and cardiovascular disease.. To compare cardiometabolic risk factors between obese and non-obese Thai patients with T2DM MATERIAL AND METHOD: The cross-sectional study was done in 20 obese (BM >25 kg/m2) and 20 non-obese (BMI 23 kg/m2) T2DM Researchers measured fasting plasma glucose and lipids, serum levels of insulin, leptin, adiponectin, and soluble tumor necrosis factor-alpha receptors type 1 and 2 (sTNF-R] andsTNF-R2). Insulin sensitivity check index (QUICIKI) and insulin resistance index (HOMA-IR) were calculated.. Thai obese adults with T2DMhad greater amounts ofsTNF-R2 and HOMA-IR, higher ratios of leptin/adiponectin, and more incidences of hypertension and hypertriglyceridemia in comparison to non-obese counterparts. Additionally, HOMA-IR values in non-obese T2DMwere greater than those reported among non-diabetic Thai adults. A reverse association between inflammatory markers (both sTNF-Rs) andHDLC was detected. Leptin/adiponectin ratios correlated directly with HOMA-IR, serum insulin, plasma triglycerides and BMI, whereas HOMA-IR did not relate to any studied plasma lipid.. The present study demonstrated an increased cardiometabolic risk in obese T2DM adults than non-obese T2DM adults among the Thai population. The leptin/adiponectin ratio may be more relevant to predict the risk of cardiovascular events in T2DMpatients than HOMA-IR.

Topics: Adiponectin; Adiposity; Adult; Aged; Asian People; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Middle Aged; Obesity; Risk Factors; Triglycerides

Obesity is associated with changes in both right (RV) and left (LV) ventricular morphology, but the biological basis of this finding is not well established. We examined whether adipokine levels were associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.. We examined relationships of leptin, resistin, TNF-α, and adiponectin with RV morphology and function (from cardiac MRI) in participants (n = 1,267) free of clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA)-RV study. Multivariable regressions (linear, quantile [25th and 75th] and generalized additive models [GAM]) were used to examine the independent association of each adipokine with RV mass, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV) and RV ejection fraction (RVEF).. Higher leptin levels were associated with significantly lower levels of RV mass, RVEDV, RVESV and stroke volume, but not RVEF, after adjustment for age, gender, race, height and weight. These associations were somewhat attenuated but still significant after adjustment for traditional risk factors and covariates, and were completely attenuated when correcting for the respective LV measures. There were no significant interactions of age, gender, or race/ethnicity on the relationship between the four adipokines and RV structure or function.. Leptin levels are associated with favorable RV morphology in a multi-ethnic population free of cardiovascular disease, however these associations may be explained by a yet to be understood bi-ventricular process as this association was no longer present after adjustment for LV values. These findings complement the associations previously shown between adipokines and LV structure and function in both healthy and diseased patients. The mechanisms linking adipokines to healthy cardiovascular function require further investigation.

Topics: Adiponectin; Adult; Aged; Atherosclerosis; Cardiovascular Diseases; Ethnicity; Female; Heart Ventricles; Humans; Leptin; Magnetic Resonance Imaging; Male; Middle Aged; Obesity; Radiography; Resistin; Stroke Volume; Tumor Necrosis Factor-alpha

The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers (BMI from 23.3 to 53 kg/m²). Anthropometric parameters were measured: body weight and height, waist and hip circumference, waist-to-hip ratio, body fat mass (BMF), subcutaneous and visceral fat mass (SFM, VFM), lean body mass (LBM), skeletal muscle mass (SMM). In serum we determined adiponectin and leptin concentrations, extracellular hemoglobin, total bilirubin, as well as lipid metabolism (TCh, HDL-Ch, LDL-Ch, TG). Mean adipokine levels were significantly higher in women (p ≤ 0.01), adiponectin significantly negatively correlated with body height and weight, systolic blood pressure and absolute LBM and SMM values. The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch. LEP negatively correlated with some percentage rates (%LBM, %SMM). Only in women, we observed a positive correlation between LEP and body weight, BMI and WHR. Studies on ADPN and the ADPN/LEP ratio as a valuable complementary diagnostic element in the prediction and prevention of cardiovascular diseases need to be continued.

Topics: Adiponectin; Adult; Anthropometry; Blood Pressure; Body Composition; Body Fat Distribution; Body Height; Body Weight; Cardiovascular Diseases; Female; Humans; Leptin; Lipids; Male; Middle Aged; Obesity; Sex Factors; Waist-Hip Ratio; Young Adult

Hypertension is one of the leading causes of cardiovascular disease (CVD) worldwide. Overweight and obesity are major risk factors for hypertension. The mechanisms linking these two diseases are incompletely understood, but abnormalities in several different pathways including insulin and glucose metabolism, inflammation, the sympathetic nervous system and the renin-angiotensin-aldosterone system have been known for decades. Lately, the attention has shifted toward the endocrine function of adipose tissue, which among others secrete adiponectin, leptin and interleukin-6 (IL-6), which stimulates liver CRP production. These substances have all been regarded as candidate intermediates between adiposity and the development of hypertension. Furthermore, the so-called "natriuretic handicap" which characterizes obesity, has also attracted a great deal of attention as a possible pathway.   Primary hypotheses: • The adipocytokines, adiponectin, leptin and CRP (used as a surrogate marker of IL-6) are independently associated with prevalent and incident hypertension.   • Five-year weight changes associate with BP alterations, even after adjustment for changes in lifestyle risk factors and serum insulin.   • NT-proBNP (used as a surrogate marker of active BNP) is positively associated with prevalent hypertension, but negatively associated with incident hypertension.   • The adipocytokines, adiponectin, leptin and CRP (used as a surrogate marker of IL-6), are independently associated with incident CVD.  . The Inter99 study provided data for this thesis. In brief, Inter99 is a randomized, non-pharmacological intervention study for the prevention of ischemic heart disease. The study included approximately 6,700 participants from the background population, who were thoroughly examined at baseline. Various measurements, including blood samples, were done at baseline and five-year follow-up. Data about cardiovascular events were gathered from national registers.  . Paper I: In the prevalent model including leptin, CRP, adiponectin, sex, age, lifestyle risk factors, lipids, insulin, haemoglobin A1c, and in the incident model which also included baseline heart rate and blood pressure, only leptin of the three candidate intermediates was significantly associated with both prevalent and incident hypertension. Paper II: Five-year weight changes were associated with blood pressure alterations and had a substantial impact on both fasting and two-hour post-glucose serum insulin levels. However, in multivariable regression analyses, additional adjustments for insulin values only attenuated the associations between weight changes and blood pressure minimally. Paper III: Higher serum concentrations of NT-proBNP associated with prevalent hypertension whereas lower concentrations associated with incident hypertension. Paper IV: Among 6,502 participants with a mean follow-up time of 11.4 years, 527 participants experienced one or multiple cardio-vascular events. Among adiponectin, leptin and CRP, only CRP were significantly positive associated with CVD in all models.  . Regarding the pathophysiology of overweight-related hypertension and CVD, our results indicate that:   • Leptin is possibly an independent risk factor for the development of hypertension.   • Albeit weight loss improves insulin-profile, the effect of insulin on blood pressure changes seems minimal, indicating that insulin does not play a major direct role in the early development of hypertension.   • A deficiency of the natriuretic peptides, resulting in reduced vasodilation and natriuresis, could be involved in the pathogenesis of hypertension in its early stages.   • Since adjustment for CRP decreased the BMI-associated CVD risk markedly, our data indirectly suggest that IL-6 originating from fat tissue could play a role in overweight and obesity-related cardiovascular disease.

Topics: Adipokines; Adiponectin; Biomarkers; Blood Pressure; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Humans; Hypertension; Insulin; Interleukin-6; Leptin; Natriuretic Peptides; Obesity; Risk Factors

Leptin, an adipokine elevated in obesity, may be related to an adverse cardiovascular risk profile in childhood. However, evidence for this relationship in pre-pubertal children is scarce. We aimed to analyze the relationship between leptin levels and lipid and insulin profiles in Spanish children.. Our population-based sample included 389 males and 369 females aged 6-8 years. Lipid levels were determined by standard methods, insulin by radioimmunoassay and leptin by sandwich ELISA. Leptin levels were higher in girls (8.6 ng/ml) than boys (4.7 ng/ml) (p < 0.001). Leptin increased from ages 6 to 8 in girls, but remained steady in boys. In both sexes, leptin increased significantly (p < 0.001) across weight category from normal weight to obese. Children in the highest tertile of leptin concentration showed significantly (p < 0.01) lower levels of HDL-cholesterol (HDL-C) and apolipoprotein-AI (apo-AI) and significantly higher triglyceride (TG) levels than children in lower tertiles. However, in linear regression analysis, after adjustment for body mass index (BMI), leptin only accounted for 1.5% of the variance of HDL-C in boys, and 2.6% of the variance of apo-AI in girls. Leptin was strongly and positively correlated with insulin and HOMA. Upon regression analysis, leptin contributed to over 20% of the variability in insulin and HOMA, independent of BMI.. Leptin levels show sex differences in pre-pubertal children. In this age group, leptin levels are strongly related to insulin, and affect lipid profile -namely HDL-C, apo-AI and TG- particularly when leptin levels are high.

Topics: Age Factors; Anthropometry; Apolipoprotein A-I; Body Mass Index; Cardiovascular Diseases; Child; Cholesterol, HDL; Cohort Studies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hyperlipidemias; Insulin; Insulin Resistance; Leptin; Linear Models; Male; Metabolic Syndrome; Multivariate Analysis; Risk Assessment; Sex Factors; Spain

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Down-Regulation; Humans; Leptin; Molecular Targeted Therapy; Up-Regulation

To assess whether waist-to-height-ratio (WHtR) is a better estimate of body fat percentage (BF%) and a better indicator of cardiometabolic risk factors than BMI or waist circumference (WC) in young children.. WHtR, WC and BMI were measured by trained staff according to standardized procedures. (2)H2O and (2)H2(18)O isotope dilution were used to assess BF% in 61 children (3-7 years) from the general population, and bioelectrical impedance (Horlick equation) was used to assess BF% in 75 overweight/obese children (3-5 years). Cardiometabolic risk factors, including diastolic and systolic blood pressure, HOMA2-IR, leptin, adiponectin, triglycerides, total cholesterol, HDL- and LDL-cholesterol, TNFα and IL-6 were determined in the overweight/obese children.. In the children from the general population, after adjustments for age and gender, BMI had the highest explained variance for BF% compared to WC and WHtR (R(2) = 0.32, 0.31 and 0.23, respectively). In the overweight/obese children, BMI and WC had a higher explained variance for BF% compared to WHtR (R(2) = 0.68, 0.70 and 0.50, respectively). In the overweight/obese children, WHtR, WC and BMI were all significantly positively correlated with systolic blood pressure (r = 0.23, 0.30, 0.36, respectively), HOMA2-IR (r = 0.53, 0.62, 0.63, respectively), leptin (r = 0.70, 0.77, 0.78, respectively) and triglycerides (r = 0.33, 0.36, 0.24, respectively), but not consistently with other parameters.. In young children, WHtR is not superior to WC or BMI in estimating BF%, nor is WHtR better correlated with cardiometabolic risk factors than WC or BMI in overweight/obese children. These data do not support the use of WHtR in young children.

Topics: Adiponectin; Adiposity; Blood Pressure; Body Height; Body Mass Index; Cardiovascular Diseases; Child; Child, Preschool; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Electric Impedance; Female; Humans; Interleukin-6; Leptin; Linear Models; Male; Overweight; Pediatric Obesity; Risk Assessment; Risk Factors; Triglycerides; Tumor Necrosis Factor-alpha; Waist Circumference

Muscular fitness, cardiorespiratory fitness (CRF) and fatness are mutually related with chronic inflammation.. To examine the independent association of muscular fitness with inflammatory biomarkers in adolescents from nine European countries.. A total of 639 adolescents (296 boys) aged from 12.5 to 17.5 year were included in this report. Data collection took place in 2006-2007 and analyses in 2012. A muscular fitness score was computed from handgrip strength and standing long jump. CRF was measured using the 20 m shuttle run test. Z-scores of C-reactive protein, complement factors C3 and C4, leptin and white blood cell counts were summed to create a cluster of inflammatory biomarkers. Sex, age, pubertal stage and centre were used as main confounders. Additional models were further adjusted for insulin resistance (HOMA-IR) and sum of four skinfolds.. Muscular fitness was negatively associated with single and clustered inflammatory biomarkers (standardized β from -0.399 to -0.100, all P-values < 0.05). Additional adjustments for CRF and HOMA-IR weakened the associations, but they still remained significant. The association was no longer significant when adjusting for skinfolds. Decreasing values of inflammatory score were observed across incremental levels of muscular fitness in both non-overweight and overweight adolescents (P ≤ 0.05).. Adolescents with higher levels of muscular fitness present a lower chronic inflammation, and this seems to be explained by lower levels of fatness. Yet, overweight and obese adolescents may exhibit a less adverse profile if they maintain appropriate levels of muscular fitness.

Topics: Adolescent; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cholesterol; Cross-Sectional Studies; Exercise; Exercise Test; Female; Hand Strength; Humans; Inflammation; Insulin Resistance; Leptin; Lipoproteins, HDL; Male; Motor Activity; Muscle Strength; Muscle, Skeletal; Overweight; Physical Endurance; Physical Fitness; Risk Factors

Acanthosis nigricans (AN) is linked to obesity and insulin resistance. Major adipokines such as leptin, adiponectin, and resistin are known to be dysregulated in obesity and are key players in the pathogenesis of metabolic syndrome.. This study was conducted to assess serum levels of the major adipokines leptin, adiponectin, and resistin, and to study their correlations with the state of insulin resistance and other risk factors for cardiovascular disease (CVD) among AN patients.. A total of 115 adult subjects were included in the study; 52 of these had benign acquired AN, and 63 (control subjects) were without AN. Thirty-three of the control group were obese, and 30 were healthy subjects of normal weight. Body mass index (BMI), blood pressure, lipid profile, fasting blood glucose, fasting insulin, serum leptin, adiponectin, and resistin were assessed in all subjects.. We found significant differences between AN patients and obese controls in serum levels of leptin (30.02 ± 15.14 ng/ml vs. 21.07 ± 7.92 ng/ml; P = 0.002), adiponectin (5.55 ± 2.89 μg/l vs. 9.02 ± 2.33 μg/ml; P = 0.00001), and resistin (20.88 ± 3.97 ng/ml vs. 16.82 ± 4.36 ng/ml; P = 0.00003). Significant positive correlations were found between serum leptin and homeostasis model assessment (HOMA) value, insulin, glucose, BMI, cholesterol, and low-density lipoprotein. There were also significant negative correlations between adiponectin and HOMA value, insulin, BMI, cholesterol, and leptin among AN patients.. Acanthosis nigricans is a likely forerunner of the finding of metabolic syndrome. High serum leptin and resistin and low serum adiponectin may increase the risk for CVD among AN patients.

Topics: Acanthosis Nigricans; Adiponectin; Adult; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Resistin; Risk Factors

Psoriasis is an inflammatory skin disease that may be associated with an adverse cardiometabolic profile including modulated plasma adiponectin and leptin levels. Whether these levels are independent of cardiometabolic risk factors, which are also prevalent in psoriasis, is not known.. A consecutive sample of 122 participants with varying degrees of psoriasis severity, and a random sample of 134 participants without psoriasis, were recruited for this case-control study. Cardiometabolic risk factors including traditional cardiovascular risk factors, waist circumference, insulin resistance, and total plasma adiponectin and leptin were measured. Total plasma adiponectin and leptin levels were compared in unadjusted and adjusted analyses by psoriasis status.. Participants with psoriasis had mostly mild disease and were mainly on topical therapies, but still had a more adverse cardiometabolic profile compared with those without psoriasis. Furthermore, plasma adiponectin levels were significantly lower in participants with psoriasis than those without {7.13 μg/mL [interquartile range (IQR) 4.9-11.3) vs. 14.5 μg/mL (IQR 8.4-24.1); P < 0.001]}. Plasma leptin (ng/mL) levels were higher in the psoriasis group but this did not reach statistical significance [11.3 (IQR 6.4-21.8) vs. 9.8 (IQR 4.9-20.5); P = 0.07]. In multivariable modelling, plasma adiponectin levels were still negatively associated with psoriasis status after adjusting for waist size (% difference = -41.2%, P < 0.001), insulin resistance (% difference = -39.5%, P < 0.001), and both waist size and insulin resistance (% difference = -38.5%, P < 0.001).. Plasma levels of adiponectin were lower in psoriasis, and this relationship persisted after adjusting for cardiometabolic risk factors known to decrease adiponectin levels. These findings suggest that inflammation present in psoriasis may be associated with adipose tissue dysfunction; however, direct studies of adipose tissue are needed to confirm this.

Topics: Adiponectin; Adult; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Multivariate Analysis; Psoriasis; Risk Factors; Waist Circumference

Growth hormone (GH) deficiency (GHD) in adults is associated with increased cardiovascular (CV) risk. Although some authors have documented the presence of early CV risk factors in untreated GHD children, results are still inconsistent. Aim of this study was to evaluate the effects of GHD and GH therapy on early cardiometabolic risk factors in a large cohort of children.. Waist-to-height ratio (WHtR), triglycerides, total-, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol, atherogenic index (AI = total /HDL cholesterol), homocysteine, leptin, adiponectin, high-sensitivity C-reactive protein (hsCRP) and fibrinogen were evaluated in seventy-one GHD children (9·8 ± 3·6 years) before and after 2 years of GH therapy. Seventy-one healthy controls comparable with patients for age, sex and body mass index (BMI) were enrolled.. Compared with controls, GHD children at study entry had higher WHtR (0·52 ± 0·05 vs 0·45 ± 0·19, P = 0·004), triglycerides (0·44 ± 0·98 vs -0·03 ± 0·73 SDS, P = 0·012), total cholesterol (0·28 ± 1·08 vs -0·46 ± 0·98 SDS, P < 0·001), LDL cholesterol (0·20 ± 0·90 vs -0·39 ± 1·06 SDS, P = 0·007), AI (3·19 ± 0·73 vs 2·77 ± 0·53, P = 0·001), homocysteine (8·45 ± 1·8 vs 7·72 ± 1·6 μm, P = 0·003), leptin (8·03 ± 4·2 vs 5·09 ± 1·9 ng/ml, P = 0·001) and fibrinogen (292·6 ± 33 vs 268 ± 31·4 mg/dl, P = 0·011). No differences were found in adiponectin or hsCRP. GH therapy was associated with a significant reduction in WHtR (P < 0·001), total cholesterol (P < 0·001), LDL cholesterol (P = 0·002), homocysteine (P = 0·044) leptin (P = 0·022) and fibrinogen (P = 0·001). Moreover, GH therapy was associated with a significant increase in adiponectin levels (P = 0·001).. Our data suggest that children with untreated GHD exhibit a cluster of early cardiovascular risk factors and that GH treatment exerts beneficial effects on these abnormalities.

Topics: Adipokines; Adiponectin; Biomarkers; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Child; Cholesterol; Female; Fibrinogen; Homocysteine; Human Growth Hormone; Humans; Inflammation; Leptin; Male; Prospective Studies; Risk Factors; Treatment Outcome

Chronic renal failure (CRF) compromises nutrition, growth, puberty, glycometabolic homeostasis, and adipokine secretion (i.e. adiponectin, resistin, and leptin). Adipokines play a role in the clinical outcome, but data in paediatric patients is scant.. To evaluate the link between kidney function, adiponectin, resistin, leptin, hormonal status, nutritional state and late outcome of CRF children.. We studied leptin, adiponectin and resistin levels in 31 CRF patients (19 males, 12 females, aged 12.1 ± 4.47 years) managed conservatively, and 30 healthy age- and gender-matched controls. Clinical, auxological, biochemical, hormonal data, glucose and insulin levels were correlated with adipokine levels.. Six percent of patients had glycaemia T0' > 126 mg/dl, 23 % glycaemia T60' > 126, and 23 % glycaemia T120' ≥ 140. Glycated haemoglobin (HbA1c) measured during follow-up was in the normal range in all patients (4-5.6 %). Insulinaemia was significantly higher in CRF patients than controls. Homeostatic model of assessment-insulin resistance (HOMA-IR) levels were more elevated in patients (32 % had HOMA-IR > 2.5) than controls. Leptin levels were significantly higher in CRF patients than controls and differed significantly between males and females. Leptin correlated significantly with creatinine, body mass index (BMI), BA, pubertal stage, insulin-like growth factor 1, and HOMA-IR in females. Adiponectin levels were significantly higher in patients than controls, higher in patients with BMI < 85th centile and significantly inversely correlated to BMI, BA, haemoglobin, ferritin, proteins, albumin, and creatininuria. Resistin levels showed a direct correlation with C-reactive protein and an inverse correlation with haemoglobin.. Normal resistin levels are an expression of both adequate nutritional state and controlled inflammatory state. Adiponectin could protect against chronic inflammation, atherosclerosis, and cardiovascular diseases. Preventing obesity and ensuring a correct nutritional state are primary goals for physicians following children with CRF. Adipokines could be a useful marker in the follow-up.

Topics: Adiponectin; Adolescent; Adolescent Nutritional Physiological Phenomena; Age Factors; Biomarkers; Blood Glucose; Cardiovascular Diseases; Case-Control Studies; Child; Disease Progression; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Kidney Failure, Chronic; Leptin; Male; Nutritional Status; Obesity; Prognosis; Resistin; Risk Factors; Time Factors

Obesity is associated with rapid growth during childhood. There is uncertainty over how to adjust for body size, when using adiposity as a proxy for cardiovascular risk. We studied associations of height, body composition (by dual-energy X-ray absorptiometry) and cardiovascular risk markers (insulin resistance (IR), leptin) in children.. Using partial correlations in 172 children aged 7-12 years, we investigated associations of (a) fat mass with IR or leptin, adjusting for height or lean mass, and (b) height or lean mass with IR or leptin, adjusting for fat mass. Analyses were conducted both cross-sectionally at each age, and for changes between 7 and 12 years.. Height, fat mass, lean mass, IR and leptin were all inter-correlated at all ages. Although fat mass was strongly associated with IR and leptin, height was independently negatively associated with leptin (whole sample, adjusting for age: boys r=-0.12, girls r=-0.13; P<0.001). Independent of adiposity, height was also associated with insulin IR (whole sample, adjusting for age: boys r=0.11, girls r=0.20; P<0.001). When analysed by year of age, these associations tended to remain significant at older ages. Change in height from 7 to 12 years was also associated with change in IR (boys: r=0.18, P<0.05; girls: r=0.34, P<0.01), independently of change in adiposity, with similar findings for lean mass.. During childhood, markers of cardiovascular risk have a complex profile, associated with growth as well as fat accumulation. Taller and faster-growing children have elevated risk markers, independently of their adiposity. These findings have implications for the interpretation of pediatric indices of adiposity that aim to adjust for body size. Adiposity indices that perform best at summarizing metabolic risk may not be those that perform best at understanding the developmental aetiology of risk.

Topics: Absorptiometry, Photon; Adipose Tissue; Adiposity; Biomarkers; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Male; Pediatric Obesity; Puberty; Risk Factors

Most of the interventional studies have investigated the impact of the diet on adiponectin and leptin concentrations only in men or in women. Consequently, it is still unknown whether the consumption of a healthy diet influences in a sex-specific manner these adipocytokines. We examined sex differences in the effects of the Mediterranean diet (MedDiet) on adiponectin and leptin concentrations, and determined whether changes in these adipocytokines are associated with changes in cardiovascular risk factors in both sexes.. Participants were 38 men and 32 premenopausal women (24-53 years) with slightly elevated low-density lipoprotein cholesterol concentrations (3.4-4.9 mmol/l) or total cholesterol/high-density lipoprotein cholesterol (HDL-C)⩾5.0. Adiponectin, leptin and cardiovascular risk factors were measured before and after a 4-week fully controlled isoenergetic MedDiet.. Adiponectin concentration decreased in response to the MedDiet, but this decrease reached statistical significance only in men (P<0.001 for men and P=0.260 for women; sex-by-time interaction, P=0.072). Adjustments for body weight or waist circumference did not change results obtained. Changes in adiponectin were positively associated with concomitant variations in HDL-C in men (r=0.52, P=0.003) and with variations in apolipoprotein A-1 and insulin sensitivity as calculated by both the homeostasis model assessment index for insulin sensitivity and Cederholm indices in women (respectively, r=0.44, P=0.021; r=0.79, P<0.001 and r=0.47, P=0.020). The MedDiet had no impact on leptin and the leptin-to-adiponectin ratio in both sexes.. Results suggest a sex difference in adiponectin response to the short-term consumption of the MedDiet, with only men experiencing a decrease. Also sex-specific patterns of associations between changes in adiponectin concentration and changes in cardiovascular risk factors were observed.

Topics: Adiponectin; Adult; Apolipoprotein A-I; Blood Pressure; Body Weight; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diet, Mediterranean; Female; Homeostasis; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Premenopause; Risk Factors; Sex Factors; Triglycerides; Waist Circumference; Young Adult

In the nontransplant setting, aberrant serum adipokine levels are associated with cardiovascular (CV) disease. The effects of liver transplantation (LT) on serum adipokine levels and their association with post-LT CV disease have not been studied. A nested case-control study of 77 patients with major CV events more than 4 months after LT analyzed serum adiponectin, resistin, leptin, C-reactive protein, and apolipoprotein levels measured before transplantation and 4, 12, and 24 months after LT. Adiponectin and resistin levels decreased dramatically after LT in all patients. Recipients with CV disease had lower levels of adiponectin and higher levels of resistin, leptin, C-reactive protein, and apolipoprotein B100 than controls. The pre-LT adiponectin level was associated with a 16% increased risk for CV events for every 1 μg/mL decrease in adiponectin [hazard ratio (HR) = 0.84, P = 0.046]. Pre-LT C-reactive protein levels (HR = 1.03, P = 0.047) and 12-month C-reactive protein levels (HR = 1.03, P = 0.03) were associated with CV events after LT. Pre-LT Diabetes (HR = 2.14, P = 0.09), and post-LT resistin (HR = 1.07, P = 0.07), and apolipoprotein B (HR = 1.08, P = 0.08) were associated with a nonsignificantly increased risk of CV events in this small sample size. In conclusion, pre- and post-LT changes in serum adipokine and inflammatory markers may be signals of an increased risk of CV events after LT, but further study is needed.

Topics: Adipokines; Adiponectin; Adult; Aged; Apolipoprotein B-100; Apolipoproteins; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; End Stage Liver Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Leptin; Liver Transplantation; Male; Middle Aged; Proportional Hazards Models; Resistin; Risk Factors; Time Factors

This study aimed to analyse the impact of obesity in type 2 diabetes (T2D) on adipocytokines (adiponectin, leptin and resistin) and inflammatory markers (TNF-α, IL-6 and hsCRP) as cardiovascular risk factors. A cross-sectional study comparing the basal levels of adipocytokines and inflammatory markers was done in 18 obese (BMI ≥ 30 kg/m²) (group A), 21 overweight (25 kg/m² ≤ BMI < 30 kg/m²) (group B), 25 non-obese T2D patients (group C) and 15 non-obese controls (group D). The lowest levels of adiponectin and the highest levels of leptin, resistin, TNF-α, IL-6 and hsCRP were found in group A. Adiponectin levels were significantly lower, and resistin, TNF-α, and hsCRP levels were elevated in group C vs. D. However, leptin and IL-6 levels differed significantly between groups A and B, but not between groups C and D. Moreover, we found a significant negative correlation between adiponectin and TNF-α, but not with other markers, which was independent of the presence of obesity. In contrast, leptin and resistin correlated with the inflammatory markers, and this correlation was obesity-dependent. Our results suggest that obesity influences cardiovascular risk primarily through changes in leptin and resistin and less efficiently at the level of adiponectin.

Topics: Adiponectin; Adult; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Resistin; Risk Factors; Tumor Necrosis Factor-alpha

Hydroxytyrosol (HT) is the most prominent phenolic component of olives, olive oil, and their by-products, e.g. olive mill waste water. As the link between HT consumption (via extra virgin olive oil intake) and better cardiovascular prognosis is being scientifically validated, HT is entering the market as a potentially useful supplement for cardiovascular disease prevention. One of the target organs in cardiometabolic prevention is the adipose tissue, where inflammation, oxidative stress, and secretion of adipocytokines contribute to cardiovascular risk.. We explored the nutrigenomic effects of long-term supplementation with nutritionally-relevant doses of HT, i.e. 0.03 gm% - with specific reference to the adipose tissue and glutathione metabolism - and we explored underlying mechanisms in vitro. We show that HT modulates the antioxidant network in the adipose tissue, as mediated by glutathione (GSH) and associated enzymes. We also confirmed the GSH-modulating activities of HT in cultured adipocytes, where low, physiological HT concentrations were able to blunt the H2O2-induced GSH/GSSG alteration indicative of oxidative stress. In terms of surrogate markers of cardiovascular disease, we recorded significantly decreased circulating leptin concentrations in mice fed with HT as compared with controls.. HT - in nutritionally relevant amounts - is able to positively modulate the glutathione-driven antioxidant enzymatic machinery in the adipose tissue. Because HT is generally recognized as safe (GRAS) and exhibits an excellent safety profile in vitro and in vivo, its future employment as adjunct treatment of metabolic syndrome can be envisioned, pending specific trials.

Topics: 3T3-L1 Cells; Adipokines; Adipose Tissue; Animals; Antioxidants; Cardiovascular Diseases; Dietary Supplements; Glutathione; Hydrogen Peroxide; Leptin; Male; Mice; Mice, Inbred C57BL; Microarray Analysis; Nutrigenomics; Olive Oil; Oxidation-Reduction; Oxidative Stress; Phenylethyl Alcohol; Plant Oils; Risk Factors; Transcriptome

Leptin and C-reactive protein (CRP) have each been linked to adverse cardiovascular events, and prior cross-sectional research suggests that increased levels of both biomarkers pose an even greater risk. The effect of increased levels of both leptin and CRP on mortality has not, however, been previously assessed.. We used data from the third National Health and Nutrition Examination Survey (NHANES III) to estimate the mortality effect of high leptin and high CRP levels. Outcomes were compared with the use of inverse-probability-weighting adjustment. Among 6259 participants included in the analysis, 766 were in their sex-specific, population-weighted highest quartiles of both leptin and CRP. Median follow-up time was 14.3 years.. There was no significant difference in adjusted all-cause mortality between the groups (risk ratio 1.22, 95% confidence interval [CI], 0.97-1.54). Similar results were noted with the use of several different analytic methods and in many subgroups, though high leptin and CRP levels may increase all-cause mortality in males (hazard ratio, 1.80, 95% CI, 1.32-2.46; P for interaction, 0.011). A significant difference in cardiovascular mortality was also noted (risk ratio, 1.54, 95% CI, 1.08-2.18), though that finding was not confirmed in all sensitivity analyses... In this observational study, no significant difference in overall all-cause mortality rates in those with high leptin and high CRP levels was found, though high leptin and CRP levels appear associated with increased mortality in males. High leptin and CRP levels also likely increase risk for cardiovascular death..

Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Cardiovascular Diseases; Cause of Death; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus; Dyslipidemias; Ethnicity; Female; Follow-Up Studies; Health Surveys; Humans; Inflammation; Kidney Diseases; Leptin; Lung Diseases; Male; Middle Aged; Mortality; Risk Factors; Sex Factors; Smoking; United States; Young Adult

Topics: Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Renal Dialysis

Prior studies evaluating the relationship between leptin and outcomes in chronic kidney disease patients have shown conflicting results. Our aim was to evaluate the association of serum leptin with all-cause and cardiovascular disease (CVD)-related mortality in stable maintenance hemodialysis patients.. We carried out an observational prospective cohort study of 53 patients on maintenance hemodialysis. The follow-up period was 5 years. Leptin levels were measured at baseline before the start of a hemodialysis session. Proportional hazards models were used to evaluate the relationship between leptin and all-cause and CVD-related mortality.. During the follow-up period, 26 patients (49.1%) died. Fifteen of 26 deaths (57.7%) were attributable to CVD. Cox proportional hazards analysis showed that a leptin level equal to or greate than the median value (3.45 ng/mL) was associated with lower mortality rates (hazard ratio, 0.211; 95% confidence interval, 0.062 to 0.723; P = .01) after multivariable adjustment for potential confounders. However, leptin was not an independent risk factor for CVD-related mortality.. There was a converse association between the serum leptin concentration and mortality in stable maintenance hemodialysis patients. Low serum leptin concentration is an independent risk factor of all-cause mortality in stable maintenance hemodialysis patients, but may not be linked with CVD-related mortality.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Cause of Death; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Survival Rate

Topics: Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Renal Dialysis

To identify metabolite patterns associated with childhood obesity, to examine relations of these patterns with measures of adiposity and cardiometabolic risk, and to evaluate associations with maternal peripartum characteristics.. Untargeted metabolomic profiling was used to quantify metabolites in plasma of 262 children (6-10 years). Principal components analysis was used to consolidate 345 metabolites into 18 factors and identified two that differed between obese (BMI ≥ 95‰; n = 84) and lean children (BMI < 85‰; n = 150). The relations of these factors with adiposity (fat mass, BMI, skinfold thicknesses) and cardiometabolic biomarkers (HOMA-IR, triglycerides, leptin, adiponectin, hsCRP, IL-6) using multivariable linear regression was then investigated. Finally, the associations of maternal prepregnancy obesity, gestational weight gain, and gestational glucose tolerance with the offspring metabolite patterns was examined.. A branched-chain amino acid (BCAA)-related pattern and an androgen hormone pattern were higher in obese vs. lean children. Both patterns were associated with adiposity and worse cardiometabolic profiles. For example, each increment in the BCAA and androgen pattern scores corresponded with 6% (95% CI: 1, 13%) higher HOMA-IR. Children of obese mothers had 0.61 (0.13, 1.08) higher BCAA score than their counterparts.. BCAA and androgen metabolites were associated with adiposity and cardiometabolic risk during mid-childhood. Maternal obesity may contribute to altered offspring BCAA metabolism.

Topics: Adiponectin; Adiposity; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Child; Female; Glycated Hemoglobin; Humans; Interleukin-6; Leptin; Male; Metabolic Diseases; Obesity; Pediatric Obesity; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Principal Component Analysis; Risk Factors; Triglycerides

To examine the relations of maternal prepregnancy body mass index (ppBMI) and gestational weight gain (GWG) with offspring cardiometabolic health.. We studied 1090 mother-child pairs in Project Viva, a Boston-area prebirth cohort. We measured overall (dual x-ray absorptiometry total fat; body mass index z-score) and central adiposity (dual x-ray absorptiometry trunk fat), and systolic blood pressure in offspring at 6 to 10 years. Fasting bloods (n = 687) were assayed for insulin and glucose (for calculation of homeostatic model assessment of insulin resistance), triglycerides, leptin, adiponectin, high sensitivity C-reactive protein, and interleukin 6. Using multivariable linear regression, we examined differences in offspring outcomes per 1 SD maternal ppBMI and GWG.. After adjustment for confounders, each 5 kg/m² higher ppBMI corresponded with 0.92 kg (95% confidence interval, 0.70-1.14) higher total fat, 0.27 BMI z-score (0.21-0.32), and 0.39 kg (0.29-0.49) trunk fat. ppBMI was also positively associated with homeostatic model assessment of insulin resistance, leptin, high sensitivity C-reactive protein, interleukin 6, and systolic blood pressure; and lower adiponectin. Each 5 kg of GWG predicted greater adiposity (0.33 kg [0.11-0.54] total fat; 0.14 kg [0.04-0.23] trunk fat) and higher leptin (6% [0%-13%]) in offspring after accounting for confounders and ppBMI.. Children born to heavier mothers have more overall and central fat and greater cardiometabolic risk. Offspring of women with higher GWG had greater adiposity and higher leptin.

Topics: Adiponectin; Adolescent; Adult; Birth Weight; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Body Weights and Measures; Boston; C-Reactive Protein; Cardiovascular Diseases; Child; Female; Health Behavior; Humans; Insulin Resistance; Leptin; Male; Mothers; Prospective Studies; Socioeconomic Factors; Triglycerides; Young Adult

Topics: Arthritis, Rheumatoid; Atherosclerosis; Cardiovascular Diseases; Humans; Leptin; Risk Factors

Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear.. Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/m²] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A1c [HbA1c] = 5.7% ± 0.3%) and 93 age- and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010.. Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P < .05) and higher postprandial levels of insulin, proinsulin, C-peptide, and GIP (P ≤ .02). Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-α, plasminogen activator inhibitor-1, and interleukin-6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin, and adiponectin did not differ between groups.. Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, nondiabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic treatment and put emphasis on the importance of implementing metabolic screening into psychiatric practice.. ClinicalTrials.gov identifier NCT00627757.

Topics: Adiponectin; Adolescent; Adult; Antipsychotic Agents; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucose Metabolism Disorders; Humans; Insulin; Interleukin-6; Leptin; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Proinsulin; Risk Factors; Tumor Necrosis Factor-alpha; Young Adult

In rabbits, mean arterial pressure (MAP) increases in response to fat feeding, but does not increase further with progressive weight gain. We documented the progression of adiposity and the alterations in endocrine/cardiovascular function in response to fat feeding in rabbits, to determine whether stabilization of MAP after 3 weeks could be explained by stabilization of neurohormonal factors. Rabbits were fed a control diet or high-fat diet for 9 weeks (n=23). Fat feeding progressively increased body mass and adiposity. Heart rate (HR) was elevated by week 3 (15±3%) but changed little thereafter. The effects of fat feeding on MAP were dependent on baseline MAP and peaked at 3 weeks. From baseline, MAP 80 mm Hg, MAP had increased by 8.1±1.3, 4.7±1.7 and 5.6±1.2 mm Hg, respectively, 3, 6 and 9 weeks after commencing the high-fat diet, but by only 2.6±1.5, 3.0±1.7 and 3.9±1.4 mm Hg, respectively, in control rabbits. Fat feeding did not increase MAP from a baseline >80 mm Hg. Plasma concentrations of leptin and insulin increased during the first 3-6 weeks of fat feeding and then stabilized (increasing by 111±17% and 731±302% by week 9, respectively), coinciding with the pattern of changes in MAP and HR. Plasma total cholesterol, triglycerides, renin activity, aldosterone and atrial natriuretic peptide were not significantly altered by fat feeding. Given that the changes in plasma leptin and insulin mirrored the changes in MAP and HR, leptin and insulin may be important factors in the development of hypertension and tachycardia in the rabbit model of obesity.

Topics: Animals; Blood Glucose; Body Composition; Body Weight; Cardiovascular Diseases; Disease Models, Animal; Endocrine System Diseases; Hemodynamics; Insulin; Leptin; Male; Obesity; Rabbits; Renin-Angiotensin System

Ozone (O₃) is a pervasive air pollutant that produces pulmonary and cardiovascular dysfunction and possible neurological dysfunction. Young and old individuals are recognized as being susceptible to O₃; however, remarkably little is known about susceptibility with senescence. This study explored the pulmonary, cardiovascular and neurological effects of O₃ exposure in adult (4 m) and senescent (20 m) Brown Norway rats exposed to 0 or 0.8 ppm O₃ for 6 h, 1 d/week, for 17 weeks. Ventilatory function was assessed 1 and 7 d after each exposure (Buxco). Heart rate, blood pressure (tail cuff) and motor activity were measured biweekly. Blood, aorta and bronchoalveolar lavage fluid (BALF) were analyzed 24 h after the last exposure for pulmonary inflammation, serum biomarkers and aorta mRNA markers of vascular disease. Measures of normal ventilatory function declined following each O₃ exposure in both adult and senescent rats, however, senescent rats took weeks to exhibit a decline. Evidence for residual respiratory effects of O₃ 7 d after exposure in both age groups was observed. O₃ had no effect on either heart rate or blood pressure, but decreased motor activity in both age groups. BALF indicated mild neutrophilic inflammation and protein leakage in adults. Age affected 17/58 serum analytes, O₃ affected 6/58; 2/58 showed an age-O₃ interaction. Leptin, adiponectin, lipocalin and insulin were increased in senescent rats. Overall, adult rats exhibited more immediate effects of episodic O₃ than senescent rats. Residual effects were, however, obtained in both ages of rat, especially for ventilatory endpoints.

Topics: Adiponectin; Age Factors; Aging; Animals; Behavior, Animal; Biomarkers; Cardiovascular Diseases; Disease Susceptibility; Heart; Hemodynamics; Insulin; Leptin; Lipocalins; Lung; Male; Motor Activity; Oxidants, Photochemical; Ozone; Rats; Rats, Inbred BN; Respiratory Function Tests

In overweight children, high leptin levels are independently associated with higher risk for cardiovascular disease, whereas adiponectin seems to be protective against type 2 diabetes and atherosclerosis. The study examines the predictive value of leptin for weight loss after a 4- to 6-wk inpatient therapy and again after 1 y; as well as the association among weight loss, leptin, and adiponectin levels and changes in cardiometabolic risk factors after therapy.. Body mass index (BMI), blood pressure, Tanner stage, and cardiometabolic risk factors were studied in 402 children (59.2% females, 13.9 ± 2.3 y, BMI 33.8 ± 5.7 kg/m(2)) before and after a 4-to 6-wk inpatient intervention (exercise, diet, and behavioral therapy) and BMI 1 y later (n = 206).. BMI was reduced from 33.8 ± 5.7 to 30.5 ± 5.1 kg/m(2) (P < 0.001) during the lifestyle intervention and remained unchanged after 1 y. Baseline BMI was positively associated with leptin (r = 0.60; P < 0.001) and cardiometabolic risk factors (blood pressure, high-density lipoprotein [HDL] cholesterol, triglycerides). Baseline leptin was associated with BMI and triglycerides (r = 0.39; P < 0.001), baseline adiponectin with HDL-cholesterol (r = 0.40; P < 0.001). Baseline BMI explained 40.7% of the variance in weight loss during therapy. The combination of BMI, sex, and leptin explained 50.4% of the variance. Neither BMI nor leptin predicted weight changes over the long term.. Overweight children maintained a substantial amount of weight loss after participation in a short-term inpatient lifestyle intervention. Baseline BMI was positively associated with weight reduction during the intervention, whereas baseline leptin had only a minor predictive value.

Topics: Adiponectin; Adolescent; Behavior Therapy; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Child; Cholesterol, HDL; Exercise; Feeding Behavior; Female; Humans; Leptin; Life Style; Linear Models; Male; Obesity; Risk Factors; Triglycerides; Weight Loss

Gestational diabetes mellitus (GDM) is associated with adverse metabolic outcomes after delivery. Physical activity practice improves the inflammatory profile; however, whether this association exists in women with prior GDM remains unknown. Our objective was to examine the cardiometabolic and inflammatory risk factors associated with accelerometer-based measures of physical activity in women with prior GDM.. Ninety-six women who had GDM between 2003 and 2010 were tested 2.9 ± 2.2 yr after delivery. The physical activity practice was measured with ActiGraph GT3X (ActiGraph™, Pensacola, FL) accelerometers worn ≥ 5 d, and the time spent weekly in moderate to vigorous physical activity (MVPA) was derived. The waist circumference was measured and the inflammatory marker or cytokine concentrations were measured in fasting plasma by the xMAP technology using the Bio-Plex 200 system. The lipid profile was also measured from fasting blood samples.. Only 31% of women accumulated at least 150 min of MVPA per week. No association was observed between the MVPA practice and any of the metabolic measurements in the whole group of women. The MVPA did not differ in groups stratified by waist circumference <88 or ≥ 88 cm. In women with waist circumference <88 cm, the MVPA was negatively correlated with circulating concentrations of C-reactive protein (r = -0.51, P = 0.006), leptin (r = -0.40, P = 0.008), plasminogen activator inhibitor-1 (r = -0.32, P = 0.04), and triglycerides (r = -0.44, P = 0.003). No association was seen with plasma interleukin-6; tumor necrosis factor-α; and total, LDL, or HDL cholesterol concentrations.. These analyses suggest that in the years after delivery, longer time spent in MVPA practice is associated with a lower cardiometabolic risk only in women with prior GDM who do not have abdominal obesity.

Topics: Accelerometry; Adolescent; Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Cytokines; Diabetes, Gestational; Female; Humans; Inflammation; Leptin; Lipids; Metabolic Diseases; Motor Activity; Obesity, Abdominal; Plasminogen Activator Inhibitor 1; Pregnancy; Risk Factors; Young Adult

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

Leptin levels are elevated in obese humans. Several studies have shown an association between hyperleptinemia and development of atherosclerosis and cardiovascular disease (CVD), but the relationship between leptin and vascular function remains unclear.. To evaluate associations between circulating plasma leptin and measures of vascular function in a large sample of elderly individuals from the community.. This cross-sectional study included 1016 subjects aged 70 (50% women) from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The invasive technique forearm plethysmography with intra-arterial infusions of acetylcholine and sodium nitroprusside was used for estimation of endothelial dependent vasodilatation (EDV) and endothelial independent vasodilatation (EIDV), respectively, in resistance arteries, and the non-invasive technique ultrasound assessed flow mediated vasodilation (FMD) in conduit arteries. The aortic augmentation index (AoAI), a surrogate measure of arterial stiffness, was evaluated by pulse wave analysis. Associations of vascular function, arterial stiffness and blood pressure with leptin were explored.. In sex-adjusted models, high levels of leptin were inversely associated with EDV and EIDV. These associations remained after stratification for sex, traditional risk factors of CVD and insulin resistance, but were attenuated after taking a measure of obesity (body mass index) into account. In addition, leptin associated with arterial stiffness and systolic and diastolic blood pressure.. Hyperleptinemia associated inversely with vasodilatation in resistance arteries. Furthermore, hyperleptinemia associated with arterial stiffness and hypertension. These associations were attenuated after adjusting for body mass index suggesting that leptin may be the mediator between obesity and impaired vascular function.

Topics: Age Factors; Aged; Aging; Arterial Pressure; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Endothelium, Vascular; Female; Humans; Infusions, Intra-Arterial; Leptin; Linear Models; Male; Multivariate Analysis; Plethysmography; Prospective Studies; Pulse Wave Analysis; Risk Factors; Sweden; Vascular Resistance; Vascular Stiffness; Vasodilation; Vasodilator Agents

Variants in the neuropeptide Y (NPY) gene have been associated with obesity and its traits. The objective of the present study was to evaluate the association of single nucleotide polymorphisms (SNPs) in the NPY gene with obesity, metabolic syndrome features, and inflammatory and cardiovascular disease (CVD) risk biomarkers in Spanish children. We recruited 292 obese children and 242 normal-body mass index (BMI) children. Height, weight, BMI, waist circumference, clinical and metabolic markers, adipokines, and inflammatory (PCR, IL-6, IL-8 and TNF-α) and CVD risk biomarkers (MPO, MMP-9, sE-selectin, sVCAM, sICAM, and PAI-1) were analyzed. Seven SNPs in the NPY gene were genotyped. The results of our study indicate that anthropometric measurements, clinical and metabolic markers, adipokines (leptin and resistin), and inflammatory and CVD risk biomarkers were generally elevated in the obese group. The exceptions to this finding included cholesterol, HDL-c, and adiponectin, which were lower in the obese group, and glucose, LDL-c, and MMP-9, which did not differ between the groups. Both rs16147 and rs16131 were associated with the risk of obesity, and the latter was also associated with insulin resistance, triacylglycerols, leptin, and HDL-c. Thus, we confirm the association of rs16147 with obesity, and we demonstrate for the first time the association of rs16131 with obesity and its possible impact on the early onset of metabolic syndrome features, mainly triacylglycerols, in children.

Topics: Adolescent; Biomarkers; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Cytokines; Female; Genotyping Techniques; Humans; Leptin; Male; Metabolic Syndrome; Neuropeptide Y; Obesity; Polymorphism, Single Nucleotide; Resistin; Risk Factors; Spain; Triglycerides; Waist Circumference

Adiponectin and leptin are likely involved in the pathophysiology of rheumatoid arthritis (RA) and therefore potential new therapeutic targets. Adiponectin inhibition could be expected to enhance cardiovascular metabolic risk. However, it is unknown whether RA changes the influence of adipokines on cardiovascular metabolic risk. We determined whether RA impacts on the independent relationships of circulating leptin and adiponectin concentrations with cardiovascular risk factors and carotid intima-media thickness (cIMT) in 277 black African subjects from a developing population; 119 had RA. RA impacted on the relationships of adiponectin concentrations with lipid concentrations and blood pressure, independent of confounders including adiposity (interaction P < 0.05). This translated into an association of adiponectin concentrations with more favorable lipid variables including HDL cholesterol (P = 0.0005), non-HDL cholesterol (P = 0.007), and triglyceride (P = 0.005) concentrations, total cholesterol-HDL cholesterol (P = 0.0002) and triglycerides-HDL cholesterol (P = 0.0003) ratios, and higher systolic (P = 0.0006), diastolic (P = 0.0004), and mean blood pressure (P = 0.0007) in RA but not non-RA subjects. Leptin was not associated with metabolic risk after adjustment for adiposity. The cIMT did not differ by RA status, and adipokine concentrations were unrelated to atherosclerosis. This study suggests that leptin and adiponectin inhibition may not alter overall cardiovascular risk and disease in RA.

Topics: Adipokines; Adiponectin; Aged; Arterial Pressure; Arthritis, Rheumatoid; Atherosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cholesterol, HDL; Female; Humans; Leptin; Male; Middle Aged; Risk Factors

The accuracy of anthropometric surrogate markers such as the body adiposity index (BAI) and other common indexes like the body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) to predict metabolic sequelae is essential for its use in clinical practice.. Thus, we evaluated the strength of BAI and other indexes to relate with anthropometric parameters, adipocytokines, blood lipids, parameters of glucose-homeostasis and blood pressure in 1,770 patients from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study in a crosssectional design. Measurements were BAI, BMI, WHR, WHtR, abdominal subcutaneous and visceral adipose tissue (aSAT and VAT), total body adipose tissue mass, body weight, waist- and hip circumference (WC and HC), leptin, adiponectin, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), fasting plasma glucose, fasting plasma insulin, the homeostasis model assessment of insulin resistance (HOMAIR), systolic and diastolic blood pressure.. BAI was significantly associated with leptin and HC. We conclude that BAI was the best calculator for leptin. BAI was inferior to BMI to predict anthropometric parameters other than HC, adiponectin, blood lipids, parameters of glucose homeostasis, and blood pressure in this cross-sectional study.

Topics: Adiponectin; Adipose Tissue; Adiposity; Adult; Aged; Austria; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Fasting; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Risk Factors; Triglycerides; Waist Circumference; Waist-Hip Ratio

Infants are at risk of vitamin D insufficiency, owing to their limited exposure to direct sunlight and the low levels of vitamin D in breast milk. Although vitamin D insufficiency has been associated with cardiometabolic risk factors in children, these associations have not been studied in infants, despite their unique risks. Therefore, we sought to determine whether vitamin D status was associated with cardiometabolic measures in infants.. Ninety-nine full-term infants were evaluated at the age of 1 y with measurement of 25-hydroxy vitamin D (25-OH-D) and an array of traditional (fasting glucose, insulin, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol, triglycerides) and emerging (C-reactive protein, adiponectin, leptin) cardiometabolic risk factors. On the basis of 25-OH-D levels, infants were classified as vitamin D sufficient (n = 59), vitamin D insufficient (n = 29), or vitamin D deficient (n = 11).. Duration of exclusive breastfeeding and prevalence of nonwhite ethnicity were highest in the vitamin D-deficient group (P = 0.05 and 0.03, respectively). Current use of vitamin D supplementation was highest in the sufficient group (P = 0.02). Of note, however, there were no significant differences among the three groups in any of the cardiometabolic risk factors, on both unadjusted and covariate-adjusted analyses.. Vitamin D insufficiency/deficiency is not associated with an adverse cardiometabolic risk factor profile in 1-y-old infants.

Topics: Adiponectin; Biomarkers; Breast Feeding; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Enzyme-Linked Immunosorbent Assay; Humans; Infant; Insulin; Leptin; Luminescent Measurements; Metabolic Diseases; Radioimmunoassay; Risk Factors; Statistics, Nonparametric; Triglycerides; Vitamin D Deficiency

Offspring of women with gestational diabetes (GDM) exhibit an adverse cardiovascular risk factor profile by as early as age 5 years. Recently, maternal glycemia has been associated with epigenetic modification of genes on the fetal side of the placenta, including those encoding emerging risk factors (adiponectin, leptin), suggesting that vascular differences may emerge even earlier in life. Thus, we sought to evaluate cardiovascular risk factors and determinants thereof in 1-year-old infants of women with and without GDM.. Traditional (glucose, lipids) and emerging (C-reactive protein (CRP), adiponectin, leptin) risk factors were assessed in pregnancy in 104 women with (n = 36) and without GDM (n = 68), and at age 1-year in their offspring. In pregnancy, women with GDM had higher triglycerides (2.49 vs 2.10 mmol/L, p = 0.04) and CRP (5.3 vs 3.6 mg/L, p = 0.03), and lower adiponectin (7.3 vs 8.5 μg/mL, p = 0.04) than did their peers. At age 1-year, however, there were no differences in cardiovascular risk factors (including adiponectin) between the infants of women with and without GDM. Of note, maternal and infant adiponectin levels were associated in the non-GDM group (r = 0.39, p = 0.001) but not in the GDM group (r = 0.07, p = 0.67). Furthermore, on multiple linear regression analyses, maternal adiponectin emerged as an independent predictor of infant adiponectin in the non-GDM group only (beta = 776.1, p = 0.0065).. Infants of women with and without GDM have a similar cardiovascular risk factor profile at age 1-year. However, there are differences in their early-life determinants of adiponectin that may be relevant to the subsequent vascular risk of GDM offspring.

Topics: Adiponectin; Blood Glucose; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Diabetes Complications; Diabetes, Gestational; Female; Humans; Infant; Leptin; Male; Pregnancy; Prospective Studies; Risk Factors; Triglycerides

In this study, it is aimed to compare the serum leptin and PAI-1 levels and evaluate their relationship in children on hemodialysis (HD) and peritoneal dialysis (PD).. Thirty-six patients on HD (mean age: 15.0 ± 2.8 years), 19 patients on PD (mean age: 13.0 ± 3.5 years) and 15 healthy subjects (mean age: 14.5 ± 2.7 years) were included in the study. Laboratory investigations included blood count, biochemical parameters, serum iron, iron binding capacity, parathormone, erythrocyte sedimentation rate, C-reactive protein (CRP), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, serum leptin and PAI-1 levels.. Serum leptin levels were significantly higher in HD group than in control group when the effects of BMI and sex were controlled, while PD and control groups had similar leptin levels. PAI-1 levels were also significantly higher in HD group than in control group, while there was no statistically significant difference in PAI-1 levels of PD and control group. PAI-1 levels and leptin levels were significantly correlated, which was independent of the effect of BMI in both HD and PD groups when they are evaluated separately.. Results of our study showed that HD patients had higher leptin and PAI-1 levels and leptin and PAI-1 levels were correlated significantly in both patient groups. The effect of elevated serum leptin and PAI-1 levels on the cardiovascular complications remains to be established.

Topics: Adolescent; Age Factors; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Child; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Peritoneal Dialysis; Plasminogen Activator Inhibitor 1; Risk Factors; Sex Factors

Telomere length is recognized as a marker of biological age, and shorter mean leukocyte telomere length is associated with increased risk of cardiovascular disease. It is unclear whether repeated exposure to ultra-endurance aerobic exercise is beneficial or detrimental in the long-term and whether it attenuates biological aging. We quantified 67 ultra-marathon runners' and 56 apparently healthy males' leukocyte telomere length (T/S ratio) using real-time quantitative PCR. The ultra-marathon runners had 11% longer telomeres (T/S ratio) than controls (ultra-marathon runners: T/S ratio = 3.5±0.68, controls: T/S ratio = 3.1±0.41; β = 0.40, SE = 0.10, P = 1.4×10(-4)) in age-adjusted analysis. The difference remained statistically significant after adjustment for cardiovascular risk factors (P = 2.2×10(-4)). The magnitude of this association translates into 16.2±0.26 years difference in biological age and approximately 324-648bp difference in leukocyte telomere length between ultra-marathon runners and healthy controls. Neither traditional cardiovascular risk factors nor markers of inflammation/adhesion molecules explained the difference in leukocyte telomere length between ultra-marathon runners and controls. Taken together these data suggest that regular engagement in ultra-endurance aerobic exercise attenuates cellular aging.

Topics: Adult; Aging; Blood Pressure; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; E-Selectin; Exercise; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Leukocytes; Linear Models; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Risk Factors; Running; Telomere; Triglycerides

Resistin is a major adipose tissue cytokine implicated in insulin resistance, inflammation and vascular damage. This cytokine is raised in patients with end-stage kidney disease (ESKD) but the relationship between resistin and major clinical outcomes has not been investigated in this population.. We studied the mutual relationship between resistin and the two major adipokines (adiponectin and leptin) and the interaction between resistin and adiponectin (ADPN) and all-cause and cardiovascular (CV) mortality in a cohort of 231 haemodialysis patients followed up for 57 ± 44 months.. Plasma resistin was substantially raised in ESKD patients when compared with healthy subjects (P < 0.001). On univariate analysis, resistin was related inversely to ADPN (r = -0.14, P = 0.04) and directly to C-reactive protein (r = 0.15, P = 0.03), but was largely independent of leptin (r = 0.08, P = 0.24) and the HOMA-IR index (r = -0.04, P = 0.51). During the follow-up, 165 patients died (96 for CV causes). On both univariate (all-cause mortality: P = 0.004; CV mortality P < 0.001) and multivariate (all-cause mortality: P = 0.01; CV mortality P < 0.001) Cox regression analyses, the effect of resistin on study outcomes was closely dependent on ADPN levels. There was a consistent excess risk for all-cause (P = 0.002) and CV mortality (P = 0.003) by plasma resistin (20 ng/mL) in patients in the first ADPN tertile, but no risk excess for these outcomes was apparent in patients in the third tertile.. This study indicates that resistin predicts death and fatal CV events depending on plasma ADPN levels. These findings underscore the importance of the interaction among adipokines for the prediction of adverse clinical outcomes in ESKD.

Topics: Adiponectin; Adipose Tissue; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Humans; Insulin Resistance; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Regression Analysis; Renal Dialysis; Resistin; Survival Rate

Variants in the FTO gene have been associated with obesity in children, but this association has not been shown with other biomarkers. We assessed the association of 52 FTO polymorphisms, spanning the whole gene, with obesity and estimated the influence of these polymorphisms on anthropometric, clinical and metabolic parameters as well as inflammation and cardiovascular disease (CVD) risk biomarkers among Spanish children.. A multicentre case-control study was conducted in 534 children (292 obese and 242 with normal-BMI). Anthropometric, clinical, metabolic, inflammation and CVD risk markers were compared using the Student's t-test for unpaired samples. The genotype relative risk was assessed by comparing the obese and normal-BMI group, calculating the odds ratio. The association of each SNP with phenotypic parameters was analysed using either logistic or linear regression analysis.. All anthropometric, clinical and metabolic factors as well as inflammatory and CVD risk biomarkers were higher in the obese than in the normal-BMI group, except adiponectin and HDL-c that were lower, and glucose, LDL-c, and metalloproteinase-9 that did not show difference. Four polymorphisms (rs9935401, rs9939609, rs9928094 and rs9930333) were positively associated with obesity and in linkage disequilibrium between each other; the haplotype including the risk alleles of these polymorphisms showed a high risk for obesity. The rs8061518 was negatively associated with obesity and the haplotype including this SNP and rs3826169, rs17818902 and rs7190053 showed a decreased risk for obesity. Additionally, the rs8061518 was associated with weight, diastolic blood pressure, insulin, homeostatic model assessment of insulin resistance, leptin, and active plasminogen inhibitor activator-1 after sex and age adjustment; however, after an additional BMI adjustment, this polymorphism remained associated only with leptin.. We validated the previous reported association of genetic variability in intron 1 of the FTO gene with the risk of obesity and found no association with other related traits in this region of the gene. We have observed strong statistical evidence for an association of rs8061518 in intron 3 of the gene with decreased risk of obesity and low concentration of leptin.

Topics: Adolescent; Alleles; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Child; Female; Genotype; Haplotypes; Humans; Inflammation; Introns; Leptin; Linkage Disequilibrium; Male; Obesity; Polymorphism, Single Nucleotide; Proteins; Risk Factors; Spain; White People

The adipocyte-derived hormone leptin plays a key role in the regulation of food intake and energy expenditure. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-associated atherosclerosis and cardiovascular disease. In this study, we investigated the associations of leptin and the soluble leptin receptor (sOb-R) with atherosclerosis in patients with type 2 diabetes.. Three hundred seventeen type 2 diabetic subjects were enrolled in this cross-sectional study. Fasting plasma leptin and sOb-R concentrations were measured by enzyme-linked immunosorbent assays. The intima-media thickness (IMT) of the common carotid artery was measured by ultrasound.. The IMT was significantly associated with sOb-R concentrations, age, diabetes duration, serum creatinine (sCre) levels, and systolic blood pressure (SBP), but not with leptin concentrations or the leptin/sOb-R ratio. The concentrations of leptin (r=0.478, p<0.001) and the sOb-R (r= -0.404, p<0.001) and the leptin/sOb-R ratio (r=0.501, p<0.001) were strongly correlated with IMT in subjects treated with insulin for glycemic control, but not in those treated with diet alone or oral hypoglycemic agents. Multiple regression analysis, including age, sex, diabetes duration, body mass index, SBP, HbA1c, triglycerides, LDL-cholesterol, sCre, smoking, and insulin therapy, revealed that plasma leptin and the leptin/sOb-R ratio were independently associated with IMT in subjects treated with insulin.. Plasma leptin and the leptin/sOb-R ratio are associated with atherosclerosis in patients with type 2 diabetes on insulin therapy, and these associations were independent of obesity and other cardiovascular risk factors.

Topics: Adipocytes; Adult; Aged; Aged, 80 and over; Atherosclerosis; Cardiovascular Diseases; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Male; Middle Aged; Obesity; Receptors, Leptin

Obesity induced by Western diets is associated with type 2 diabetes mellitus and cardiovascular diseases, although underlying mechanisms are unclear. We investigated a murine model of diet-induced obesity to determine the effect of transient potential receptor vanilloid 1 (TRPV1) deletion on hypertension and metabolic syndrome. Wild-type and TRPV1 knockout mice were fed normal or high-fat diet from 3 to 15 weeks. High-fat diet-fed mice from both genotypes became obese, with similar increases in body and adipose tissue weights. High-fat diet-fed TRPV1 knockout mice showed significantly improved handling of glucose compared with high-fat diet-fed wild-type mice. Hypertension, vascular hypertrophy, and altered nociception were observed in high-fat diet-fed wild-type but not high-fat diet-fed TRPV1 knockout mice. Wild-type, but not high-fat diet-fed TRPV1 knockout, mice demonstrated remodeling in terms of aortic vascular hypertrophy and increased heart and kidney weight, although resistance vessel responses were similar in each. Moreover, the wild-type mice had significantly increased plasma levels of leptin, interleukin 10 and interleukin 1β, whereas samples from TRPV1 knockout mice did not show significant increases. Our results do not support the concept that TRPV1 plays a major role in influencing weight gain. However, we identified a role of TRPV1 in the deleterious effects observed with high-fat feeding in terms of inducing hypertension, impairing thermal nociception sensitivity, and reducing glucose tolerance. The observation of raised levels of adipokines in wild-type but not TRPV1 knockout mice is in keeping with TRPV1 involvement in stimulating the proinflammatory network that is central to obesity-induced hypertension and sensory neuronal dysfunction.

Topics: Adipose Tissue; Animals; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Diet, High-Fat; Hypertension; Insulin Resistance; Interleukin-10; Interleukin-1beta; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; TRPV Cation Channels

Inflammatory processes contribute to both diabetes and cardiovascular risk. We wanted to investigate whether circulating concentrations of proinflammatory immune mediators and adiponectin in diabetic patients are associated with incident cardiovascular events.. In 1,038 participants with diabetes of the population-based ESTHER study, of whom 326 showed signs of renal dysfunction, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the association of increasing concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), IL-18, macrophage migration inhibitory factor (MIF), adiponectin, and leptin with cardiovascular events (myocardial infarction, stroke, or fatal cardiovascular event) during a follow-up period of 8 years.. During follow-up, 161 subjects with diabetes experienced a primary cardiovascular event. Proinflammatory markers were not associated with a higher risk for primary cardiovascular events in the total study population after adjustment for multiple confounders. However, IL-6 and MIF were associated with cardiovascular events in subjects with renal dysfunction (HR for the comparison of top vs. bottom tertile 1.98 [95% CI 1.12-3.52], P [trend] = 0.10 for IL-6; 1.48 [0.87-2.51], P [trend] = 0.04 for MIF). Adiponectin levels were associated with cardiovascular events in the total population (1.48 [1.01-2.21], P [trend] = 0.03), and the association was even more pronounced in the subgroup with renal dysfunction (1.97 [1.08-3.57], P [trend] = 0.02).. In particular, the absence of an association between CRP and a U-shaped association of adiponectin levels with incident cardiovascular events show that associations between circulating immune mediators and cardiovascular risk differ between diabetic patients and subjects of the general population.

Topics: Adiponectin; Aged; C-Reactive Protein; Cardiovascular Diseases; Cytokines; Diabetic Retinopathy; Female; Humans; Interleukin-18; Interleukin-6; Leptin; Macrophage Migration-Inhibitory Factors; Male; Middle Aged; Proportional Hazards Models

The obesity prevalence is growing worldwide and largely responsible for cardiovascular disease, the most common cause of death in the western world. The rationale of this study was to distinguish metabolically healthy from unhealthy overweight/obese young and adult patients as compared to healthy normal weight age matched controls by an extensive anthropometric, laboratory, and sonographic vascular assessment.. Three hundred fifty five young [8 to < 18 years, 299 overweight/obese(ow/ob), 56 normal weight (nw)] and 354 adult [>18-60 years, 175 (ow/ob), 179 nw)] participants of the STYJOBS/EDECTA (STYrian Juvenile Obesity Study/Early DEteCTion of Atherosclerosis) cohort were analyzed. STYJOBS/EDECTA (NCT00482924) is a crossectional study to investigate metabolic/cardiovascular risk profiles in normal and ow/ob people free of disease except metabolic syndrome (MetS).. From 299 young ow/ob subjects (8-< 18 years), 108 (36%), and from 175 adult ow/ob subjects (>18-60 years), 79 (45%) had positive criteria for MetS. In both age groups, prevalence of MetS was greater among males. Overweight/obese subjects were divided into "healthy" (no MetS criterion except anthropometry fulfilled) and "unhealthy" (MetS positive). Although percentage body fat did not differ between "healthy" and "unhealthy" ow/ob, nuchal and visceral fat were significantly greater in the "unhealthy" group which had also significantly higher values of carotid intima media thickness (IMT). With MetS as the dependent variable, two logistic regressions including juveniles <18 years or adults >18 years were performed. The potential predictor variables selected with the exception of age and gender by t test comparisons included IMT, ultrasensitive c-reactive protein (US-CRP), IL-6, malondialdehyde (MDA), oxidized LDL, leptin, adiponectin, uric acid (UA), aldosterone, cortisol, transaminases, fibrinogen. In both groups, uric acid and in adults only, leptin and adiponectin, turned out as the best predictor.. Serum levels of UA are a significant predictor of unhealthy obesity in juveniles and adults.

Topics: Adiponectin; Adiposity; Adolescent; Adult; Age Factors; Cardiovascular Diseases; Case-Control Studies; Child; Cohort Studies; Cross-Sectional Studies; Endothelium, Vascular; Female; Humans; Intra-Abdominal Fat; Leptin; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors; Sex Factors; Uric Acid; Young Adult

The objective was to test the hypothesis that traditional and novel cardiometabolic risk factors would be significantly different in groups of men of different fatness and fitness. Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, high-sensitivity C-reactive protein, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, leptin, adiponectin, tumor necrosis factor-α, interleukin-6, interleukin-10, fibrinogen, and insulin resistance were assessed in 183 nonsmoking white men aged 35 to 53 years, including 62 who were slim and fit (waist girth ≤90 cm and maximal oxygen consumption [VO(2)max] above average), 24 who were slim and unfit (waist girth ≤90 cm and VO(2)max average or below), 39 who were fat and fit (waist girth ≥100 cm and VO(2)max above average), and 19 who were fat and unfit (waist girth ≥100 cm and VO(2)max average or below). Seventy-six percent gave blood on 2 occasions, and the average of 1 or 2 blood tests was used in statistical tests. Waist girth (centimeters) and fitness (milliliters of oxygen per kilogram of fat-free mass) were associated with high-density lipoprotein cholesterol, leptin, and insulin resistance after adjustment for age, saturated fat intake, and total energy intake. High-density lipoprotein cholesterol, triglycerides, alanine aminotransferase, and insulin resistance were significantly different in men who were fat and fit and those who were fat and unfit. These data suggest that differences in lipid and lipoprotein concentrations, liver function, and insulin resistance may explain why the risks of chronic disease are lower in men who are fat and fit than those who are fat and unfit.

Topics: Adiposity; Adult; Blood Pressure; Body Fat Distribution; Cardiovascular Diseases; Cholesterol, HDL; Cross-Sectional Studies; Exercise; gamma-Glutamyltransferase; Humans; Leptin; Male; Metabolic Diseases; Middle Aged; Physical Fitness; Risk Factors; Triglycerides; White People

Obesity is a risk factor for both cardiovascular disease and cancer development. Leptin, a cytokine produced by adipose tissue, controls different processes in peripheral tissues, including cancer development and thrombotic disorders in patients with a variety of clinical disorders. Tissue factor (TF), the trigger of blood clotting, is abundant in the adipose tissue. Since TF, often expressed by cancer cells, is considered a hallmark of cancer progression, we investigated whether leptin could modulate TF in the human metastatic breast carcinoma cell line MCF-7.. MCF-7 cells were incubated with or without the different reagents at 37 °C. At the end of incubation, cells were tested for procoagulant activity by a one-stage clotting assay, TF and TNF-α antigen levels and mRNA by ELISA and real-time RT-PCR, respectively. Leptin receptor was studied by FACS.. Both TF activity and antigen constitutively expressed by MCF-7 were significantly increased by leptin in a dose-dependent fashion. TF mRNA levels were also enhanced indicating that leptin exerts its effect at the transcription level. The effect of leptin was specific and required binding to its receptor (Ob-R), which was found on the surface of the cells, since antibodies against leptin and Ob-R completely prevented TF expression upregulation. In addition, leptin enhanced both TNF-α mRNA synthesis and secretion from MCF7. An anti-TNF-α MoAb completely abolished the leptin-induced TF expression.. These data support the hypothesis that leptin, by its upregulation of TF, possibly mediated by TNF-α synthesis, may contribute to processes underlying both cancer and vascular cell disorders.

Topics: Breast Neoplasms; Cardiovascular Diseases; Cell Line, Tumor; Female; Humans; Leptin; Obesity; Receptors, Leptin; Thromboplastin; Up-Regulation

Some studies have pointed to a role of uncoupling protein 3 (UCP3) in the regulation of fat distribution. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on fat mass and adipocytokines in naïve patients with Type 2 diabetes mellitus.. A population of 57 patients with Type 2 diabetes mellitus and obesity was analyzed in a cross-sectional study. Genotype of UCP3 gene -55CT was studied.. Forty-six patients (80.7%) had the 55CC genotype and 11 patients (19.3%) the 55CT genotype. Fat mass (39.1±15.4 vs 53.3±16.8 kg; p<0.05), weight (92.6±17.7 vs 106.3±17.3 kg; p<0.05), body mass index (36.2±6.5 vs 42.8±5.2 kg/m²; p<0.05), waist circumference (112.8±13.6 vs 127.9±12.3 cm; p<0.05), waist-to-hip ratio (0.96±0.1 vs 1.1±0.2; p<0.05), C reactive protein (6.1±5.1 vs 12.4±6.1 mg/dl; p<0.05) and leptin (92.8±86 vs 114±89 ng/ml; p<0.05) were higher in patients with mutant genotype than in those with wild genotype.. C reactive protein and fat mass were higher in the mutant group of -55 CT UCP3 gene diabetic patients than in wild type patients.

Topics: Adiposity; Aged; Body Fat Distribution; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Genetic Association Studies; Humans; Ion Channels; Leptin; Male; Middle Aged; Mitochondrial Proteins; Mutation; Obesity; Polymorphism, Genetic; Promoter Regions, Genetic; Risk Factors; Spain; Uncoupling Protein 3

1. Overconsumption of fructose produces glucose intolerance, autonomic abnormalities and renal dysfunction and may be related to the worldwide epidemic of obesity and diabetes. 2. Experiments were conducted to determine whether the time period (light or dark) of fructose consumption influenced the pathological consequences. C57BL mice were given standard chow and assigned to one of three groups: (i) control (n = 10), which received water over a 24 h period; (ii) FL (n = 11), which received 10% fructose solution during the 12 h light period; and (iii) FD (n = 11), which received 10% fructose solution during the 12 h dark period. 3. There was a time related increase in body weight for all groups (P < 0.01, 2 vs 6 wks). There was a greater increase in body fat in the FL group compared with the control and FD groups. The changes in adiposity occurred even though the total caloric intake was not significantly different among the groups (approximately 18 kcal/day). Total fluid (water + fructose) consumption was greater in the FD and FL groups compared with control at 6 weeks. Significant increases were noted for plasma insulin and leptin at 8 weeks, with highest levels in the FL compared with FD group (P < 0.05). There were no significant changes in glucose, glucose tolerance, cholesterol, triglycerides or adiponectin. 4. The results of the present study suggest that there is a mismatch in caloric consumption, metabolism and adiposity as related to the light-dark cycle of fructose consumption. These findings have clinical implications in the control of bodyweight, abdominal fat accumulation and Type 2 diabetes.

Topics: Adipose Tissue, White; Adiposity; Animals; Cardiovascular Diseases; Cell Size; Cholesterol; Circadian Rhythm; Feeding Behavior; Fructose; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Random Allocation; Risk Factors; Triglycerides; Weight Gain

To evaluate leptin, insulin resistance (IR), and changes in body composition and lipid profile within 5 years after renal transplantation.. Longitudinal study.. Hospital de Clínicas de Porto Alegre/RS, Brazil.. Thirty-two renal transplant recipients were followed up for 5 years after transplantation.. Data were collected at transplantation time (T₁) and after 3 months (T₂), 1 year (T₃), and 5 years (T₄). Leptin serum levels, IR assessed by homeostasis model assessment (HOMA) index, lipid profile, and anthropometric measurements were analyzed. Data were compared with a control group at baseline.. At T₁, pretransplant patients had leptin levels (ng/mL) (11.9 [9.2 to 25.2]) higher than the control group (7.7 [5.2 to 9.9]; P < .0001). After transplantation, levels decreased at T₂ and T₃, but increased at T₄ to values similar to those seen at T₁ (T₄: 9.2 [5.7 to 21]; P = 1). HOMA also decreased at T₂, but increased at T₄ to identical levels (T₁: 2.1 [1.63 to 2.23], T₄: 2.1 [1.6 to 2.85]; P = 1). No significant changes in body fat percentage (BF%) were observed; however, the arm muscle circumference increased significantly at T₄ (P < .0001). At T₂, total cholesterol, triglycerides, and low-density lipoprotein cholesterol increased, whereas at T₄, lipid profile moved toward T₁ levels. By linear regression analysis, gender, BF%, and HOMA were independent predictors of leptin levels. A trend toward higher body mass index was observed in woman who also presented higher leptin and lower HOMA levels.. Leptin levels and HOMA decrease in the immediate posttransplant period and remain reduced for at least 1 year. Five years post transplantation, leptin, IR, BF%, and lipids have a profile similar to those in the pretransplant period. This metabolic profile is possibly associated with the elevated incidence of cardiovascular diseases observed in the late posttransplant period.

Topics: Adult; Biomarkers; Body Composition; Body Mass Index; Cardiovascular Diseases; Cholesterol, LDL; Female; Follow-Up Studies; Humans; Incidence; Insulin Resistance; Kidney Transplantation; Leptin; Linear Models; Longitudinal Studies; Male; Metabolome; Middle Aged; Triglycerides

Sedentary behavior is associated with adiposity and cardiometabolic risk.. To determine the associations between sedentary behavior and measures of adiposity-associated inflammation.. Between 2002 and 2005, a total of 1543 Multi-Ethnic Study of Atherosclerosis participants completed detailed health history questionnaires, underwent physical measurements, and had blood assayed for adiponectin, leptin, tumor necrosis factor-alpha (TNF-α) and resistin. Analyses included linear regression completed in 2010. The mean age was 64.3 years and nearly 50% were female. Forty-one percent were non-Hispanic white, 24% Hispanic-American, 20% African-American, and 14% Chinese-American.. In linear regression analyses and with adjustment for age, gender, ethnicity, education, BMI, smoking, alcohol consumption, hypertension, diabetes mellitus, dyslipidemia, hormone therapy and waist circumference, sedentary behavior was associated with higher natural log ("ln") of leptin and ln TNF-α but a lower ln adiponectin-to-leptin ratio (β=0.07, β=0.03 and -0.07, p<0.05 for all). Compared to the first tertile, and after the same adjustment, the second and third tertiles of sedentary behavior were associated with higher levels of ln leptin (β=0.11 and β=0.12, respectively; p<0.05 for both) but lower levels of the adiponectin-to-leptin ratio (β=-0.09 and -0.11, respectively; p<0.05 for both).. Sedentary behavior is associated with unfavorable levels of adiposity-associated inflammation.

Topics: Adiponectin; Adiposity; Aged; Aged, 80 and over; Atherosclerosis; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Ethnicity; Female; Humans; Inflammation; Leptin; Linear Models; Longitudinal Studies; Male; Metabolic Diseases; Middle Aged; Sedentary Behavior; Tumor Necrosis Factor-alpha

Increased arterial stiffness is a risk factor for adverse cardiovascular events in adults with obesity-related insulin resistance (IR) or type 2 diabetes mellitus. Adolescents with type 2 diabetes have stiffer vessels. Whether stiffness is increased in obesity/IR in youth is not known. We sought to determine if IR was a determinant of arterial stiffness in youth, independent of obesity and cardiovascular risk factors.. We measured cardiovascular risk factors, IR, adipocytokines and arterial stiffness (brachial artery distensibility [BrachD], pulse wave velocity [PWV]) and wave reflection (augmentation index [AIx]) in 343 adolescents and young adults without type 2 diabetes (15-28 years old, 47% male, 48% non-white). Individuals <85th percentile of BMI were classified as lean (n = 232). Obese individuals were grouped by HOMA index as not insulin resistant (n = 46) or insulin resistant (n = 65) by the 90th percentile for HOMA for lean. Mean differences were evaluated by ANOVA. Multivariate models evaluated whether HOMA was an independent determinant of arterial stiffness.. Risk factors deteriorated from lean to obese to obese/insulin resistant (all p ≤ 0.017). Higher AIx, lower BrachD and higher PWV indicated increased arterial stiffness in obese and obese/insulin-resistant participants. HOMA was not an independent determinant. Age, sex, BMI and BP were the most consistent determinants, with HDL-cholesterol playing a role for BrachD and leptin for PWV (AIx R²= 0.34; BrachD R² = 0.37; PWV R² = 0.40; all p ≤ 0.02).. Although IR is associated with increased arterial stiffness, traditional cardiovascular risk factors, especially obesity and BP, are the major determinants of arterial stiffness in healthy young people.

Topics: Adiposity; Adolescent; Adolescent Development; Adult; Blood Pressure; Body Mass Index; Brachial Artery; Cardiovascular Diseases; Cholesterol, HDL; Cohort Studies; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Longitudinal Studies; Male; Obesity; Ohio; Risk Factors; Vascular Stiffness; Young Adult

Inflammation is an important component of the metabolic syndrome (MetS) which could be the link between the metabolic and the cardiovascular consequences of this condition. Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for MetS and an inflammation component has been described in this disease. The aim of the study was to evaluate the relationships between cytokine concentrations, components of MetS and cardiovascular risk markers in women with late-onset GDM. Women (n=63) with late-onset GDM and 63 controls were enrolled. Clinical variables, and obstetrics and perinatal outcomes were recorded. Relationships between cytokines (TNF-α, leptin, IL6, adiponectin) and endothelial injury markers (VCAM, ICAM and selectine) were analyzed. Control vs. patient data indicated: pre-gestational body mass index (BMI) 23.46±3.73 vs. 26.97±5.07kg/m(2) (p=0.001); TNF-α 2.2±0.8 vs. 3.1±1.5pg/mL (p=0.002); leptin 18714.78±8859.08 vs. 27365.79±16209.67pg/mL (p=0.001); adiponectin 162.42±34.19 vs. 141.54±41.33ng/mL (p=0.04). Multivariate analyses showed that adiponectin had a protective effect (OR=0.9; p=0.02) and BMI carried a significant risk (OR=8.4; p=0.01) for GDM. No differences were found in endothelial injury markers. In conclusion, the cytokine profile in women with late-onset GDM is characterized by high concentrations of TNF-α and leptin and low adiponectin. This profile is related, in large extent, to an increased pregravid BMI which, potentially, may be linked to the future development of both metabolic and cardiovascular disease.

Topics: Adiponectin; Adult; Body Mass Index; Cardiovascular Diseases; Diabetes, Gestational; Female; Humans; Leptin; Metabolic Syndrome; Pregnancy; Pregnancy Trimester, Third; Risk; Tumor Necrosis Factor-alpha

Studies in adults have reported associations of low circulating total 25-hydroxyvitamin D with increased cardiovascular disease and risk factors. Evidence of associations in children, however, is limited, and it is unknown whether associations with risk factors differ for each 25-hydroxyvitamin D analog [25-hydroxyvitamin D(2) (25[OH]D(2)) and 25-hydroxyvitamin D(2) (25[OH]D(3))].. The objective of the study was to compare associations of 25(OH)D(2) and 25(OH)D(3) with cardiovascular risk factors in children.. The design of the study was a cross-sectional study of 4274 children (mean age 9.9 yr) from the Avon Longitudinal Study of Parents and Children.. The main outcomes included blood pressure, lipids [triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C)], apolipoproteins (Apo-A1 and Apo-B), adiponectin, leptin, C-reactive protein, and IL-6.. In confounder-adjusted models, 25(OH)D(2) was inversely associated with Apo-A1 (change per doubling of exposure: -0.74 mg/dl; 95% confidence interval -0.14, -0.04) and triglycerides (relative percentage change per doubling of exposure: -1.64%; -3.27, 0.01) and positively associated with C-reactive protein (8.42%; 3.40, 13.58) and IL-6 (5.75%; 1.83, 9.25). 25(OH)D(3) was positively associated with HDL-C (0.04 mmol/liter; 0.02, 0.06), Apo-A1 (1.96 mg/dl; 0.65, 3.24), and adiponectin (0.47 μg/ml; 0.15, 0.79). There was statistical evidence that associations of 25(OH)D(2) and 25(OH)D(3) with HDL-C, Apo-A1, and IL-6 differed from each other (all P values for differences ≤0.02).. Higher circulating 25(OH)D(3) was associated with cardioprotective levels of HDL-C, Apo-A1, and adiponectin in children. Associations of 25(OH)D(2) with cardiovascular risk factors were in mixed directions. It is necessary to see whether these associations are replicated in large prospective studies.

Topics: 25-Hydroxyvitamin D 2; Adiponectin; Apolipoproteins; Blood Pressure; C-Reactive Protein; Calcifediol; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Humans; Interleukin-6; Leptin; Lipids; Male; Risk Factors

Cushing's Disease (CD) alters fat distribution, muscle mass, adipokine profile, and cardiovascular risk factors. It is not known whether remission entirely reverses these changes.. Our objective was to determine whether the adverse body composition and cardiovascular risk profile in CD change after remission.. Fourteen CD patients were studied prospectively: before surgery (active disease) and again postoperatively 6 months after discontinuing oral glucocorticoids (remission). Whole-body magnetic resonance imaging was used to examine lean and fat tissue distributions.. Body composition (skeletal muscle and fat in the visceral, bone marrow, sc, and inter-muscular compartments) and cardiovascular risk factors (serum insulin, glucose, leptin, high-molecular-weight adiponectin, C-reactive protein, and lipid profile) were measured in active CD and remission (mean 20 months after surgery).. Remission decreased visceral, pelvic bone marrow, sc (including trunk and limb sc), and total fat; waist circumference; and weight (P < 0.05). Remission altered fat distribution, resulting in decreased visceral/total fat (P = 0.04) and visceral fat/skeletal muscle ratios (P = 0.006). Remission decreased the absolute muscle mass (P = 0.015). Cardiovascular risk factors changed: insulin resistance, leptin, and total cholesterol decreased (P < 0.05), but adiponectin, C-reactive protein, and other lipid measures did not change.. CD remission reduced nearly all fat depots and reverted fat to a distribution more consistent with favorable cardiovascular risk but decreased skeletal muscle. Remission improved some but not all cardiovascular risk markers. Remission from CD dramatically improves body composition abnormalities but may still be associated with persistent cardiovascular risk.

Topics: Adiponectin; Adipose Tissue; Adult; Biomarkers; Blood Glucose; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Female; Glucocorticoids; Humans; Insulin; Insulin Resistance; Leptin; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Pituitary ACTH Hypersecretion; Prospective Studies; Risk; Risk Factors

To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m² for the body mass index (BMI).. Forty-seven patients (30 men, 11 diabetics, 53.8 ± 12.2 y of age, 58.2 ± 50.9 mo on HD) were studied. Anthropometric data and handgrip strength were evaluated. C-reactive protein, tumor necrosis factor-α, leptin, and interleukin-6 were measured. Mortality was assessed after 24 mo of follow-up.. Nineteen patients (40.4%) presented BMI values lower than 23 kg/m² and leptin levels, midarm muscle area, and free-fat mass were significantly lower in these patients. The prevalence of functional muscle loss according to handgrip strength was not different between the BMI groups. The sum of skinfold thicknesses, the percentage of body fat, fat mass, the fat mass/free-fat mass ratio, and waist circumference were significantly lower in patients with a BMI lower than 23 kg/m², but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m² presented a higher prevalence of inflammation and higher waist circumference and body fat values. The adiposity parameters were correlated with C-reactive protein and leptin. A Cox multivariate regression analysis demonstrated that C-reactive protein, tumor necrosis factor-α, and interleukin-6 predict cardiovascular mortality.. Patients on HD with a BMI lower than 23 kg/m² did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m² had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m² does not seem to be a reliable marker of protein-energy wasting in patients on HD.

Topics: Adult; Aged; Biomarkers; Body Composition; Body Fluid Compartments; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Diabetes Complications; Female; Humans; Inflammation; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Muscle, Skeletal; Obesity; Proportional Hazards Models; Protein-Energy Malnutrition; Reference Values; Renal Dialysis; Reproducibility of Results; Wasting Syndrome

Serum C-reactive protein (CRP) and leptin levels have been independently associated with the cardiovascular risk factors. The aim of the present study was to determine if their serum levels were associated with cardiovascular risk factors or metabolic syndrome as well as their correlation in the Taiwanese population.. This retrospective study included 999 subjects (> 18 y), who underwent a physical examination in Chang-Gung Memorial Hospital-Linkou and Chiayi in Taiwan. The associations between CRP and/or leptin levels and cardiovascular risk factors and metabolic syndrome were determined using independent two sample t-tests to detect gender differences and chi-square tests to evaluate differences in frequencies. To compare the means of the variables measured among the four groups (high and low leptin and high and low CRP), analysis of variance (ANOVA) was used.. Both CRP and leptin levels were independently associated with several cardiovascular risk factors, including diabetes, hypercholesterolemia and metabolic syndrome in both men and women (P < 0.05). In addition, a positive correlation between leptin and CRP levels was observed in both genders. Both high-CRP and high-leptin were associated with high blood glucose, waist circumference and serum triglyceride. Whereas increased metabolic syndrome incidence was observed in males with elevated leptin regardless of CRP levels, females with elevated CRP or leptin had increased incidence of metabolic syndrome.. Both leptin and CRP levels were associated with cardiovascular risk factors as well as metabolic syndrome score in both men and women although gender-specific differences were observed. Thus, CRP and leptin may represent useful biomarkers for predicting the onset of cardiovascular disease or metabolic syndrome in Taiwanese adults.. IRB/CGMH 100-3514B.

Topics: Adult; Age Factors; Analysis of Variance; Asian People; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Incidence; Leptin; Male; Metabolic Syndrome; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors; Taiwan

Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for metabolic syndrome and CVD. The aim of the study was to evaluate the relationships between levels of cytokines, components of metabolic syndrome and cardiovascular risk markers in women with previous gestational diabetes.. Women (n = 41) with gestational diabetes background (cases) and 21 healthy women (controls) in the postpartum period were enrolled. Demographic and clinical data, lipid and carbohydrate metabolism and uric acid and adipokine levels (TNF-α, IL-6, leptin and adiponectin) were compared and their relationships analysed. Metabolic syndrome prevalence was calculated by WHO and NCEP-ATPIII definitions.. There were significant differences between cases and controls: body mass index (kg/m(2) ) 27.4 ± 5.6 vs 23.9 ± 3.6 (p = 0.013), waist circumference (cm) 85.2 ± 12.9 vs 77.5 ± 9.0 (p = 0.017), metabolic syndrome (WHO definition) 14.6% vs 0% (p = 0.012), metabolic syndrome (NCEP-ATPIII definition) 22% vs 0% (p = 0.002), low HDL 36.6% vs 9.5% (p = 0.024), fasting glucose (mmol/L) 5.4 ± 0.6 vs 4.9 ± 0.2 (p < 0.001), glucose 120' oral glucose tolerance test (mmol/L) 5.8 ± 1.7vs 4.7 ± 0.8 (p = 0.007), fasting insulin (μU/mL) 13.4 ± 8.1 vs 8.4 ± 4.3 (p = 0.004), HOMA index 3.3 ± 2.3 vs 1.8 ± 1.0 (p = 0.002), HbA(1c) (%) 5.4 ± 0.2 vs 5.2 ± 0.2 (p = 0.021), uric acid (mg/dL) 4.1 ± 1 vs 3.5 ± 0.6 (p = 0.009), leptin (ng/mL) 32 025.5 ± 19 917.3 vs 20 258.9 ± 16 359.9 (p = 0.023), respectively.. Women with previous gestational diabetes have central adiposity, atherogenic lipid profile, carbohydrate intolerance and adverse adipokine profile, all of which are risk factors for the future development of metabolic disease and CVD.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Diabetes, Gestational; Fasting; Female; Humans; Insulin; Leptin; Lipids; Metabolic Syndrome; Postpartum Period; Pregnancy; Prevalence; Risk Factors

Cardiovascular disease (CVD) and osteoporosis share some common risk factors such as old age, smoking, alcoholic drinking, hypertension, diabetes mellitus, and hyperlipidemia. Although previous studies have investigated the association of bone mineral density (BMD) with CVD, the results were conflicting. There are limited studies on the association of BMD loss rate with CVD. We therefore conducted a 5-year prospective study to examine the relation among BMD, bone loss, and risk of CVD in a Chinese cohort. Of 9,657 community residents 30 to 75 years old, 6,092 were enrolled in the study and followed annually for 5 years. At baseline demographic data, BMD, smoking and drinking statuses, medical history, and blood samples were collected. Cox proportional hazards analysis was used to evaluate the association of BMD and incidence of CVD. Over the 5-year follow-up period, CVD developed in 118 subjects. Baseline BMD, bone loss rate, current smoking, daily alcoholic ingestion, and higher osteoprotegerin and leptin levels were independently associated with increased risk of CVD, whereas higher baseline adiponectin level was associated with decreased risk of CVD in women and men. In conclusion, uncovering the relation linking osteoporosis and CVD is important for understanding the pathogenesis of these 2 common disorders.

Topics: Absorptiometry, Photon; Adiponectin; Adult; Aged; Alcohol Drinking; Biomarkers; Bone Density; Cardiovascular Diseases; China; Female; Humans; Incidence; Leptin; Male; Middle Aged; Osteoporosis; Osteoprotegerin; Proportional Hazards Models; Prospective Studies; Risk; Risk Factors; Smoking; Statistics, Nonparametric

The plasma leptin/adiponectin (L/A) ratio has been proposed as a preferential marker of atherosclerosis susceptibility compared to leptin and adiponectin alone. We determined the extent to which the L/A ratio predicts incident cardiovascular disease (CVD) taking account of clinical risk factors, microalbuminuria, the total cholesterol/HDL cholesterol (TC/HDL-C ratio), triglycerides, high sensitive C-reactive protein (hs-CRP) and insulin sensitivity (homeostasis model assessment (HOMA(ir))).. A community-based prospective nested case-control study was carried out in 103 non-diabetic men who developed a first cardiovascular event (cases) and 106 male control subjects (no clinically manifest CVD and no lipid lowering drug use at baseline; median follow-up of 3.0 and 10.5 years, respectively). Plasma leptin, adiponectin, the leptin/adipnectin (L/A) ratio, as well as hs-CRP, HOMA(ir) and the TC/HDL-C ratio were determined at baseline.. Plasma leptin levels and the L/A ratio were higher in cases vs. controls (p=0.002 for both), but the difference in adiponectin was not significant (p=0.10). Age-adjusted incident CVD was associated with plasma leptin, adiponectin and the L/A ratio (p=0.045 to p=0.001). The relationships of incident CVD with plasma leptin (p=0.19) and adiponectin (p=0.073) lost statistical significance after additional adjustment for smoking, waist circumference, hypertension, microalbuminuria, the TC/HDL-C ratio, hs-CRP and HOMA(ir). In this fully adjusted analysis, the L/A ratio remained predictive of incident CVD (hazard ratio: 1.40 (95% CI 1.05-1.87), p=0.024).. This study suggests that the L/A ratio may be a preferential marker of a first cardiovascular event in men compared to plasma leptin and adiponectin levels alone.

Topics: Adiponectin; Adult; Aged; Albuminuria; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Follow-Up Studies; Humans; Incidence; Insulin Resistance; Leptin; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Triglycerides

Most studies evaluating the conjoint effects of leptin and human soluble leptin receptor (hs-LR) on cardiometabolic risk factors have been conducted in well-characterized ethnic groups. We aimed to assess the associations of leptin and hs-LR with the cardiometabolic risk factors that reflect the components of metabolic syndrome (MetS) in a Brazilian population with varying degrees of adiposity.. This is a cross-sectional analysis of adult subjects (n=173, age 45 ± 12 years, 124 women; body mass index [BMI] 35.6 ± 9.5 kg/m(2)) for association of leptin and its soluble receptor with cardiometabolic risk factors (glucose, BMI, waist circumference, hip circumference, blood pressure, insulin, cholesterol and triglycerides). Plasma hs-LR was measured by ELISA; insulin and leptin were determined by RIA. Metabolic syndrome was defined by NCEP/ATP III.. Leptin was positively associated with blood pressure, BMI, waist circumference, hip circumference, triglycerides, glucose, insulin and HOMA and inversely correlated with HDL-cholesterol. The hs-LR exhibited inverse relationship with cardiometabolic risk factors (P ≤ 0.006), except for glucose and lipid parameters. Leptin increased, whereas hs-LR decreased, with increasing number of MetS components (P for trend<0.001). In multivariable models, sex, BMI and insulin were independently associated with leptin, whereas age, sex, BMI and systolic blood pressure were the independent correlates of hs-LR.. In a Brazilian population with complex interethnic admixture, levels of hs-LR and leptin were independently associated with systolic blood pressure and insulin, respectively. Leptin increased with increasing number of MetS components. In turn, hs-LR decreased as the number of MetS components increased.

Topics: Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Brazil; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Receptors, Leptin; Risk Factors; Sex Factors; Triglycerides; Waist Circumference

Adipose tissue possess endocrine functions that include synthesis of various adipocytokines, which affect the metabolism of lipids and glucoses, development of atherosclerotic processes, and are involved in the development of hypertension and cardiovascular diseases. Body fat distribution is a significant risk factor for the development of obesity related diseases. Leptin and adiponectin are adipokines whose concentrations vary with the level of obesity. The aim of this research is to determine the relation of the changes in leptin and adiponectin concentrations in overweight persons with anthropometric parameters of the subjects.. The study included 40 adult, hypertensive subjects - divided into two groups according to sex, with the body mass index 25-30 kg/m², with regular glycemia and renal function. All subjects underwent biochemical (serum lipid, glucose and creatinine level) and anthropometric measurements. Leptin concentration was determined by radioimmunoassay, while adiponectin concentration was determined by enzyme immunoassay.. Both leptin and adiponectin concentrations significantly correlated with the waist circumference in both groups of subjects. In male subjects, leptin concentration correlated positively with the body mass index and the hip circumference, while adiponectin concentration correlated negatively with the hip circumference.. Being overweight is a condition marked by pathologically altered values of leptin concentration (increased level) and adiponectin (decreased level), that are changing as the obesity level and the waist circumference increase. It can be concluded that abdominal obesity and higher body mass index increase the risk for the development of overweight-obesity-related diseases.

Topics: Adiponectin; Adult; Body Mass Index; Body Size; Cardiovascular Diseases; Female; Humans; Hypertension; Leptin; Male; Overweight; Waist Circumference

Adiponectin and leptin link metabolic disorders and coronary artery disease (CAD). We analysed their relationship with CAD, classical risk factors and biomarkers in 287 CAD patients (cases) and 477 unaffected family members (controls) selected from the Indian Atherosclerosis Research Study (IARS). Classical risk factors included diabetes, hypertension, dyslipidaemia and obesity markers. Novel biomarkers were measured according to manufacturer recommendations. Adverse clinical events were recorded through telephonic follow-up. Cases showed lower adiponectin levels (4684.62 ± 190.73 ng/ml) than controls (5768.86 ± 152.87 ng/ml) (p=1.58X10(-5)); Leptin levels were higher in affected males (12.47 ± 1.32 ng/ml) than in male controls (9.53 ± 1.19 ng/ml, p=0.017). Adiponectin 1st quartile showed significant protection against CAD in females when compared to 3rd (odds ratio [OR] 0.39, 0.16-0.92, p=0.032) or 4th (OR 0.32, 0.14-0.72; p=0.006) quartile group. Leptin 3rd quartile showed higher CAD risk in males as compared to 1st quartile group (OR 2.09, 1.09-4.01, p=0.028). Subjects with metabolic syndrome showed low adiponectin and high leptin levels. Adipokines showed opposing association trend with lipids, inflammatory and coagulation markers and strong correlation (r=-0.14 to 0.52) with obesity markers. Cases with recurrent event and controls who developed new cardiac event during follow up showed high adiponectin levels (p<0.05). A model that combined adiponectin, leptin and conventional risk factors yielded the best 'C' index (0.890, 0.067-0.912). CAD patients in the top adiponectin tertile showed relatively poor survival curve as compared to the bottom Adiponectin tertile group. In conclusion, our findings strengthen the reported association between low adiponectin, high leptin, obesity-related metabolic disturbances and incident CAD in Asian Indians.

Topics: Adiponectin; Adult; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Coronary Artery Disease; Female; Humans; India; Leptin; Male; Metabolic Syndrome; Middle Aged; Models, Cardiovascular; Obesity; Prognosis; Risk Factors

Epicardial adipose tissue (EAT) produces a wide range of adipokines and has recently been linked to the physiopathology of cardiovascular (CV) and metabolic diseases. We aimed to study whether EAT and subcutaneous (SAT) adiponectin and leptin expression levels are associated with CV complications during long-term follow-up.. EAT and SAT samples were obtained during surgery - mainly CABG (n=77) - from 137 patients (mean age 69.9 years, 31% women). Adiponectin and leptin mRNA levels were analyzed by RT-PCR. Plasma adiponectin levels were determined in a subsample of subjects (n=43). Thirty-four patients developed CV complications during 41 (SD 23) months of mean follow-up. Patients with CV events had lower EAT and SAT adiponectin levels at baseline (12.4 (3.0) vs. 15.7 (3.8) a.u., P=0.001; and 13.7 (2.6) vs. 15.7 (4.4) a.u., P=0.048, respectively). However, baseline EAT and SAT leptin levels and plasma adiponectin levels were not significantly different between patients with/without CV events during follow-up. Cox proportional hazards models adjusting for covariates in stages revealed that only baseline EAT adiponectin levels and heart failure could predict CV events.. EAT adiponectin levels are strong predictors of CV prognosis in patients with CV diseases. EAT is likely to play a major role in the development of CV complications mainly through local effects.

Topics: Adiponectin; Adipose Tissue; Aged; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Leptin; Male; Pericardium; RNA, Messenger; Treatment Outcome

Leptin, involved in energy homeostasis and a predictor of cardiovascular disease, has recently been recognized as mediator in stress reactions. We aimed to explore the association between leptin levels and two stress-related conditions, social isolation and depressed mood, both associated with increased cardiovascular mortality.. We analysed leptin levels in 1229 subjects (643 men, 586 women), derived from the population-based MONIKA/KORA study. Standardized questionnaires were used to assess depressive mood and social isolation. In a multiple linear regression adjusted for body weight, age and survey, the association between leptin, social isolation and depressed mood and its interaction was explored in men and women separately. Leptin was then dichotomized and four analyses, adjusted for age, BMI, lifestyle factors, psychosomatic complaints and metabolic variables were performed to compare the risk of elevated leptin levels in the risk groups.. Increased leptin levels were associated with social isolation (p=0.04) and the interaction between social isolation and depressed mood (p=0.02) in men but not in women. In socially isolated and depressed men, leptin levels (mean: 6.07 ng/ml) were significantly increased compared to neither depressed nor isolated men (mean: 4.51 ng/ml, p=0.04). In the multivariate adjusted logistic regression model, the combination of depressed state and social isolation was associated with a 4-fold increased risk (p<0.001) for elevated leptin levels.. The finding of elevated leptin levels in socially isolated and depressed men raises the possibility that increased cardiovascular mortality in socially isolated men is partially mediated by hyperleptinemia.

Topics: Adult; Affect; Aged; Cardiovascular Diseases; Cross-Sectional Studies; Depression; Female; Germany; Humans; Leptin; Male; Middle Aged; Prevalence; Risk Factors; Sex Characteristics; Social Isolation; Up-Regulation

To assess whether endocrine dysfunction may cause derangement in energy homeostasis in patients undergoing hemodialysis (HD), we profiled hormones, during a 3-day period, from the adipose tissue and the gut and the nervous system around the circadian clock in 10 otherwise healthy HD patients and 8 normal controls. The protocol included a 40-h fast. We also measured energy-protein intake and output and assessed appetite and body composition. We found many hormonal abnormalities in HD patients: 1) leptin levels were elevated, due, in part, to increased production, and nocturnal surge in response to daytime feeding, exaggerated. 2) Peptide YY (PYY), an anorexigenic gut hormone, was markedly elevated and displayed an augmented response to feeding. 3) Acylated ghrelin, an orexigenic gut hormone, was lower and did not exhibit the premeal spike as observed in the controls. 4) neuropeptide Y (NPY), a potent orexigenic peptide, was markedly elevated and did not display any circadian variation. 5) Norepinephrine, marginally elevated, did not exhibit the normal nocturnal dip. By contrast, α-melanocyte-stimulating hormone and glucagon-like peptide-1 were not different between the two groups. Despite these hormonal abnormalities, HD patients maintained a good appetite and had normal body lean and fat mass, and there was no evidence of increased energy expenditure or protein catabolism. We explain the hormonal abnormalities as well as the absence of anorexia on suppression of parasympathetic activity (vagus nerve dysfunction), a phenomenon well documented in dialysis patients. Unexpectedly, we noted that the combination of high leptin, PYY, and NPY with suppressed ghrelin may increase arterial blood pressure, impair vasodilatation, and induce cardiac hypertrophy, and thus could predispose to adverse cardiovascular events that are the major causes of morbidity and mortality in the HD population. This is the first report attempting to link hormonal abnormalities associated with energy homeostasis to adverse cardiovascular outcome in the HD patients.

Topics: Adult; Anorexia; Appetite; Body Composition; Cardiovascular Diseases; Circadian Rhythm; Endocrine System Diseases; Energy Metabolism; Fasting; Female; Ghrelin; Homeostasis; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Peptide YY; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency; Risk Factors

Disturbances in mineral metabolism define an increased cardiovascular risk in patients with chronic kidney disease. Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has recently been implicated as a putative pathogenic factor in cardiovascular disease. Because other members of the FGF family play a role in lipid and glucose metabolism, we hypothesized that FGF23 would associate with metabolic factors that predispose to an increased cardiovascular risk. The goal of this study was to investigate the relationship between FGF23 and metabolic cardiovascular risk factors in the community.. Relationships between serum FGF23 and body mass index (BMI), waist circumference, waist-to-hip ratio, serum lipids, and fat mass were examined in 2 community-based, cross-sectional cohorts of elderly whites (Osteoporotic Fractures in Men Study: 964 men aged 75±3.2; Prospective Investigation of the Vasculature in Uppsala Seniors study: 946 men and women aged 70). In both cohorts, FGF23 associated negatively with high-density lipoprotein and apolipoprotein A1 (7% to 21% decrease per 1-SD increase in log FGF23; P<0.01) and positively with triglycerides (11% to 14% per 1-SD increase in log FGF23; P<0.01). A 1-SD increase in log FGF23 was associated with a 7% to 20% increase in BMI, waist circumference, and waist-to-hip ratio and a 7% to 18% increase in trunk and total body fat mass (P<0.01) as determined by whole-body dual x-ray absorptiometry. FGF23 levels were higher in subjects with the metabolic syndrome compared with those without (46.4 versus 41.2 pg/mL; P<0.05) and associated with an increased risk of having the metabolic syndrome (OR per 1-SD increase in log FGF23, 1.21; 95% CI, 1.04 to 1.40; P<0.05).. We report for the first time on associations between circulating FGF23, fat mass, and adverse lipid metabolism resembling the metabolic syndrome, potentially representing a novel pathway(s) linking high FGF23 to an increased cardiovascular risk.

Topics: Absorptiometry, Photon; Adiponectin; Adiposity; Age Factors; Aged; Biomarkers; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Dyslipidemias; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Insulin; Leptin; Linear Models; Lipids; Logistic Models; Male; Metabolic Syndrome; Prospective Studies; Risk Assessment; Risk Factors; Sweden; Up-Regulation; Waist Circumference; Waist-Hip Ratio

the relationships between the adipose tissue cytokines leptin and adiponectin (ADPN) and clinical outcomes have not been well studied in haemodialysis (HD) patients and remain highly controversial. As central obesity is an important modifier of the effect of various risk factors for clinical outcomes, we tested the hypothesis that waist circumference (WC) modifies the link between these cytokines and both overall and cardiovascular death in HD patients.. a total of 537 HD patients participated in a prospective cohort study.. leptin and ADPN were inversely related to each other and robustly associated with WC (P < 0.001). During follow-up (average 29 months, range 1-47 months) 182 patients died, including 115 from cardiovascular causes. In analyses adjusting for potential confounders, there were strong interactions between leptin and WC in relationship to both all-cause (P < 0.001) and cardiovascular death (P = 0.002). Accordingly, a fixed excess of leptin signalled a gradually increasing risk for all-cause and cardiovascular mortality in patients with a large WC but an opposite effect in those with a relatively small WC. An interaction between ADPN and WC for all-cause (P = 0.01) and cardiovascular mortality (P = 0.01) emerged only in models excluding the leptin-WC interaction, suggesting that these adipokines share a common pathway leading to adverse clinical events in HD patients.. the predictive value of leptin and ADPN for all-cause and cardiovascular death in HD patients appears to be critically dependent on WC. These findings support the hypothesis that disturbances in adipokine levels are involved in adverse clinical outcomes in HD patients with abdominal obesity.

Topics: Adiponectin; Adipose Tissue; Aged; Anthropometry; Biomarkers; Cardiovascular Diseases; Epidemiologic Methods; Female; Hemodynamics; Humans; Italy; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Obesity, Abdominal; Renal Dialysis; Waist Circumference

Recent studies have provided evidence that intrauterine exposure to maternal diabetes has lifelong effects on adult offspring, including increased risks of obesity, type 2 diabetes and cardiovascular disease. The aim of this study was to assess the relationship between exposure to maternal diabetes in utero and cardiovascular risk factors in healthy children and to investigate whether these associations are independent of maternal prepregnancy BMI and offspring attained BMI.. Data were from a retrospective cohort of children aged 6-13 years born during 1994-2002. Multiple linear regression was used to examine the associations between exposure and cardiovascular risk factors with adjustment for demographic factors and pubertal stage and additionally for maternal prepregnancy BMI and offspring attained BMI.. Ninety-nine offspring of diabetic pregnancies had significantly increased E-selectin, vascular adhesion molecule 1 (VCAM1), leptin, waist circumference, BMI and systolic blood pressure and decreased adiponectin levels compared with 422 offspring of non-diabetic pregnancies after adjustment for age, sex and race/ethnicity (p < 0.05 for each risk factor). Additional adjustment for maternal prepregnancy BMI substantially attenuated group differences in the risk factors except for E-selectin, VCAM1 and waist circumference, which remained significantly higher in exposed children.. Compared with unexposed children, healthy offspring exposed to maternal diabetes in utero have a worse cardiovascular risk profile. In particular, offspring have substantially increased levels of circulating cellular adhesion molecules, which are biomarkers of adverse endothelium perturbation and may be related to the earliest preclinical stages of atherosclerosis and diabetes.

Topics: Adiponectin; Adolescent; Amine Oxidase (Copper-Containing); Cardiovascular Diseases; Cell Adhesion Molecules; Child; Diabetes, Gestational; E-Selectin; Female; Humans; Leptin; Linear Models; Male; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Waist Circumference

The adipokine adiponectin is decreased in severe obesity and is inversely associated with adipose mass. Adiponectin is associated with insulin sensitivity and cardioprotection. Obesity frequently results in the development of a "cardiometabolic syndrome" characterized by increased circulating insulin and leptin, and cardiac hypertrophy and dysfunction. This study examined if adiponectin-deficiency affects the development of metabolic and cardiac abnormalities in response to modest obesity. Mice were studied under normal conditions and with mild cardiac pressure-overload induced by abdominal aortic banding. After surgery, wild type and adiponectin-deficient mice were fed a high-fat diet for 8 weeks (45% energy from fat vs. 10%). In wild type mice the high-fat diet increased fat and whole body mass, which corresponded with elevated circulating insulin and leptin and a decrease the glucose/insulin ratio. On the other hand, in adiponectin-deficient mice the high-fat diet had less impact on body mass and no effect on fat mass, insulin, leptin, or glucose/insulin. There was modest cardiac hypertrophy with aortic banding, but no cardiac dysfunction or effects of adiponectin deficiency or diet. The results suggest that the increase in adipose mass, leptin and insulin induced by a high fat diet is dependent on adiponectin. The lack of accelerated cardiac hypertrophy and dysfunction in the adiponectin-deficient mice subjected to aortic banding and the high-fat diet suggest that adiponectin may not play a major role in protecting the heart during the early stages of diet-induced obesity.

Topics: Adiponectin; Adipose Tissue; Animals; Blood Pressure; Body Weight; Cardiovascular Diseases; Dietary Fats; Disease Models, Animal; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity

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

Ghrelin abnormalities contribute to anorexia, inflammation, and cardiovascular risk in hemodialysis patients, leading to worse outcome. However, ghrelin levels are influenced by the nutritional status of the individual. We hypothesized that the consequences of ghrelin alterations in hemodialysis patients are context sensitive and dependent on the presence of protein-energy wasting (PEW). In this cross-sectional study of 217 prevalent hemodialysis patients followed for 31 months, we measured ghrelin, leptin, PEW (subjective global assessment), and C-reactive protein (an index of inflammation). Compared to patients in the middle and upper tertile of ghrelin levels, those in the lowest tertile were older, had higher leptin levels and body mass index, and presented an increased mortality risk that persisted after adjustment for age, gender, and dialysis vintage. This risk was lost after correction for comorbidities. Patients with PEW and low ghrelin values had abnormally high C-reactive protein and leptin by multivariate analysis of variance, and the highest mortality risk compared to non-PEW with high ghrelin from all-cause and cardiovascular-related mortality (adjusted hazard ratios of 3.34 and 3.54, respectively). Low ghrelin values in protein-energy wasted hemodialysis patients were linked to a markedly increased cardiovascular mortality risk. Thus, since these patients were more anorectic, our results provide a clinical scenario where ghrelin therapies may be particularly useful.

Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Cross-Sectional Studies; Female; Ghrelin; Humans; Inflammation; Kaplan-Meier Estimate; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proportional Hazards Models; Protein-Energy Malnutrition; Renal Dialysis; Risk Assessment; Risk Factors; Sweden; Time Factors

Increased levels of C-reactive protein (CRP) and serum amyloid A (SAA) are associated with an increased risk of cardiovascular disease. It is hypothesized that dysregulation of the autonomic nervous system (ANS) leads to increased inflammation via the cholinergic anti-inflammatory pathway. Heart rate variability (HRV) is a marker of ANS function. HRV has been shown to be associated with CRP levels. Currently, there are no studies addressing the relationship between HRV and SAA.. The purpose of this study was to compare the associations between HRV, CRP and SAA in healthy young adults. CRP and SAA concentrations and short-term HRV indices [high frequency (HF), low frequency (LF), total spectral component of HRV, root mean square differences of successive R-R intervals, the standard deviation of all R-R intervals and ratio between LF and HF) were measured in 1601 men and women aged 24-39 taking part in the Cardiovascular Risk in Young Finns study.. A significant inverse correlation (P < 0·05) between HRV indices and inflammatory markers was observed. However, in linear regression analyses, only inverse association between HRV indices and CRP levels remained significant (P < 0·05), while association between HRV indices and SAA levels was attenuated to the null (P > 0·05) after adjusting for age, sex, body mass index, cholesterol levels, leptin and other common traditional cardiovascular risk factors.. Reduced HRV indices are independently associated with increased CRP levels, but not with SAA levels. This association supports the hypothesis that dysregulation of the ANS may lead to increased inflammation early in adulthood.

Topics: Adult; Autonomic Nervous System; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Finland; Heart Rate; Humans; Leptin; Linear Models; Male; Risk Assessment; Risk Factors; Serum Amyloid A Protein; Young Adult

Sibutramine is an anti-obesity agent that induces weight loss by selective inhibition of neuronal reuptake of serotonin and norepinephrine; however, it is associated with the risk of cardiovascular diseases (CVD), including heart attack and stroke. Here, we analyzed global protein expression patterns in plasma of control and sibutramine-treated rats using proteomic analysis for a better understanding of the two conflicting functions of this drug, appetite regulation, and cardiovascular risk. The control (n=6) and sibutramine-treated groups (n=6) were injected by vehicle and sibutramine, respectively, and 2-DE combined with MALDI-TOF/MS were performed. Compared to control rats, sibutramine-administered rats gained approximately 18% less body weight and consumed about 13% less food. Plasma leptin and insulin levels also showed a significant decrease in sibutramine-treated rats. As a result of proteomic analysis, 23 differentially regulated proteins were discovered and were reconfirmed by immunoblot analysis. Changed proteins were classified into appetite regulation and cardiovascular risk, according to their regulation pattern. Because the differential levels of proteins that have been well recognized as predictors of CVD risk were not well matched with the results of our proteomic analysis, this study does not conclusively prove that sibutramine has an effect on CVD risk.

Topics: Adipose Tissue; Animals; Appetite Depressants; Appetite Regulation; Blood Proteins; Body Weight; Cardiovascular Diseases; Chromatography, Liquid; Cyclobutanes; Electrophoresis, Gel, Two-Dimensional; Insulin; Leptin; Male; Obesity; Proteome; Rats; Rats, Sprague-Dawley; Risk Factors; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Weight Loss

A link between psoriasis and risk for cardiovascular disease (CVD) is supposed. Adipokines (adiponectin and leptin) playing roles in inflammation as well as lipid metabolism could have impact on CVD.. We investigated links between adiponectin and leptin levels and several inflammation- and oxidative stress-related CVD risk makers in patients with psoriasis.. Sixty patients with plaque-type psoriasis with normal total cholesterol levels belonging to three body mass index (BMI) categories: BMI < 24.9, BMI 25.0-29.9 and BMI ≥ 30.0 kg/m(2) were studied. Fasting blood samples were analysed for adiponectin, leptin, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), oxidized low density lipoprotein (oxLDL), oxidized LDL/β(2) -glycoprotein complexes (oxLDL-β(2)-GPI) and standard blood lipid panel.. In patients, adiponectin was negatively (P < 0.005), and leptin, oxLDL and oxLDL-β(2) -GPI levels were positively correlated to BMI (P < 0.005, P < 0.05, and P < 0.01, respectively). Patients had higher hsCRP and IL-6 levels as compared with the endemic reference values. High adiponectin was strongly associated with higher TNF-α and high density lipoprotein cholesterol (P = 0.001), and lower triglycerides (TG) (P = 0.01) as well as oxLDL-β(2) -GPI levels (P < 0.05). After multivariate adjustment, the association for TNF-α and TG remained significant (P < 0.01 for both). Multiple regression analysis also revealed that leptin concentration was significantly associated with hsCRP, oxLDL and TG levels.. The data suggest that in addition to the strong effect of inflammation and LDL oxidation, adipokine level may be one of the mechanisms behind the close association between psoriasis and CVD. Given the significant relations of several markers with BMI, health consequences of excessive weight should be better communicated to patients with psoriasis.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; Cardiovascular Diseases; Female; Humans; Leptin; Male; Psoriasis

COPD is characterized by a multi-component character involving a state of low-grade systemic inflammation and an increased prevalence of cardiovascular co-morbidity. The role of circulating leptin and other adipokines in the involvement of the systemic inflammation in COPD is only studied scarcely.. To investigate gender related differences in the adipokine metabolism in relation to systemic inflammatory biomarkers in clinically stable subjects with COPD.. In total, 91 clinically stable COPD patients and 35 healthy control subjects, matched for body mass index (BMI) with the COPD subjects, were included. Lung function measurement and body composition were performed in patients with COPD. In the total group, plasma concentration of the adipokines (leptin, adiponectin and resistin) and systemic inflammatory biomarkers C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor α (TNFα), and its soluble receptors 55 and 75 (sTNFα-R55, R75) were analyzed.. The COPD group was characterized by increased levels of CRP, IL-6 and leptin. Plasma adiponectin and resistin concentrations were not different between the COPD and the control group. Within the COPD group, there was a significant interaction between gender and BMI on the leptin/fat mass ratio. In COPD women, a significant correlation between leptin and CRP was present.. In men with clinically stable COPD, leptin, adiponectin and resistin appear to be physiologically regulated, while in women, leptin metabolism is altered. Leptin secretion is increased in COPD women when compared to healthy women and compared to COPD men, and to a greater extent in overweight women with COPD.

Topics: Adipokines; Adipose Tissue; Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sex Factors; Tumor Necrosis Factor-alpha

Ghrelin is involved in the pathogenesis of protein-energy wasting (PEW), inflammation, and cardiovascular complications in end-stage renal disease (ESRD). Plasma ghrelin may prove to be a powerful biomarker of mortality in ESRD but should be considered in the context of assay specificity, other weight-regulating hormones, nutritional status, systemic inflammation, and cardiovascular risk factors. ESRD patients with PEW, systemic inflammation, and low ghrelin and high leptin concentrations have the highest mortality risk and may benefit the most from ghrelin therapy.

Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Protein-Energy Malnutrition; Renal Dialysis; Risk Assessment; Risk Factors; Time Factors

To investigate the markers of endothelial injury, adipocytokine and thrombotic activity and explore whether there are cardiovascular disease risk factors in antiretroviral-naive HIV patients.. Clinical data and venous blood samples were collected from 43 anti-retroviral naive HIV-infected patients during February-October 2009 in our center, and compared with 17 healthy subjects. Plasma leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), D-dimer were measured by ELISA. Four markers and cholesterol, triglyceride, fasting plasma glucose were compared between the two groups. The CD(4)(+)T cells and percentages of CD(38), HLA-DR on CD(8)(+)T were determined by flow cytometry and plasma HIV copies were detected with bDNA analyzer among HIV-infected participants. Spearman correlations between the significant markers and CD(4)(+) T cells, CD(8)(+) CD(38)(+)/CD(8)(+), CD(8)(+) HLA-DR(+)/CD(8)(+), HIV viral load were examined among HIV-infected participants. Analyses were conducted by using Stata version 7.. Thirty-eight of the 43 patients were sexually infected by HIV and the median absolute CD(4)(+)T cell count was (133 ± 82) cells/µl, HIV RNA was (4.42 ± 0.66) lg copies/ml. HIV-infected patients, compared with healthy subjects, had lower leptin [11.41(7.91, 14.53) µg/L vs 55.31 (16.49, 229.65) µg/L, P = 0.0005], adiponectin [1.79 (1.40, 4.00) mg/L vs 3.36 (2.92, 4.18) mg/L, P = 0.003] and higher sICAM-1 [1.71(1.11, 2.40) mg/L vs 0.69 (0.57, 0.80) mg/L, P = 0.0000]. No significant differences exist in cholesterol, triglyceride, fasting plasma glucose. For HIV-infected participants, sICAM-1 tended to correlate with CD(8)(+)CD(38)(+)/CD(8)(+) and HIV viral load (r = 0.3378, P = 0.0267; r = 0.3904, P = 0.0096).. Patients with untreated HIV infection have lower leptin, adiponectin and higher sICAM-1 levels and the relationship of these markers to HIV-mediated atherosclerotic risk requires further study.

Topics: Adiponectin; Adolescent; Adult; Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Endothelium, Vascular; Female; HIV Infections; Humans; Intercellular Adhesion Molecule-1; Leptin; Male; Middle Aged; Young Adult

We aimed to evaluate the relationship between serum leptin and the leptin/body mass index (BMI) ratio with prevalent cardiovascular disease (CVD), and their influence on all-cause and CVD-related mortality in patients on hemodialysis (HD).. 118 stable HD patients (50 women, median [interquartile range] age, 65.1 [54.7-72.2] years) were studied. All patients had baseline measurement of serum leptin concentrations. Relationships between leptin and all-cause and CVD mortality were studied by means of survival analysis and Cox regression analysis.. The leptin/BMI ratio was similar in patients with and without CVD at baseline (0.65 [0.29-2.23] vs. 0.68 [0.29-1.49] ng·m2/ml·kg, respectively, NS). Multiple logistic regression analysis showed that there was not an independent association between leptin/BMI ratio and prevalent CVD. During the follow-up time, 52 (44.1%) patients died. CVD was the cause of death in 27 out of 52 (51.9%) deceased patients. Survival analysis and Cox proportional multivariate regression analysis showed that there were no significant relationships between leptin levels or the leptin/BMI ratio and all-cause and CVD-related mortality.. These results do not support that, in stable HD patients, serum leptin concentrations and the leptin/BMI ratio are related with prevalent CVD. Leptin/BMI ratio seems not to be a risk factor for mortality in these patients.

Topics: Aged; Body Mass Index; Cardiovascular Diseases; Cause of Death; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Humans; Italy; Kaplan-Meier Estimate; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Mortality; Obesity; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Risk Factors; Spain; Statistics, Nonparametric

Leptin is associated with cardiovascular disease (CVD); however, few studies have assessed its relationship with metabolic syndrome, especially in an Asian population. Therefore, the aim of the present study was to assess leptin levels and evaluate its association with CVD and metabolic syndrome.. In 2009, 957 subjects, who underwent a routine physical examination and choose leptin examination, were selected to participate. Participants (269 females and 688 males) were stratified according to leptin level quartiles. Metabolic syndrome was defined by NCEP ATP III using waist circumference cutoffs modified for Asian populations, and CVD risk was determined using the Framingham Heart Study profile.. Leptin levels were correlated with CVD risk in men and women. With the exception of fasting plasma glucose, increased leptin levels were observed as factors associated with metabolic syndrome increased in both males and females. After adjusting for age, an association between leptin levels and metabolic syndrome was observed. After adjusting for age alone or with tobacco use, subjects in the highest leptin quartile had a higher risk of having metabolic syndrome than those in the lowest quartile (OR=6.14 and 2.94 for men and women, respectively). After further adjustment for BMI, metabolic syndrome risk remained significantly increased with increasing leptin quartiles in men. Finally, increased leptin levels were a predictor of metabolic syndrome in men and women.. Serum leptin levels are correlated with CVD risk and metabolic syndrome. Analysis of leptin as part of routine physical examinations may prove beneficial for early diagnosis of metabolic syndrome.

Topics: Adult; Age Factors; Analysis of Variance; Asian People; Biomarkers; Body Mass Index; Cardiovascular Diseases; Chi-Square Distribution; Female; Humans; Leptin; Linear Models; Logistic Models; Male; Metabolic Syndrome; Odds Ratio; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Smoking; Taiwan; Waist Circumference

Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease when PCOS first occurs and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated.. This study characterized the cardiovascular-renal consequences of hyperandrogenemia in a female rat model.. Female Sprague-Dawley rats (aged 4-6 weeks) were implanted with dihydrotestosterone or placebo pellets lasting 90 days. After 10 to 12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein, and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, and oral glucose tolerance test), inflammation (plasma tumor necrosis factor-α), oxidative stress (mRNA expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox), p47(phox), gp91(phox), and NOX4), nitrate/nitrite excretion and mRNA expression of components of the renin-angiotensin system (angiotensinogen, angiotensin-I-converting enzyme [ACE], and AT1 receptor) were determined.. Plasma dihydrotestosterone increased 3-fold in hyperandrogenemic female (HAF) rats, whereas plasma estradiol levels did not differ compared with control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression.. The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model to study the mechanisms responsible for PCOS-mediated hypertension.

Topics: Angiotensinogen; Animals; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Dihydrotestosterone; Disease Models, Animal; Estradiol; Female; Glomerular Filtration Rate; Glucose Tolerance Test; Kidney Diseases; Leptin; Metabolic Syndrome; Oxidative Stress; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System

We investigated the effects of the EVASYON program on body fatness, cardiometabolic risk factors, gut appetite-controlling hormones and serum levels of cytokines in adolescents with overweight or obesity (OW/OB).. This study comprised 13 boys (10 obese) and 12 girls (8 obese), aged 13-16 years, from a Madrid Hospital. The EVASYON program was based on a calorie-restricted diet (10-40%), increased physical activity (at least 60 min/day 5 days a week), psychological therapy and nutritional education for 13 months. Anthropometric and blood pressure measurements were measured before and after intervention. Serum glucose, total cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, total peptide YY and insulin levels were determined before and after intervention. Serum levels of cytokines IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNF-α were also assessed before and after intervention.. A decrease in body mass index (BMI), BMI z-score, skinfolds (triceps, biceps, subscapular, thigh, and calf), sum of six skinfolds and body circumferences (arm relaxed and flexed, waist, hip, and proximal thigh) values were observed after the intervention program (all p < 0.05). In addition, diastolic blood pressure also decreased (p < 0.05). A decrease in serum leptin levels (-48.4%, p < 0.001) was observed after intervention without changes in total peptide YY and insulin levels. Levels of IL-8, IL-10, and TNF-α also decreased (all p < 0.05) after the intervention program.. These preliminary results evidence that the EVASYON program may improve body fat, leptin, and some pro-inflammatory cytokines in adolescents with OW/OB.

Topics: Adiponectin; Adipose Tissue; Adolescent; Cardiovascular Diseases; Cytokines; Female; Humans; Insulin; Leptin; Male; Obesity; Overweight; Peptide YY; Risk Factors

Topics: Atherosclerosis; Cardiovascular Diseases; Caveolin 1; Coronary Artery Disease; Endothelial Cells; Female; Humans; Leptin; Male

Women with gestational diabetes mellitus (GDM) have an enhanced cardiovascular risk factor profile at 3-months postpartum and an elevated risk of future cardiovascular disease, as compared to their peers. Recently, it has emerged that even mild dysglycemia on antepartum oral glucose tolerance test (OGTT) predicts an increased risk of future cardiovascular disease, although it is not known whether there exists an identifiable high-risk subgroup within this patient population. Since gestational impaired glucose tolerance (GIGT) due to isolated hyperglycemia at 1-h during the OGTT (1-h GIGT) bears metabolic similarity to GDM, we hypothesized that, like GDM, 1-h GIGT may predict a high-risk postpartum cardiovascular phenotype.. In this prospective cohort study, 485 women underwent antepartum OGTT, followed by cardiovascular risk factor assessment at 3-months postpartum. The antepartum OGTT identified 4 gestational glucose tolerance groups: GDM (n = 137); 1-h GIGT (n = 39); GIGT at 2- or 3-h (2/3-h GIGT)(n = 50); and normal glucose tolerance (NGT)(n = 259). After adjustment for age, ethnicity, breastfeeding and waist circumference, mean levels of the following cardiovascular risk factors progressively increased from NGT to 2/3-h GIGT to 1-h GIGT to GDM: LDL cholesterol (p = 0.0026); total cholesterol:HDL (p = 0.0030); apolipoprotein B (p = 0.004); apolipoprotein B:apolipoprotein A1 (p = 0.026); leptin (p = 0.018); and C-reactive protein (p = 0.011).. Amongst women without GDM, 1-h GIGT predicts an enhanced postpartum cardiovascular risk factor profile. It thus emerges, that amongst young women with mild dysglycemia in pregnancy, those with 1-h GIGT may comprise an unrecognized patient population at risk for future cardiovascular disease.

Topics: Adult; Apolipoproteins B; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Leptin; Postpartum Period; Pregnancy; Prospective Studies; Risk Factors

Obesity is more common in African than Asian-Indian populations and yet type 2 diabetes and cardiovascular diseases are more common in the latter populations. The main purpose of the current study was therefore to determine whether ethnic differences in body fat distribution, adipokine levels, and socio-economic status may explain population differences in the prevalence of these metabolic disorders. Leptin, IL-6, CRP, visceral fat, education level, and socio-economic status were measured in 50 African and the same number of Indian women residing in Johannesburg, South Africa. Serum leptin levels were significantly higher in Indian than African subjects (41.3±2.0 and 34.2±2.9 ng/ml, respectively; p<0.05). TNF-α levels were significantly higher in the African group, (5.22±0.86 vs. 2.54±0.52 pg/ml; p<0.05), whilst visceral fat levels were significantly lower (56.1±5.5 vs. 77.9±6.5 cm(2); p<0.05). The CRP and IL-6 levels were not different between groups. Education levels (p<0.005) and socio-economic status (p<0.0001) were both lower in the African subjects, however, adjusting for these variables in ANCOVA did not attenuate differences in adipokine or visceral fat levels. We hypothesise that one of the reasons for the higher prevalence of obesity in the African than Indian population may be related to lower leptin levels, whilst ethnic differences in the prevalence of metabolic disorders cannot be explained by differences in adipokine levels, but maybe related to higher visceral adiposity in the Indian group.

Topics: Adipokines; Adult; Anthropometry; Asian People; Black People; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Education; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Prevalence; Socioeconomic Factors

Insulin resistance has a central role in the pathophysiology of cardiovascular atherosclerotic disease. Adipose tissue is of capital importance in view of its production of adipokines. The present study aims to determine the association of metabolic syndrome components, which constitute risk factors for cardiovascular atherosclerotic disease, and leptin and adiponectin with insulin resistance in prepubertal children.. We conducted a cross-sectional study involving 197 children. Of these, 112 children were obese, 36 were overweight and 49 had normal weight. The association of sex, waist circumference, Acanthosis nigricans, age, BMI Z-score, serum lipids, leptin and adipocytokines with insulin resistance [defined as the homeostatic model assessment for insulin resistance (HOMA-IR) index higher than or equal to 2.5] was investigated using logistic regression.. There was positive association of sex (female), age, BMI Z-score, triglycerides and leptin with insulin resistance (p<0.05).. Among the conventional components of metabolic syndrome, the role of BMI Z-score and triglycerides stands out in insulin resistance of prepubertal children. Sex (female), age and leptin also showed to be of major importance.

Topics: Acanthosis Nigricans; Adipokines; Adiponectin; Body Weight; Brazil; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Lipids; Logistic Models; Male; Metabolic Syndrome; Obesity; Overweight; Risk Factors

Alterations in plasma leptin and adiponectin concentrations are associated with an adverse metabolic profile in obese children.. To simultaneously assess multiple factors with possible effects on plasma leptin and adiponectin concentrations in healthy, non-obese children.. We studied 170 healthy non-obese children (86 males, age 10+1.5 years), with available medical records from birth.. Plasma leptin and adiponectin concentrations were assessed by immunoassay. The ratio of current weight/birth weight (WBWR) was used as an index of children growth from birth. Children's intensity of physical activity and parental characteristics were also assessed.. Leptin was positively associated with WBWR (p<0.0001); parental smoking (analysis of variance, ANOVA; p-=0.03) and parental obesity (ANOVA; p<0.001) were negatively associated with breastfeeding (p<0.01) and children's access to exercise (p<0.0001). Adiponectin was negatively associated with WBWR (p<0.0001) and parental smoking (p=0.04), with an additive negative effect of parental smoking status and parental obesity on children's adiponectin levels (ANOVA; p=0.02).. Children's and parental factors are related and could possibly influence leptin and adiponectin concentrations in healthy non-obese children. Early preventive strategies that target both children and parents could improve the profile of adipocytokine in these children.

Topics: Adiponectin; Birth Weight; Body Mass Index; Body Weight; Cardiovascular Diseases; Child; Child Development; Female; Greece; Humans; Leptin; Male; Motor Activity; Obesity; Parents; Reference Values; Risk Factors; Tobacco Smoke Pollution; Weight Gain

Plasminogen activator inhibitor-1 (PAI-1) has been considered as a cardiovascular risk factor, mainly because of its strong association with insulin resistance.. To detect independent predictors of circulating PAI-1 levels in obese pediatric patients, we evaluated 86 subjects (mean age 10.7 +/- 2.8 years), 42 of whom were male (49%). Subjects were divided in two groups according to body mass index (BMI): obese subjects (n=61) and healthy non-obese controls (n=25). They were also divided by pubertal status. Besides anthropometric data, levels of PAI-1, leptin and biochemical markers of metabolic syndrome were measured.. The obese group had higher levels of PAI-1, leptin and biochemical markers of metabolic syndrome than nonobese controls (p<0.05). However, multivariate regression analysis showed that only puberty progression (p=0.005) and abdominal circumference/height index (p=0.002) remained independent predictors of PAI-1 levels.. In pediatric obesity, fat mass accumulation, mainly of visceral fat, and puberty progression were related to high PAI-1 levels, which might in turn contribute to cardiovascular risk.

Topics: Biomarkers; Blood Pressure; Cardiovascular Diseases; Case-Control Studies; Child; Cross-Sectional Studies; Female; Humans; Insulin; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Multivariate Analysis; Obesity; Plasminogen Activator Inhibitor 1; Puberty; Risk Factors; Sex Characteristics; Triglycerides

Topics: Cardiovascular Diseases; Female; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Protein-Energy Malnutrition; Renal Dialysis

High prevalence of obesity and cardiovascular disease is attributable to sedentary lifestyle and eating diets high in fat and refined carbohydrate while eating diets low in fruit and vegetables. Epidemiological studies have confirmed a strong association between eating diets rich in fruits and vegetables and cardiovascular health. The aim of this pilot study was to determine whether drinking fresh carrot juice influences antioxidant status and cardiovascular risk markers in subjects not modifying their eating habits.. An experiment was conducted to evaluate the effects of consuming 16 fl oz of daily freshly squeezed carrot juice for three months on cardiovascular risk markers, C-reactive protein, insulin, leptin, interleukin-1α, body fat percentage, body mass index (BMI), blood pressure, antioxidant status, and malondialdehyde production. Fasting blood samples were collected pre-test and 90 days afterward to conclude the study.. Drinking carrot juice did not affect (P > 0.1) the plasma cholesterol, triglycerides, Apo A, Apo B, LDL, HDL, body fat percentage, insulin, leptin, interleukin-1α, or C-reactive protein. Drinking carrot juice decreased (P = 0.06) systolic pressure, but did not influence diastolic pressure. Drinking carrot juice significantly (P < 0.05) increased the plasma total antioxidant capacity and decreased (P < 0.05) the plasma malondialdehyde production.. Drinking carrot juice may protect the cardiovascular system by increasing total antioxidant status and by decreasing lipid peroxidation independent of any of the cardiovascular risk markers measured in the study.

Topics: Adult; Antioxidants; Beverages; Blood Pressure; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Daucus carota; Drinking; Female; Humans; Insulin; Interleukin-1alpha; Leptin; Lipid Metabolism; Lipid Peroxidation; Male; Pilot Projects; Risk

Topics: Cardiovascular Diseases; Female; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Protein-Energy Malnutrition; Renal Dialysis

We sought to verify if an oral contraceptive (OC) containing drospirenone affects the cardiovascular risk of patients with polycystic ovary syndrome (PCOS).. A total of 28 women with PCOS (16 lean [group A] and 12 overweight [group B]) were assessed at baseline and after 6 months therapy with an OC. Leptin, homocysteine, endothelin-1, and flow-mediated dilatation of brachial artery were measured.. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, did not change in group A; it improved significantly in group B after 6 months of treatment. At baseline and after therapy the plasma levels of homocysteine and endothelin-1 did not differ among the groups. Leptin was significantly lower at baseline in group A compared to group B.. The OC containing drospirenone does not seem to affect the surrogate markers of cardiovascular risk in lean patients with PCOS.

Topics: Adolescent; Adult; Androstenes; Brachial Artery; Cardiovascular Diseases; Contraceptives, Oral; Endothelin-1; Female; Homocysteine; Humans; Insulin; Insulin Resistance; Leptin; Mineralocorticoid Receptor Antagonists; Obesity; Pilot Projects; Polycystic Ovary Syndrome

Leptin predicts cardiovascular diseases and type 2 diabetes, diseases to which Asian Indians are highly susceptible. As a risk marker, leptin's intra-individual and seasonal stability is unstudied and only small studies have compared leptin levels in Asian Indians with other populations. The aim of this study was to explore ethnicity related differences in leptin levels and its intra-individual and seasonal stability.. Leptin and anthropometric data from the northern Sweden MONICA (3513 Europids) and the Mauritius Non-communicable Disease (2480 Asian Indians and Creoles) studies were used. In both studies men and women, 25- to 74-year old, participated in both an initial population survey and a follow-up after 5-13 years. For the analysis of seasonal leptin variation, a subset of 1780 participants, 30- to 60-year old, in the Västerbotten Intervention Project was used.. Asian Indian men and women had higher levels of leptin, leptin per body mass index (BMI) unit (leptin/BMI) or per cm in waist circumference (WC; leptin/waist) than Creoles and Europids when adjusted for BMI (all P<0.0005) or WC (all P<0.005). In men, Creoles had higher leptin, leptin/BMI and leptin/waist than Europids when adjusted for BMI or WC (all P<0.0005). In women, Creoles had higher leptin/BMI and leptin/waist than Europids only when adjusted for WC (P<0.0005). Asian Indian ethnicity in both sexes, and Creole ethnicity in men, was independently associated with high leptin levels. The intra-class correlation for leptin was similar (0.6-0.7), independently of sex, ethnicity or follow-up time. No seasonal variation in leptin levels was seen.. Asian Indians have higher levels of leptin, leptin/BMI and leptin/waist than Creoles and Europids. Leptin has a high intra-individual stability and seasonal leptin variation does not appear to explain the ethnic differences observed here.

Topics: Adult; Aged; Asian People; Blood Glucose; Body Composition; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leptin; Male; Mauritius; Middle Aged; Obesity; Risk Factors; Seasons; Sex Factors; Sweden; Waist Circumference

Apolipoprotein(a) [or apo(a)] isoform size, which is strongly genetically determined, showed significant association with the cardiovascular risk. Subjects on a fish diet have lower lipoprotein(a) levels, larger apo(a) isoform sizes and lower leptin levels than their vegetarian diet counterparts. We hypothesized that leptin may contribute to a potential association between the type of diet and the size of apo(a) isoforms.. Anthropometric data, dietary nutrients, lipoprotein profile, plasma leptin levels, and apo(a) isoforms were evaluated in two related homogenous African tribal populations of Tanzania, one on a primarily freshwater fish diet (n=278), and the other on a vegetarian diet (n=326).. We observed a strong negative association between leptin levels and size of each of the apo(a) isoforms in both fish and vegetable diet groups, and in both genders. However, leptin was not associated with levels of lipoprotein(a). In multivariate analysis, a strong and independent association between leptin and size of apo(a) isoforms was observed. The size of apo(a) isoforms was strongly associated with high and low leptin states. Subjects with low leptins had 30% larger sizes of apo(a) isoforms than their high leptin counterparts.. High leptin subjects have smaller, potentially more atherogenic, apo(a) isoform sizes than low leptin ones. We suggest that omega-3 rich diet can influence the levels of apo(a) and/or Lp(a) even though they are mainly genetically determined. These findings may have implications for understanding the interaction between leptin and cardiovascular risk.

Topics: Adult; Animals; Apolipoproteins A; Black People; Cardiovascular Diseases; Diet; Diet, Vegetarian; Ethnicity; Fatty Acids, Omega-3; Feeding Behavior; Female; Fishes; Humans; Leptin; Male; Middle Aged; Protein Isoforms; Risk Factors; Tanzania

Socioeconomic gradients in adiposity were not present during childhood for previous generations, but have emerged in contemporary children. It is unknown whether this translates to socioeconomic gradients in associated cardiovascular risk factors in children, with consequent implications for inequalities in coronary heart disease (CHD) and diabetes when these children reach adulthood.. Using data from 7772 participants aged 10-years from the Avon Longitudinal Study of Parents and Children, we examined the association between maternal education and a large number of cardiovascular risk factors (cholesterol, triglycerides, high-density lipoprotein, apolipoprotein, adiponectin, leptin, C-reactive protein (CRP), interleukin-6 (IL-6) and systolic and diastolic blood pressure), and examined whether inequalities were mediated by adiposity, measured by dual energy X-ray absorptiometry (DXA)-assessed total fat mass.. There were socioeconomic differences in a number of the cardiovascular risk factors (apolipoprotein B, systolic and diastolic blood pressure, CRP, leptin and IL-6). Inequalities were greater in girls than boys. Inequalities in CRP and leptin were completely mediated by adiposity. Inequalities in other cardiovascular risk factors were partially mediated by adiposity.. This study showed important socioeconomic inequalities in adiposity and associated cardiovascular risk factors in a contemporary UK population of 10-year-old children. Differences between contemporary children and previous generations in the socioeconomic patterning of cardiovascular risk factors suggest future adults may have greater inequalities in diabetes and CHD than current adults. These findings highlight the importance of interventions aimed at preventing obesity in childhood, particularly among those of lower socioeconomic position.

Topics: Adiposity; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Child; Female; Glycation End Products, Advanced; Health Services Accessibility; Humans; Interleukin-6; Leptin; Lipoproteins, LDL; Male; Obesity; Prospective Studies; Risk Factors; Socioeconomic Factors

A recent report showed no benefit of the leptin:adiponectin ratio (L:A ratio) over individual adipokine levels in CHD prediction [8]. We determined associations of carotid intima media thickness (IMT) with the L:A ratio taking account of cardiovascular risk factors in a high risk population.. IMT, plasma leptin, adiponectin and the L:A ratio were determined in 161 middle-aged men and women (45% metabolic syndrome).. IMT was associated inversely with adiponectin and positively with the L:A ratio in age- and sex-adjusted multiple linear regression analyses (P<0.001 for both). After controlling for metabolic syndrome, the independent association with adiponectin remained (P<0.001), but the relationship with the L:A ratio disappeared (P=0.126). Results were similar after additional adjustment for diabetes status or for insulin resistance.. This study does not support the preferential use of the leptin:adiponectin ratio as a marker of atherosclerosis susceptibility.

Topics: Adiponectin; Cardiovascular Diseases; Carotid Arteries; Female; Gene Expression Regulation; Humans; Leptin; Male; Metabolic Syndrome; Regression Analysis; Risk Factors; Tunica Intima; Tunica Media

Adipokines such as leptin and adiponectin are adipocyte-specific secretory proteins that play important roles in the metabolic regulation of body weight, insulin resistance and cardiovascular complications. The relationship between the malnutrition-inflammation complex syndrome and high levels of some adipokines in peritoneal dialysis (PD) patients is still unclear. An association between high body mass index (BMI) and improved survival in PD patients has also been proposed. The purpose of this study was to investigate the levels of plasma adipokines and inflammation and oxidative stress markers in overweight and normal weight PD patients.. Thirty PD patients (12 M, 18 F; mean age 57.3 ± 16.6 years) were examined and 23 healthy volunteers were included as a control group. The levels of high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, leptin, the leptin receptor, adiponectin, malondialdehyde/4-hydroxynonenal, oxidized low-density lipoprotein, carbonyl groups and asymmetric dimethylarginine (ADMA) were measured in both groups. The nutritional status of each patient was determined by albumin levels, BMI, percentage of body fat (%F), lean body mass (LBM) and the Subjective Global Assessment (SGA) score. The adequacy of dialysis was estimated by weekly Kt/V measurements.. According to the seven-point SGA scores and the albumin levels, the nutrition status of 15 patients was good (6-7 points), while 15 patients were mildly malnourished (3-5 points). The concentrations of hsCRP, leptin and adiponectin were statistically higher in the PD group than in the control group (p < 0.05). Markers of oxidative stress and inflammation were also higher in the PD group. The adiponectin level was inversely correlated with %F and BMI (Spearman's R = -0.3, p ≤ 0.05) and positively correlated with hsCRP level (R = -0.4). The level of leptin was positively correlated with %F, BMI and LBM (R = 0.4, p ≤ 0.05). Patients with normal BMI values had lower leptin concentrations (50.2 vs 242.8 μg/l) and higher adiponectin levels (30.0 vs 20.3 μg/ml) than overweight patients. The statistical analysis indicated that there were no differences in oxidative stress, inflammation and ADMA concentration between the lean and overweight PD patients.. The nutritional status of lean and overweight patients was comparable. Signs of malnutrition were detected in both groups. The severity of chronic inflammation and oxidative stress were not related to BMI in PD patients.

Topics: Adiponectin; Adult; Aged; Aldehydes; Arginine; Biomarkers; Body Mass Index; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Endothelium; Female; Humans; Inflammation; Interleukin-6; Leptin; Lipoproteins, LDL; Male; Malnutrition; Malondialdehyde; Middle Aged; Nutritional Status; Oxidative Stress; Peritoneal Dialysis; Risk Factors; Tumor Necrosis Factor-alpha

Survivors of childhood acute lymphoblastic leukemia (ALL) may face an increased risk of metabolic and cardiovascular late effects. To determine the prevalence of and risk factors for adverse cardiometabolic traits in a contemporary cohort of pediatric ALL survivors, we recruited 48 off-therapy patients in remission treated with conventional chemotherapy and 26 treated with total body irradiation (TBI)-based hematopoietic cell transplantation (HCT) in this cross-sectional pilot study. At a median age of 15 years (range, 8-21 years), HCT survivors were significantly more likely than non-HCT survivors to manifest multiple cardiometabolic traits, including central adiposity, hypertension, insulin resistance, and dyslipidemia. Overall, 23.1% of HCT survivors met the criteria for metabolic syndrome (≥ 3 traits), compared with 4.2% of non-HCT survivors (P = .02). HCT survivors also had increased C-reactive protein and leptin levels and decreased adiponectin, suggestive of underlying inflammation and increased visceral fat. In multivariate analyses, history of HCT remained associated with ≥ 2 traits (odds ratio [OR]. 5.13; 95% confidence interval [CI], 1.54-17.15) as well as with ≥ 3 traits (OR, 16.72; 95% CI, 1.66-168.80). Other risk factors included any cranial radiation exposure and family history of cardiometabolic disease. In summary, pediatric ALL survivors exposed to TBI-based HCT as well as to any cranial radiation may manifest cardiometabolic traits at an early age and should be screened accordingly.

Topics: Adolescent; Adult; C-Reactive Protein; Cardiovascular Diseases; Child; Cohort Studies; Cross-Sectional Studies; Hematopoietic Stem Cell Transplantation; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Risk Factors; Survivors; Whole-Body Irradiation; Young Adult

Few studies have evaluated the relation between phase angle (PA) and metabolic syndrome. As long as we know, there are not studies of association between phase angle and adipocytokines. The aim of our study was to evaluate the association of adipocytokines levels and classical cardiovascular risk factors with tertiles of phase angle in obese women.. A cross-sectional study was designed to establish whether phase angle from 228 adult female patients with obesity are related with adipocitokynes and cardiovascular risk factors. These patients were studied in a Nutrition Clinic Unit after signed informed consent. All patients with a 2 weeks weight-stabilization period before recruitment were enrolled. Weight, blood pressure, basal glucose, C-reactive protein (CRP), insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides blood and adypocitokines (leptin, adiponectin, resistin Interleukin-6 and TNF-alpha) levels were measured. The phase angle alpha was determined by bioimpedance with the equation [PA degrees =(Xc/R)x(180 degrees/pi)].. Two hundred and twenty-eight females gave informed consent and were enrolled in the study. The mean age was 38.2 +/- 14.7 years and the mean BMI 35.27 +/- 6.5. Patients were divided by tertiles of phase angle. Fat mass was higher in first tertile than third tertile (43.6 +/- 12.6 vs 40.9 +/- 15 kg: p<0.05). HOMA (2.4 +/- 1.6 vs 1.46 +/- 1.6: p<0.05), insulin (14.4 +/- 8.5 vs 11.3 +/- 9.4 mUI/L: p<0.05) and glucose (102.1 +/- 20 vs 90 +/- 19.5 mg/dl: p<0.05) levels were higher in first tertile than second and third tertiles. Leptin (167.3 +/- 98 vs 104.5 +/- 80 ng/ml: p<0.05) and IL-6 (3.84 +/- 5.7 vs 1.8 +/- 2.9 pg/ml: p<0.05) levels were higher in first phase angle tertile than third tertile phase angle.. Obese women with a low PA tertile have high fat mass with a secondary high level of glucose, HOMA, IL-6 and leptin. Perhaps, a low tertile of phase angle could be a new subrogate cardiovascular risk factor to categorize the obese patients.

Topics: Adipokines; Adult; Cardiovascular Diseases; Cross-Sectional Studies; Electric Impedance; Female; Humans; Insulin Resistance; Interleukin-6; Leptin; Middle Aged; Obesity; Risk Factors

Little is known about the impact of having one cardiovascular (CV) risk factor on the levels of other CV risk factors in the general adolescent population. We hypothesized that when adolescents have one CV risk factor, the levels of other CV risk factors worsen simultaneously.. Subjects consisted of 1,257 healthy adolescent volunteers (549 males and 708 females) aged 15-18 years. Abdominal obesity, hypertension, raised triglyceride levels, decreased HDL-cholesterol levels and hyperglycemia were used as CV risk factors. Homeostasis assessment of insulin resistance (HOMA-IR) was used as a surrogate marker of insulin resistance. Levels of four biomarkers, leptin, adiponectin, high-sensitive C-reactive protein, and desacyl-ghrelin, were also determined. Cut-offs for gender-specific individual CV risk factor levels were based on the 90th (or 10th) percentile values of the subjects in the present study.. The levels of all CV risk factors and HOMA-IR significantly and simultaneously worsened when adolescents had one CV risk factor in both genders. Having any one CV risk factor indicated the development of other CV risk factors in adolescents; in particular, we found that the development of abdominal obesity in male subjects had a harmful effect on the levels of other CV risk factors and was associated with the worsening of all four biomarkers examined.. It is important to determine the presence or absence of these CV risk factors before and/or during adolescence, because having one CV risk factor indicates the start of an accumulation of CV risk factors in the general adolescent population.

Topics: Adiponectin; Adolescent; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Female; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Male; Obesity; Risk Factors; Triglycerides

In obese rheumatoid arthritis (RA) patients inflammatory mechanisms and cardiovascular secondary disorders are possibly related to changed expression of adipocytokines. Various adipocytokines and inflammatory parameters were examined in 112 patients (23.2% men; 76.8% women) suffering from RA: leptin, adiponectin, visfatin, sCD40 L, CRP, and ESR. Average BMI was 27.6 (+/-5.6). Leptin and BMI as well as visfatin and BMI correlated positively, BMI and adiponectin, however, showed a negative correlation. Significant differences between normal-weight and obese RA patients were found in both leptin and adiponectin measurements. Visfatin showed a positive correlation with CRP; sCD40 ligand which is a marker for increased T-cell activity correlated with CRP and ESR. Patients with low adiponectin levels (<10 microg/ml) more often suffered from cardiovascular diseases (28.6%) than those with enhanced adiponectin (14.3%). Increased pro-inflammatory leptin and decreased anti-inflammatory adiponectin in obese RA patients can be associated with RA activity and enhanced cardiovascular risk.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Blood Sedimentation; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; CD40 Ligand; Cytokines; Female; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Reference Values; Risk Factors; Statistics as Topic; Young Adult

Obesity, the most common nutritional disorder in industrialized countries, is associated with an increased mortality and morbidity of cardiovascular disease (CVD). Obesity is primarily considered to be a disorder of energy balance, and it has recently been suggested that some forms of obesity are associated with chronic low-grade inflammation. The present paper focuses on the current status of our knowledge regarding chronic inflammation, a link between obesity and CVDs, including heart diseases, vascular disease and atherosclerosis. The paper discusses the methods of body fat evaluation in humans, the endocrinology and distribution of adipose tissue in the genders, the pathophysiology of obesity, the relationship among obesity, inflammation, and CVD, and the adipose tissue-derived cytokines known to affect inflammation. Due to space limitations, this paper focuses on C-reactive protein, serum amyloid A, leptin, adiponectin, resistin, visfatin, chemerin, omentin, vaspin, apelin, and retinol binding protein 4 as adipokines.

Topics: Adiponectin; Animals; Cardiovascular Diseases; Humans; Inflammation; Leptin; Obesity; Resistin; Serum Amyloid A Protein

Topics: Cardiovascular Diseases; Humans; Leptin

To study the serum leptin and adiponectin levels among relatively healthy older people and their association with traditional cardiovascular risk factors.. Personal medical history and blood sample were collected from 1515 older people of Guangzhou. Fasting serum glucose, lipids, leptin and adiponectin were measured.. (1) In relatively healthy older adults aged 50 or above, from Guangzhou, the following data were seen: serum leptin levels (x(-) ± s) in men and women were (3.90 ± 2.36) ng/ml and (12.17 ± 2.01) ng/ml respectively; serum adiponectin levels in men and women were (5.33 ± 2.78) mg/L and (7.18 ± 2.58) mg/L respectively. (2) Serum leptin and adiponectin level increased with age. After adjusting for body mass index, the trend for serum leptin level in men (P < 0.001) and adiponectin level in women (P < 0.05) were significantly associated with age. (3) No association was found between cigarette smoking and levels of leptin or adiponectin in both men and women after adjusting for age (P from 0.09 to 0.76). (4) In both men and women, serum leptin and adiponectin levels were positively associated with waist circumference/body mass index, systolic blood pressure, low-density lipoprotein cholesterol and triglyceride (P from 0.04 to < 0.001). In men, leptin was also significantly associated with the increase of diastolic blood pressure and glucose but decreased with high-density lipoprotein cholesterol (P from 0.03 to 0.02). (5) Decreased adiponectin level was associated with increased waist circumference and triglyceride in both men and women (P from 0.003 to < 0.001) and with the increased body mass index, fasting plasma glucose as well as with decreased high-density lipoprotein cholesterol in men (P from 0.05 to < 0.001) but with increased systolic blood pressure and total cholesterol in women (P from 0.05 to 0.006).. In Guangzhou city, among relatively healthy older adults aged 50 or above, their serum leptin and adiponectin levels were lower in men than in women. Serum leptin level in men and adiponectin level in women were significantly associated with the increase of age. Increased leptin and decreased adiponectin levels were associated with increased traditional cardiovascular risk factors.

Topics: Adiponectin; Aged; Cardiovascular Diseases; China; Cohort Studies; Female; Humans; Leptin; Male; Middle Aged; Risk Factors; Smoking

Topics: Adult; Cardiovascular Diseases; Female; Humans; Inflammation Mediators; Leptin; Male; Obesity; Risk Factors

To clarify the association of circulating levels of leptin with risk for cardiovascular disease (CVD) events and new-onset diabetes in men and women.. We related baseline leptin levels to CVD events (n = 864) and incident diabetes (n = 289) in an elderly population (n = 5,672) over 3.2 years of follow-up.. In treatment-, age-, and country-adjusted models, leptin was not associated with risk of CVD in men (hazard ratio 1.02 [95% CI 0.90-1.16] per unit log-leptin increase) or women (1.05 [0.91-1.20]) but was associated with risk of diabetes in men (2.75 [2.14-3.52]) and women (1.54 [1.22-1.94]). After adjusting for classic risk factors and BMI, C-reactive protein, and glucose, the diabetes association retained significance in men (1.85 [1.30-2.63]) but not in women (0.89 [0.64-1.26]).. Leptin, similar to other markers of adiposity in general, is more strongly related to risk of diabetes than CVD in the elderly.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Female; Humans; Ireland; Leptin; Male; Myocardial Infarction; Netherlands; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Scotland; Stroke

Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals.. We evaluated 818 elderly (mean age 79 years, 62% women) Framingham Study participants attending a routine examination at which plasma leptin was assayed.. Leptin levels were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up (mean 8.0 years), 129 (of 775 free of CHF) participants developed CHF, 187 (of 532 free of CVD) experienced a first CVD event, and 391 individuals died. In multivariable Cox regression models adjusting for established risk factors, log-leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR] per SD increment 1.26 [95% CI 1.03-1.55] and 1.28 [1.09-1.50], respectively). Additional adjustment for BMI nullified the association with CHF (0.97 [0.75-1.24]) but only modestly attenuated the relation to CVD incidence (1.23 [1.00-1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin and mortality (P = 0.005 for quadratic term) with greater risk of death evident at both low and high leptin levels.. In our moderate-sized community-based elderly sample, higher circulating leptin levels were associated with a greater risk of CHF and CVD, but leptin did not provide incremental prognostic information beyond BMI. Additional investigations are warranted to elucidate the U-shaped relation of leptin to mortality.

Topics: Aged; Aged, 80 and over; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Cholesterol, HDL; Female; Heart Failure; Humans; Incidence; Leptin; Male; Massachusetts; Obesity; Regression Analysis; Risk Factors

Steroid sex hormones modulate the expression of adipocytokines implicated in the pathogenesis of athero-thrombotic cardiovascular disease. We used exploratory factor analysis to search for latent associations between circulating sex steroid hormones, adipocytokines, and cardiovascular risk factors in a well-characterized cohort of postmenopausal women. Among participants in the Rancho Bernardo community study we identified 515 Caucasian women with a mean age of 74+/-8 years and mean body mass index of 24.2+/-3.7 kg/m(2). All had intact ovaries and none was using estrogen therapy. We constructed models aiming for structural clarity and high loading of variables on individual factors. Total adiponectin loaded with major lipid subfractions (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and fasting triglycerides) and with sex hormone-binding globulin. Leptin loaded with central obesity (waist circumference) and fasting insulin levels. Neither adipocytokine loaded with total or bioavailable testosterone or with estradiol or dehydroepiandrosterone sulfate. Sex hormones consistently loaded together on a separate factor; this co-segregation was not influenced by body mass index. Exclusion of women with diabetes did not alter these observations. In conclusion, we identified evidence of latent associations between adipocytokines and a range of cardiovascular risk factors in postmenopausal women. Our results suggest that cardiovascular risk in older women may be modulated through a hitherto unrecognized association between adiponectin, lipid subfractions, and sex hormone bioavailability.

Topics: Adiponectin; Aged; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Cohort Studies; Estradiol; Factor Analysis, Statistical; Female; Humans; Insulin; Interleukin-6; Leptin; Middle Aged; Postmenopause; Sex Hormone-Binding Globulin; Testosterone

Excess body fat is associated with increased cardiovascular disease (CVD) risk. The hypothesis of the study was that physical activity and omega-3 index, a marker of past long chain n-3 polyunsaturated fatty acids consumption, counteract the negative associations between fatness and CVD risk factors in young overweight and obese adults. A total of 324 subjects (20-40 years, body mass index [BMI], 27.5-32.5 kg/m(2), from Iceland, Spain, and Ireland) were investigated cross-sectionally. Dietary intake, anthropometric measurements, blood pressure, CVD risk factors, and fatty acids in erythrocyte membrane were analyzed. Information on physical activity was collected. Linear models were constructed to find out the associations of BMI, physical activity (quartiles), and omega-3 index with CVD risk factors. The most frequently increased risk factors were blood lipids (41.4%) and blood pressure (32.1%); fewer participants experienced disturbed glucose metabolism (11.8%). Body mass index was significantly associated with increased CVD risk factors (P = .001-.029), with the exception of total cholesterol, low-density lipoprotein, and high-density lipoprotein. The highest physical activity quartile had a lower fat mass (P = .005, at a given BMI), leptin (P = .008, in male participants only), and interleukin 6 (P = .021) but higher high-density lipoprotein (P = .020) than other quartiles; however, an approximate dose-response relationship could only be observed for leptin. The omega-3 index was not associated with lower low-density lipoprotein (P = .056), but docosahexaenoic acid in erythrocyte membrane was associated to it (P = .016). It is concluded that physical activity and docosahexaenoic acid diminish some of the negative health effects associated with overweight and obesity; however, body fatness remains the most important variable associated with increased CVD risk factors in young overweight and obese adults.

Topics: Adipose Tissue; Adult; Age Factors; Blood Glucose; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Europe; Exercise; Fatty Acids, Omega-3; Female; Humans; Interleukin-6; Leptin; Linear Models; Lipids; Lipoproteins, HDL; Male; Obesity; Overweight; Risk Factors; Sex Factors; Sports

Increased body mass index (BMI) is associated with reduced all-cause and cardiovascular (CV) mortality in hemodialysis (HD) patients, whereas CV risk increases with BMI in the general population. In the general population, obesity is associated with inflammation, decreased high-density lipoprotein (HDL) cholesterol, increased low-density lipoprotein (LDL) cholesterol, and triglycerides (TGs), all risk factors for CV disease. Low-density lipoprotein cholesterol does not predict CV risk in HD, whereas increased C-reactive protein and interleukin-6 (IL-6), low HDL and apolipoprotein (apo) AI, and increased fasting TGs do predict risk. Renal failure is associated with dyslipidemia and inflammation in normal-weight patients. We hypothesized that the effects of obesity may be obscured by renal failure in HD.. We explored the relationship between adipose tissue pools and distribution, i.e., subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) (measured by magnetic resonance imaging) and measures of inflammation (C-reactive protein, IL-6, ceruloplasmin, and alpha1 acid glycoprotein), HDL and LDL cholesterol, total TGs, apo AI, apo B, apo CII (an activator of lipoprotein lipase), apo CIII (an inhibitor of lipoprotein lipase), and the adipokines, leptin and adiponectin, in 48 patients with prevalent HD.. Total TG concentrations were positively correlated with VAT controlled for age, sex, and weight. Both apo CII and apo CIII were correlated only with VAT. Adiponectin was inversely correlated with VAT, and leptin was positively associated with SAT. C-reactive protein and alpha1 acid glycoprotein were weakly associated with SAT, whereas ceruloplasmin was strongly associated with VAT according to multiple regression analysis. In contrast, apo B, LDL, apo AI, HDL, and IL-6 were not correlated with any measure of body composition, potentially mitigating the effects of obesity in HD.

Topics: Adiponectin; Adiposity; Adult; Aged; Aged, 80 and over; Apolipoprotein A-I; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Ceruloplasmin; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Inflammation; Interleukin-6; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity; Renal Dialysis; Risk Factors; Subcutaneous Fat; Triglycerides

Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine involved into the pathogenesis of atherosclerosis and has prognostic value in the acute and chronic phases in patients with acute coronary syndromes.. MCP-1/CCL2 concentration was measured in plasma fractions of 363 middle-aged overweight/obese individuals (aged 61 +/- 12 years, BMI 30.1 +/- 6.6 kg/m(2), 15% with type 2 diabetes, and 12% with impaired glucose tolerance) of a population survey carried out in 1990-1991 in Lombardy, Italy (Cremona Study), and cardiovascular disease (CVD) mortality was assessed in 2006 through Regional Health Registry files.. At baseline MCP-1/CCL2 was increased in individuals with type 2 diabetes (P < 0.05) and showed significant correlations with biochemical risk markers of atherosclerosis. After 15 years, among the 363 subjects, there were 82 deaths due to CVD. In univariate analysis age, sex, fasting glucose and insulin, fibrinogen, glucose tolerance status, smoking habit, and MCP-1/CCL2 were associated with CVD mortality. Age, sex, fasting serum glucose, MCP-1/CCL2, and smoking habit maintained an independent association with CVD mortality in multiple regression analysis. In a subgroup of 113 subjects in whom data for C-reactive protein (CRP) were available, its level was not predictive of CVD mortality.. In middle-aged overweight/obese individuals MCP-1/CCL2 was independently associated with CVD mortality. Further studies will be necessary to establish its role as a surrogate biomarker and as a potential therapeutic target.

Topics: Atherosclerosis; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Chemokine CCL2; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glucose Tolerance Test; Humans; Insulin; Italy; Leptin; Life Style; Middle Aged; Prognosis; Risk Factors; Stroke

Experimental evidence indicates that leptin-deficient animals develop left ventricular (LV) hypertrophy, but data relating circulating leptin levels to cardiac structure and function in subjects >70 years old are lacking. We related circulating leptin concentrations to echocardiographic measurements of cardiac structure and function in 432 participants of the community-based Framingham Heart Study (mean age 75 years, 67% women) who underwent echocardiography at a routine examination (approximately 4 years before leptin concentrations were assayed). In multivariable linear regression, logarithmically transformed gender-standardized leptin concentrations were related to the following echocardiographic measurements: LV mass, left atrial size, and fractional shortening (primary analysis); LV wall thickness and LV end-diastolic dimensions (the 2 components of LV mass); and transmitral early/late diastolic filling velocities (secondary analysis). Leptin concentrations were inversely associated with LV mass, LV wall thickness, and left atrial size (p <0.04 for all). The top gender-specific tertile of leptin was associated with an adjusted LV mass 16 g lower compared with the lowest tertile (p = 0.007 for trend across tertiles). Leptin levels were not associated with LV fractional shortening, transmitral early/late diastolic filling velocities, or LV end-diastolic diameter (p >0.16). In conclusion, our cross-sectional observations suggest a cardioprotective influence of leptin on LV remodeling consistent with experimental data and may provide insight into the potential role of leptin resistance as a mediator of obesity-associated cardiomyopathy.

Topics: Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Female; Heart Atria; Heart Ventricles; Humans; Leptin; Male; Retrospective Studies; Stroke Volume; Ventricular Remodeling

Craniopharyngioma patients without GH therapy are at an increased cardiovascular disease (CVD) risk and particularly concerning women. No previous study on long-term GH therapy in adults with childhood onset (CO) craniopharyngioma was identified.. To investigate CVD risk in adults with CO craniopharyngioma on complete hormone replacement, including long-term GH therapy, and to investigate the impact of disease-related factors on CVD risk.. In a cross-sectional study of operated CO craniopharyngiomas (1958-2000) from a defined area of Sweden (2.5 million), we enrolled 42 patients (20 women) with a median age of 28 years (range 17-57) and assessed CVD risk of 20 (4-40) years after first operation. Comparisons were made with matched controls and between patients with tumor growth into the third ventricle (TGTV) versus non-TGTV. GH therapy was 10-12 years in women and men. Results In comparison with controls, both male and female patients had increased body mass index, fat mass, insulin, and leptin levels. Overall, while not significantly increased in male patients, 55-60% of female patients had a medium-high CVD risk, compared with 10-20% in controls. An increased CVD risk (all P<0.05) and higher levels of fat mass and insulin were recorded in the TGTV group versus the non-TGTV group. Late puberty induction and lack of androgens were shown in female patients.. Adult patients with CO craniopharyngioma, especially those with TGTV, have persistently increased CVD risk. Conventional hormone substitution, including GH, is insufficient to normalize CVD risk, suggesting an important role for irreversible hypothalamic dysfunction.

Topics: Adolescent; Adult; Age of Onset; Body Composition; Body Mass Index; Cardiovascular Diseases; Craniopharyngioma; Cross-Sectional Studies; Female; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hypothalamus; Insulin; Leptin; Male; Middle Aged; Pituitary Neoplasms; Young Adult

In type 2 diabetes mellitus, circulating C-reactive protein (CRP) is increased, whereas the high density lipoprotein (HDL)-associated, anti-oxidative and anti-inflammatory enzyme, paraoxonase-I, is decreased. Both high CRP and low paraoxonase-I activity may predict cardiovascular disease. It is unknown whether lower paraoxonase-I activity contributes to higher CRP levels in diabetes. In type 2 diabetic and control subjects, we determined the relationship of CRP with paraoxonase-I when taking account of plasma levels of pro- and anti-inflammatory adipokines.. In 81 type 2 diabetic patients and 89 control subjects, plasma high-sensitive CRP, serum paraoxonase-I activity (arylesterase activity, assayed as the rate of hydrolysis of phenyl acetate into phenol), plasma leptin, adiponectin, resistin and lipids were determined.. Body mass index (BMI), waist, insulin resistance, triglycerides, CRP, leptin and resistin levels were higher (P < 0.05 to P < 0.001), whereas HDL cholesterol, paraoxonase-I activity and adiponectin levels were lower (P = 0.02 to P < 0.001) in diabetic compared to control subjects. Multiple linear regression analysis demonstrated that, after controlling for age and gender, CRP was inversely related to paraoxonase-I activity (beta = -0.15, P = 0.028) and adiponectin (beta = -0.18, P = 0.009), and positively to leptin (beta = 0.33, P < 0.001) and BMI (beta = 0.22, P = 0.007), independently of the diabetic state (or of fasting glucose or HbA1c), insulin resistance and lipids (P > 0.20 for all).. Low paraoxonase-I activity is related to higher CRP, independently of adipokines, as well as of obesity and lipids. Low paraoxonase-I activity in type 2 diabetes mellitus may contribute to increased cardiovascular risk via an effect on enhanced systemic low-grade inflammation.

Topics: Adiponectin; Aged; Aryldialkylphosphatase; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leptin; Linear Models; Male; Middle Aged; Resistin; Risk Factors

To determine the presence of traditional and emergent cardiovascular risk factors and to evaluate the triglyceride/high-density lipoprotein cholesterol (Tg/HDL-C) ratio as a marker for cardiovascular disease and metabolic syndrome (MS) in obese children.. Sixty-seven prepubertal children of both sexes, between the ages of 6 and 12 yr, 20 normal-weight children, 18 overweight, and 29 obese subjects, were studied. Anthropometric measures, blood pressure, body mass index (BMI), and fat mass (FM), were measured. Plasma glucose, serum insulin, lipid profile, C-reactive protein (CRP), and leptin concentrations were quantified. Glucose and insulin concentrations 2 h post-glucose load were determined. The Tg/HDL-C ratio, homeostasis model assessment index (HOMA), and quantitative insulin sensitivity check index (QUICKI) were calculated.. Systolic, diastolic, and mean blood pressures (MBP), low-density lipoprotein cholesterol (LDL-C), Tg/HDL-C, total cholesterol/HDL-C, LDL-C/HDL-C ratios, basal and 2 h postload insulin, CRP, and leptin were significantly higher and the QUICKI index were lower in the obese group. MBP, Tg/HDL-C ratio, HOMA, CRP, and leptin levels showed a positive and significant correlation and QUICKI a negative correlation with abdominal circumference, BMI, and FM. The Tg/HDL-C ratio correlated positively with MBP. The frequency of MS in the obese group was 69%. While Tg/HDL-C ratio, CRP, and leptin were higher and the values of QUICKI were lower in subjects with MS, it was the Tg/HDL-C ratio and the BMI that significantly explained the MS.. Obesity increases the cardiovascular risk in childhood. The Tg/HDL-C ratio could be a useful index in identifying children at risk for dyslipidemia, hypertension, and MS.

Topics: Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Child; Cholesterol, HDL; Female; Homeostasis; Humans; Hypertension; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Risk Factors; Triglycerides

This article sets out the clinical context of the research presented by Romero-Corral et al. in an accompanying article in this journal. Obesity is an important risk factor for the development of cardiovascular disease. Among other metabolic abnormalities, obesity is associated with elevated levels of the inflammatory biomarker C-reactive protein (CRP) and of leptin. Here, we discuss the study carried out by Romero-Corral and colleagues-an analysis of leptin, CRP and cardiovascular risk factors. These researchers found that raised leptin concentrations were a more robust predictor of cardiovascular events than CRP; the highest risk was observed in participants with raised concentrations of both markers. We explore the possible mechanism for this interaction, and propose that leptin's stimulatory effect on the sympathetic nervous system and its ability to impair baroreceptor control might be involved.

Topics: C-Reactive Protein; Cardiovascular Diseases; Exercise; Humans; Leptin; Obesity; Pressoreceptors; Risk Factors; Sympathetic Nervous System

To investigate the association between smoking and leptin, and to discuss their influence on diabetes in a large-scale study of Japanese men.. A cross-sectional study was carried out in 2002. The subjects were 2836 men aged 35-66. Smoking history was investigated in a self-administered questionnaire. Blood leptin, glucose and insulin were measured.. Significant differences in leptin levels and homeostasis model assessment of insulin resistance (HOMA-IR) related to smoking status were observed (P=0.001 and P=0.008, respectively). The multivariate-adjusted geometric means of leptin in current, past and never smokers were 3.88, 4.08 and 4.12 ng/ml, respectively, while the means of HOMA-IR were 1.64, 1.61 and 1.49, respectively. The age-, body mass index-, and other lifestyle-adjusted prevalences of diabetes in current and never smokers were 9.2 and 4.7%, respectively. That of current smokers was significantly higher than in never smokers (P<0.001). The dose-dependent association found between the intensity of smoking and leptin levels in current smokers was statistically significant (P=0.030).. The present finding may explain in part an association among smoking, leptin levels and diabetes. Smoking is one of the important modifiable risk factors for the prevention of diabetes.

Topics: Adult; Alcohol Drinking; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Energy Intake; Humans; Hyperlipidemias; Insulin Resistance; Japan; Leptin; Life Style; Male; Middle Aged; Smoking

Atherosclerotic vascular diseases such as cerebrovascular and cardiovascular diseases are major causes for fatality of hemodialysis (HD) patients. Since adipocytokines are key players for arteriosclerosis in the concept of metabolic syndrome (MetS), we aimed to determine whether circulating levels of major three adipocytokines, adiponectin, TNF-alpha, and leptin, could be associated with various parameters and clinical events in HD patients who are diagnosed as MetS using a new criteria designed for the Japanese population.. We enrolled 53 very stable patients under maintenance HD at Minami-Senju Hospital. Basically, clinical and laboratory data were taken just before HD therapy. HD sessions were performed regularly and all the participants took oral administration and injection as usual. A cross-sectional study was performed to evaluate clinical and laboratory data related to three major adipocytokines, adiponectin, TNF-alpha and leptin.. We observed no significant differences of three adipocytokines when the participants were divided in accordance with existence of MetS or past cerebrocascular/cardiovascular diseases. Only the serum adiponectin levels were significantly different in two groups categorized by existence of diabetes mellitus. Serum triglycerides (TG) were significantly correlated with two circulating adipocytokines, adiponectin (r=-0.328, p<0.016) and leptin (r=0.397, p<0.003), when we analyzed all 53 patients together.. Plasma adiponectin and leptin are expected as contributors related to dyslipidemia, suggesting these may be targets of prevention of vascular diseases in maintenance HD patients.

Topics: Adipokines; Adiponectin; Aged; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Metabolic Syndrome; Middle Aged; Renal Dialysis; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha

Rheumatoid arthritis (RA) is a multisystem disease with high rates of morbidity and mortality. In recent years, there has been increasing focus on the growing rates of cardiovascular disease (CVD) in RA, over and above expected levels allowing for 'traditional' risk factors. In this paper the impact of CVD in RA, the relative contributions of traditional risk factors and novel risk factors (including homocysteine, oxidised low-density lipoprotein, high-sensitivity C-reactive protein and leptin), and the need to address cardiovascular risk in the fight against premature death from coronary artery and stroke disease in RA are discussed.

Topics: Arthritis, Rheumatoid; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, LDL; Comorbidity; Coronary Artery Disease; Endothelium, Vascular; Homocysteine; Humans; Leptin

The aim was to investigate etiologic and cardiovascular risk factors in obese children from Extremadura, Spain, and their relationship with insulin resistance and plasma adipocytokine levels.. The study included 373 children (age, 3-13 years) who were randomly selected from schools in the city and province of Badajoz and from two health centers in the Spanish autonomous community of Extremadura.. Some 9.5% of children were obese. Compared with normal weight children, obese children exhibited a greater weight gain in the first year of life (7.3+/-1.5 kg vs. 6.3+/-0.8 kg), were less physically active (9.6+/-7.2 h/week vs. 13.1+/-8.1 h/week), and had more screen time (18.0+/-12.4 h/week vs. 12.8+/-8.2 h/week), a lower high-density lipoprotein cholesterol level (46.0+/-11.4 mg/dL vs. 64.6+/-22.9 mg/dL), higher arterial systolic pressure (102.3+/-8.5 mmHg vs. 89.9+/-13.4 mmHg), increased insulin resistance (6.2+/-3.6 vs. 4.6+/-4.5), a higher level of leptinemia (24.8+/-13.8 ng/mL vs. 12.9+/-10.8 ng/mL) and a lower level of adiponectinemia (8.4+/-5.7 microg/mL vs. 15.6+/-7.9 microg/mL).. Our findings demonstrate that there is a relationship between a sedentary lifestyle and the development of insulin resistance and altered adipocytokines levels in obese children, and that these changes are related to a number of cardiovascular risk factors.

Topics: Adiponectin; Adolescent; Cardiovascular Diseases; Child; Child, Preschool; Female; Humans; Insulin Resistance; Leptin; Male; Obesity; Resistin; Risk Factors; Spain

The aim of this study was to investigate serum leptin, adiponectin and paraoxonase1 levels in adult females receiving pharmacotherapy for various psychiatric disorders.. The study group consisted of 32 obese females (mean age 40.53 +/- 11.00 years, mean body mass index 35.44 +/- 5.33 kg/m(2)) who were receiving treatment for psychiatric disorders, and the control group included 22 obese females (mean age 35.95 +/- 9.16 years, mean body mass index 30.78 +/- 3.33 kg/m(2)) who were free of psychiatric disorders. Analyses were performed using a bioelectrical impedance device. Fasting blood samples were obtained for complete blood count and various biochemical tests, including determination of leptin, adiponectin and paraoxonase1 activity.. Body mass index, waist and hip circumference, body fat percentage, fasting blood glucose, insulin, glycosylated hemoglobin, homeostasis model assesement of insulin resistance, alanine transaminase, aspartate tarnsaminase, and leptin levels were significantly higher in the study group than in controls. Although body weight was positively correlated with leptin levels in both groups, body weight was negatively correlated with adiponectin levels in the control group and positively correlated with adiponectin levels in the study group. In the study group, body mass index and hip circumference correlated positively with leptin levels, hip circumference correlated positively with adiponectin levels, and waist to hip ratio correlated positively with paraoxonase levels. In the control group, body mass index as well as waist and hip circumferences were positively correlated with leptin levels. Weight, body mass index, and hip circumference were also negatively correlated with the adiponectin/leptin ratio in the control group.. This study indicates a higher risk for obesity-related disorders, particularly metabolic syndrome, diabetes and cardiovascular disease, in patients treated with psychiatric drugs.

Topics: Adiponectin; Adult; Antidepressive Agents; Aryldialkylphosphatase; Biomarkers; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Mental Disorders; Metabolic Syndrome; Obesity; Waist-Hip Ratio

This study investigated the effect of curcumin (0.05-g/100-g diet) supplementation on a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) fed to hamsters, one of the rodent species that are most closely related to humans in lipid metabolism. Curcumin significantly lowered the levels of free fatty acid, total cholesterol, triglyceride, and leptin and the homeostasis model assessment of insulin resistance index, whereas it elevated the levels of high-density lipoprotein cholesterol and apolipoprotein (apo) A-I and paraoxonase activity in plasma, compared with the control group. The levels of hepatic cholesterol and triglyceride were also lower in the curcumin group than in the control group. In the liver, fatty acid beta-oxidation activity was significantly higher in the curcumin group than in the control group, whereas fatty acid synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and acyl coenzyme A:cholesterol acyltransferase activities were significantly lower. Curcumin significantly lowered the lipid peroxide levels in the erythrocyte and liver compared with the control group. These results indicate that curcumin exhibits an obvious hypolipidemic effect by increasing plasma paraoxonase activity, ratios of high-density lipoprotein cholesterol to total cholesterol and of apo A-I to apo B, and hepatic fatty acid oxidation activity with simultaneous inhibition of hepatic fatty acid and cholesterol biosynthesis in high-fat-fed hamsters.

Topics: Animals; Apolipoprotein A-I; Aryldialkylphosphatase; Cardiovascular Diseases; Cholesterol, HDL; Cricetinae; Curcumin; Dietary Fats; Fatty Acids; Hyperlipidemias; Hypolipidemic Agents; Insulin Resistance; Leptin; Lipid Peroxidation; Male; Mesocricetus

Previous studies of leptin with cardiovascular disease (CVD) risk factors have been limited by clinical samples or lack of representation of the general population. This cross-sectional study, designed to examine whether leptin or insulin may mediate the endogenous relation of obesity with metabolic, inflammatory, and thrombogenic cardiovascular risk factors, included 522 men and 514 women aged >or=40 years who completed a physical examination during the third National Health and Nutrition Examination Survey. Participants were free of existing CVD, cancer (except non-melanoma skin cancer), diabetes, or respiratory disease. In multivariable analyses adjusted for race/ethnicity and lifestyle factors, waist circumference (WC) was positively associated with blood pressure, triglyceride, LDL cholesterol, total cholesterol:HDL ratio, apolipoprotein B, C-reactive protein (CRP), and fibrinogen concentrations, and negatively associated with HDL cholesterol and apolipoprotein A1 levels. The associations of WC with the metabolic CVD risk factors were largely attenuated after adjustment for insulin levels, while the associations of WC with the inflammatory and thrombogenic factors (CRP and fibrinogen, respectively) were largely explained by adjustment for leptin concentrations. However, leptin levels were not independently associated with CRP and fibrinogen in men and CRP in women when adjusted for WC. Positive associations of leptin and insulin with fibrinogen in women, independent of WC, were noted. These results suggest that insulin may be an important mediator of the association of obesity with metabolic but not inflammatory or thrombogenic CVD risk factors, while leptin does not appear to influence cardiovascular risk through a shared association with these risk factors. However, we cannot rule out the possibility that leptin and insulin influence cardiovascular risk in women through independent effects on fibrinogen concentrations.

Topics: Adult; Aged; C-Reactive Protein; Cardiovascular Diseases; Female; Fibrinogen; Humans; Insulin; Leptin; Male; Middle Aged; Nutrition Surveys; Obesity; Risk Factors; Sex Factors; United States

Possible correlations between adiponectin, leptin, CD146, a novel adhesion molecule localized at the endothelial junction, and other markers of endothelial cell injury, von Willebrand factor, thrombomodulin, vascular cell adhesion molecule, and intracellular adhesion molecule, and markers of inflammation, tumor necrosis factor-alpha, interleukin-6, and high-sensitivity C-reactive protein in nondiabetic hemodialyzed patients with and without coronary artery disease were studied. Markers of endothelial dysfunction were elevated in hemodialyzed patients, predominantly with coronary artery disease. In multivariate analysis, kinetic urea modeling and plasminogen activator inhibitor-1 remained the only positive predictors of adiponectin. In multivariate analysis, predictors of leptin were triglycerides, tissue plasminogen activator, CD146, and coronary artery disease. In multivariate analysis, predictors of CD146 were age, hemoglobin, and adiponectin. Elevated adiponectin correlated to CD146 may be the expression of a counterregulatory response aimed at mitigating the consequences in endothelial damage and increased cardiovascular risk in renal failure. The data provide further support for a link between adipocytokines, endothelial dysfunction, cardiovascular risk, and renal failure.

Topics: Adipocytes; Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Case-Control Studies; CD146 Antigen; Endothelium, Vascular; Female; Humans; Leptin; Male; Middle Aged; Renal Dialysis; Renal Insufficiency; Risk Factors

Hypocaloric diet-induced weight loss produces a coordinated decrease in plasma leptin levels and an increase in plasma ghrelin levels. The aim of the present study was to determine whether subjects who lose significant weight experience changes in circulating ghrelin and leptin levels.. A population of 66 obese patients was analyzed. Leptin, active ghrelin blood levels, and other cardiovascular risk factors were measured before and after 3 mo of a hypocaloric diet.. Sixty-six patients (17 male, 49 female) gave informed consent and were enrolled in the study. Forty-six patients did not lose 5% of initial weight (group I, weight loss 1.4 +/- 2.5 kg) and 20 patients lost weight (>5% of initial weight; group II, weight loss 7.1 +/- 2.6 kg). In group I, active ghrelin levels increased (7.40 +/- 8 versus 19.40 +/- 32 pg/mL, P < 0.05) and leptin levels decreased (102.6 +/- 86 versus 89.30 +/- 76 ng/mL, P < 0.05). In group II, leptin levels also decreased significantly (69.80 +/- 67 versus 53.50 +/- 59 ng/mL, P < 0.05). Active ghrelin in this group did not show differences (24.20 +/- 41 versus 10.30 +/- 12 pg/mL, NS). In the multivariate analysis with a dependent variable (change in active ghrelin levels, pg/ml) in group II adjusted by age and sex, only basal fat mass and basal intake of protein remained in the model. In the multivariate analysis with a dependent variable (change in leptin levels, pg/ml) in group II adjusted by age and sex, only basal fat mass and BMI remained in the model.. Patients with weight loss secondary to a hypocaloric diet did not change active ghrelin levels and decreased leptin levels after treatment.

Topics: Anthropometry; Calorimetry, Indirect; Cardiovascular Diseases; Diet, Reducing; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Risk Factors; Weight Loss

Leptin could be a key regulator of C-reactive protein (CRP) levels, which serve as a marker of systemic inflammation. Both leptin and CRP are predictors of cardiovascular disease (CVD). However, the interactions between leptin and CRP, and their association with CVD, remain unclear. We therefore studied them in a large, multiethnic population.. We analyzed leptin and CRP levels, anthropometric variables and cardiovascular risk factor data from 6,251 participants from the Third National Health and Nutrition Examination Survey (NHANES III). Logistic regression was used to estimate the association between leptin, CRP and CVD (defined as history of myocardial infarction or stroke). Receiver operating characteristic curves were created to study the additional value of leptin and CRP for the association with CVD.. The mean age was 44.4 +/- 0.21 years (52.5% women). After adjustment for age, race, dyslipidemia, hypertension, diabetes, smoking, obesity and CRP, high levels of leptin were significantly associated with CVD in men (odds ratio 2.47, 95% CI 1.19-5.19) and in women (odds ratio 3.30, 95% CI 1.47-7.99). After adjustment for leptin, CRP was not associated with CVD. There was a significant correlation between levels of leptin and CRP (Spearman correlation rho = 0.22 in men and rho = 0.32 in women, both P < 0.0001). The area under the curve, representing the association between cardiovascular risk factors and CVD, increased after the addition of high levels of both leptin and CRP together.. High leptin levels are independently associated with CVD even after adjustment for CRP; elevated CRP levels are not associated with CVD after adjustment for leptin. However, increased concentrations of both leptin and CRP confer the highest risk for CVD.

Topics: Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Leptin; Male; Middle Aged; Risk Factors; Sex Factors

The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown.. The objective of the study was to study the cross-sectional relations of these adipokines to cardiometabolic risk factors in a community-based sample.. We measured circulating ghrelin, leptin, and sOB-R in 362 participants (mean age 45 yr; 54% women) of the Framingham Third Generation Cohort.. Body mass index, waist circumference (WC), blood pressure, lipid measures, fasting glucose, smoking, and metabolic syndrome (MetS) were measured.. Ghrelin and leptin concentrations were significantly higher in women (P < 0.0001). In multivariable models, ghrelin was inversely associated with age and systolic blood pressure, and leptin was positively related to body mass index and WC. sOB-R was positively associated with age, total cholesterol, and fasting glucose and inversely with WC and high-density lipoprotein cholesterol. Ghrelin and sOB-R concentrations were significantly lower with number of MetS components (P for trend = 0.022 and < 0.0001, respectively), whereas leptin concentrations were higher (P for trend = 0.0001). Relating all adipokines to MetS conjointly, higher ghrelin and leptin concentrations were associated with decreased and increased odds of MetS (odds ratio 0.55, P < 0.0001; odds ratio 4.44, P = 0.0002, per 1 sd increase of respective log adipokine).. In our community-based sample, we observed a sexual dimorphism in circulating ghrelin and leptin concentrations. Ghrelin, leptin, and sOB-R were associated with number of MetS components cross-sectionally, consistent with the hypothesis that these adipokines may have a central role in cardiometabolic risk.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Energy Metabolism; Female; Ghrelin; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Receptors, Leptin; Risk Factors; Sex Characteristics

Leptin, an adipocyte-derived protein, regulating food intake and metabolism has been implicated in the development of coronary heart disease. We have examined the relationship between leptin and vascular risk factors including insulin resistance, metabolic, inflammatory and haemostatic risk factors.. The study was carried out in 3640 non-diabetic men aged 60-79 years drawn from general practices in 24 British towns and who were not on warfarin. Leptin was strongly positively correlated with waist circumference (r=0.58; p<0.0001). Leptin concentrations decreased significantly with increasing physical activity and were lowered in cigarette smokers and elevated in men with pre-existing coronary heart disease and stroke; alcohol intake showed no association with leptin concentration. After adjustment for waist circumference and these lifestyle factors, increased leptin was independently associated with significant increases in insulin resistance, triglycerides, inflammatory markers (interleukin-6, C-reactive protein, fibrinogen, plasma viscosity), coagulation factor VIII, endothelial markers von Willebrand factor, tissue plasminogen activator, and fibrin D-dimer levels; and a decrease in HDL-cholesterol. No association was seen between leptin and blood pressure, total cholesterol, glucose or white cell count after adjusting for waist circumference. Further adjustment for insulin resistance abolished the relationships between leptin and triglycerides and HDL-cholesterol, weakened the associations with the haemostatic factors although they remained significant, but made minor differences to the associations with inflammatory markers.. Plasma leptin is associated with insulin resistance, inflammation and disturbances in haemostasis independent of waist circumference, suggesting possible pathways by which leptin may influence risk of cardiovascular disease.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Endothelium, Vascular; Follow-Up Studies; Hemostasis; Humans; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Male; Middle Aged; Obesity; Prospective Studies; Registries; Risk Assessment; Risk Factors; Time Factors; United Kingdom

Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular disorders. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring (UN offspring) showed an increase in systolic blood pressure (8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivascular fibrosis of the coronary artery (16 wk, P < 0.05) and cardiac cardiomegaly (16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen (P < 0.05) and endothelin-1 (P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles (16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.

Topics: Angiotensin II; Animals; Blood Pressure; Cardiovascular Diseases; Female; Fetal Nutrition Disorders; Heart Ventricles; Leptin; Malnutrition; Mice; Mice, Inbred C57BL; Nitric Oxide; Pregnancy; Prenatal Exposure Delayed Effects; Renin-Angiotensin System; Sodium Glutamate; Ventricular Remodeling

Primary hyperparathyroidism (PHPT) has been associated with high cardiovascular morbidity and mortality; its pathogenesis is not fully understood. Moreover, many metabolic abnormalities are frequently present in patients with PHPT. Several substances (such as leptin and adiponectin) are secreted from adipocytes, which may contribute to regulate energy homeostasis and the development of cardiovascular diseases. We examined the relationship between leptin and adiponectin levels and metabolic disorders in 67 newly diagnosed never-treated patients with PHPT and in 46 healthy subjects (HS). Twenty (29.8%) patients with PHPT presented a metabolic syndrome (as defined by Adult Treatment Panel III criteria). Serum leptin and adiponectin levels in HS were 6.28 +/- 3.3 ng/mL (range, 1.7-19.2 ng/mL) and 6.65 +/- 1.7 microg/mL (range, 3.72-10.86 microg/mL), respectively. In all patients with PHPT, the mean leptin levels (34.28 +/- 20.4 ng/mL) were significantly higher than those of HS (P < .01) and, in particular, in PHPT patients with metabolic syndrome (52.63 +/- 31.2 ng/mL) and positively correlated with body mass index, waist circumference, and cholesterol. The mean adiponectin level was significantly lower (4.34 +/- 3.5 mug/mL) only in PHPT patients with metabolic syndrome (P < .005) and negatively correlated with waist circumference and fasting glucose. We concluded that increased serum level of leptin and decreased serum level of adiponectin coexist in patients with PHPT and may represent a pathogenetic factor for cardiovascular disease in this condition.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Mass Index; Calcium; Cardiovascular Diseases; Cholesterol; Female; Heart Rate; Humans; Hyperparathyroidism; Leptin; Magnesium; Male; Metabolic Syndrome; Middle Aged; Parathyroid Hormone; Phosphorus; Uric Acid

A very strong epidemiological link exists between obesity, the metabolic syndrome, diabetes and diabetes-associated cardiovascular pathologies. For this reason the peripheral effects of the centrally-acting satiety adipokines, adiponectin and leptin, and of non-adipose-derived hormones with similar effects, like ghrelin, have received considerable attention. In this report, we have extended our previous studies of the pro-thrombotic effects of leptin and determined the effects of adiponectin or ghrelin on human platelet activation. Thus, while leptin stimulated human platelet aggregation and adhesion, addition of adiponectin or of ghrelin did not affect either aggregation or adhesion of these cells; even at supra-physiological concentrations. In addition, we compared the impact of these three important hormones on microvascular endothelial cell permeability, an important parameter of endothelial function that when impaired contributes to several vascular pathologies. While physiologically relevant concentrations of either leptin or adiponectin increased the integrity of the diffusion barrier formed by a monolayer of human microvascular endothelial cells, only supra-physiological concentrations of ghrelin had this effect. None of these agents reduced microvascular endothelial barrier function. Taken together, our data are consistent with the ideas that leptin activates human platelets and limits transendothelial cell diffusion but that adiponectin only influences endothelial cell permeability. In contrast, ghrelin had neither of these effects. We propose that these data identify important differences in the effects of leptin, adiponectin or ghrelin on microvascular endothelial cells and platelets and may provide a basis on which to pharmacologically manipulate the selective effects of these peptides on these cell types in human cardiovascular or thrombotic diseases associated with obesity.

Topics: Adiponectin; Capillary Permeability; Cardiovascular Diseases; Dose-Response Relationship, Drug; Endothelial Cells; Ghrelin; Humans; Leptin; Obesity; Peptide Hormones; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation

Leptin, an adipocyte-secreted hormone, plays an important role in regulating neuroendocrine and immune function as well as insulin resistance and metabolism. Our objective was to examine the relationship between leptin levels and cardiovascular morbidity and overall mortality in women with type 2 diabetes.. This prospective cohort study included 1,194 women with a confirmed diagnosis of type 2 diabetes, who provided a blood sample at baseline in 1989-1990. Participants were followed for 12 years for the development of health outcomes including cardiovascular disease (CVD) events as well as total mortality.. There were 218 new CVD events and 228 deaths from all causes. Cox proportional hazards analysis was used to estimate the relative risks (RRs) for each quintile level of leptin compared with the lowest quintile. Leptin levels were positively associated with several CVD risk factors including BMI and inflammatory markers, but were not independently associated with the incidence of CVD or total mortality in women with diabetes. The multivariate RRs (95% CIs) for CVD across the quintiles of leptin were 0.96 (0.61-1.53), 0.99 (0.61-1.61), 1.04 (0.63-1.71), 1.02 (0.59-1.75) (p for trend = 0.83).. Although circulating leptin levels are associated with obesity and inflammatory markers, they are not significantly related to the risk of CVD or mortality in women with diabetes.

Topics: Adult; Aged; Blood Specimen Collection; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Leptin; Life Style; Middle Aged; Prospective Studies; Risk Factors; Surveys and Questionnaires; Survival Analysis

Obesity is a major modifiable risk factor for cardiovascular disease. Leptin, the hormone synthesized and released primarily by adipose tissue and found increased in obese individuals, has been implicated in the regulation of inflammation and arterial and venous thrombosis.. To investigate the role of tissue factor (TF), the pivotal agonist of the clotting cascade, as a link between obesity and cardiovascular disease.. In 15 obese patients, plasma levels of leptin and TF as well as TF expression in resting and endotoxin-stimulated mononuclear leukocytes (MN) were increased when compared with healthy donors. In a selected sample of obese patients, loss of body weight led to decreased circulating leptin levels, accompanied by a reduction in plasma TF as well as in TF expression, both in resting and endotoxin-stimulated MN. In subsequent in vitro experiments, leptin was incubated with MN from healthy subjects. Leptin induced TF activity and antigen in a dose-dependent fashion, as assessed by clotting assay and ELISA, respectively. Increased migration of c-Rel/p65 into the nucleus, as determined by EMSA, and development of TF mRNA in monocytes, as assessed by RT-PCR, were observed. Experiments with mitogen-activated protein kinase (MAPK) inhibitors, indicated the involvement of p38 and ERK1/2 pathways.. The presence of TF-expressing MN in blood from obese subjects and the in vitro induction of TF by pharmacologic concentrations of leptin in MN from healthy subjects suggest that TF expression by leptin-stimulated monocytes may contribute to the cardiovascular risk associated with obesity.

Topics: Cardiovascular Diseases; Dimerization; Gene Expression Regulation; Humans; In Vitro Techniques; Leptin; Leukocytes, Mononuclear; Obesity; Proto-Oncogene Proteins c-rel; RNA, Messenger; Thromboplastin; Transcription Factor RelA

The aim of the study was to investigate, whether the degree of metabolic risk factors for atherosclerotic complications in a very rare kind of obesity, the Multiple Symmetrical Lipomatosis, also known as the Launois-Bensaude Syndrome (LBS), are comparable or different from "simple" truncal obesity. 10 patients with LBS (Body mass index 34.4 +/- 1.8 kg/m(2), age: 62 +/- 3 yrs) were compared with 19 BMI - matched patients with "simple" truncal obesity and obstructive sleep apnoea syndrome (OSAS) and 20 BMI- matched patients with "simple" truncal obesity without OSAS. Markers of subclinical inflammation and thrombocyte activation (sCD62p = soluble p-selectin, highly sensitive C-Reactive protein = CRP, Interleukin-6 = IL-6, ICAM-1 = Intracellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule = VCAM -1, leptin), as well as adiponectin and resistin were studied. The prevalence of atherogenic risk factors as hypertension (80%), type 2 diabetes (30%), OSAS (50%), smoking (30%) and alcohol abuse (80%) was high in the (obese) LBS group. The markers of subclinical inflammation and thrombocyte activation showed an indifferent picture with lower levels of circulating IL-6 and sCD62p, comparable CRP and higher ICAM-1 and VCAM-1 than in controls. Leptin and adiponectin were higher than in controls. However, the accumulation of "classic" cardiovascular risk factors in the LBS group was well reflected by the presence of symptomatic cardiovascular disease in 3 of the 10 LBS patients, putting LBS patients - if obese - at an atherosclerotic risk at least comparable to obese persons.

Topics: Adiponectin; Atherosclerosis; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Lipomatosis, Multiple Symmetrical; Male; Middle Aged; Obesity; P-Selectin; Resistin; Sleep Apnea, Obstructive; Vascular Cell Adhesion Molecule-1

To determine the effect of acute psychotic stress on adipokine secretion in non-diabetic subjects.. Adiponectin, leptin, and cortisol serum levels were determined in 39 non-diabetic patients with acute psychotic stress reaction admitted to a psychiatric ward. The clinical global impression (CGI) score was used to evaluate the level of psychotic stress. Insulin sensitivity (IS) was determined by the homeostasis model assessment (HOMA). Patients were re-assessed 2 weeks after admission. During hospitalization patients were treated for variable times with either phenothiazines or thioxanthenes.. The mean CGI score decreased significantly with time: 5.3+/-0.8 and 2.6+/-0.8 on admission and after 2 weeks respectively (p<0.001). On admission, the mean adiponectin level was significantly lower in patients compared to normal controls: 15.3+/-8.2 mug/ml and 26+/-12.8 mug/ml, respectively (p=0.02). It increased significantly after 2 weeks to 18.2+/-10 mug/ml (p=0.003). By contrast, the leptin and cortisol levels did not change significantly. No correlation was found between the changes in individual CGI scores and adiponectin levels. However, female patients with the highest stress on admission demonstrated the lowest adiponectin levels and insulin sensitivity: p=0.002 and 0.03 respectively.. These data suggest a link between acute psychotic stress reaction and decreased serum adiponectin levels. Further studies are recommended to determine the strength of this association.

Topics: Acute Disease; Adiponectin; Adult; Cardiovascular Diseases; Female; Homeostasis; Humans; Hydrocortisone; Insulin Resistance; Leptin; Male; Middle Aged; Phenothiazines; Psychotic Disorders; Stress, Physiological; Thioxanthenes

The objectives of this study were to determine 1) whether the extent of weight loss is predictive of the degree of changes in hormone and lipid levels; 2) the interactions between energy regulating hormones after weight loss through an energy deficit/exercise protocol diet and exercise; 3) whether initial metabolic parameters are indicative of the extent of weight loss.. Thirty-five hyperlipidemic females (BMI 28-39 kg/m2) 35-60 years old participated in a six month weight loss trial. Weight loss resulted from a diet and exercise program that when combined produced a 30% energy deficit. Fasting plasma taken during 2 wk stabilization periods at the beginning and end of the study was analysed for lipids, hormone and glucose levels.. Average weight loss was 11.7 +/- 2.5 kg (p < 0.0001). TC, LDL-C, and triacylglycerols decreased 9.3 +/- 9.5% (p < 0.0001), 7.4 +/- 12.2% (p < 0.001), and 26.8 +/- 19.6% (p < 0.05), respectively, while HDL-C increased (p < 0.05) by 8.2 +/- 16.3%. Leptin levels declined (p < 0.001) 48.9 +/- 16.0% and ghrelin levels rose (p < 0.001) 21.2 +/- 26.7%. While overall levels of adiponectin did not differ, individual values changed such that weight loss predicted increases in adiponectin levels. Though initial weight did not predict weight loss, baseline lipid and insulin levels positively predicted weight loss.. Initial metabolic parameters may be predictors of weight loss. Beneficial effects of weight loss as achieved through diet and exercise on measured parameters indicate moderate weight loss reduces key risk factors of cardiovascular disease in overweight individuals.

Topics: Adiponectin; Adult; Blood Glucose; Cardiovascular Diseases; Combined Modality Therapy; Diet, Reducing; Energy Metabolism; Exercise; Female; Ghrelin; Humans; Hyperlipidemias; Leptin; Lipids; Middle Aged; Obesity; Peptide Hormones; Predictive Value of Tests; Risk Factors; Weight Loss

Increasing evidence suggests that alterations in sleep duration are associated with cardiovascular disease (CVD) and mortality. Additionally, sleep disordered breathing (SDB), which is associated with disturbed nighttime sleep and hypoxemia, may be an independent risk factor for CVD. The inflammatory marker, C-reactive protein (CRP), is an important predictor of CVD. We investigated potential associations between circulating CRP, sleep duration, and SDB.. Cross-sectional Study.. Participants were 907 adults from the Wisconsin Sleep Cohort Study (WSCS).. CRP was measured after overnight polysomnography. The relationships between CRP and sleep parameters were evaluated using multiple linear regression with and without controlling for age, sex, and body mass index (BMI) and other potential confounders. CRP was found to be higher for women and had a strong positive correlation with age and BMI. CRP showed a significant positive association with current smoking, waist-hip ratio (WHR), LDL-cholesterol, triglycerides, leptin, and insulin, independent of age, sex, and BMI. Significant independent negative associations for CRP were observed with HDL-cholesterol (HDL), insulin sensitivity (quantitative insulin sensitivity check index [QUICKI]), and hours of exercise. There was a significant positive association between CRP levels and the apnea-hypopnea index (AHI, the measure of SDB), but these relationships were not significant after adjustment for age, sex, and BMI. No significant association between CRP levels and measures of sleep duration (polysomnographic and self-reported) were found.. There was no significant association between CRP levels and sleep duration. The lack of an independent association between CRP levels and SDB suggests that the reported relationship between these 2 variables may be primarily driven by their association with obesity.

Topics: Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Female; Humans; Insulin; Leptin; Life Style; Male; Polysomnography; Risk Factors; Sleep Apnea Syndromes; Smoking; Statistics as Topic; Waist-Hip Ratio

Recent studies suggest that adipocyte-secreted factors called adipokines are involved in obesity-associated complications including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Among those, adiponectin is an antidiabetic and antiatherogenic protein, concentrations of which are decreased in obesity-associated metabolic and vascular disorders. In contrast, leptin, tumor necrosis factor a, interleukin-6, monocyte chemoattractant protein-1, and plasminogen activator inhibitor-1 are upregulated in obesity and contribute to the development of diabetes and vascular disease. In this review, the relevance of adipokines in obesity, insulin resistance, diabetes mellitus, atherosclerosis, and cardiovascular diseases is discussed.

Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Atherosclerosis; Cardiovascular Diseases; Chemokine CCL2; Diabetes Mellitus; Humans; Inflammation; Interleukin-6; Leptin; Metabolic Syndrome; Mice; Obesity; Plasminogen Activator Inhibitor 1; Species Specificity; Tumor Necrosis Factor-alpha

Obesity and insulin resistance are associated with cardiovascular risk factors, including altered levels of inflammatory markers and adipocytokines. The aim of the present study was to examine the relationship between circulating adipocytokines and cardiovascular risk factors.. A population of 95 obese, nondiabetic outpatients was analyzed prospectively. A complete nutritional evaluation was performed.. In the multivariate analysis, with leptin as a dependent variable, only fat mass remained in the model (F = 66.6; p < 0.05), with an increase of 2.24 (95% CI 1.68-2.8) ng/ml of leptin with each 1 kg of fat mass. In a new model, with adiponectin as a dependent variable, the HDL cholesterol levels remained in the model (F = 8.46; p < 0.05), with an increase of 5.38 (95% CI 1.7-9.1) ng/ml of adiponectin with each 1 mg/dl of HDL cholesterol. In a third model, with interleukin 6 (IL-6) as a dependent variable, the resistin and C-reactive protein (CRP) levels remained in the model (F = 16.8; p < 0.01), with an increase of 0.48 (95% CI 0.27-0.85) pg/ml of IL-6 with each 1 ng/ml of resistin and an increase of 0.12 (95% CI 0.029-0.214) pg/ml with each 1 mg/dl of CRP.. Circulating adipocytokine concentrations are associated with different cardiovascular risk factors in nondiabetic obese patients.

Topics: Adipokines; Adult; Anthropometry; Basal Metabolism; C-Reactive Protein; Calorimetry, Indirect; Cardiovascular Diseases; Cholesterol, HDL; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Resistin; Risk Factors; Tumor Necrosis Factor-alpha

Primary aim: To evaluate the modulating effects of age and sex on changes in plasma lipid levels in the response to highly active antiretroviral therapy (HAART). Secondary aim: To study insulin, leptin, adiponectin, E-selectin and P-selectin levels and their relation to demographics.. Comparative, longitudinal, open cohort-study.. Tertiary care center at a University Hospital.. Eighty-two consecutive HIV-seropositive patients of either sex were enrolled in the study. Subjects were between 19 and 60 years of age and naive to HAART. Patients were treated with nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitor(s) (PIs) or reverse transcriptase inhibitors (RTIs) only. Subjects were evaluated at baseline and after 3, 6 and 12 months.. Total cholesterol levels increased in all patients. The greatest increase was seen in patients of older age treated with PI. Male gender was another risk factor for higher cholesterol but also for higher triglyceride levels. Therapy with protease inhibitors and/or stavudine had a negative influence on plasma triglyceride levels. Selectins, adipokines and insulin were less influenced by HAART.. Based on the results of this study selection of therapy regimen according to the demographic risk factors sex and age can offer an easy strategy to help to minimize lipid elevations.

Topics: Adiponectin; Adult; Age Factors; Antiretroviral Therapy, Highly Active; Atherosclerosis; Cardiovascular Diseases; CD4-Positive T-Lymphocytes; Cohort Studies; E-Selectin; Female; HIV Seropositivity; Humans; Insulin; Leptin; Male; Middle Aged; P-Selectin; Risk; Risk Factors; Sex Factors; Time Factors

No data have been so far reported on the relationship between polymorphisms of LEP gene and cardiovascular disease.. We genotyped a tetranucleotide repeat mapped in the 3'UTR of the LEP gene (LEP-tet) in 109 subjects with cardiovascular events and in 109 control subjects.. Univariate analysis and multivariate logistic regression analysis adjusted for age, gender, smoking status, history of hyperlipidemia, hypertension or diabetes showed not significant association between the genotype of the LEP-tet and cardiovascular diseases. Moreover, no differences were observed in the plasma leptin concentrations between cases and control subjects (22 +/- 19 vs 22 +/- 14 ng/ml, P = 0.52) and in relation to the LEP-tet classes or carriage of specific alleles (P = 0.76 for the association between LEP-tet classes and leptin levels in overall analysis).. In conclusion, our data do not support an association between the LEP-tet microsatellite polymorphism of the human LEP gene and cardiovascular diseases.

Topics: 3' Untranslated Regions; Age Factors; Aged; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Hypertension; Leptin; Logistic Models; Male; Microsatellite Repeats; Middle Aged; Polymorphism, Genetic; Sex Factors; Smoking

To study the relationships between nontraditional cardiovascular (CV) risk factors and components of the metabolic syndrome in Native Canadian children, a population at risk of future CV disease.. CV risk factors were evaluated in a population-based study of a Canadian Oji-Cree community, involving 236 children aged 10 to 19 years.. Using an age- and sex-specific case definition, 18.6% of the children met criteria for pediatric metabolic syndrome. As the number of metabolic syndrome component criteria increased, C-reactive protein, leptin, and ratio of apolipoprotein B to apolipoprotein A1 levels rose (all P < .0001) and adiponectin concentration decreased (P = .0006). Principal factor analysis using both traditional and nontraditional CV risk factors revealed 5 underlying core traits, defined as follows: adiposity, lipids/adiponectin, inflammation, blood pressure, and glucose.. Nontraditional CV risk factors accompany the accrual of traditional risk factors early in the progression to pediatric metabolic syndrome. Furthermore, inclusion of these factors in factor analysis suggests that 5 core traits underlie the early development of an enhanced CV risk factor profile in Native children.

Topics: Adiponectin; Adolescent; Adult; Apolipoprotein A-I; Blood Glucose; Blood Pressure; Body Constitution; C-Reactive Protein; Canada; Cardiovascular Diseases; Child; Cholesterol, HDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Factor Analysis, Statistical; Fasting; Female; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Risk Factors; Serum Amyloid A Protein; Sex Factors; Triglycerides

To evaluate the effect of weight loss after bariatric surgery (BS) on peripheral adipocytokines, renal parameters and other cardiovascular risk factors (CVRFs).. A total of 70 (41 women) extremely obese adults were prospectively studied before and 12 months after surgery.. 24 (15 women) normal-weight adults. Anthropometric, biochemical and renal parameters were recorded.. Presurgery, adiponectin (ADPN) was lower, whereas leptin, insulin resistance, C-reactive protein, creatinine clearance and albuminuria were higher in patients than controls (P<0.001). All parameters improved postsurgery. Changes in ADPN correlated negatively with leptin, insulin resistance, albumin, C-reactive protein, and creatinine clearance. Multiple regression analysis: using changes in ADPN as the dependent variable, only changes in insulin resistance (P=0.005) and albumin (P=0.019) were significant independent determinants for changes in ADPN. No statistical differences were found in relation to the degree of obesity.. Patients changed to obesity type I after surgery. This implies a substantial improvement of CVRFs including ADPN, creatinine clearance and albuminuria. Changes in plasma ADPN correlated negatively with insulin resistance and with albuminemia but not with renal parameters. The lack of differences between different degrees of obesity suggests that the relationship between weight and CVRFs no longer exists when obesity becomes very extreme.

Topics: Adiponectin; Adult; Albuminuria; Bariatric Surgery; C-Reactive Protein; Cardiovascular Diseases; Creatinine; Female; Humans; Insulin Resistance; Kidney; Leptin; Male; Metabolic Clearance Rate; Middle Aged; Obesity; Prospective Studies; Serum Albumin; Weight Loss

Epidemiological studies have shown that obesity is associated with increased blood concentrations of proinflammatory factors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), and von Willebrand factor (vWF). We analyzed the association of these markers with percentage of body fat (BF), and the influence of leptin in a cross-sectional study of 1,089 subjects (366 men) aged 44 (34-53) [median (interquartile range)] years, who were classified as obese or nonobese according to BF estimated by whole-body air displacement plethysmography. Obesity was defined as BF >or= 25% in men and >or= 35% in women. Compared with non-obese subjects (mean +/- SD), obese patients had higher concentrations of fibrinogen (312 +/- 78 vs. 342 +/- 81 mg/dl, P < 0.001), CRP (0.41 +/- 0.75 vs. 0.75 +/- 1.04 mg/l, P = 0.014), vWF (107 +/- 29 vs. 123 +/- 55%, P < 0.001), and leptin (10.4 +/- 6.5 vs. 37.5 +/- 26.1 ng/ml, P < 0.0001). A positive correlation was observed between BF and fibrinogen (r = 0.266; P < 0.0001), logCRP (r = 0.409; P < 0.0001), and vWF (r = 206; P < 0.0001). Leptin was correlated with fibrinogen (r = 0.219, P < 0.0001), logCRP (r = 0., P < 0.0001), and vWF (r = 0.124, P = 0.002), but the statistical significance was lost after including BF in adjusted-correlation and multivariate analysis, suggesting that they are not regulated by leptin per se. In conclusion, the obesity-associated increase in the circulating concentrations of fibrinogen, CRP, and vWF is highly associated to BF and apparently not determined by leptin.

Topics: Adiposity; Adult; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Female; Fibrinogen; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Risk Factors; Sex Factors; von Willebrand Factor

The metabolic syndrome (MS) describes a cluster of metabolic disturbances including type 2 diabetes and/or insulin resistance, hypertension, dyslipidemia and obesity, which predict a high risk of cardiovascular disorders. The associated hyperinsulinemia and hyperleptinemia may contribute to the cardiovascular risk. However, the operational value of the MS in elderly patients is questionable. We therefore investigated the prevalence and significance of the MS in geriatric care. In a survey of 98 consecutive admissions of diabetic patients, <40% had a MS; this is a low value compared to younger diabetic adults, due to a low prevalence of obesity and dyslipidemia. We found a high prevalence of low BMI (<20 kg/m2), hypoalbuminemia and low total cholesterol levels, suggesting that the MS may be modified by undernutrition. The interplay between the MS and undernutrition was further studied in 30 non-diabetic patients. Both leptinemia and insulin resistance indexes (HOMA-IR and QUICKI) were strongly associated with BMI and body fat (measured by Bioelectrical impedance Analysis). BMI, leptinemia and insulin resistance indexes were associated with the Mini Nutritional Assessment (MNA) score. Thus, undernutrition is associated with low leptin and insulin levels and may obscure the association of these parameters with cardiovascular risk. In conclusion, the MS has a low prevalence in our population of elderly diabetic patients, and is of questionable prognostic value. It can be oveshadowed by undernutrition, which is associated with low body weight, leptinemia and insulin resistance indexes. Prevention of undernutrition and/or adjustment to its consequences should receive higher priority in the care of elderly diabetic patients.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Hospitals, Special; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Malnutrition; Metabolic Syndrome; Nutrition Assessment; Risk Factors

Death rate is unacceptably elevated in end-stage renal disease patients treated with hemodialysis. Excessive body fat, or obesity, is the well-known risk factor for cardiovascular disease and other health problems in the general population. However, hemodialysis patients with a higher body mass index (BMI) have a lower risk of death, as shown by many studies. There are several explanations for the paradox of BMI in dialysis patients. First, although body mass is composed of fat mass and fat-free mass (lean mass), it is unknown which is more important, fat mass or lean mass, in predicting outcome of hemodialysis patients. Second, it is also possible that functions of adipose tissue are altered in renal failure so that accumulation of body fat leads to less atherogenicity and beneficial properties become predominant. Third, an increased fat mass may be protective against death after harmful events. In this article, we explore these possibilities using either the data of our own cohort of hemodialysis patients or the existing registry data of Japan. We conclude that in hemodialysis patients, fat mass rather than lean mass plays a protective role against mortality, that the fat mass-adipocytokine relationship is altered, and that a low BMI is associated with increased risk of fatality after cardiovascular events rather than the risk of occurrence of such events.

Topics: Adiponectin; Adipose Tissue; Body Composition; Body Mass Index; Cardiovascular Diseases; Cytokines; Humans; Kidney Failure, Chronic; Leptin; Renal Dialysis; Retrospective Studies; Risk Factors

Topics: Biomarkers; Black People; C-Reactive Protein; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Confounding Factors, Epidemiologic; Female; Fibrinogen; Humans; Inflammation Mediators; Insulin Resistance; Leptin; Obesity; White People

Topics: Cardiovascular Diseases; Humans; Leptin; Vasodilation

To evaluate the relation between cardiovascular disease (CVD) risk factors and hormone therapy, serum hormone levels, glucose tolerance, and psychosocial and psychological conditions in subjectively healthy obese female subjects.. The study included 606 women, aged 50-64 years, with BMI 30-40 kg/m(2) and no history of cardiovascular or other severe diseases. One group with a CVD risk profile (n = 473) (i.e., cholesterol >7.0 mmol/l, HDL cholesterol <1.2 mmol/l, triglycerides >2.0 mmol/l, systolic or diastolic blood pressure >140/90 mmHg, or waist-to-hip ratio >0.85) was compared with women without such risk (n = 133). Steroid hormones, leptin, insulin, and oral glucose tolerance tests (OGTTs) were analyzed. A subgroup of women with baseline impaired glucose tolerance (IGT) completed a 2.5-year follow-up OGTT.. Fewer obese postmenopausal women with CVD risk had ever used hormone therapy (odds ratio 0.24 [95% CI 0.07-0.75]), after multivariate adjustments. Furthermore, women with CVD risk had a higher testosterone index (1.07 [1.01-1.13]) and more had insulin resistance (1.04 [1.00-1.08]) and IGT (2.92 [1.50-5.69]), while OGTT was similar at follow-up. No differences were observed regarding family history or lifestyle, except that fewer women with CVD risk consumed fruits, boiled vegetables, or whole-grain cereals. More women with CVD risk lived alone (3.26 [1.28-8.31]) and had more mental problems (1.16 [1.05-1.28]).. Previously healthy obese women with a CVD risk profile seemed to have a high risk of diabetes, as well as psychosocial or psychological problems. Hormone therapy was associated with reduced CVD risk. Obesity's growing burden on society makes it more important to further target individuals that are at greatest risk of future health hazards.

Topics: Adult; Cardiovascular Diseases; Cholesterol; Estradiol; Estrogen Replacement Therapy; Family Health; Feeding Behavior; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Leptin; Life Style; Multivariate Analysis; Obesity; Occupations; Psychology; Quality of Life; Risk Factors; Testosterone

To investigate the association between plasma leptin and adiponectin and insulin sensitivity in children, 580 school children (294 boys and 286 girls) with mean age of 13.3 years (12-16 years) were randomly selected from the Taipei Children Heart Study. Baseline measurements included body weight, body mass index (BMI), plasma glucose, insulin, proinsulin, leptin and adiponectin levels. Insulin resistance and beta-cell function were assessed using the method of homeostatic model, HOMA-IR and HOMA-beta, respectively. We found that girls had higher levels of plasma leptin, adiponectin and HOMA-beta than boys. There was no significant difference in HOMA-IR between boys and girls. Plasma leptin concentrations were positively correlated with body weight, BMI, insulin and proinsulin concentrations, HOMA-IR and HOMA-beta, whereas plasma adiponectin levels were inversely associated with body weight, BMI and proinsulin levels in both sexes. In girls, adiponectin concentrations were negatively correlated with insulin concentration and HOMA-IR. In multiple regression analyses, plasma leptin was more positively associated with insulin and proinsulin levels, HOMA-IR and HOMA-beta than was adiponectin in boys. This association persisted even after adjusting for body weight, BMI and pubertal status. In conclusion, plasma leptin was more strongly associated with insulin sensitivity and beta-cell function than was adiponectin among children, particularly in boys.

Topics: Adiponectin; Adolescent; Analysis of Variance; Cardiovascular Diseases; Child; Female; Homeostasis; Humans; Insulin Resistance; Insulin-Secreting Cells; Leptin; Male; Sex Factors

Obstructive sleep apnea (OSA) is one of the most often sleep disturbance. Not treated patients have 2-3 times more risk for death because of the cardiovascular diseases. Leptin and homocysteine are the risk factors for cardiovascular diseases. Treatment by nCPAP has positive influence for health care and reduction of hypertension in this group. The aim of this study was to evaluate an effect of 3 weeks nCPAP therapy on a serum leptin and homocysteine concentrations in patients with OSA.. The study group consisted of 48 male patients in the age x=51,2?7,5 years old, OSA was diagnosed by polisomnographic study The leptin concentration was evaluated by RIA methods (HUMAN LEPTIN RIA KIT), the homocysteine concentration was evaluated byAxis Homocysteine EIA test. Patients were treated by nCPAP during 3 weeks. Only 29 patients were effectively treated for this time. The compliance was: 5.07 +/-1.81 h. In the group of 29 patients the serum leptin and homocysteine concentration before and after treatment were 11,05+/-5,59 ng/mL vs 11,07+/-7,16 ng/mL i 10,98+/-2,79 micromol/L vs 10,34+/-2,99 micromol/L. In the all study group the statistical important correlation between leptin and AHI, mean and minimal saturation overnight, fibrinogene concentration, BMI, WHR, waist circumference, heart rate and between homocysteine and heart rate were observed.. 3 weeks therapy does not have any effect on leptin and homocysteine concentrations in the studied group of patients with OSA. Serum leptin concentration correlates with AHI, TMB90, as well as with mean and minimal saturation during a sleep. This indicates a potentially higher risk of cardiovascular diseases in the studied group.

Topics: Biomarkers; Cardiovascular Diseases; Continuous Positive Airway Pressure; Homocysteine; Humans; Leptin; Male; Middle Aged; Polysomnography; Risk Factors; Sleep Apnea, Obstructive

Thirty-four children were assessed for body composition, blood pressure, lipids, glucose tolerance, markers of insulin resistance, oxidative stress, and adipokines. Children were divided into 3 groups: (1) normal weight, (2) overweight but otherwise healthy, and (3) overweight with the metabolic syndrome. There were no differences among any of the groups for age or Tanner stage, and anthropometric variables were similar between the overweight and the overweight with the metabolic syndrome groups. Differences across groups were found for high-density lipoprotein cholesterol (P < .001), triglycerides (P < .01), fasting insulin (P < .001), homeostasis model assessment (P < .01), adiponectin (P < .05), leptin (P < .0001), C-reactive protein (P < .0001), interleukin 6 (P < .0001), and 8-isoprostane (P < .001). In children, oxidative stress and adipokine levels worsen throughout the continuum of obesity and especially in the presence of components of the metabolic syndrome. Overweight children with components of the metabolic syndrome may be at elevated risk for future cardiovascular disease.

Topics: Adiponectin; Adolescent; Biomarkers; Blood Glucose; Blood Pressure; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Child; Cholesterol, HDL; Dinoprost; Female; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Syndrome; Minnesota; Obesity; Oxidative Stress; Risk Assessment; Risk Factors; Triglycerides

We examined the relationships among IGF binding protein (IGFBP)-1, insulin sensitivity, and leptin in different ethnic groups (Asian Indians, Chinese, and Caucasians) using the euglycemic hyperinsulinemic clamp. Ten healthy, young and nondiabetic subjects of each ethnic group, matched for body mass index, age, and physical activity were studied. A euglycemic clamp was performed on all subjects. IGFBP-1, insulin, and leptin were measured after fasting and during the clamp. Fasting IGFBP-1 concentration was highest in Chinese (P = 0.027). Asian Indians had the lowest insulin sensitivity index (P = 0.006). The ratio of insulin to IGFBP-1 at fasting and throughout the euglycemic clamp was higher in Asian Indians. Fasting IGFBP-1 had a strong negative correlation with fasting leptin levels (r = -0.715, P = 0.001). Multiple linear regression demonstrated that fasting insulin, leptin, ethnicity, and insulin sensitivity were significant predictors for fasting IGFBP-1. IGFBP-1 is independently determined by ethnicity, insulin sensitivity, and leptin in glucose-tolerant men. The presence of relative insulin resistance and low fasting IGFBP-1 levels in Asian Indians may contribute to their higher risk of developing diabetes and cardiovascular disease.

Topics: Adult; Asian People; Cardiovascular Diseases; Diabetes Mellitus; Fasting; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Leptin; Male; Risk Factors; White People

The adipose-borne hormone leptin circulates in free and protein-bound forms but little information is available about their biological significance. Free leptin (FL) levels are related to changes in fat mass, whereas bound leptin (BL) appears to be associated with resting energy expenditure (REE). Our aim was to assess FL and BL levels in normal weight and obese subjects and correlate them with metabolic and nutritional variables.. The partitioning of plasma leptin between FL and BL was evaluated in a population (n = 44) including both genders and different degrees of adiposity [body mass index (BMI) range 18.6-79.6 kg/m2].. Total leptin and FL and BL concentrations were measured by fast protein liquid chromatography (FPLC) followed by radioimmunoassay (RIA). Body composition, REE, insulin sensitivity, lipid parameters associated with cardiovascular risk and macronutrient preference were also assessed.. The BL/FL ratio was significantly reduced in obese subjects due to a major increase in FL compared with BL. Consequently, the gender difference of the %BL/%FL ratio present in lean subjects (35/65 in women; 65/35 in men) was lost in obese subjects. REE was negatively correlated with total leptin (P < 0.0001) and %FL (P < 0.0001), and positively with %BL (P < 0.001). Total leptin and FL were correlated with the diet carbohydrate content in all subjects.. FL increases with the amount of fat mass; the prevalence of FL in normal weight women in comparison to men suggests that this fraction is particularly linked to the amount of subcutaneous fat. Moreover, the correlation of BL with REE and the relationship of FL with food intake favours the view of different biological activities for the two circulating forms of leptin.

Topics: Adipose Tissue; Adolescent; Adult; Basal Metabolism; Blood Proteins; Body Composition; Cardiovascular Diseases; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Dietary Carbohydrates; Energy Intake; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Risk Factors; Triglycerides

High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease.. We studied 82 dialysis patients treated by PD (n = 44, 23 males and 21 females, mean age 54.4 +/- 1.8 years) or HD (n = 38, 22 males and 16 females, age 60.8 +/- 1.6 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of leptin, adiponectin and resistin were measured in all subjects. Information on vascular disease (cerebral vascular, peripheral vascular and heart disease) was obtained from a detailed medical history.. PD patients showed significantly higher serum leptin concentrations [median (interquartile range), 28.7 (13.0-71.9) microg/l] than those found in patients on HD [9.7 (4.7-31.9) microg/l, P < 0.01] or in conservative management [5.9 (4.3-38.6) microg/l, P < 0.05]. Adiponectin concentrations were similar in the three groups of patients (mean +/- SEM, 48.0 +/- 4.5 mg/l in PD, 57.7 +/- 4.4 mg/l in HD, and 44.4 +/- 7.0 mg/l in controls, NS). Patients treated by both PD and HD exhibited resistin concentrations significantly higher than those found in controls (26.3 +/- 0.99 and 27.5 +/- 1.4 microg/l, respectively, vs. 17.3 +/- 1.0 microg/l, P < 0.001). Leptin concentrations were positively correlated with body mass index (BMI) (r = 0.287, P < 0.01) and adiponectin levels were negatively related to BMI (r = -0.416, P < 0.001) and the homeostatic model assessment (HOMA-R) index (r =-0.216, P < 0.05). Leptin, adiponectin and resistin levels in patients with previous vascular events were similar to those found in patients without these complications. Logistic regression analysis did not demonstrate any relationship between serum adipocytokine concentrations and the presence of vascular disease of any type. A significant relationship between resistin and heart disease [odds ratio (OR) 1.80 (1.03-3.15), P = 0.039] was found when analysing subgroups of patients.. These data suggest that leptin levels are higher in PD patients, and resistin levels are higher in PD and HD patients in relation to patients on conservative management, whereas adiponectin concentrations are similar in the three groups. These results do not support the presence of a clinically relevant relationship between adipocytokines and previous episodes of vascular disease in the whole population or in patients classified in subgroups, with the only exception of a relationship between resistin levels and heart disease.

Topics: Adiponectin; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Female; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Regression Analysis; Renal Dialysis; Resistin

The aim of this study was to evaluate the relationship of obesity, leptin, insulin resistance and C-reactive protein (CRP) with coronary heart disease (CHD) risk factors in patients with Type 2 diabetes mellitus (DM) with CHD compared with those with Type 2 DM without CHD.. Leptin, CRP (high sensitivity assay), fasting plasma insulin, glucose, HbA(1c) and full lipid profile were determined in 58 Type 2 diabetic patients with CHD and 87 Type 2 DM patients without CHD.. were compared between those with and without CHD. Univariate correlation as well as logistic regression analyses were used to relate these markers with traditional CHD risk factors.. Leptin showed significant correlations with BMI (r = 0.59; P < or = 0.0001), waist circumference (r = 0.45; P < 0.0001), CRP (r = 0.36; P < 0.0001), and fasting insulin (r = 0.53; P < 0.0001) as well as with systolic (r = 0.23; P = 0.007) and diastolic (r = 0.23; P = 0.007) blood pressure. However, when those with and without CHD were compared only age (P < 0.0001), duration of diabetes (P < 0.001) and degree of microalbuminuria (P = 0.02) were significantly higher in patients with CHD. Leptin (P = 0.49), CRP (P = 0.19) and lipid parameters were not significantly different between the two groups.. Our study confirms a relationship between leptin and CRP with CHD risk factors. The lack of significant difference when patients with and without CHD are compared may be due to the potential confounding effects of treatment with aspirin and statins.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Risk Factors; Sex Factors; Statistics, Nonparametric

Adiponectin plays a significant role in the modulation of glucose tolerance and insulin sensitivity. We attempted to evaluate the relationship between adiponectin level and parameters of the menopausal metabolic syndrome: body mass index, waist-to-hip ratio, lipid profile and insulin resistance indices.. Thirty-two women and ten men aged 40-63 years were included. The percentage of body fat and of abdominal fat deposits were measured with dual-energy X-ray absorptiometry. Serum adiponectin, tumour necrosis factor-a (TNFalpha) and leptin were measured with commercially available radioimmunoassay kits. To exclude the influence of nutritional factors on adiponectin secretion, diet content was analysed in the preceding three days.. Postmenopausal non-obese women had a non-significantly lower level of adiponectin compared with premenopausal women of corresponding body mass. Serum adiponectin level was significantly lower in postmenopausal obese women than in non-obese women (p = 0.0023). Men with similar age and body mass to the women had the lowest level of adiponectin (p = 0.06). Three months of estrogen replacement therapy in women with surgical menopause did not significantly change the serum level of adiponectin. We found a negative correlation of adiponectin with leptin, insulin resistance index and total cholesterol, and a positive correlation with high-density lipoprotein cholesterol. Adiponectin level was negatively correlated with free testosterone, but we did not find such a relationship with estradiol. There was no correlation of adiponectin level with TNFalpha; however, serum TNFalpha correlated positively with leptin. The dietary analysis showed no differences between the diets of obese and non-obese women over the preceding three days. Moreover, mean diastolic and systolic blood pressures were noted to be significantly lower in premenopausal women than in postmenopausal non-obese women (p = 0.05).. Our results suggest that adiponectin could be a marker of risk for developing menopausal metabolic syndrome. Moreover, it is possible that sex steroids have an influence on adiponectin secretion.

Topics: Absorptiometry, Photon; Adiponectin; Adipose Tissue; Adult; Biomarkers; Body Composition; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Menopause; Middle Aged; Risk Factors; Triglycerides; Tumor Necrosis Factor-alpha

Topics: Cardiovascular Diseases; Diet, Reducing; Female; Health Education; Health Status; Humans; Incidence; Leptin; Life Style; Male; Obesity; Primary Prevention; Prognosis; Severity of Illness Index

The complex pathology of disease has sparked the development of novel protein expression profiling techniques that require validation in clinical settings. This study focuses on multiplexed analyses of adipocytokines and biomarkers linked to the metabolic syndrome, diabetes, and cardiovascular disease.. Multiplexed immunoassays using fluorescent microspheres and the Luminex-100 system were performed on plasma from 80 obese patients (40 with the metabolic syndrome) before and after 6-8 weeks of diet-induced weight loss. Leptin, insulin, C-peptide, monocyte chemoattractant protein-1 (MCP-1), eotaxin, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and IL-6 concentrations measured with multiplex panels from 3 different manufacturers were compared with results from commercial ELISAs. Detection limits and between- and within-run imprecision were determined for each analyte. Bland-Altman analysis was used to determine agreement between multiplexed immunoassays and ELISAs.. Correlation between the Luminex multiplexed assays and ELISAs was good for leptin (Linco), insulin (Linco), MCP-1 (Biosource and Upstate), and eotaxin (Biosource) with correlation coefficients of 0.711-0.895; fair for eotaxin (Upstate) and C-peptide (Linco) with correlation coefficients of 0.496-0.582; and poor for TNF-alpha, IL-8, and IL-6 (Linco, Biosource, Upstate, and R&D) with correlation coefficients of -0.107 to 0.318. Within- and between-run imprecision values for the multiplex method were generally <15%. Relative changes in plasma leptin and insulin concentrations after diet-induced weight loss were similar whether assessed by multiplex assay or ELISA.. Although this technology appears useful in clinical research studies, low assay sensitivity and poor correlations with conventional ELISA methods for some analytes with very low plasma concentrations should be considered when using the Luminex platform in clinical studies.

Topics: Adipose Tissue; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Cytokines; Female; Fluorescent Dyes; Humans; Immunoassay; Insulin; Interleukin-6; Interleukin-8; Leptin; Male; Metabolic Syndrome; Microspheres; Middle Aged; Obesity; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss

Familial combined hyperlipidemia (FCH) is characterized by hypercholesterolemia and/or hypertriglyceridemia and is associated with premature cardiovascular disease (CVD). Other features of FCH are obesity and insulin resistance. Serum leptin levels have been associated with obesity, insulin resistance and CVD. The aim of this study was to determine whether increased leptin levels contribute to the FCH phenotype and its increased risk for CVD. The study population comprised 644 subjects, including 158 FCH patients. Leptin levels were determined, using a commercially available ELISA. For both males and females, the mean leptin level (ng/ml) was higher in FCH patients compared to normolipidemic relatives and spouses. However, after standardization for BMI and insulin resistance, these differences disappeared. The 90th percentile of the leptin level, standardized for BMI, insulin resistance and gender, was associated with an increased risk for CVD in FCH patients (odds ratio=2.9, 95% CI=1.1-8.0) and in non-FCH subjects (odds ratio=3.4, 95% CI=1.3-9.0). The overall increased risk for CVD, associated with a leptin level >90th percentile, was 3.3 (95% CI=1.7-6.4). We conclude that in patients with FCH, leptin levels are increased in proportion to their higher BMI and the presence of insulin resistance. These increased leptin levels are associated with an increased risk for CVD both in FCH patients and non-FCH subjects, independent of BMI, insulin resistance and gender.

Topics: Adult; Biomarkers; Body Mass Index; Cardiovascular Diseases; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hyperlipidemia, Familial Combined; Incidence; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Nephelometry and Turbidimetry; Obesity; Phenotype; Radioimmunoassay; Risk Factors

Although obesity is strongly associated with cardiovascular disease (CVD), the endogenous relationship between obesity and CVD is still not fully clear. Emerging evidence from both animal and human studies indicates that leptin may play an important role in obesity-related CVD. Besides modulating appetite and metabolism, leptin has also been shown to increase sympathetic nerve activity, stimulate generation of reactive oxygen species, upregulate endothelin-1 production and potentiate platelet aggregation. These effects of leptin may contribute to hypertension, endothelial dysfunction and atherosclerosis in obese individuals. Better understanding the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance. These recent discoveries could lead to novel strategies for treatment of obesity-associated CVD.

Topics: Animals; Cardiovascular Diseases; Endothelin-1; Humans; Hypertension; Leptin; Obesity; Reactive Oxygen Species

We compared cardiovascular risk factors in younger and older patients with Type 2 diabetes mellitus and higher than normal body mass index (BMI) and percentage of body fat (% BF) after a 1-yr weight-reduction program in order to clarify the benefits of weight loss in the overweight elderly. Groups of 52 younger and 50 older patients consumed low-calorie diets and participated in a simple moderate-intensity aerobic exercise program for 1 yr. At three times during the program (start, 6 months, 12 months), 10 measures were taken for each participant: BMI, total cholesterol (TC), triglyceride (TG), % BF, waist circumference (WC), fasting plasma glucose, hemoglobulin A1c (HbA1c), leptin, high-sensitivity C-reactive protein (hs-CRP), and adiponectin levels. While changes in BMI, TC and TG were evidently the same in both age groups (p-value: 0.11, 0.33, 0.70, respectively), raw figures for change in % BF, WC, fasting plasma glucose, HbA1c, leptin, hs-CRP, and adiponectin values were significantly greater in the older group (p-value: 0.02, 0.01, 0.03, 0.04, 0.02, 0.01, 0.03 respectively). However, after adjusting for % BF and WC, these changes were no longer significant (p-values: 0.08, 0.07, 0.08, 0.06, 0.10, respectively), indicating that weight loss is equally beneficial for overweight patients with Type 2 diabetes in both age groups. Benefits were gained mainly through reduced body fat. Simple life-style modification of adding 20-min daily aerobic exercise and an adequate but restricted calorie diet is more effective in elderly diabetic patients.

Topics: Adiponectin; Adipose Tissue; Adult; Aged; Blood Glucose; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Diet, Fat-Restricted; Exercise Therapy; Fasting; Female; Humans; Leptin; Male; Obesity; Risk Factors; Taiwan; Triglycerides; Waist-Hip Ratio; Weight Loss

In the present study, we used high sensitivity C-reactive protein (hs-CRP) analysis in combination with lipid screening [which has been reported to be a more valuable risk marker than other novel markers such as homocysteine (Hcy) and lipoprotein a] to perform cardiovascular risk assessment in peritoneal dialysis (PD) and hemodialysis (HD) patients. We selected 9 PD patients, 10 HD patients, and 9 control subjects for the study. In those patients, we determined levels of serum lipids, hs-CRP, Hcy, vitamin B12, folic acid, and leptin. Patients on PD had a significantly elevated hs-CRP concentration (3.14 +/- 0.79 mg/L) and ratio of total cholesterol (TC) to high density lipoprotein (HDL) cholesterol (4.71 +/- 0.40), and their cardiovascular risk was found to be three times that of control subjects. In HD patients, the elevation of hs-CRP was more profound (5.66 +/- 1.30), but their TC:HDL ratio fell within the normal range (3.18 +/- 0.13). However, a cardiovascular risk assessment of the HD group showed the same risk as in the PD group. Serum Hcy was also elevated in patients on PD (54.95 +/- 18.08 microl/L) and on HD (25.33 +/- 3.70 micromol/L) as compared with healthy subjects (13.76 +/- 0.94 micromol/L). Folic acid and vitamin B12 levels (needed to remethylate Hcy to methionine) were not compromised in the dialysis population. On the other hand, leptin secreted by adipose tissue was found to be mildly higher in PD patients (37.08 +/- 12.59 ng/mL). The mean leptin level in control subjects was 14.14 +/- 3.60 ng/mL. The proinflammatory and proangiogenic action of excess leptin may aggravate cardiovascular risk in PD patients. Increased values of known risk factors were found in dialysis patients on PD and on HD. However, lower levels of HDL cholesterol, higher cardiovascular risk assessment and Hcy levels, and mildly increased leptin levels seem to increase the potential threat of vascular disease in PD patients more than in HD patients.

Topics: Adult; C-Reactive Protein; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Leptin; Lipids; Peritoneal Dialysis; Renal Dialysis; Risk Assessment; Risk Factors; Vitamin B Complex

The rising epidemic worldwide in overweight and obese children requires urgent attention. Leptin has been found to be associated with body weight control and possibly affects insulin sensitivity. Since insulin resistance is associated with obesity in adults and possibly in adolescents, we set out to investigate the association of plasma leptin level with various anthropometric indices, body fat mass (FM), lipids, and insulin resistance (IR) index in nondiabetic adolescents.. A cross-sectional study from three high schools in Taipei City in Taiwan.. A total of 402 nondiabetic subjects (162 boys and 240 girls; age range, 10-19 y; mean age, 15.8+/-1.9 y, and mean body mass index (BMI), 24.8+/-4.6 kg/m(2)) were recruited.. The fasting plasma leptin, plasma glucose, insulin, lipids, and anthropometric indices including height, weight, waist (WC) and hip circumferences, and waist-to-hip ratio (WHR) were examined. Total body FM and percentage body fat (FM%) were obtained from dual-energy X-ray absorptiometry. The homeostasis model was applied to estimate the degree of IR.. The plasma leptin levels were significantly higher in girls (17.45+/-10.13 ng/ml) than boys (8.81+/-6.71 ng/ml, P<0.001). The plasma leptin levels were positively correlated to BMI, WC, WHR, FM, FM%, and triglycerides (TG). The IR index was positively correlated to BMI, WC, WHR, FM, FM%, TG, and leptin. Using the multivariate linear regression models, we found that plasma leptin remains significantly associated with IR index even after adjusting for age, gender, BMI, FM, WC, Tanner stage, and TG.. Plasma leptin was associated with IR index independent of age, gender, BMI, FM, WC, Tanner stage, and TG. Plasma leptin levels in adolescents could be a predictor for the development of the metabolic syndrome disorders and cardiovascular diseases.

Topics: Adipose Tissue; Adolescent; Adult; Aging; Anthropometry; Biomarkers; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Lipids; Male; Puberty; Risk Factors; Sex Characteristics

C-reactive protein (CRP) is synthesized from the liver and is regulated by cytokines, especially interleukin-6. Leptin, the adipocyte-derived protein product of the ob gene, is related to amount of body fat. The long form of the leptin receptor resembles cytokine receptors, which include the interleukin-6 receptor. Both leptin and CRP may be increased in women, in obesity, and in inflammation, and both have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk. We tested the hypothesis that leptin is associated with CRP levels independently of the influences of gender, body mass index (BMI), waist-to-hip ratio, and other variables.. We studied 100 healthy volunteers (48 men, and 52 women). For all subjects, leptin was independently associated with CRP after adjustment for age, gender, BMI, waist-to-hip ratio, smoking, and alcohol consumption (F=12.39, P=0.0007). There was a strong and significant positive relationship between leptin and CRP in both women (R=0.61, P<0.0001) and men (R=0.55, P<0.0001) considered separately. The association between leptin and CRP was significant even after adjustment for age, BMI, waist-to-hip ratio, smoking, and alcohol consumption in women (F=7.13, P=0.01) and men (F=5.69, P=0.02). When only subjects with BMI <25 kg/m2 were considered (n=47), CRP was not linked to BMI (R=0.02, P=0.96), but a significant association between leptin and CRP was still evident (R=0.55, P<0.0001).. Leptin and CRP levels are independently associated in normal humans, providing further evidence linking metabolic and inflammatory cardiovascular disease mechanisms.

Topics: Adult; Alcohol Drinking; Body Constitution; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Leptin; Male; Reference Values; Smoking

Leptin and dyslipidemia are risk factors for cardiovascular disease. We measured leptin and lipid levels, and examined whether there is an effect of leptin on lipid profile in marasmic children.. Fifty children (25 marasmic, 25 healthy) aged between 0.3 and 2.5 years were evaluated. Leptin levels were compared with lipid profile in marasmic and healthy children. The relationships between leptin and sex, body mass index and lipid profile were investigated in marasmic children.. In the marasmic group, body mass index, leptin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol levels were lower (p < 0.0001, p < 0.0001, p < 0.0001, p = 0.01, respectively), and triglyceride levels higher than in the control group. In females, leptin was correlated positively with high-density lipoprotein cholesterol (p = 0.002), and inversely correlated with the triglyceride level (p = 0.003). In males, a positive correlation was found between leptin and low-density lipoprotein cholesterol (p = 0.026). In female patients, body mass index, leptin and high-density lipoprotein cholesterol levels were lower (p < 0.0001, for all) when compared to their female controls. In male patients, body mass index, leptin, high-density lipoprotein and low-density lipoprotein cholesterol levels were lower (p < 0.0001, p = 0.031, p = 0.002, p = 0.017, respectively) than those in their male controls.. As a result, we found low leptin (an independent cardiovascular risk factor) levels, but dyslipidemia in our marasmic patients. Dyslipidemia may be a risk factor for cardiovascular complications in marasmic children in the future.

Topics: Cardiovascular Diseases; Case-Control Studies; Child, Preschool; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Infant; Leptin; Lipids; Male; Protein-Energy Malnutrition; Risk Factors; Sex Factors; Triglycerides

Topics: C-Reactive Protein; Cardiovascular Diseases; Electron Spin Resonance Spectroscopy; Female; Humans; Inflammation; Leptin; Male; Membrane Fluidity; Metabolic Syndrome; Nitric Oxide; Obesity; Reference Values

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and until recently prophylactic cranial radiotherapy (CRT) was important for achieving long-term survival. Hypothalamic-pituitary hormone insufficiency is a well-recognized consequence of CRT for childhood cancer. Another problem is increased cardiovascular risk, which has been shown in long-term survivors of other childhood cancers. In the only previously reported study on cardiovascular risk after childhood ALL, obesity and dyslipidemia were recorded in a small subgroup treated with CRT, compared with patients treated with chemotherapy. The mechanisms behind the increase in cardiovascular risk in survivors of childhood cancer are not clarified. The aim of the present study was to elucidate mechanisms of increased cardiovascular risk in former childhood ALL patients. A group of 44 ALL survivors (23 males, median age 25 yr, range 19-32 yr at the time of study) treated with CRT (median 24 Gy, 18-30 Gy) at a median age of 5 yr (1-18 yr) and chemotherapy were investigated for prevalence of GH deficiency and cardiovascular risk factors. Comparison was made with controls randomly selected from the general population and individually matched for sex, age, smoking habits, and residence. All patients and controls underwent a GHRH-arginine test, and patients with a peak GH 3.9 microg/liter or greater were further investigated with an additional insulin tolerance test. Significantly higher plasma levels of insulin (P = 0.002), blood glucose (P = 0.01), and serum levels of low-density lipoprotein cholesterol, apolipoprotein (Apo) B, triglycerides, fibrinogen, and leptin (all P

Topics: Adolescent; Apolipoproteins B; Arginine; Blood Glucose; Body Height; Cardiovascular Diseases; Carotid Arteries; Child; Child, Preschool; Cholesterol, LDL; Echocardiography, Doppler; Exercise; Female; Fibrinogen; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Infant; Insulin; Leptin; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Risk Factors; Triglycerides

The lower mortality from coronary ischemic disease in populations living at high altitude has been related to an increase of high-density lipoprotein (HDL)-cholesterol at altitude. Leptin has been proposed as a cardiovascular risk factor. We investigated whether leptin varies according to the altitude at which people live.. This was a cross-sectional study of the first 889 people enrolled in a cohort study in the Canary Islands, Spain. The relationship among serum leptin, altitude, obesity, and other cardiovascular risk factors was analyzed by bivariate and multivariate tests.. Leptin levels showed an inverse correlation to altitude expressed in meters (r = -0.10). Obese subjects had this leptin-altitude association (r = -0.19), but they also had a direct correlation of leptin to HDL-cholesterol (r = 0.27) and an inverse correlation of leptin to the total cholesterol-to-HDL-cholesterol ratio (r = -0.34), triglycerides (r = -0.29), apolipoprotein B (r = -0.21), and glycemia (r = -0.19). Nonobese subjects had only the leptin-altitude association (r = -0.11). The final regression model included altitude as predictor. Other associated variables were gender, physical activity, BMI, age, smoking (reducing leptin independently of BMI), alcohol, heart rate, and income.. Serum leptin level decreases when altitude increases, and this association could help to explain the lower cardiovascular mortality rate at high altitude. However, because in obese subjects there is a direct association of leptin with HDL-cholesterol and an inverse association with the lipid atherogenic fractions, we suggest the hypothesis of different roles for bound and free leptin, with free leptin being a cardiovascular protective factor in obese people.

Topics: Adult; Altitude; Atlantic Islands; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cross-Sectional Studies; Female; Humans; Leptin; Male; Middle Aged; Obesity; Reference Values; Regression Analysis; Triglycerides

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Humans; Hyperinsulinism; Leptin; Metabolic Syndrome; Risk Factors

Serum sialic acid (TSA) has been shown to be a cardiovascular risk factor and an acute phase reactant, with elevated concentrations associated with increased cardiovascular mortality and to precede the onset of type 2 diabetes.. The purpose of this present study was to test the hypothesis that serum TSA may be related to serum leptin concentrations in healthy individuals.. Thirty Fijian individuals were studied (8 males and 22 females). They were urban Melanesians living in Raiwaga, a suburb of Suva in Fiji.. Serum TSA significantly correlated with subject body mass index (BMI, rho 0.39, P<0.05) and serum leptin concentration (rho 0.44, P<0.05). In stepwise multiple regression analysis serum TSA independently correlated with subject waist/hip ratio (r(2)=0.167, P<0.02) and diastolic blood pressure (r(2)=0.300, P<0.01) but not with age, BMI, serum insulin-like growth factor binding protein (IGFBP-1), fasting plasma glucose or systolic or diastolic blood pressure.. Serum TSA is related to markers of obesity and adipose tissue metabolism which may help to explain why it is a reputed cardiovascular risk factor and why elevated serum TSA concentrations precede the development of type 2 diabetes mellitus.

Topics: Adult; Anthropometry; Blood Glucose; Blood Pressure; Body Constitution; Body Mass Index; Cardiovascular Diseases; Fasting; Female; Fiji; Humans; Insulin-Like Growth Factor Binding Protein 1; Leptin; Male; Middle Aged; Obesity; Risk Factors; Sialic Acids

Impaired lung function is a risk factor for cardiovascular morbidity. Whether circulating factors are responsible for this association is unknown. A study was undertaken to determine whether leptin, a hormone that can promote atherothrombosis, is raised in individuals with impaired lung function.. Data from non-obese participants in the Third National Health, Nutrition, and Examination Survey (n=2808) were analysed to determine the relationship between circulating leptin levels and forced expiratory volume in 1 second (FEV(1)) values divided into quintiles (quintile 1, FEV(1) predicted < or =85.2%; quintile 2, 85.3-94.3%; quintile 3, 94.4-101.4%; quintile 4, 101.5-110.0%; and quintile 5, > or =110.1%).. Serum leptin levels changed along the FEV(1) gradient. The highest leptin levels were found in quintile 1 (geometric mean (GM) 5.42; interquartile range (IQR) 3.00-9.60 fg/l) and the lowest in quintile 5 (GM 4.94; IQR 2.80-9.10 fg/l). Adjustments for age, body mass index, and other confounders strengthened this relationship. Compared with quintile 5, the odds of having an increased serum leptin level in quintiles 1, 2, 3, and 4 were 2.26 (95% confidence interval (CI) 1.54 to 3.31), 2.20 (95% CI 1.52 to 3.17), 1.46 (95% CI 1.01 to 2.09), and 1.28 (95% CI 0.90 to 1.83), respectively.. Individuals with impaired lung function have raised serum leptin levels. Leptin may play a role in the pathogenesis of cardiovascular morbidity and mortality related to impaired lung function.

Topics: Adult; Age Distribution; Aged; Body Mass Index; Body Weight; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Female; Forced Expiratory Volume; Humans; Leptin; Lung Diseases; Male; Middle Aged; Multivariate Analysis; Risk Factors; Vital Capacity

Topics: Adaptation, Physiological; Animals; Cardiovascular Diseases; Causality; Comorbidity; Diabetes Mellitus; Energy Intake; Humans; Hypertrophy, Left Ventricular; Leptin; Mice; Obesity; Risk

To examine the relation of leptin to insulin resistance, as measured by euglycemic insulin clamp, and insulin resistance syndrome factors in thin and heavy children.. Anthropometrics, insulin, blood pressure, and leptin were measured in 342 11- to 14-year-old children (189 boys, 153 girls, 272 white, 70 black). Insulin sensitivity (M) was determined by milligrams glucose uptake per kilogram per minute and expressed as M/lean body mass (Mlbm). Children were divided by median BMI (boys = 20.5 kg/m(2); girls = 21.4 kg/m(2)) into below-median (thin) and above-median (heavy) groups. Correlation coefficients between log-leptin and components of insulin resistance syndrome were adjusted for Tanner stage, gender, and race.. BMI was related to leptin in boys (r = 0.70, p < 0.001) and girls (r = 0.75, p < 0.001). Leptin was higher in girls than boys (32.6 vs. 12.3 ng/mL, p = 0.0001). Leptin levels increased in girls and decreased in boys during puberty, paralleling the changes in body fat. Leptin was significantly correlated with insulin, Mlbm, triglycerides, and blood pressure in heavy children and only with insulin in thin children. After adjustment for body fat, the correlations remained significant for insulin and Mlbm in heavy children and with insulin in thin children.. Significant associations were found between leptin and insulin resistance in children, and these associations were attenuated by adjustment for adiposity. These findings at age 13 likely have long-term consequences in the development of the obesity-insulin resistance-related cardiovascular risk profile.

Topics: Adolescent; Aging; Anthropometry; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Clamp Technique; Humans; Leptin; Male; Metabolic Syndrome; Obesity; Puberty; Risk Factors; Sex Characteristics

Leptin and tumor necrosis factor (TNF)-alpha are associated with insulin resistance and cardiovascular disease. In vitro studies suggested that these effects may be mediated via overproduction of monocyte chemoattracting protein (MCP)-1/CCL2, which is a chemokine involved in the pathogenesis of atherosclerosis.. In this study, fasting plasma leptin, soluble TNF-alpha receptor 2 (TNF-alpha-R2), and MCP-1/CCL2 concentrations were measured in 207 middle-aged women (age 61 +/- 12 years, BMI 30.1 +/- 6.6 kg/m(2)), including 53 patients with type 2 diabetes, 42 with impaired glucose tolerance, and 112 with normal glucose tolerance, to assess cross-sectionally their relationship with markers of atherosclerosis and, longitudinally over 7 years, whether their circulating levels were associated with cardiovascular disease (CVD) mortality.. At baseline, leptin and TNF-alpha-R2 were not different among groups; meanwhile, MCP-1/CCL2 was increased in type 2 diabetes (P < 0.05). All showed significant associations with biochemical risk markers of atherosclerosis. In a univariate analysis, age, fasting insulin, leptin, and MCP-1/CCL2 were associated with CVD mortality at 7 years. When a multivariate analysis was performed, only age, leptin, and insulin retained an independent association with CVD mortality, with leptin showing a protective effect (hazard ratio 0.88; P < 0.02).. In middle-aged women, MCP-1/CCL2, leptin, and TNF-alpha-R2 were all related to biochemical risk markers of atherosclerosis. MCP-1/CCL2 concentration was the only one to be increased in type 2 diabetes with respect to nondiabetic women and the only one to be associated with increased risk of CVD mortality after a 7-year follow-up period in the univariate analysis. In the multivariate analysis, neither MCP-1/CCL2 nor TNF-alpha-R2 was associated with CVD mortality, and inspection of the data showed that leptin, in both the univariate and multivariate analysis, was associated with a protective effect.

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Chemokine CCL2; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Humans; Leptin; Middle Aged; Multivariate Analysis; Risk Factors; Tumor Necrosis Factor-alpha

Leptin has been implicated in cardiovascular disease. A diet rich in fish has been associated with decreased cardiac and vascular risk.. We examined the relationship between diet and leptin in 2 related homogeneous African tribal populations of Tanzania. One tribe consumes freshwater fish as their main diet component (n=279), and the other tribe consumes a primarily vegetarian diet (n=329). In multivariate analysis, plasma leptin levels were associated with type of diet (F=14.3, P<0.001), independent of age, body mass index, body fat, alcohol consumption, or insulin. Both male (2.5+/-2 [fish diet] versus 11.2+/-2.4 [vegetarian diet] ng/mL, P=0.017) and female (5.0+/-1.9 [fish diet] versus 11.8+/-1.4 [vegetarian diet] ng/mL, P=0.007) fish eaters had lower plasma leptin levels than did their vegetable diet counterparts, even though body mass index values were virtually identical.. A diet rich in fish is associated with lower plasma leptin, independent of body fat. These findings may have implications for understanding the reduced cardiovascular risk in subjects on a high-fish diet.

Topics: Animals; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Diet; Diet, Vegetarian; Female; Fishes; Fresh Water; Humans; Leptin; Male; Risk Factors; Tanzania

Recent epidemiologic studies have shown that obesity is associated with elevated blood concentrations of prothrombotic-proinflammatory factors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), von Willebrand factor (vWF), and homocysteine. We have assessed whether these markers are associated with percentage of body fat (BF), insulin sensitivity as well as with leptin concentrations.. Twenty-five men aged 49.6 +/- 12.7 yr (mean +/- SD) underwent whole-body air displacement plethysmography (Bod-Pod(R)) for estimating BF. Blood analyses for leptin and several other metabolic and cardiovascular markers were carried out.. Obese subjects had higher levels as compared to controls of BF (37.5 +/- 5.1 vs. 26.0 +/- 6.6, p < 0.01), fibrinogen (3.30 +/- 0.43 vs. 2.67 +/- 0.11, p < 0.01), vWF (136.4 +/- 50.4% vs. 81.6 +/- 12.6%, p < 0.05), and leptin (17.6 +/- 8.7 vs. 6.2 +/- 3.3, p < 0.01), lower concentrations of HDL-cholesterol (1.09 +/- 0.20 vs. 1.51 +/- 0.10, p < 0.001) and lower QUICKI (1/[log(Ins(0)) + log(Glu(0))]) (0.31 +/- 0.03 vs. 0.34 +/- 0.02, p < 0.05). No significant changes were observed in CRP (5.7 +/- 3.4 vs. 3.8 +/- 1.6, p = 0.327) and homocysteine (9.4 +/- 4.2 vs. 8.3 +/- 0.9, p = 0.749). A positive correlation was observed between BF and fibrinogen (r = 0.67, p = 0.0003). Plasma leptin concentrations were correlated with fibrinogen (r = 0.71, p = 0.0001) and CRP (r = 0.43, p = 0.044). After adjustment for BF leptin emerged as a significant predictor of fibrinogen (beta = 0.47, p = 0.023; R(2) = 0.59, p < 0.001). QUICKI was positively correlated with HDL-cholesterol (r = 0.59, p = 0.010) and negatively with fibrinogen (r = -0.53, p = 0.025), CRP (r = -0.52, p = 0.028) and vWF (r = -0.56, p = 0.013).. Increased BF and impaired insulin sensitivity are associated with increased concentrations of cardiovascular risk factors. Leptin seems to be involved in this elevation and emerges as a predictor of circulating fibrinogen concentrations.

Topics: Adipose Tissue; Adult; Aged; Body Composition; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Fibrinogen; Glucose; Homocysteine; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Risk Factors; Triglycerides; von Willebrand Factor

To determine the influence of weight loss on multiple cardiovascular disease (CVD) risk factors.. Overweight women (n = 12; mean 44.2% fat) and men (n = 10; mean 30.7% fat) participated in an 8 week weight-loss program that included dietary, exercise, multi-vitamin/mineral supplementation, and behavior modification components. Measurement of total and regional body composition assessed using dual energy X-ray absorptiometry (DEXA), circumferences and blood sampling for total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, homocysteine, insulin and leptin were performed before and after the weight loss intervention.. Subjects increased their physical activity and decreased their energy intake, resulting in a mean decrease in body mass of - 4.3 +/- 3.4 kg in women and -4.7 +/- 3.1 kg in men. Fat accounted for 88 and 58% of the decrease in body mass in men and women, respectively. Proportionally, men lost significantly more fat mass from the trunk region compared to women. Serum total and LDL cholesterol were significantly decreased in men (-11 and -14%, respectively) but not women (-3 and -3%, respectively) and there were no changes in HDL cholesterol and triacylglycerols. Serum leptin was significantly decreased (-36%) and highly correlated to fat mass (r= 0.839). There were no changes in serum insulin and plasma homocysteine.. These data indicate that short-term weight loss resulting from reducing percentage energy from fat, increasing physical activity and vitamin/mineral supplements including folic acid has a favorable effect on regional body composition and total and LDL cholesterol with minimal effects on HDL cholesterol, triacylglycerols, homocysteine and insulin and the effects are greater in men compared to women. Supplementation with folic acid or emphasis on folic acid-rich foods may be an important component of a weight loss program to prevent increases in homocysteine.

Topics: Absorptiometry, Photon; Adult; Body Composition; Body Constitution; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Energy Intake; Exercise; Female; Folic Acid; Homocysteine; Humans; Insulin; Leptin; Lipids; Male; Obesity; Risk Factors; Sex Factors; Weight Loss

s: To determine whether traditional risk factors for cardiovascular disease (CVD) and regional fat distribution, especially the central obesity type and increased parapharyngeal fat pads, are associated with the degree of obstructive sleep apnea (OSA). To determine whether there are interrelationships between body fat, serum leptin levels, and the degree of OSA.. Prospective mono-center cross-sectional study in a university hospital in Germany.. Eighty-five consecutive male patients who were referred for evaluation of suspected OSA.. The major dependent outcome variable was the apnea-hypopnea index (AHI), the average number of apneas and hypopneas per hour of sleep, determined by overnight polysomnography. Independent measures were anthropometric data, body composition analysis (bioelectrical impedance analysis [BIA]), cardiovascular risk factor evaluation (smoking, hypertension, serum lipoproteins, diabetes or impaired glucose tolerance, uric acid, fibrinogen), and leptin. Adipose tissue quantification of the abdominal and neck regions was performed by nuclear MRI (NMR). Significant linear relationships of AHI with fasting blood glucose, uric acid, fibrinogen, body weight, body mass index (BMI), sum of fat skin folds, and percentage of body fat could be established, whereas there was no correlation with age. The presence of OSA was independent of smoking, hypertension, and lipoproteins. NMR scans showed that AHI was significantly correlated with intra-abdominal fat and subcutaneous abdominal fat, whereas subcutaneous fat in the neck region and parapharyngeal fat in the airway vicinity were not correlated. Leptin concentrations correlated with AHI and with biochemical markers of the metabolic syndrome (lipoproteins, glucose) but were not dependent on AHI. Logistic regression analysis found percentage of body fat (BIA) and BMI as good predictors of AHI > 10 with a sensitivity of 95.5% but a low specificity (46.2%). Multiple regression analysis identified the sum of fat skin folds, body weight, and BMI as good predictors for the degree of OSA.. We conclude that OSA is independent from most traditional risk factors for CVD. Regional body fat distribution predicts the presence and degree of OSA, but fat accumulation in the neck and parapharyngeal region are of minor importance. Leptin concentrations when controlled for body fat are not related to the degree of OSA.

Topics: Adult; Aged; Body Composition; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Polysomnography; Prospective Studies; Risk Factors; Sleep Apnea, Obstructive

Topics: Blood Vessels; Cardiovascular Diseases; Compliance; Endothelium, Vascular; Humans; Leptin; Obesity; Vascular Diseases; Vasodilation

The mechanisms by which obesity increases the risk of atherosclerotic cardiovascular disease (CVD) are poorly understood. In experimental models, leptin, a hormone produced by adipose tissue, has been shown adversely to affect vascular health. Therefore, we tested the hypothesis that high leptin concentrations are associated with lower arterial distensibility, an index of circulatory function relevant to the atherosclerotic process.. Noninvasive, high-resolution, vascular ultrasound was used to measure brachial artery distensibility in 294 healthy adolescents (aged 13 to 16 years) who had a broad range of body mass indexes. Fat mass was measured by bioelectric impedance analysis; fasting serum leptin concentration by radioimmunoassay; and lipid profile, fasting insulin, glucose, and C-reactive protein concentrations by standard laboratory techniques. Higher leptin concentrations were associated with impaired arterial distensibility (regression coefficient, -1.3% change in arterial distension per 10% increase in leptin; 95% CI, -1.9% to -0.8%; P<0.001). This association was independent of fat mass, blood pressure, and C-reactive protein, fasting insulin, or LDL cholesterol concentrations.. Elevation in leptin was associated with impaired vascular function, independent of the metabolic and inflammatory disturbances associated with obesity. Our observations are consistent with data from experimental models and suggest that high leptin concentration is an important mechanism for the adverse influence of body fatness on CVD.

Topics: Adipose Tissue; Adolescent; Arteries; Body Mass Index; Brachial Artery; Cardiovascular Diseases; Compliance; Female; Humans; Leptin; Male; Obesity; Risk Factors; Ultrasonography; Vasodilation

Anorexia and protein malnutrition, occasionally associated with obesity, are frequently observed in peritoneal dialysis (PD) patients. Both are recognized risk factors for cardiovascular (CV) morbidity and mortality. Leptin is produced by adipocytes and regulates body-fat mass through a satiety central effect. Leptin accumulates in the uremic state. We analyzed the relationship between plasma leptin levels, nutritional status, obesity, CV risk factors, and atherosclerosis in PD patients. Leptin was determined using a polyclonal antibody [radioimmunoassay: Linco Research, St. Louis, MO, U.S.A.]. The normal range was 1-7.8 ng/mL. We studied 38 PD patients. Mean leptin levels were 59.1 +/- 57.5 ng/mL (elevated in 32 patients). Women (n = 21) showed higher leptin levels than did men (80.4 +/- 60 ng/mL vs. 32.3 +/- 43.3 ng/mL, p < 0.01), in spite of both groups having a similar body mass index (BMI). A statistically significant direct correlation was found between leptin and BMI (r = 0.7, p < 0.01) and triceps skin-fold measurement (r = 0.77, p < 0.01). Leptin levels and renal creatinine clearance (CCr) showed no significant correlation. Independent of BMI, higher leptin levels were associated with parameters considered to be CV risk factors (Framingham study), such as serum triglycerides < 150 mg/dL (n = 29) as compared with > 150 mg/dL (44.2 +/- 53.2 ng/mL vs. 80 +/- 58.4 ng/mL, p < 0.05), cholesterol < 250 mg/dL (n = 28) as compared with > 250 mg/dL, (50 +/- 55.6 mg/dL vs. 84.7 +/- 57.7 mg/dL, p < 0.05), uric acid < 7 mg/dL (n = 28) as compared with > 7 mg/dL (47 +/- 53.7 mg/dL vs. 93.1 +/- 56.6 mg/dL, p < 0.05), and the presence or lack of presence of left ventricular hypertrophy [68.8 +/- 60 (n = 30) vs. 29.5 +/- 23.7 (n = 5), p < 0.05]. The patients were classified into two groups according to a clinical atherosclerosis score (CAS). Nineteen patients had low CAS scores, and they showed higher plasma leptin values than did the other patients (82.4 +/- 65.7 ng/mL vs 35.8 +/- 36.6 ng/mL, p < 0.05). Twelve patients with anorexia had lower leptin values than did patients with normal appetite (19.2 +/- 15.8 ng/mL vs. 91.3 +/- 58.8 ng/mL, p < 0.001). In non obese patients (BMI < 25 and CCr < 3 mL/min, n = 14), leptin had a statistically significant direct linear correlation with markers of nutrition, including albumin (r = 0.63, p < 0.05), transferrin (r = 0.4, p < 0.05), cholesterol (r = 0.65, p < 0.05), and triglycerides (r = 0.6, p < 0.05). Finally, plasma l

Topics: Adult; Aged; Aged, 80 and over; Arteriosclerosis; Biomarkers; Cardiovascular Diseases; Female; Humans; Kidney; Leptin; Logistic Models; Male; Middle Aged; Nutrition Disorders; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Risk Factors

Topics: Alcohols; Animals; Apolipoproteins E; Arteriosclerosis; Biomarkers; Carbohydrate Metabolism; Cardiovascular Diseases; Dietary Fats, Unsaturated; Fatty Acids, Omega-3; Feeding Behavior; Fish Oils; Flavonoids; Garlic; Genes; Glycine max; Health Education; Homocysteine; Humans; Hyperlipidemias; Insulin Resistance; Leptin; Life Style; Lipid Metabolism; Nutritional Physiological Phenomena; Obesity; Phenols; Polymers; Polyphenols; Probiotics

Postmenopausal women exhibit an increased incidence of cardiovascular diseases, and type 2 diabetes mellitus compared with younger women. However, women receiving hormonal replacement therapy (HRT) seem to be protected. Since chromium (Cr) functions in glucose, lipid and corticosteroid metabolism and these variables, as well as Cr status, decline with age, Cr status may be a contributing factor in the effects of hormone replacement therapy. Therefore, the objective of this study was to determine the effects of hormonal replacement therapy (HRT) on serum and urinary Cr, plasma lipids, glucose, fructosamine and the related hormonal variables, estradiol, insulin, leptin, cortisol, and DHEA-sulfate.. Forty-four healthy postmenopausal women 50-60 years old participated in the study. Eighteen were treated by combined oral hormonal replacement therapy (estradiol 2 mg per day during days 1-25 and 10 mg of dydrogesterone on days 10-25) for at least 2 years, and 26 were untreated.. Serum Cr concentrations were significantly lower in untreated postmenopausal women than in women receiving HRT (0.070+/-0.008 vs. 0.100+/-0.008 ng/ml) whereas urinary Cr excretion was increased (0.14+/-0.02 vs. 0.07+/-0.01 ng of Cr/mg creatinine). The urinary losses of Cr were inversely correlated with plasma estradiol. Median value of urinary Cr was higher in postmenopausal women exhibiting endogenous estradiol levels below 250 pmol/l, whereas women with estradiol levels >250 pmol/l, exhibited lower Cr values. Plasma fructosamine, total and LDL cholesterol and TC/HDL ratio, which are all decreased by improved Cr nutrition, were also improved in the women receiving HRT. There were also nonsignificant decreasing trends in DHEA-sulfate (P<0.06) and cortisol (0.07).. Chromium status, based upon blood and urinary analyses, and glucose, insulin and lipid variables were improved in postmenopausal women receiving HRT. Additional studies are needed to determine if improved Cr status due to supplemental Cr can elicit effects consistent with those of hormone replacement therapy.

Topics: Administration, Oral; Blood Glucose; Cardiovascular Diseases; Cholesterol, LDL; Chromium; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 2; Drug Administration Schedule; Dydrogesterone; Estradiol; Estrogen Replacement Therapy; Female; Fructosamine; Humans; Hydrocortisone; Insulin; Leptin; Middle Aged; Postmenopause; Reference Values

Leptin, an adipose tissue-derived of gene product, is important in energy metabolism. However, the role of leptin in the metabolism of lipids is still not clear in humans. The purpose of this study was to evaluate the association of plasma leptin concentrations and lipid profiles among school children in Taiwan. After multistage sampling of 85 junior high schools in Taipei, we randomly selected 1264 children (617 boys and 647 girls) aged 12-16 years for this study. We measured the anthropometric variables, lifestyle factors and biochemical parameters among these children. Anthropometric measurements included body height (BH) and weight (BW) and we calculated body mass index (BMI) as the ratio of the BW to the square of the BH, expressed in kg/m2. Plasma leptin levels were measured by radioimmunoassay. We also measured lipid profiles including serum total cholesterol (CHOL), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), and lipoprotein(a) (Lp(a)) levels, and calculated low density lipoprotein-cholesterol (LDL-C) levels and CHOL to HDL-C ratio (TCHR). Girls had higher leptin, CHOL, TG, HDL-C, (LDL-C), Apo-A1, Apo-B, and Lp(a) levels and lower BMI than boys did. Plasma leptin concentrations were significantly positively correlated with TG, LDL-C, and Apo-B, but negatively with HDL-C and Apo-A1 in both the genders. Children with higher plasma leptin levels (>75th percentiles) have significantly higher TG, HDL-C, LDL-C, TCHR, and Apo-B than those with relatively lower leptin levels. In multivariate regression analyses, the association between plasma leptin level and lipid profiles (such as CHOL, TG, and Apo-B) were still significant (p < 0.05) even after adjusting for BMI among boys. However, this association became attenuated and insignificant among girls. Finally, in the model that included the standard covariates, plasma leptin was the most predictive of CHOL, TG and Apo-B levels among those school children in Taiwan. Our results suggest that plasma leptin and BMI were independently associated with the lipids and lipoprotein profiles among Taiwanese Children. In both genders, children in the top 25% of the leptin distribution have more adverse lipid and lipoprotein profiles.

Topics: Adolescent; Analysis of Variance; Anthropometry; Body Mass Index; Cardiovascular Diseases; Child; Female; Humans; Leptin; Lipids; Male; Radioimmunoassay; Sex Factors; Statistics, Nonparametric; Surveys and Questionnaires; Taiwan

Obesity is related to cardiovascular disease (CVD) morbidity and mortality, however, the mechanisms for the development of obesity-induced CVD risk remain unclear. Hyperinsulinemia and insulin resistance are considered key components in the metabolic cardiovascular syndrome and as independent risk factors for CVD. Plasma leptin and tumor necrosis factor-alpha (TNF-alpha), two adipocyte products, are also proposed to be associated with the development of CVD risk. The purpose of this study is to evaluate the association of plasma leptin, soluble TNF receptors (sTNF-R), and insulin levels as possible mediators of the effect of obesity on atherogenic and thrombogenic CVD risk factors among men. From the Health Professionals Follow-up Study (HPFS), we selected 268 men, aged 47--83 years, who were free of CVD, diabetes, and cancer (except non-melanoma skin cancer), and who had provided a fasting blood sample in 1994. We measured plasma insulin and leptin levels by radioimmunoassay and sTNF-R levels by ELISA. Men in the highest quintile of body mass index (BMI, mean=30.5 kg/m(2)) were less physically active and had a more adverse cardiovascular lipid and homeostatic profile, as indicated by levels of insulin, triglyceride (TG), tissue plasminogen activator (t-PA) antigen levels, and apolipoprotein A1 (Apo-A1). In a multivariate regression model controlling for age, smoking, alcohol intake, physical activity and diet, BMI was inversely associated with HDL-cholesterol (HDL-C) and Apo-A1 and positively associated with TG, Apo-B and t-PA antigen levels. The associations between BMI and these CVD risk factors were only slightly changed after adjusting for leptin and/or sTNF-R; but were substantially attenuated after controlling for insulin levels. These data suggest that the association between obesity and biological predictors of CVD may be mediated through changes in plasma insulin, rather than leptin or sTNF-R levels. However, plasma leptin may still play a role in CVD through independent effects on lipid metabolism.

Topics: Adult; Aged; Arteriosclerosis; Body Mass Index; Cardiovascular Diseases; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Risk Factors; Solubility; Thrombosis

Leptin plays a role in fat metabolism and correlates with insulin resistance and other markers of the metabolic syndrome, independent of total adiposity. Therefore, we hypothesized that raised leptin levels may identify men at increased risk of a coronary event in the West of Scotland Coronary Prevention Study (WOSCOPS). Methods and Results- Plasma leptin levels were measured at baseline in 377 men (cases) who subsequently experienced a coronary event and in 783 men (controls) who remained free of an event during the 5-year follow-up period of the study. Controls were matched to cases on the basis of age and smoking history and were representative of the entire WOSCOPS cohort. Leptin levels were significantly higher in cases than controls (5.87+/-2.04 ng/mL versus 5.04+/-2.09 ng/mL, P<0.001). In univariate analysis, for each 1 SD increase in leptin, the relative risk (RR) of an event increased by 1.25 (95% confidence interval [CI], 1.10 to 1.43; P<0.001). There was minimal change in this RR with correction for body mass index (RR, 1.24; 95% CI, 1.06 to 1.45; P=0.006) or with further correction for classic risk factors, including age, lipids, and systolic blood pressure (RR, 1.20; 95% CI, 1.02 to 1.42; P=0.03). Leptin correlated with C-reactive protein (r=0.24, P<0.001) and, even with this variable added to the model, leptin retained significance as a predictor of coronary events (RR, 1.18; 95% CI, 1.00 to 1.39; P=0.05) at the expense of C-reactive protein.. We show, for the first time, in a large prospective study that leptin is a novel, independent risk factor for coronary heart disease.

Topics: Age Factors; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Coronary Disease; Follow-Up Studies; Humans; Leptin; Lipids; Middle Aged; Multivariate Analysis; Risk Factors; Smoking; Triglycerides

Obesity is a prevalent disorder that increases the risk for premature cardiovascular disease. The adipose tissue itself plays an active role in the regulation of fuel metabolism and energy homeostasis by expressing a number of regulatory genes, such as leptin, peroxisome proliferator-activated receptor-gamma (PPARgamma), and CCAAT/enhancer binding protein-alpha (C/EBPalpha). To study the in vivo relationships among these genes and their associations with cardiovascular risk factors, plasma levels of leptin, lipids, apolipoproteins (apo), insulin, and glucose were measured in 216 obese, 165 nonobese, and 36 weight-losing postobese subjects. mRNA expression of leptin, PPARgamma, and C/EBPalpha in the extraperitoneal and intraperitoneal adipose tissue was quantified in subsets of subjects. In obese individuals, plasma leptin was associated with apoA-I (r=0.2346, P<0.001) and insulin (r=0.2125, P<0.002). Leptin and C/EBPalpha mRNA expression in extraperitoneal and intraperitoneal adipose tissue of obese patients was higher than in the respective tissues of nonobese or postobese subjects. No significant differences among the study groups were found for PPARgamma mRNA expression. Leptin, PPARgamma, and C/EBPalpha mRNA levels correlated with each other in the intraperitoneal and extraperitoneal fat of obese subjects, but multivariate analysis revealed that only C/EBPalpha was a predictor of leptin expression in extraperitoneal tissue (partial r=0.6096, P<0.001). Intraperitoneal PPARgamma expression was inversely related to fasting insulin (r=-0.2888, P<0.017) and a fasting insulin resistance index (r=-0.2814, P<0.021) in obese subjects. In postobese patients, intraperitoneal PPARgamma expression was associated with plasma HDL cholesterol (r=0.5695, P<0.018) and apoA-I (r=0.6216, P<0.008) but was inversely related to LDL cholesterol (r=-0.5101, P<0.03) and apoB (r=-0.6331, P<0.007). These findings suggest a relationship between plasma leptin and HDL metabolism as well as adipose-tissue site-dependent associations among leptin, C/EBP-alpha, and PPAR-gamma mRNA expression. Furthermore, our results suggest that C/EBP-alpha enhances leptin expression in vivo and that PPARgamma mRNA expression is inversely associated with cardiovascular risk factors.

Topics: Adipose Tissue; Adult; Body Mass Index; Cardiovascular Diseases; CCAAT-Enhancer-Binding Proteins; DNA-Binding Proteins; Female; Humans; Leptin; Male; Middle Aged; Nuclear Proteins; Obesity; Receptors, Cytoplasmic and Nuclear; Reference Values; Risk Factors; RNA, Messenger; Sex Characteristics; Transcription Factors; Weight Loss

Topics: Cardiovascular Diseases; Humans; Leptin; Neoplasms; Obesity

To systematically examine the correlations between insulin resistance, plasma leptin concentration, obesity and the distribution of fat assessed by anthropometry and magnetic resonance imaging in Asian women.. A cross sectional study of non-diabetic, normal weight women.. Twenty-one healthy women aged 38.8 y (s.d. 11.7) and BMI 22.6 kg/m2 (s.d. 2.3).. Intraperitoneal, retroperitoneal and subcutaneous abdominal fat volume was assessed by magnetic resonance imaging. Anthropometric data were collected. Total fat mass was assessed by bioelectric impedance analysis. Fasting serum lipids, insulin and plasma leptin were assayed.. Generalized obesity correlated with subcutaneous abdominal fat mass (r=0.83, P<0.001), but not with intra-abdominal fat mass. Both intraperitoneal fat mass and retroperitoneal fat mass increased with age (r=0.58, P=0.005 and r=0. 612, P=0.003, respectively). Abdominal subcutaneous fat mass was the most important determinant of insulin resistance and plasma leptin. Of the serum lipids, only fasting triglyceride correlated significantly with the waist-to-hip ratio.. It is possible that the large size of the subcutaneous depot compared to the intra-abdominal depot overwhelms any metabolic differences between adipose tissue from these two sites, resulting in the stronger correlation between insulin resistance and subcutaneous abdominal fat mass rather than intra-abdominal fat mass. On the other hand, the distribution of fat between subcutaneous fat depots may be important in the metabolic syndrome given the correlation of fasting triglyceride with waist to hip ratio but not with abdominal fat. However, the study population was small, younger and leaner compared to previous studies and we may not be able to generalize these results to all segments of the population. We confirm that subcutaneous fat mass is the major determinant of plasma leptin.

Topics: Abdomen; Adipose Tissue; Adult; Body Composition; Body Constitution; Body Weight; Cardiovascular Diseases; Female; Humans; Insulin Resistance; Leptin; Lipids; Magnetic Resonance Imaging; Middle Aged; Risk Factors; Triglycerides

To investigate the effect of polymorphisms in codon 16 (Arg16Gly) and codon 27 (Gln27Glu) of the beta2-adrenergic receptor gene (ADRB2) on anthropometric, endocrine, metabolic and haemodynamic variables.. A cross-sectional study.. A subgroup of 284 Swedish men from a population sample of 1040 at the age of 51 years.. Genotype examination of ADRB2 polymorphisms in codon 16 and codon 27 with polymerase chain reaction and restriction fragment length polymorphism. Anthropometric measurements included body mass index, waist-to-hip ratio and abdominal sagittal diameter. Endocrine measurements included blood levels of testosterone, insulin-like growth factor I, and leptin plus salivary cortisol. Overnight fasting values of serum insulin, blood glucose, triglycerides, total, low and high density lipoprotein cholesterol, as well as blood pressure and resting heart rate, were also determined.. Polymorphisms were frequent in both codon 16 and codon 27. The Arg16Gly genotype showed significant relationships to elevated central distribution of body fat and to systolic blood pressure, whilst the Glu27Glu genotype was associated with elevated leptin and triglyceride levels but not to other measurements, including obesity variables.. We conclude that only a few cardiovascular risk factors are associated with DNA sequence variation in the ADRB2 in Swedish men.

Topics: Alleles; Anthropometry; Blood Pressure; Cardiovascular Diseases; Chi-Square Distribution; Codon; Cohort Studies; Cross-Sectional Studies; Genotype; Heart Rate; Humans; Leptin; Linkage Disequilibrium; Lipids; Male; Middle Aged; Obesity; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Receptors, Adrenergic, beta-2; Risk Factors; Sweden

Leptin, an adipose tissue-derived product of the obesity (OB) gene, is an important regulator of energy metabolism and may be associated with the occurrence of insulin resistance and diabetes in humans. The purpose of this study was to evaluate the association of plasma leptin concentration with obesity and the components of insulin resistance syndrome (IRS) among school children in Taiwan.. After multistage sampling of 85 junior high schools in Taipei, we randomly selected 1,264 children (617 boys and 647 girls) aged 12-16y. Obesity measurements included body mass index (BMI) and waist-to-hip circumference ratio (WHR). We calculated an IRS summary score for each individual by adding the quartile ranks from the distribution of systolic blood pressure (BP), serum triglyceride (TG), HDL-cholesterol (inverse), and insulin levels.. Boys had a higher BMI and WHR, BP and IRS score and lower leptin, insulin, TG and HDL-C levels than girls. BMI, WHR and plasma leptin levels were significantly associated with the IRS summary score and each of its components in both genders. Children with higher plasma leptin levels (> 75th percentiles) have significantly higher BP, TG, insulin levels and IRS score than children with low leptin levels. The associations between plasma leptin level and the IRS components and score were still significant after adjusting for BMI in boys, but less so in girls. In both genders, after adjusting for WHR, plasma leptin levels were still significantly associated with the IRS components and summary score (P< 0.001). The final model that included the standard covariates, BMI and leptin, but not WHR, was the most predictive of the IRS summary score among school children.. Insulin resistance syndrome in childhood, characterized by high blood pressure, dyslipidemia, and hyperinsulinemia, may be an early marker of cardiovascular risk. From the present BMI and leptin in combination are the most predictive markers of insulin resistance syndrome among school children in Taiwan.

Topics: Adolescent; Body Composition; Body Constitution; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Obesity; Regression Analysis; Sex Characteristics; Taiwan

This was the first Korean-Polish seminar on renal replacement therapies which provided a survey of current research being carried out in both countries, delivered by leading experts in this field. The topics included malnutrition in uremia, biocompatibility, risk factors and complications in renal replacement therapy, diabetic nephropathy, new solutions for peritoneal dialysis, and peritoneal transport. The organizers strove to select the topics which are currently of interest to researchers from both countries with the purpose to compare results and stimulate discussion concerning possible collaboration in the future.

Topics: Cardiovascular Diseases; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Leptin; Nutrition Disorders; Peritoneal Dialysis, Continuous Ambulatory; Risk Factors; Uremia

To determine if fat deposition within mid-thigh muscle, represented by low density lean tissue density, is associated with age, low physical fitness, hyperleptinemia, hyperinsulinemia and dyslipidemia in women.. Seventy-two women aged 18-69y with a wide range of total body fat (10-55%) and maximal aerobic capacity (VO2max: 17-61 ml/kg(-1)/min(-1)).. Mid-thigh muscle, mid-thigh fat, low density lean tissue, intra-abdominal adipose tissue (IAAT) and subcutaneous abdominal fat (by computed tomography, CT), fat mass (FM) and fat-free mass (FFM) (by dual energy x-ray absorptiometry, DEXA), plasma insulin and leptin (by radioimmunoassay, RIA) and lipoprotein lipid profiles (by enzymatic methods).. VO2max declined with age (r=-0.59, P<0.0001) while IAAT and subcutaneous abdominal fat increased with age (r=0.68, r=0.57, r=0.63, P<0.0001). Mid-thigh low density lean tissue correlated with age (r=0.52), VO2max (r=-0.56), FFM (r=0.35), fat mass (r=0.68), IAAT (r=0.66) and subcutaneous abdominal fat (r=0.67, all P<0.005). Mid-thigh low density lean tissue also correlated with fasting plasma leptin, insulin, triacylglycerol (TG), total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels (r=0.44, 0.34, 0.41, 0.50, 0.53, respectively, all P<0.005), but not after controlling for body fat and age. Subcutaneous abdominal fat, IAAT, FFM and age were independent predictors of low density lean tissue (P<0.05).. Mid-thigh low density lean tissue is directly related to age and adiposity. Furthermore, it appears that fat accretion in skeletal muscle adversely influences plasma insulin and lipoprotein metabolism in women, but not independently of total adiposity and age.

Topics: Adipose Tissue; Adolescent; Adult; Aged; Aging; Blood Glucose; Body Composition; Body Mass Index; Body Weights and Measures; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Female; Humans; Insulin; Leptin; Lipoproteins; Menopause; Middle Aged; Obesity; Oxygen Consumption; Physical Fitness; Proteins; Radiography; Risk Factors; Thigh

In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insulin, and insulin sensitivity. We therefore considered that alterations in plasma leptin concentrations could constitute an additional component of a metabolic syndrome of cardiovascular risk. To explore this hypothesis, we employed factor analysis, a multivariate statistical technique that allows reduction of large numbers of highly intercorrelated variables to composite, biologically meaningful factors. Seventy-four men [age, 48.4+/-1.3 years (mean+/-SEM); body mass index (BMI), 25.6+/-0.3 kg/m2] who were free of coronary heart disease and diabetes underwent anthropometric measurements (subscapular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickness ratios, measurement of fasting plasma leptin, and an intravenous glucose tolerance test (IVGTT) for assessment of insulin sensitivity. Plasma leptin concentrations were correlated with BMI (r=0.57, P<0.001), S:T (r=0.34, P=0.003), S:B (r=0.37, P<0.001), systolic and diastolic blood pressures (both r=0.24, P=0.044), fasting triglycerides (r=0.31, P=0.007), serum uric acid (r=0.35, P=0.003), fasting glucose (r=0.32, P=0.003) and insulin (r=0.33, P=0.004), and IVGTT insulin (r=0.63, P<0.001). A negative correlation was observed between leptin and insulin sensitivity (r=-0.32, P=0.006). No significant correlations emerged between plasma leptin concentrations and age, high density lipoprotein cholesterol, or IVGTT glucose. In multivariate regression analyses, BMI (standardized coefficient [SC]=0.40, P=0.001), fasting insulin (SC=0.23, P=0.036), and IVGTT insulin (SC=0.51, P<0.001) emerged as independent predictors of plasma leptin concentrations (R2=0.56, P<0.001). After adjustment for BMI, only IVGTT insulin emerged as a significant predictor of plasma leptin concentrations (SC=0.56, P<0.001, R2=0.45, P<0.001). Factor analysis of plasma leptin concentrations and the variables that are considered relevant to the insulin resistance syndrome revealed a clustering of plasma leptin concentrations with a factor dominated by insulin resistance and high IVGTT insulin, separate from a high IVGTT glucose/central obesity factor and a high triglyceride/low high density lipoprotein cholesterol factor. Together, these factors accounted for 55.9% of the total variance in the dataset. In conclusion, interindividual variations in plasma leptin concentrations are strongly related to the principal components of the insuli

Topics: Blood Pressure; Body Mass Index; Cardiovascular Diseases; Glucose Tolerance Test; Humans; Insulin; Leptin; Male; Middle Aged; Multivariate Analysis; Proteins; Risk Factors; Syndrome

The aim of this study was to examine familial patterns of plasma leptin levels and the potential association with cardiovascular risk factors in a population sample of African-American families recruited from metropolitan Chicago. The study included 68 mothers, 31 fathers, 143 daughters, and 119 sons, for a total of 361 individuals from 118 families. Leptin levels were adjusted for the effect of age separately for mothers, fathers, daughters, and sons. Residuals were then standardized before estimating familial correlation using the maximum-likelihood method available in SEGPATH. With the exception of height, plasma leptin level was strongly correlated with all measured anthropometric variables. Familial effect (i.e., heritability) of leptin levels was estimated as 39% in this population at high risk for over weight. A significant sex difference was observed, and most of the estimated familial effect may be attributed to genetic influences since the spouse correlation was not statistically different from zero. A strong nonshared environmental effect is also suggested, however.

Topics: Anthropometry; Black People; Blood Pressure; Blood Proteins; Cardiovascular Diseases; Female; Humans; Leptin; Likelihood Functions; Male; Obesity; Proteins; Regression Analysis; Risk Factors

Leptin is the peptide product of the OB gene, which is associated with obesity in some strains of mice. Because dyslipidemias are frequently associated with obesity, we have begun to characterize the pathways connecting these related traits. In this investigation we tested for correlation of HDL phenotype measures with leptin concentrations using data from 1159 participants in the San Antonio Family Heart Study, a study of risk factors for cardiovascular disease in Mexican Americans living in and around San Antonio, Texas. In a subset of 288 unrelated individuals, we tested for correlation of leptin with nine different measures of HDL phenotype and found that only three were significantly related. However, stepwise regression analysis suggested that only two measures, HDL triglyceride concentrations (HDL-TG) and the proportion of apo A-I on HDL particles larger than HDL3 (Large HDL-apo A-I), were independently correlated with leptin. Because obesity and HDL phenotypes are both under strong genetic control, we conducted a trivariate genetic analysis, using the entire data set, to test the hypothesis that the phenotypic correlations were due to the effects of shared genes (i.e., pleiotropy). Heritabilities for the three traits were estimated to be 0.47 for leptin, 0.46 for HDL-TG, and 0.46 for Large HDL-apo A-I. Results from the genetic analyses revealed that the phenotypic correlation of leptin with HDL-TG was nongenetic (i.e., shared environment), while the phenotypic correlation with Large HDL-apo A-I was due to pleiotropy (i.e., shared genes). These results confirmed the result derived from the subset of unrelated individuals that the two measures of HDL are independently correlated with leptin. To our knowledge, this is the first report of a relationship between leptin and any aspect of lipoprotein phenotype. A better understanding of the genes responsible for this relationship may provide a molecular explanation for the aggregation of atherogenic phenotypes, such as diabetes, obesity, and dyslipoproteinemia.

Topics: Adult; Animals; Cardiovascular Diseases; Female; Humans; Leptin; Lipoproteins, HDL; Male; Mexican Americans; Mice; Middle Aged; Obesity; Proteins; Risk Factors; Texas

The cloning of the obese gene and the characterization of its protein product, leptin, has permitted the study of a new hormone potentially involved in the regulation of adipose tissue mass. The present study examined the gender differences in fasting plasma leptin concentration and its relationship to body fatness, adipose tissue distribution and the metabolic profile in samples of 91 men (mean age +/- SD: 37.3 +/- 4.8 years) and 48 women (38.5 +/- 6.8 years). Plasma leptin concentrations were strongly associated with body fat mass measured by underwater weighing [men: r = 0.80, p < 0.0001; women: r = 0.85, p < 0.0001]. In both genders, plasma leptin levels were also strongly correlated with waist girth as well as cross-sectional areas of abdominal subcutaneous and visceral adipose tissue measured by computed tomography. Women had, on average, plasma leptin concentrations that were three times higher than men. Furthermore, this gender difference remained significant when comparing men and women matched for similar levels of body fat mass. The associations between plasma leptin and lipoprotein concentrations were dependent of adiposity. In both men and women, elevated fasting plasma leptin levels were associated with higher plasma insulin concentrations, but only in women was the association maintained after correction for fat mass. Thus, results of the present study show that women have higher plasma leptin levels compared to men, independent of the concomitant variation in total body fat mass. Furthermore, our results also suggest that, in women, the association between plasma leptin and insulin concentrations is independent of adiposity, a finding which provides further support to the observation that adipose tissue leptin secretion may be upregulated by insulin.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Composition; Cardiovascular Diseases; Female; Humans; Insulin; Leptin; Lipids; Male; Obesity; Proteins; Risk Factors; Sex Factors