leptin and Heart-Diseases

Obesity and metabolic syndrome are one of the most devastating risk factors for cardiovascular diseases. The obesity gene product leptin plays a central role in the regulation of food intake and energy expenditure. The physiological and pathophysiological roles of leptin in cardiovascular system have been investigated extensively since its discovery in 1994. In addition to its well-established metabolic effects, more recent evidence have depicted a rather pivotal role of leptin in inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis and tissue remodeling en route to the pathogenesis of type 2 diabetes mellitus, hypertension, atherosclerosis, and insulin resistance. Under physiological condition, leptin is known to reduce appetite, promote energy expenditure, increase sympathetic activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin may regulate cardiac and vascular function through a nitric oxide-dependent mechanism. However, hyperleptinemia usually occurs with progressively increased body weight and metabolic syndrome development, leading to a state of global or selective leptin resistance. Both central and peripheral leptin resistance may be present under pathophysiological conditions such as inflammation, insulin resistance, hyperlipidemia and a cadre of other cardiovascular diseases including hypertension, atherosclerosis, obesity, ischemic heart disease and heart failure. In this review, we will discuss cardiovascular actions of leptin related to various components of metabolic syndrome. Particular emphasis will be given to insights derived from therapeutic interventions with lifestyle modification, cardiovascular drugs, anti-diabetic and anti-obesity drugs.

Topics: Animals; Cardiovascular System; Disease Progression; Endothelium, Vascular; Heart Diseases; Humans; Leptin; Metabolic Syndrome; Models, Cardiovascular; Receptors, Leptin; Signal Transduction

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

Growing evidence links the stress at the endoplasmic reticulum (ER) to pathologies such as diabetes mellitus, obesity, liver, heart, renal and neurodegenerative diseases, endothelial dysfunction, atherosclerosis, and cancer. Therefore, identification of molecular pathways beyond ER stress and their appropriate modulation might alleviate the stress, and direct toward novel tools to fight this disturbance. An interesting resident of the ER membrane is protein tyrosine phosphatase 1B (PTP1B), an enzyme that negatively regulates insulin and leptin signaling, contributing to insulin and leptin resistance. Recently, new functions of PTP1B have been established linked to ER stress response. This review evaluates the novel data on ER stressors, discusses the mechanisms beyond PTP1B function in the ER stress response, and emphasizes the potential therapeutic exploitation of PTP1B to relieve ER stress.

Topics: Diabetes Mellitus; Dyslipidemias; Endoplasmic Reticulum Stress; Fatty Liver; Heart Diseases; Humans; Insulin; Kidney Diseases; Leptin; Obesity; Protein Tyrosine Phosphatase, Non-Receptor Type 1

The incidence and prevalence of obesity has risen markedly in the last decade, and this epidemic represents a serious health hazard with significant morbidity and mortality. Although hypertension is recognized as one of the most serious consequences of obesity, its pathophysiology remains incompletely understood. Contemporary research suggests that the recently discovered hormone leptin may represent a common link between these 2 pathologic conditions. Leptin is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance. By binding to receptors in the hypothalamus, it reduces food intake and promotes elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. Although the relevance of endogenous leptin needs further clarification for the control of renal sodium excretion and vascular tone, it appears to be a potential pressure and volume-regulating factor in normal situations. However, in conditions of chronic hyperleptinemia, such as obesity, leptin may function pathophysiologically for the development of hypertension as well as cardiac and renal disease. Thus, in addition to weight control, reduction of circulating leptin may confer cardiovascular and renal protective effects in patients with obesity-hypertension.

Topics: Blood Pressure; Heart Diseases; Humans; Hypertension; Kidney Diseases; Leptin; Obesity; Sympathetic Nervous System

Obesity is an independent risk factor for cardiovascular diseases. As the first obese gene product identified, leptin participates in many physiological processes. Besides its well known effects on food intake and energy metabolism, leptin has been shown to regulate cardiovascular function, glucose and lipid metabolism. Although the precise role of leptin on cardiac health is still at large, the peptide may initiate both hypertrophic and anti-hypertrophic effects on hearts. Circulating leptin levels are believed to correlate closely with body mass index (BMI) and total amount of body fat, and predict change of heart morphology and function. This is evidenced by that fact that compromised cardiac function is present in both hyperleptinemic (db/db) and hypoleptinemic (ob/ob) mouse models. Leptin replenishment may reconcile depressed cardiac contractile function in ob/ob mice, indicating the permissive effect of leptin on cardiac function. Multiple signal pathways including NO, Jak/STAT, p38 MAP kinase, ET-1 and NADPH oxidase have been implicated to participate in the cardiac regulatory response of leptin. In addition, elevated plasma leptin levels are speculated to be an independent risk factor for cardiovascular diseases such as hypertension and myocardial infarction. The current dogma indicates that physiological range of leptin may be essential for normal cardiomyocyte structure and function whereas disrupted leptin signaling due to too much or too little leptin may trigger functional and morphological alterations leading to cardiac dysfunction.

Topics: Animals; Appetite Regulation; Energy Metabolism; Heart; Heart Diseases; Humans; Insulin; Leptin; Models, Biological; Myocardial Contraction; Obesity; Physical Fitness; Receptors, Leptin; Signal Transduction

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

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

Topics: Animals; Energy Metabolism; Glucose; Heart Diseases; Leptin; Mice; Neurons; Obesity; Receptors, Leptin; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins

Lipodystrophy syndromes are rare complex multisystem disorders caused by generalized or partial lack of adipose tissue. Adipose tissue dysfunction in lipodystrophy is associated with leptin deficiency. Lipodystrophy leads to severe metabolic problems. These abnormalities include, but are not limited to, insulin-resistant diabetes, severe hypertriglyceridemia, and lipid accumulation in ectopic organs such as the liver, and are associated with end-organ complications. Metabolic abnormalities can be present at the time of diagnosis or may develop over time as the disease progresses. In addition to metabolic abnormalities, subtype-specific presentations due to underlying molecular etiology in genetic forms and autoimmunity in acquired forms contribute to severe morbidity in lipodystrophy.

Topics: Autoimmune Diseases; Diabetes Mellitus; Heart Diseases; Humans; Hypertriglyceridemia; Insulin Resistance; Kidney Diseases; Leptin; Lipid Metabolism; Lipodystrophy; Liver; Metabolic Syndrome; Neuromuscular Diseases; Non-alcoholic Fatty Liver Disease; Pancreatitis; Syndrome

Chagas disease affects approximately 7 million people, causing disability and mortality in the most productive life stages of infected individuals. Considering the lifestyle of the world population, metabolic syndrome is a synergistic factor for an increased cardiovascular risk of patients with Chagas disease.This study transversally evaluated the metabolic and immunological profiles of patients with indeterminate (IF) and cardiac (CF) forms of Chagas disease and their correlations with left ventricular dysfunction (LVD).Clinical and electrical bioimpedance analysis, levels of cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-17, IL-10, and IL-33) and adipocytokines (adiponectin, leptin, and resistin), metabolic syndrome components, and brain natriuretic peptide (BNP) levels were assessed in 57 patients (13 IF and 44 CF) with a mean age of 61.63 ± 12.1 years. Chest x-ray, electrocardiogram, and echocardiogram were performed to classify the clinical forms.The CF group had a higher number of individuals with metabolic syndrome components blood pressure altered, while more participants in the CF group with LVD had low high-density lipoprotein (HDL) levels. The IF group had more participants with a higher waist-to-hip ratio (WHR). No significant difference was observed between metabolic syndrome, cytokine and adipocytokine level, and clinical forms of the disease or in relation to LVD.Individuals with the IF showed metabolic and immunological profiles compatible with increased disease control, whereas those with CF showed marked inflammatory immune response.

Topics: Adiponectin; Aged; Analysis of Variance; Biomarkers; Chagas Disease; Female; Heart Diseases; Humans; Interleukin-10; Interleukin-17; Interleukin-33; Leptin; Male; Middle Aged; Resistin; Statistics, Nonparametric

Cardiac disease is a major cause of morbidity and mortality for adult gorillas. Previous research indicates a sex-based difference with predominantly males demonstrating evidence of left ventricular hypertrophy. To evaluate these findings, we analyzed serum markers with cardiac measures in a large sample of gorillas. The study sample included 44 male and 25 female gorillas housed at American Association of Zoo and Aquariums (AZA)-accredited zoos. Serum samples were collected from fasted gorillas during routine veterinary health exams and analyzed to measure leptin, adiponectin, IGF-1, insulin, ferritin, glucose, triglycerides, and cholesterol. Cardiac ultrasonography via transthoracic echocardiogram was performed simultaneously. Three echocardiographic parameters were chosen to assess cardiac disease according to parameters established for captive lowland gorillas: left ventricular internal diameter, inter-ventricular septum thickness, and left ventricular posterior wall thickness. Our data revealed that high leptin, low adiponectin, and lowered cholesterol were significantly and positively correlated with measures of heart thickness and age in males but not in females. Lowered cholesterol in this population would be categorized as elevated in humans. High leptin and low adiponectin are indicative of increased adiposity and suggests a potential parallel with human obesity and cardiovascular disease in males. Interestingly, while females exhibited increased adiposity with age, they did not progress to cardiac disease.

Topics: Adiponectin; Adiposity; Animals; Animals, Zoo; Ape Diseases; Biomarkers; Cholesterol; Female; Gorilla gorilla; Heart Diseases; Heart Ventricles; Leptin; Male; Risk Factors; Sex Factors

Topics: Animals; Cardiovascular System; Female; Heart Diseases; Lactation; Leptin; Malnutrition; Models, Theoretical; Nutritional Status; Rats

Reduced cardiac β-adrenoceptor (β-AR) expression and cardiovascular dysfunction occur in models of hyperglycemia and hypoinsulinemia. Cardiac β-AR expression in type-2 diabetes models of hyperglycemia and hyperinsulinemia, remain less clear. This study investigates cardiac β-AR expression in type-2 diabetic Zucker diabetic fatty (ZDF) rats.. Ex vivo biodistribution experiments with [3H]CGP12177 were performed in Zucker lean (ZL) and ZDF rats at 10 and 16 weeks of age as diabetes develops. Blood glucose, body mass, and diet consumption were measured. Western blotting of β-AR subtypes was completed in parallel. Echocardiography was performed at 10 and 16 weeks to assess systolic and diastolic function. Fasted plasma insulin, free fatty acids (FFA), leptin and fed-state insulin were also measured.. At 10 weeks, myocardial [3H]CGP12177 was normal in hyperglycemic ZDF (17±4.1mM) compared to ZL, but reduced 16-25% at 16 weeks of age as diabetes and hyperglycemia (22±2.4mM) progressed. Reduced β-AR expression not apparent at 10 weeks also developed by 16 weeks of age in ZDF brown adipose tissue. In the heart, Western blotting at 10 weeks indicated normal β1-AR (98±9%), reduced β2-AR (76±10%), and elevated β3-AR (108±6). At 16 weeks, β1-AR expression became reduced (69±16%), β2-AR expression decreased further (68±14%), and β3-AR remained elevated, similar to 10 weeks (112±9%). While HR was reduced at 10 and 16 weeks in ZDF rats, no significant changes were observed in diastolic or systolic function.. Cardiac β-AR are reduced over 6 weeks of sustained hyperglycemia in type-2 diabetic ZDF rats. This indicates cardiac [3H]CGP12177 retention and β1- and β2-AR expression are inversely correlated with the progression of type-2 diabetes.

Topics: Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Disease Models, Animal; Disease Progression; Echocardiography; Fatty Acids, Nonesterified; Gene Expression Regulation; Heart Diseases; Hyperglycemia; Insulin; Leptin; Male; Myocardium; Rats; Rats, Zucker; Receptors, Adrenergic, beta

It has been shown that visceral fat accumulation is associated with autonomic dysfunction, though the precise mechanism remains unclear. A recent basic study found that leptin can directly modulate autonomic function through the dorsomedial hypothalamus in relation to obesity. Here, we investigated the mutual relationships among plasma leptin, visceral fat accumulation, and cardiac autonomic dysfunction in patients with type 2 diabetes.. This cross-sectional study included 100 diabetic patients, and 100 age- and gender-matched non-diabetic patients with cardiovascular risk factors. Plasma leptin and soluble leptin receptor levels, visceral fat area (VFA), and heart rate variability (HRV) were determined in addition to classical cardiovascular risk factors.. In the type 2 diabetic patients, VFA was significantly (p < 0.05) and inversely associated with HRV parameters (SDNN: r = -0.243; SDANN5: r = -0.238), while the plasma level of leptin, but not soluble leptin receptor, was also significantly (p < 0.05) and inversely associated with HRV parameters (SDNN: r = -0.243; SDANN5: r = -0.231). Multiple regression analysis showed that plasma leptin was significantly associated with SDNN and SDANN5 independent of other factors, including age, gender, presence of hypertension and dyslipidemia, duration of diabetes, HbA1c, and eGFR. Furthermore, the relationship of leptin with SDNN and SDANN5 (β = -0.279 and -0.254, respectively) remained significant (p < 0.05) after adjustment for VFA. In patients without diabetes, no significant associations were observed between leptin and any of the HRV parameters.. Hyperleptinemia may be involved in cardiac autonomic dysfunction in patients with type 2 diabetes and visceral obesity.

Topics: Adiposity; Aged; Autonomic Nervous System; Biomarkers; Case-Control Studies; Chi-Square Distribution; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Heart; Heart Diseases; Heart Rate; Humans; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Receptors, Leptin; Risk Factors; Up-Regulation

In obesity, the excessive synthesis of aldosterone contributes to the development and progression of metabolic and cardiovascular dysfunctions. Obesity-induced hyperaldosteronism is independent of the known regulators of aldosterone secretion, but reliant on unidentified adipocyte-derived factors. We hypothesized that the adipokine leptin is a direct regulator of aldosterone synthase (CYP11B2) expression and aldosterone release and promotes cardiovascular dysfunction via aldosterone-dependent mechanisms.. Immunostaining of human adrenal cross-sections and adrenocortical cells revealed that adrenocortical cells coexpress CYP11B2 and leptin receptors. Measurements of adrenal CYP11B2 expression and plasma aldosterone levels showed that increases in endogenous (obesity) or exogenous (infusion) leptin dose-dependently raised CYP11B2 expression and aldosterone without elevating plasma angiotensin II, potassium or corticosterone. Neither angiotensin II receptors blockade nor α and β adrenergic receptors inhibition blunted leptin-induced aldosterone secretion. Identical results were obtained in cultured adrenocortical cells. Enhanced leptin signaling elevated CYP11B2 expression and plasma aldosterone, whereas deficiency in leptin or leptin receptors blunted obesity-induced increases in CYP11B2 and aldosterone, ruling out a role for obesity per se. Leptin increased intracellular calcium, elevated calmodulin and calmodulin-kinase II expression, whereas calcium chelation blunted leptin-mediated increases in CYP11B2, in adrenocortical cells. Mineralocorticoid receptor blockade blunted leptin-induced endothelial dysfunction and increases in cardiac fibrotic markers.. Leptin is a newly described regulator of aldosterone synthesis that acts directly on adrenal glomerulosa cells to increase CYP11B2 expression and enhance aldosterone production via calcium-dependent mechanisms. Furthermore, leptin-mediated aldosterone secretion contributes to cardiovascular disease by promoting endothelial dysfunction and the expression of profibrotic markers in the heart.

Topics: Adipocytes; Adrenal Cortex; Aldosterone; Animals; Cell Line, Tumor; Cells, Cultured; Endothelium, Vascular; Female; Fibrosis; Heart Diseases; Humans; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Rats; Rats, Inbred WKY; Rats, Zucker

Obesity and diabetes mellitus type 2 (DM2) frequently coexist and increase the propensity of cardiovascular dysfunction by numerous mechanisms. Chief among them are oxidative stress and Ca(2+) dysregulation, and both are inducers of the mitochondrial permeability transition pore (MPTP). Nevertheless, it is unknown whether MPTP formation is triggered in DM2 animals, and thereby contributing to cardiac dysfunction. We assessed MPTP sensitivity and reactive oxygen species production in cardiac mitochondria, as well as cytosolic Ca(2+) handling in ventricular myocytes from rats with DM2.. Male Zucker Fa/fa rats (Fa/fa) 32weeks old presenting DM2, concentric hypertrophy, and diastolic dysfunction were used. MPTP formation was evaluated in isolated mitochondria and Ca(2+) handling in ventricular myocytes, by spectrophotometric and confocal microscope techniques, respectively.. We found that the systolic Ca(2+) transient relaxation was ~40% slower, while mitochondrial H2O2 production increased by ~6-fold. MPTP opening in isolated mitochondria from Fa/fa (mFa/fa) was more sensitive to Ca(2+) than in mitochondria from lean rats (mLean), and correlated with increased thiol group exposure. The mFa/fa showed decreased oxidative phosphorylation capacity. The ATP content decreased in myocytes, while the PCr/ATP ratio remained unchanged and caspase 9 activity largely increased in myocytes from Fa/fa animals.. Our results showed that oxidative stress and diastolic Ca(2+) dysregulation increased MPTP sensitivity leading to mitochondrial dysfunction and apoptosis. Mitochondrial dysfunction could compromise ATP synthesis, and lower ATP could be linked to decreased SERCA2 activity, which might underlie diastolic dysfunction. Prolonged Ca(2+) transients might further exacerbate mitochondrial dysfunction.

Topics: Animals; Atractyloside; Calcium Signaling; Diabetes Mellitus, Type 2; Heart Diseases; Leptin; Lipids; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial ADP, ATP Translocases; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocytes, Cardiac; Oxidative Stress; Oxygen Consumption; Permeability; Rats; Rats, Zucker; Ultrasonography

We examined the potential impact of demographic characteristics on the independent leptin-metabolic cardiovascular risk factor and leptin-endothelial activation relationships in black and white patients with RA. Leptin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 were measured in 217 RA patients (51.6% black). We determined associations in potential confounder and mediator-adjusted mixed regression models. No independent associations between leptin concentrations and cardiovascular risk were present in all patients and either women and men or black and white patients. However, age impacted on several leptin-cardiovascular risk relations (interaction P < 0.05). In patients aged <50 years (lower quartile), after but not before adjustment for waist circumference and body mass index in addition to other confounders, leptin concentrations associated with overall endothelial activation as estimated by an SD (z) score of endothelial activation molecule concentrations (partial R = 0.341, P = 0.04). In patients aged 50-58 years (second quartile), leptin concentrations related to those of HDL cholesterol (partial R = -0.365, P = 0.01) and total cholesterol-HDL cholesterol ratio (partial R = 0.299, P = 0.04), and in those aged 59-63 years (third quartile), paradoxically related to low systolic and mean blood pressure (partial R = -0.438, P = 0.005 and partial R = -0.370, P = 0.02, respectively). Patients with RA aged <50 years experience an independent adiposity-driven leptin-endothelial activation relationship in the absence of leptin-metabolic risk factor associations. Young but not older patients with RA may sustain obesity-induced endothelial activation that is directly mediated by leptin.

Topics: Adult; Age Factors; Aged; Aging; Arthritis, Rheumatoid; Atherosclerosis; Biomarkers; Black People; Chemokine CCL2; Cholesterol, HDL; Comorbidity; Cross-Sectional Studies; E-Selectin; Female; Heart Diseases; Humans; Intercellular Adhesion Molecule-1; Leptin; Male; Metabolic Diseases; Middle Aged; Risk Factors; Vascular Cell Adhesion Molecule-1; White People

To investigate the characteristic changes in serum estradiol and leptin levels in patients with cerebral-cardiac syndrome (CCS) induced by subarachnoid hemorrhage (SAH).. Ninety-six female patients with early stage of SAH (within 48 h of onset), who were admitted in our department between February 2008 and February 2014, were included in this study. Clinical conditions of patients were rated using Hunt-Hess scale. Serum levels of estradiol, leptin and echocardiography were determined in patients with various neurological injuries as well as in post-SAH patients and patients with SAH-induced CCS.. No significant differences (p > 0.05) were observed in the levels of estradiol or leptin between patients with different Hunt-Hess grades. While serum levels of estradiol and leptin were significantly elevated in SAH and CCS patients compared to normal controls (p < 0.05) but the elevated levels were more profound in CCS patients. Meanwhile there were also variable extents of left ventricular expansion and decrease of ejection fraction in CCS patients, with the same trends of estradiol and leptin.. Thus the results show that a significant increase in estradiol and leptin levels occurred in post-SAH CCS patients.

Topics: Adult; Aged; Cerebrovascular Disorders; Estradiol; Female; Heart Diseases; Humans; Leptin; Middle Aged; Subarachnoid Hemorrhage; Syndrome; Ultrasonography

The metabolic syndrome (MS) leads to myocardial fibrosis (MF) and diastolic dysfunction. Statins have proven beneficial effects in MS, but their impact on cardiac remodelling is uncertain. We examined the effects and mechanisms of chronic statin treatment on cardiac remodelling, e.g. fibrosis and diastolic properties.. We used a mouse model deficient in leptin and the LDL-receptor (DKO) that reproduces this MS phenotype. DKO mice (12 weeks) were treated with rosuvastatin (R) for 6 months vs. placebo. Morphometric and echocardiographic measurements showed that R reduced cardiac mass and increased left-ventricular end-diastolic diameter despite unchanged cardiomyocyte dimensions. Similarly, R had no effect on the hypertrophic response to neurohormones in isolated cardiomyocytes. Conversely, R reversed the age-dependent development of MF as well as mRNA expression of TGF-β1 and several pro-fibrotic markers (procollagen type I, its carboxy-terminal proteinase, Lysyl oxidase). R similarly inhibited the pro-fibrotic effects of TGF-β1 on procollagen type I, alpha Smooth Muscle Actin expression and migratory properties of cardiac fibroblasts in vitro. In parallel, R increased the activation of AMP-activated protein kinase (AMPK), a known inhibitor of fibrosis, in vivo and in vitro, and the anti-fibrotic effects of R were abrogated in fibroblasts transfected with AMPKα1/α2 siRNA. The reversal of MF by R in DKO mice was accompanied with improved diastolic properties assessed by P-V loop analysis (slope of EDPVR, dP/dt min and cardiac output).. In this model of MS, statin treatment reverses myocardial remodelling and improves ventricular relaxation through AMPK-mediated anti-fibrotic effects.

Topics: Actins; AMP-Activated Protein Kinases; Animals; Cells, Cultured; Collagen Type I; Diastole; Disease Models, Animal; Enzyme Activation; Fibroblasts; Fibrosis; Fluorobenzenes; Heart Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Procollagen; Pyrimidines; Rats; Receptors, LDL; Recovery of Function; Rosuvastatin Calcium; Signal Transduction; Sulfonamides; Time Factors; Transfection; Transforming Growth Factor beta1; Ventricular Function, Left; Ventricular Remodeling

Competitive endogenous RNAs (ceRNAs) regulate mRNA transcripts containing common microRNA (miRNA) recognition elements (MREs) through sequestration of shared miRNAs. Interactions of ceRNA have been demonstrated in cancerous cells. However, a paucity of information is available relative to the interactions of ceRNAs interaction in diabetes mellitus and the myocardium. The purpose of this study is to assess the potential role of DKK1 and PTEN in ceRNA regulation utilizing their common miRNAs in diabetic cardiomyocytes. The interactions' regulation between PTEN and DKK1 were determined in two diabetic models in vivo (streptozotocin-induced type-1 DM mice and db/db mice) and in vitro (human cardiomyocytes cells exposed to hyperglycemia). The levels of DKK1 and PTEN (mRNA and protein) were upregulated in parallel in all three diabetic models. DKK1 modulates PTEN protein levels in a miRNA and 3'UTR-dependent manner. RNAi-mediated DKK1 gene silencing resulted in a decreased PTEN expression and vice versa. The effect was blocked when Dicer was inhibited. Silencing either PTEN or DKK1 resulted in an increase of the availabilities of shared miRNAs. The silencing of either PTEN or DKKI resulted in a suppression end of the luciferase-PTEN 3'UTR activity. However, the over expression of DKK1 3'UTR or PTEN 3'UTR resulted in an increase in the activity. The attenuation of DKK1 increased AKT phosphorylation, improved glucose uptake and decreased apoptosis in HCMs exposed to hyperglycemia. The effects were blocked by PI3K inhibition. DKK1 and PTEN transcripts are co-upregulated in DM and hyperglycemia. DKK1 and PTEN serve as ceRNA, affecting the expression of each other via competition for miRNAs binding.

Topics: 3' Untranslated Regions; Animals; Apoptosis; Binding Sites; Binding, Competitive; Blood Glucose; Cells, Cultured; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Gene Expression Regulation; Genes, Reporter; Heart Diseases; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Myocytes, Cardiac; Phosphatidylinositol 3-Kinase; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; RNA Interference; RNA, Messenger; Signal Transduction; Transfection

Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population-based cohort of obese adults.. Among obese participants in the Dallas Heart Study, we examined the cross-sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation (n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography (n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index.. In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA-IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number (p < 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque (p < 0.001 for each). VAT independently associated with C-reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA-IR were significant in univariable analyses but attenuated after multivariable adjustment.. VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub-phenotypes with heterogeneous metabolic and atherosclerosis risk.

Topics: Adiponectin; Adult; Atherosclerosis; Biomarkers; Body Fat Distribution; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Dyslipidemias; Female; Heart Diseases; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Obesity; Phenotype; Subcutaneous Fat

Accelerated infant growth is associated with an altered, mostly adverse adult cardiometabolic risk profile. The importance of genetic and environmental factors to these associations is unclear.. The objective was to examine the importance of genetic and environmental factors in the associations between infant growth and adult cardiometabolic risk factors (anthropometric characteristics, lipids, insulin sensitivity, leptin, blood pressure, and fibrinogen) in twins.. Cardiometabolic risk factors were assessed in 240 twin pairs (aged 18-34 y) from the East Flanders Prospective Twin Survey. Infant growth was defined as change in weight z score. We regressed intrapair differences in growth during 4 growth windows (0-1, 1-6, 6-12, and 12-24 mo) against intrapair differences in the risk factors in monozygotic and dizygotic twins separately.. Within monozygotic twin pairs only, associations between infant growth and most adult lipids, glucose, leptin, and blood pressure (eg, systolic blood pressure: b = 5.95 mm Hg per change in z score, P = 0.01 in monozygotic twins; b = -1.64, P = 0.82 in dizygotic twins from 12 to 24 mo) were found. Within dizygotic twin pairs only, associations between growth and triglycerides and fibrinogen (eg, fibrinogen: b = 0.07 ln mg/dL per change in z score, P = 0.31 in monozygotic twins; b = 0.79, P = 0.01 in dizygotic twins from 0 to 1 mo) were identified. Most associations showed a detrimental effect of accelerated growth, but beneficial associations were also identified (eg, total-to-high-density-lipoprotein cholesterol ratio: b = -0.22 per change in z score from 1 to 6 mo, P = 0.008 in monozygotic twins).. Our data showed that environmental factors play a role in the associations between infant growth and most adult lipids, glucose, leptin, and blood pressure, whereas genetic factors are involved regarding triglycerides and fibrinogen.

Topics: Adolescent; Adult; Belgium; Blood Glucose; Blood Pressure; Child, Preschool; Environment; Female; Fibrinogen; Heart Diseases; Humans; Infant; Infant, Newborn; Insulin Resistance; Leptin; Lipids; Male; Metabolic Diseases; Prospective Studies; Risk Factors; Triglycerides; Twins; Twins, Dizygotic; Twins, Monozygotic; Weight Gain

To study the effect of strict prolonged fasting on lipid profile, serum leptin, and high- sensitivity C-reactive protein (hs-CRP) in patients with different stable cardiac illnesses and look for associated new cardiac events and any correlation between entire variables.. A total of 56 patients of different stable cardiac illnesses were followed in our cardiology outpatient for 3 months. Data concerning their ability to fast were collected: New York Heart Association class of congestive cardiac failure, angina class, previous myocardial infarction, previous coronary artery bypass graft, percutaneous coronary intervention, severity of valvular lesion, metallic prosthetic valve, and traditional risk factors (diabetes mellitus, insulin requirement, hypertension, hypercholesterolemia, smoking habit, and obesity). Detailed clinical examination and electrocardiography were performed in all patients in three consecutive visits before, during, and after Ramadan. Echocardiographic and angiographic findings and medication plans were collected from patient records. Lipid profile, serum leptin, and hs-CRP were assessed before, during, and after Ramadan.. All patients fasted during Ramadan: 80.4% were male, 67.9% were aged >50 years, 71.4% had no change in their symptoms during fasting while 28.6% felt better. No patient has deteriorated. 91.1% of the patients were compliant with medicine during Ramadan, 73.2% after. 89.3% were compliant with diet during Ramadan with no significant change in body weight in the follow-up period. No cardiac or noncardiac morbidity or mortality was reported. High- density lipoprotein-cholesterol (HDL-C) decreased significantly during compared to before fasting (P = 0.012). Low-density lipoprotein-cholesterol (LDL-C) significantly increased during compared to before fasting (P = 0.022). No statistically significant changes were observed in total cholesterol (TC), triglycerides (TG), serum leptin, or hs-CRP. Significant correlation was observed between TC and hs-CRP during fasting (P = 0.036), but not with TG, LDL-C, or HDL-C (P > 0.05). Neither of these correlated with serum leptin (P > 0.05), but significant correlation was observed between hs-CRP and serum leptin (P < 0.05).. Ramadan fasting in stable cardiac patients has no effect on their clinical status, serum leptin, or hs-CRP, but results in decrease in HDL-C, increase in LDL-C, with significant correlation between TC and hs-CRP during Ramadan, but not with TG, LDL-C, or HDL-C, and with significant correlation between hs-CRP and serum leptin before, during, and after fasting.

Topics: Adult; C-Reactive Protein; Cholesterol; Fasting; Female; Heart Diseases; Humans; Islam; Leptin; Male; Middle Aged; Prospective Studies; Triglycerides

Cardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited.Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients.. A total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay.. Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2nd, 3rd tertiles when compared with first tertile (p-value for trend = 0.022).. In the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.

Topics: Adipokines; Adiponectin; Adult; Aged; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Heart Diseases; Heart Rate; Humans; Korea; Leptin; Logistic Models; Male; Middle Aged; Severity of Illness Index; Tumor Necrosis Factor-alpha

An adverse pattern of blood lipids and atherosclerosis begin in childhood. Unfortunately, data for children and adolescents, particularly those in the Indian population, are scarce. The present study aims to evaluate the levels of serum E-selectin in Indian children and adolescents and its correlation with anthropometric and biochemical parameters.. The study groups included 338 school children and adolescents. There were 96 obese children, 97 overweight children and 42 children with congenital heart disease who were compared with 103 normal controls, aged 10-17 years. Serum E-selectin and serum leptin were analyzed with enzyme-linked immunosorbent assay kits. Lipid profile and fasting glucose were analyzed using an autoanalyzer.. Serum E-selectin levels were significantly increased in obese (65.3 ± 8.39 ng/mL) and overweight (56.01 ± 6.96 ng/mL) subjects (P < 0.001). However, these levels were lower in children with congenital heart disease (40.99 ± 6.54 ng/mL) than in controls (43.79 ± 6.71 ng/mL).. Serum E-selectin levels showed good positive association with body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, leptin, total cholesterol, triglycerides and low-density lipoprotein cholesterol and showed negative correlation with fasting glucose and no significant association with high-density lipoprotein cholesterol. These findings indicate that higher E-selectin levels can induce endothelial activation and play an essential role in the earliest stage of the atherosclerotic process in obese and overweight children. Regular camps at schools to counsel the identified overweight and obese children and to encourage physical exercise would help to reduce the risk of these children being prone to major cardiovascular anomalies in adulthood.

Topics: Adolescent; Atherosclerosis; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Child; Cholesterol; E-Selectin; Enzyme-Linked Immunosorbent Assay; Female; Heart Diseases; Humans; India; Leptin; Male; Obesity; Overweight; Triglycerides

Acute leptin increase as well as endogenous hyperleptinemia evoked by high-fat diets (HF) activate fatty acid metabolism in nonadipose tissues. This supports the notion that hyperleptinemia is pivotal to prevent/delay steatosis during periods of positive energy balance. We have previously shown that long-term HF spares ectopic accumulation of lipids specifically in the miocardium. Because carnitine palmitoyltransferase I (CPT-I) allows mitochondrial uptake/oxidation of fatty acids, we have hypothesized that leptin drives cardiac CPT-I activity. In the current study, hyperleptinemia was induced in C57BL/6J mice either by exogenous leptin administration or by means of HF, and the ability of malonyl-coenzyme A (malonyl-CoA) (the main endogenous inhibitor of CPT-I) to inhibit cardiac CPT was analyzed. IC(50) values of malonyl-CoA were 8.1 +/- 1.5 micromol/liter in controls vs. 69.3 +/- 5.2 micromol/liter (P < 0.01) in leptin-treated mice. This effect was also observed in cardiac explants incubated with leptin and was blocked by triciribine, a compound shown to inhibit protein kinase B (Akt) phosphorylation (pAkt). In accordance, acute leptin evoked an increase of cardiac pAkt levels, which correlated with CPT sensitivity to malonyl-CoA. Otherwise, the inhibitory effect of malonyl-CoA was hindered in HF hyperleptinemic mice, and in this case, pAkt levels also correlated with CPT sensitivity to malonyl-CoA. Our data show that leptin reduces the sensitivity of cardiac CPT-I to malonyl-CoA and suggest the involvement of an Akt-related signaling pathway in this effect. This mechanism appears to be sensitive to both acute and chronic hyperleptinemia. We conclude that this action of leptin is pivotal to drive cardiac metabolism under situations associated to hyperleptinemia.

Topics: Animals; Carnitine O-Palmitoyltransferase; Dietary Fats; Disease Models, Animal; Heart Diseases; Leptin; Lipid Metabolism; Male; Malonyl Coenzyme A; Mice; Mice, Inbred C57BL; Myocardium; Phosphorylation; Proto-Oncogene Proteins c-akt; Ribonucleosides; STAT3 Transcription Factor; Triglycerides

Treated HIV infection and HIV-lipoatrophy increases risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Circulating inflammatory molecules may, in part, explain this increased risk. This study examined circulating inflammatory molecules in treated HIV infection in relation to insulin sensitivity, lipids total body, and intramyocellular fat, compared to insulin-resistant obesity (an index group at high risk of diabetes). Detailed metabolic phenotypes were measured in 20 treated HIV-infected men (with and without subcutaneous lipoatrophy) vs. 26 insulin-resistant obese men (IR-O, n = 26), including inflammatory molecules, insulin sensitivity, total body fat (TBF), visceral fat (visceral adipose tissue (VAT)), and intramyocellular lipid (IMCL). C-reactive protein (CRP) levels in treated HIV were similar to those in IR-O, despite lower TBF and greater insulin sensitivity in treated HIV. In HIV-lipoatrophy, CRP was higher than that found in IR-O. Adiponectin was similar between treated HIV and IR-O, but significantly lower in those with HIV-lipoatrophy. In treated HIV, subjects with higher CRP had significantly higher total cholesterol, VAT, and IMCL. In treated HIV, subjects with lower adiponectin had significantly lower HDL and higher triglycerides, glucose, VAT, and IMCL. In conclusion, a proinflammatory milieu equivalent to that of insulin-resistant obesity characterizes lean men with treated HIV infection, worse in those with subcutaneous lipoatrophy. These factors may contribute to the accelerated diabetogenesis and cardiac risk observed in treated HIV infection.

Topics: Adiponectin; Adult; Antiretroviral Therapy, Highly Active; Biomarkers; Body Composition; C-Reactive Protein; Heart Diseases; HIV Infections; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Diseases; Risk Factors; Tumor Necrosis Factor-alpha

Previous studies suggest that both overfeeding and undernutrition during development increase the risk of obesity and hypertension in adulthood. In this study, we examined both short- (24 d) and long- (16 wk) term effects of early postnatal over- and underfeeding in rats on body weight, body composition, plasma hormones, adiposity markers, and hypothalamic neuropeptide Y content. Cardiovascular changes were also examined by measuring blood pressure and cardiac fibrosis. Rats raised in litters of 3, 12, or 18 pups per mother were used to model early onset overfeeding, control, and underfeeding, respectively. At 24 d of age, pups raised in small litters (SL) were 10% heavier than pups from normal litters, accompanied by increased organ mass and fat mass, elevated plasma leptin, corticosterone, and uncoupling protein-1 mRNA in brown adipose tissue. On the other hand, pups raised in large litters were 17% lighter with no significant changes in plasma leptin. Overfeeding during the first 3 wk of life led to increased plasma leptin concentration in adulthood, whereas underfed rats remained significantly lighter throughout the study, with no evidence of catch-up growth. Rats raised in SL were more susceptible to developing cardiac fibrosis with a 22% increase in collagen deposition compared with control rats at 16 wk of age (P < 0.05). This was independent of any changes in blood pressure. This study demonstrates that nutritional changes early in postnatal development can have long-lasting effects on body weight, adiposity, and some mediators involved in energy homeostasis and can also lead to structural changes in the heart in adulthood. This highlights the importance of identifying potential early life risk factors involved in the modulation of childhood nutrition.

Topics: Adiposity; Aging; Animals; Animals, Newborn; Blood Pressure; Body Weight; Corticosterone; Energy Intake; Female; Fibrosis; Food Deprivation; Heart Diseases; Hyperphagia; Hypothalamus; Insulin; Leptin; Litter Size; Longitudinal Studies; Male; Neuropeptide Y; Obesity; Random Allocation; Rats; Rats, Sprague-Dawley

The objective was to examine cardiovascular autonomic (cANS) function and its potential relationships with leptin resistance, insulin resistance, oxidative stress, and inflammation in a pediatric sample with varying levels of obesity.. Participants were normal-weight (NW; BMI <85th percentile, 6 male, 4 female), overweight (OW; 85th percentile < BMI <95th percentile, 6 male, 4 female), and obese children (OB; BMI >95th percentile, 6 male, 10 female) who had cANS function assessed via heart rate variability (HRV) methods during resting conditions. Standard time-domain and frequency-domain measures [high-frequency normalized units (HFnu; measure of parasympathetic nervous system activity) and low frequency:high-frequency ratio (LF:HF; overall sympathovagal balance)] of HRV were calculated. Fasting blood samples were drawn for measurement of glucose, insulin, lipids, 8-isoprostane, leptin, soluble leptin-receptor (sOB-R), C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Results were reported as mean +/- standard error of the mean.. OB had significantly elevated LF:HF and decreased HFnu when compared with NW (p < 0.05), but no differences between OW and NW were observed. Measures of HRV were significantly related to leptin, insulin resistance, 8-isoprostane, and CRP (p < 0.05), but these relationships were not significant after adjustment for fat mass.. When compared with NW, OB but not OW children are characterized by cANS dysfunction and increased leptin, insulin resistance, oxidative stress, and inflammation (CRP). The relationships between these factors seem to be dependent on quantity of fat mass and/or other factors associated with being obese.

Topics: Blood Glucose; C-Reactive Protein; Child; Female; Heart; Heart Conduction System; Heart Diseases; Heart Rate; Humans; Insulin; Interleukin-6; Leptin; Male; Metabolic Diseases; Minnesota; Obesity; Reference Values; Tumor Necrosis Factor-alpha

Intake of whole grains is inversely associated with risk of diabetes and ischemic heart disease in observational studies. The lower risk associated with high whole-grain intakes may be mediated through improvements in glycemic control, lipid profiles, or reduced inflammation.. The aim was to examine whether the intake of whole grains, bran, and germ is related to homocysteine, plasma markers of glycemic control (fasting insulin, hemoglobin A1c, C-peptide, and leptin), lipids (total cholesterol, triacylglycerol, HDL cholesterol, and LDL cholesterol), and inflammation (C-reactive protein, fibrinogen, and interleukin 6).. This was a cross-sectional study of the relations of whole grains, bran, and germ intakes with homocysteine and markers of glycemic control, lipids, and inflammation in 938 healthy men and women.. Whole-grain intake was inversely associated with homocysteine and markers of glycemic control. Compared with participants in the bottom quintile of whole-grain intake, participants in the highest quintile had 17%, 14%, 14%, and 11% lower concentrations of homocysteine (P < 0.01), insulin (P = 0.12), C-peptide (P = 0.03), and leptin (P = 0.03), respectively. Inverse associations were also observed with total cholesterol (P = 0.02), HDL cholesterol (P = 0.05), and LDL cholesterol (P = 0.10). Whole-grain intake was not associated with the markers of inflammation. Whole-grain intake was most strongly inversely associated with markers of glycemic control in this population.. The results suggest a lower risk of diabetes and heart disease in persons who consume diets high in whole grains.

Topics: Adult; Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Edible Grain; Female; Fibrinogen; Health Surveys; Heart Diseases; Homocysteine; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Lipid Metabolism; Male; Middle Aged; Risk Factors

Cardiopulmonary bypass often causes a stress hormonal response with subsequent changes in hemodynamics and organ perfusion. Leptin, an adipocyte-derived factor, has been proposed to play a role in systemic inflammation. We examined perioperative release of leptin and cortisol in patients undergoing open heart surgery with or without cardiopulmonary bypass.. Forty-nine patients were enrolled in this prospective study. Conventional coronary artery bypass grafting was performed in 19 patients (ONCABG; group I), and heart valve surgery in 15 patients (group II). Fifteen patients (group III) received off-pump coronary artery bypass grafting (OPCABG). Blood samples were collected preoperatively and for as long as 72 hours postoperatively. Plasma levels of leptin and cortisol were measured by enzyme-linked immunosorbent assay.. Leptin serum levels decreased during the operation, reaching 73.2% of the baseline in group I, 85.3% in group II, and 38.9% in group III (p < 0.05), 2 hours postoperatively. Thereafter, leptin levels increased gradually to 218.6% of the baseline in group I and 313.7% in group II 24 hours after the operation (p < 0.01). However, patients in the OPCABG group showed only a moderate increase in serum leptin levels. Plasma cortisol levels rose to a maximum of 532.9% of baseline in group I, 526.4% in group II, and 280% in group III 12 hours postoperatively (p < 0.01).. Open heart surgery is associated with acute perioperative changes in plasma levels of neurohormonal stress factors leptin and cortisol. A different pattern of leptin and cortisol release was observed in patients operated on without cardiopulmonary bypass.

Topics: Aged; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Female; Heart Diseases; Heart Valve Prosthesis Implantation; Humans; Hydrocortisone; Leptin; Male; Middle Aged; Prospective Studies

Topics: Aged; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Coronary Artery Bypass, Off-Pump; Female; Heart Diseases; Humans; Hydrocortisone; Leptin; Male; Middle Aged; Prospective Studies

The control of body weight and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) are important because both factors have significant effects on the mortality of these patients. It has recently been reported that OSAHS has a significant effect on the secretion of leptin, a hormone involved in the control of body weight and sympathetic nerve activity. In addition to the circadian rhythm of leptin secretion, the effects of one night of treatment with nasal continuous positive airway pressure (nCPAP) and the mechanism of the effects of nCPAP on nocturnal leptin secretion in patients with OSAHS has not yet been elucidated.. Blood samples were obtained at 21.00 hours, 00.00 hours, 03.00 hours, and 06.30 hours from 21 subjects with OSAHS (mean apnoea and hypopnoea index 52.4/h), with and without nCPAP treatment. Iodine-123 (I(123))-meta-iodobenzylguanidine (MIBG) imaging was used to evaluate myocardial sympathetic function before nCPAP treatment.. Plasma leptin reached a peak level at 00:00 hours (p<0.01) in patients with OSAHS, both with and without nCPAP treatment. The first night of nCPAP treatment significantly decreased the plasma leptin levels at 03.00 hours (without nCPAP: mean (SE) 21.6 (4.7) ng/ml; with nCPAP: 19.3 (4.1) ng/ml, p<0.02) and at 06.30 hours (without nCPAP: 17.6 (3.8) ng/ml; with nCPAP: 15.2 (3.2) ng/ml, p<0.01). The magnitude of the decrease in leptin levels after nCPAP treatment was significantly correlated with cardiac sympathetic function measured before nCPAP treatment (p<0.03).. Patients with OSAHS undergo nocturnal increases in leptin levels in spite of interruption of sleep due to apnoea and hypopnoea, a trend seen in normal subjects. Plasma leptin levels in patients with OSAHS decreased significantly after the first night of nCPAP treatment. Enhanced cardiac sympathetic function in these patients may contribute to the leptin levels before nCPAP treatment and vice versa.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Autonomic Nervous System Diseases; Blood Glucose; Heart Diseases; Humans; Insulin; Leptin; Male; Middle Aged; Positive-Pressure Respiration; Radionuclide Imaging; Sleep Apnea Syndromes