leptin and Atherosclerosis

Leptin is a hormone secreted primarily by adipose tissue. It regulates an organism's metabolism, energy balance, and body weight through a negative feedback mechanism. When a person or animal has low body fat and little energy, the leptin level in the body decreases, and conversely, when there is an excess of nutrients, the leptin level increases, giving a feeling of satiety. However, when leptin levels are abnormal (too high or too low) for a number of reasons, it can negatively affect your health, inducing inflammatory responses, obesity, and other problems. Many studies have shown that abnormal leptin levels, such as hyperleptinemia, are closely associated with common risk factors for atherosclerosis (AS). This review systematically states the relationship between leptin and common risk factors for AS (inflammation, obesity, diabetes mellitus, hypertension, and sleep disorders) and provides some new thoughts on the future direction of research on both. Because the abnormal level of leptin will have adverse effects on multiple atherosclerotic risk factors, how to regulate the leptin level of patients with AS, and whether we can treat and prevent AS by intervening the leptin level, these may be our new research directions in the future.

Topics: Adipose Tissue; Animals; Atherosclerosis; Humans; Leptin; Obesity; Risk Factors

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

Increasing adipose tissue mass in obesity directly correlates with elevated circulating leptin levels. Leptin is an adipokine known to play a role in numerous biological processes including regulation of energy homeostasis, inflammation, vascular function and angiogenesis. While physiological concentrations of leptin may exhibit multiple beneficial effects, chronically elevated pathophysiological levels or hyperleptinemia, characteristic of obesity and diabetes, is a major risk factor for development of atherosclerosis. Hyperleptinemia results in a state of selective leptin resistance such that while beneficial metabolic effects of leptin are dampened, deleterious vascular effects of leptin are conserved attributing to vascular dysfunction. Leptin exerts potent proatherogenic effects on multiple vascular cell types including macrophages, endothelial cells and smooth muscle cells; these effects are mediated via an interaction of leptin with the long form of leptin receptor, abundantly expressed in atherosclerotic plaques. This review provides a summary of recent in vivo and in vitro studies that highlight a role of leptin in the pathogenesis of atherosclerotic complications associated with obesity and diabetes.

Topics: Animals; Atherosclerosis; Diabetes Mellitus; Endothelial Cells; Humans; Leptin; Macrophages; Myocytes, Smooth Muscle; Obesity

Topics: Adiponectin; Animals; Atherosclerosis; Humans; Inflammation; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome; Risk Factors

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

Smoking is an established risk factor for atherosclerosis through several underlying pathways. Moreover, in the development of atherosclerotic plaque formation, obesity, defined as excess fat mass accumulation, also plays a vital role in dyslipidemia and insulin resistance. Substantial evidence shows that cigarette smoking induces multiple pathological effects in adipose tissue, such as differentiation of adipocytes, lipolysis, and secretion properties in adipose tissue. Therefore, there is an emerging speculation in which adipose tissue abnormality induced by smoking or nicotine is likely to accelerate the progression of atherosclerosis. Herein, this review aims to investigate the possible interplay between smoking and adipose tissue dysfunction in the development of atherosclerosis.

Topics: Adipocytes; Adipose Tissue; Atherosclerosis; Cigarette Smoking; Humans; Leptin; Lipid Metabolism; Receptors, Nicotinic

Statins are known to influence the status of adipokines, which play a key role in the pathophysiology of cardiometabolic diseases. As the effect of ezetimibe as an add-on to statin therapy on the impact of statins on plasma adipokines levels is currently unclear, the aim of the present study was to investigate this through a meta-analysis of controlled trials.. A systematic review was performed, followed by a bibliographic search in PubMed, Medline, SCOPUS, Web of Science and Google Scholar databases. Quantitative data synthesis was performed using a fixed- or random-effects model (based on the level of interstudy heterogeneity) and the generic inverse variance weighting method. Effect sizes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI).. Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124). However, significantly greater reductions in plasma concentrations of tumour necrosis factor α (TNF-α) (SMD -0.48, 95% CI -0.87, -0.08; P = 0.018) were achieved with ezetimibe/statin combination therapy.. The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect compared with statin monotherapy. Owing to the emerging role of TNF-α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF-α-lowering effect.

Topics: Adiponectin; Anticholesteremic Agents; Atherosclerosis; Drug Therapy, Combination; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Leptin; Plasminogen Activator Inhibitor 1; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha

Adipose tissue is recognized as a rich source of proinflammatory mediators that may directly contribute to vascular injury, insulin resistance, and atherogenesis. Many studies have shown that adiponectin has antiatherogenic and anti-inflammatory properties. Adiponectin acts not only as a factor increasing insulin sensitivity, and the protective effect may result from its ability to suppress production of proinflammatory cytokines. It negatively regulates the expression of TNF-alpha and C-reactive protein (CRP) in adipose tissue; reduces expression of vascular and intracellular adhesion molecules (VCAM-1, ICAM-1), E-selectin, interleukin-8 (IL-8). Hyperleptinemia has been linked with the development of hypertension and endothelial dysfunction/atherosclerosis, two main pathophysiological conditions associated with cardiovascular disease development. Leptin-mediated increases in sympathetic nervous system activity may be among the principal mechanisms evoking obesity related hypertension. Leptin stimulates the secretion of proinflammatory cytokines, and increases the release of endothelin-1 (ET-1), which may promote hypertension. Increased serum levels of asymmetric dimethylarginine (ADMA), a physiological regulator of the biosynthesis of nitric oxide (NO), promote the process of atherosclerosis, leading to the occurrence of endothelial dysfunction and cardiovascular disease.

Topics: Adiponectin; Arginine; Atherosclerosis; C-Reactive Protein; E-Selectin; Endothelin-1; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Leptin; Nitric Oxide; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

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

A world-wide obesity epidemic is threatening to have a major impact on the prevalence of chronic and acute vascular diseases. In addition to weight loss interventions, which have met with modest success to date, it will be important to understand mechanisms by which obesity promotes vascular disease processes. Studies of leptin, a hormone produced by the adipocyte, have supported the concept that adipocyte-specific products may be mediating some of the vascular risk associated with obesity. This mini-review provides an overview of some of the preclinical studies demonstrating causal relationships between leptin and vascular endpoints. Therapeutic strategies designed to block leptin-mediated signaling events in cells contributing to vascular disease may prove beneficial in obese subjects at risk for vascular complications.

Topics: Animals; Arteries; Atherosclerosis; Endothelium, Vascular; Humans; Leptin; Models, Cardiovascular; Muscle, Smooth, Vascular; Obesity; Receptors, Leptin; Signal Transduction; Thrombosis; Tunica Intima

Leptin has received much attention since its cloning in 1994. Initially, leptin research centered on satiety, energy balance and sympathetic activation. However, hyperleptinemia has since been identified as an independent risk factor for various cardiovascular pathologies including atherosclerotic coronary artery disease. Over the last decade, multiple studies have implicated leptin as an important mediator in endothelial dysfunction and neointimal hyperplasia, both key steps in the evolution of atherosclerotic vascular changes. Additionally, more recent evidence indicates that paracrine leptin release from perivascular adipose tissue (PVAT) has deleterious effects on the underlying endothelium and vascular smooth muscle cells (SMC), including the coronary circulation. This report reviews pertinent literature on leptin-mediated endothelial dysfunction, SMC proliferation and the role of PVAT-derived leptin with an emphasis on the coronary circulation and discussions of currently proposed molecular mechanisms of PVAT-mediated coronary endothelial dysfunction and neointimal hyperplasia.

Topics: Adipose Tissue; Animals; Atherosclerosis; Cardiovascular Agents; Down-Regulation; Endothelium, Vascular; Humans; Hyperplasia; Leptin; Models, Cardiovascular; Molecular Targeted Therapy; Systemic Vasculitis; Tunica Intima; Up-Regulation

This review concerns the influence of leptin on vascular smooth muscle cells (VSMC). VSMC express different isoforms of the leptin receptor (Ob-R) able to activate a wide range of intracellular signalling pathways, mediating many relevant biological actions. In particular, leptin promotes processes deeply involved in atherogenesis, such as VSMC migration, hypertrophy, proliferation, osteogenic differentiation and metalloproteinase expression. The intracellular signalling molecules involved are JAK/STAT, PI3K/Akt, ERK 1/2, p38 MAPK, mTOR, and RhoA/ROCK. Some of these leptin actions are particularly evident in stretching conditions; others are mediated by the NAD(P)H-induced increase of Reactive Oxygen Species. A leptin-induced activation of angiotensin and endothelin systems, with up-regulation of the synthesis of the two hormones and of their receptors, has also been demonstrated. Other studies, however, showed that leptin increases in VSMC the nitric oxide production by activating the inducible nitric oxide synthase, and, via nitric oxide, exerts a vasodilating effect and impairs the proliferative and vasoconstricting actions of angiotensin II. Both the potentially harmful and the potentially beneficial effects exerted by leptin in VSMC are lost in VSMC from animal models of genetically determined leptinresistance. Cultured VSMC from leptin-resistant animals are also resistant to insulin and to nitric oxide. It is not known, however, whether in human obesity, a condition characterized by hypothalamic leptin resistance and by compensatory hyperleptinemia, VSMC are sensitive or resistant to leptin: only in the first case the predictive role of circulating leptin on cardiovascular events could support a pathogenetic influence of the hormone on atherosclerosis.

Topics: Animals; Atherosclerosis; Cell Movement; Cell Proliferation; Humans; Hypertrophy; Leptin; Models, Cardiovascular; Muscle, Smooth, Vascular; Protein Isoforms; Receptors, Leptin; Signal Transduction; Up-Regulation

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

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

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

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

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

Insulin resistance is the main pathologic mechanism that links the constellation of clinical, metabolic and anthropometric traits with increased risk for cardiovascular disease and type II diabetes mellitus. These traits include hyperinsulinemia, impaired glucose intolerance, endothelial dysfunction, dyslipidemia, hypertension, and generalized and upper body fat redistribution. This cluster is often referred to as insulin resistance syndrome. The progression of insulin resistance to diabetes mellitus parallels the progression of endothelial dysfunction to atherosclerosis leading to cardiovascular disease and its complications. In fact, insulin resistance assessed by homeostasis model assessment (HOMA) has shown to be independently predictive of cardiovascular disease in several studies and one unit increase in insulin resistance is associated with a 5.4% increase in cardiovascular disease risk. This review article addresses the role of insulin resistance as a main causal factor in the development of metabolic syndrome and endothelial dysfunction, and its relationship with cardiovascular disease. In addition to this, we review the type of lifestyle modification and pharmacotherapy that could possibly ameliorate the effect of insulin resistance and reverse the disturbances in insulin, glucose and lipid metabolism.

Topics: Adiponectin; Animals; Atherosclerosis; Blood Glucose; Blood Pressure; Endothelium, Vascular; Humans; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Risk Factors; Risk Reduction Behavior

Obstructive sleep apnea syndrome (OSAS) is an often underestimated sleep disorder that has been associated with cardiovascular disease. OSAS is characterized by cycles of apnea and/or hypopnea during sleep caused by the collapse of the upper airways. Intermittent hypoxia deriving from the cycles of apnea/arousals (to retrieve the ventilation) plays a pivotal role in the pathogenesis of the disease. Obesity is the most frequent predisposing condition of OSAS. Recent evidence suggests that OSAS could be considered as a pro-atherosclerotic disease, independently of visceral fat amount. Oxidative stress, cardiovascular inflammation, endothelial dysfunction, and metabolic abnormalities in OSAS could accelerate atherogenesis. The present review is focused on the possible pathophysiological mediators which could favor atherosclerosis in OSAS.

Topics: Atherosclerosis; Cytokines; Disease Progression; Humans; Hypoxia; Inflammation; Leptin; Oxidative Stress; Platelet Aggregation; Risk Factors; Sleep Apnea, Obstructive

Metabolic syndrome (MSX) identifies clinical symptoms and lab results, including abdominal obesity, insulin resistance, hyperglycemia, hyperlipidemia, and hypertension, that lead to an increased risk of cardiovascular disease (CVD). Obesity typically results in insulin and leptin resistance and a shift from expansion of subcutaneous fat to deposition of abdominal and ectopic fat. These conditions cause metabolic dysregulation, elevated fatty acids (FFA), and increased secretion of pro-inflammatory "adipokines". Left untreated, these conditions cause lipotoxicity, chronic inflammation, hypertension, atherosclerosis, and CVD.

Topics: Atherosclerosis; Fatty Acids, Nonesterified; Humans; Hydrocortisone; Leptin; Metabolic Syndrome; Obesity, Abdominal; Signal Transduction

Obesity as a pathogenic disorder is a predisposing factor for cardiovascular diseases and shows an increasing incidence in the industrialized countries. Adipokines such as leptin, adiponectin and resistin have a great impact on the development of atherosclerosis in obesity. Elevated levels of leptin have been found to be atherogenic whereas decreased levels of adiponectin have been proved to be anti-atherogenic in recent studies. The exact role of resistin in the process of atherosclerosis has so far remained uncertain and controversial. In our recent work, we studied the alteration in human paraoxonase-1 (PON1) activity and adipokine levels; furthermore, we also aimed at identifying the potential correlation between these parameters in this metabolic disorder. We investigated the above-mentioned parameters both in adults and in children, with regard to the emerging role of childhood obesity and to get a clearer view of these factors during a whole lifetime. Investigating the adult population with a broad range of body mass index (BMI) we found significantly increased leptin and significantly decreased adiponectin and resistin levels and PON1 activity in the obese group compared to the lean controls. Adiponectin and resistin levels showed significantly positive correlation, while leptin and BMI showed significantly negative correlation with PON1 activity. Our findings were similar in childhood obesity: leptin showed significantly negative correlation, while adiponectin showed significantly positive correlation with PON1 activity. We found gender differences in the univariate correlations of leptin and adiponectin levels with PON1 activity in the adult population. In multiple regression analysis, adiponectin proved to be an independent factor of PON1 activity both in childhood and adult obesity, furthermore thiobarbituric acid-reactive substances (TBARS) also proved to be an independent predictor of the enzyme in adults, reflecting the important role of oxidative stress in obesity. Investigating PON 192 Q/R polymorphism by phenotypic distribution (A/B isoenzyme) in obese children, we found a significant correlation of PON1 arylesterase activity with leptin and adiponectin levels, and of body fat percentage with PON1 192 B isoenzyme. According to our studies, these metabolic changes in obesity predispose to the early development of atherosclerosis throughout our whole lifetime. Decreased activity of PON1 and alterations in adipokine levels in childhood obes

Topics: Adipokines; Adult; Animals; Aryldialkylphosphatase; Atherosclerosis; Child; Gene Expression Regulation, Enzymologic; Humans; Leptin; Lipid Peroxidation; Models, Biological; Obesity; Phenotype; Polymorphism, Genetic; Thiobarbituric Acid Reactive Substances

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

The classical perception of adipose tissue as a storage place of fatty acids has been replaced over the last years by the notion that adipose tissue has a central role in lipid and glucose metabolism and produces a large number of hormones and cytokines, e.g. tumour necrosis factor-alpha, interleukin-6, adiponectin, leptin, and plasminogen activator inhibitor-1. The increased prevalence of excessive visceral obesity and obesity-related cardiovascular risk factors is closely associated with the rising incidence of cardiovascular diseases and type 2 diabetes mellitus. This clustering of vascular risk factors in (visceral) obesity is often referred to as metabolic syndrome. The close relationship between an increased quantity of visceral fat, metabolic disturbances, including low-grade inflammation, and cardiovascular diseases and the unique anatomical relation to the hepatic portal circulation has led to an intense endeavour to unravel the specific endocrine functions of this visceral fat depot. The objective of this paper is to describe adipose tissue dysfunction, delineate the relation between adipose tissue dysfunction and obesity and to describe how adipose tissue dysfunction is involved in the development of diabetes mellitus type 2 and atherosclerotic vascular diseases. First, normal physiology of adipocytes and adipose tissue will be described.

Topics: Adipocytes; Adipose Tissue; Atherosclerosis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Energy Metabolism; Female; Humans; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Obesity; Risk Reduction Behavior; Subcutaneous Fat, Abdominal; Transcription Factors

Recent work shows a high prevalence of low testosterone and inappropriately low LH and FSH concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity, and other features of the metabolic syndrome (obesity and overweight, hypertension and hyperlipidemia) in patients with type 2 diabetes. However, the duration of diabetes or HbA1c were not related to HH. Furthermore, recent data show that HH is also observed frequently in patients with the metabolic syndrome without diabetes but is not associated with type 1 diabetes. Thus, HH appears be related to the two major conditions associated with insulin resistance: type 2 diabetes and the metabolic syndrome. CRP concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and CRP concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations in type 2 diabetic men have also been related to a significantly lower hematocrit and thus to an increased frequency of mild anemia. Low testosterone concentrations are also related to an increase in total and regional adiposity, and to lower bone density. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates symptoms related to sexual dysfunction, and features of the metabolic syndrome, insulin resistance and inflammation.

Topics: Animals; Atherosclerosis; Bone Density; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Hematocrit; Humans; Hypogonadism; Inflammation Mediators; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Models, Biological; Obesity; Prostatic Neoplasms; Sexual Dysfunction, Physiological; Testosterone

The prevalence of obesity, especially among the young, is dramatically increasing in the United States. Obesity is associated with accelerated atherosclerosis and increased rates of cardiovascular death. There are many plausible mechanisms by which an increase in adipose tissue could adversely affect the vessel wall. These include the changes in blood pressure, glucose level, lipid/lipoprotein metabolism, and systemic inflammation. In addition, factors secreted by adipose tissue may directly influence vessel wall homeostasis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in the vessel wall. There is general agreement that central, as opposed to peripheral, adipose tissue confers the most cardio-metabolic risk. Although the basis of this differential risk has not been not 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. Numerous studies have shown the beneficial effects of weight loss on markers of cardiovascular risk but fewer have demonstrated improvement in direct measures of large vessel disease. The unfolding role of adipose tissue as an important metabolic and secretory organ provides new opportunities for developing more effective approaches for preventing obesity and its atherosclerotic complications.

Topics: Adiponectin; Adipose Tissue; Atherosclerosis; Endothelium, Vascular; Humans; Insulin Resistance; Leptin; Obesity; Prevalence; Prognosis; Risk Factors; United States

Topics: Adiponectin; Adiposity; Atherosclerosis; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Leptin; Lipid Metabolism; Lipid Metabolism Disorders; Obesity; Peptide Hormones; Resistin

Atherosclerosis and related forms of cardiovascular disease (CVD) are associated with several genetic and environmental risk factors, including hypercholesterolemia, diabetes mellitus (DM), hypertension, obesity and smoking. Human DM is a multi-system disorder that results from progressive failure of insulin production and insulin resistance. Most diabetic patients die from complications of atherosclerosis and CVD, and DM is also associated with increased risk of restenosis post-angioplasty. Furthermore, the incidence of DM, particularly type 2-DM, is expected to increase significantly during the next decades owing to the unhealthy effects of modern life-style habits (e.g., obesity and lack of physical exercise). Thus, it is of utmost importance to develop novel preventive and therapeutic strategies to reduce the social and health-care burden of CVD and DM. Although a number of physiological alterations thought to promote atherosclerosis have been identified in diabetic patients, the precise molecular mechanisms that link DM and atherosclerosis are largely unknown. Thus, the aim of this review is to discuss current murine models of combined DM and atherosclerosis and to explore how these experimental systems are being utilized to gain mechanistic insights into diabetes-induced neointimal lesion development, as well as their potential use in evaluating the efficacy of new therapies. Our discussion includes models generated by streptozotocin treatment and those resulting from naturally occurring or targeted mutations in the mouse.

Topics: Animals; Atherosclerosis; Constriction, Pathologic; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Disease Models, Animal; Glucose; Insulin; Leptin; Mice; Recurrence; Tunica Intima

This review deals with the question whether resistance to obesity affects resistance to atherosclerosis.. Resistance to diet-induced obesity in inbred mouse strains involves an adequate response to Leptin, the main regulator of the energy balance cycle. Leptin, an adipokine with both central and peripheral targets, regulates food intake and energy expenditure. Adequate response to leptin involves repression of stearoyl-CoA desaturase, activation of Amp-activated protein-kinase and uncoupling proteins, resulting in fatty acid oxidation and energy expenditure. Most of the obesity-resistant strains are also resistant to atherosclerosis, but so far no information concerning the response to the leptin cycle is available in these strains when bred onto a LDLR(-/-) or apoE(-/-) background. Recent studies in mouse strains on an atherosclerosis permissive background have identified genetic links between obesity and atherosclerosis. Moreover, information derived from studies on mice was applied in order to learn about the metabolic effectors in humans and is included in this review.. The data presented in this review provide recent information concerning metabolic pathways that play an important role in the regulation of energy balance, a prerequisite for resistance to obesity. Hopefully they will provide a background for future genetic studies involved in resistance to atherosclerosis.

Topics: Animals; Atherosclerosis; Disease Models, Animal; Energy Metabolism; Genetic Predisposition to Disease; Humans; Leptin; Mice; Mice, Inbred Strains; Mice, Obese; Obesity

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

The role of the adipose tissue in immunity has recently emerged, and there is now ample evidence that this role is elucidated by a number of cytokine-like hormones produced by adipocytes - called adipokines. The most relevant adipokines are leptin, adiponectin and visfatin, and all have marked effects on metabolic and immune function. The discovery of adipokines has led to the development of a novel concept that the pathogenesis of atherosclerosis can be associated with low-degree inflammation associated with slow (auto)immune attack of the endothelial wall of arteries. This model considers therefore adipokines as the bridge between atherosclerosis, inflammation and immunity. We review here the most recent advances on adipokine research, with a particular emphasis on the model that considers atherosclerotic lesions as effects of the (auto)immune-mediated damage of the endothelium that is sustained by low-degree chronic inflammation typical of obesity and metabolic syndrome.

Topics: Adipokines; Adipose Tissue; Animals; Atherosclerosis; Autoimmunity; Endothelium, Vascular; Humans; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Signal Transduction

Obesity and its related metabolic diseases, including type 2 diabetes, are associated with alterations in the circulating levels of various peptides. These include the adipocytokines (peptides released by adipocytes which circulate, such as leptin, adiponectin and resistin), and other peptides whose levels are altered in association with obesity (such as ghrelin, neuropeptide Y, interleukin-1 beta and tumour necrosis factor-alpha). While the primary action of these peptides is linked with the regulation and maintenance of energy balance and metabolism, many of them have also been shown to possess vasoactive, inflammatory and other properties that influence vascular biology, vascular physiology and atherogenesis. As such, they may form an important mechanistic link between obesity and cardiovascular disease. In this review, we will outline the vasoactive properties of adipocytokines and other obesity-related peptides. In particular, as pharmacotherapies suggested to achieve weight loss will alter the pathways associated with these peptides, such treatments might have either beneficial or deleterious effects on the incidence and progression of cardiovascular disease.

Topics: Adiponectin; Adipose Tissue; Atherosclerosis; Diabetes Mellitus, Type 2; Ghrelin; Humans; Leptin; Muscle, Smooth, Vascular; Obesity; Peptide Hormones

Leptin, a 167-amino acid peptide hormone produced by white adipose tissue, is primarily involved in the regulation of food intake and energy expenditure. Leptin receptors are expressed in many tissues including the cardiovascular system. Plasma leptin concentration is proportional to body adiposity and is markedly increased in obese individuals. Recent studies suggest that hyperleptinemia may play an important role in obesity-associated cardiovascular diseases including atherosclerosis. Leptin exerts many potentially atherogenic effects such as induction of endothelial dysfunction, stimulation of inflammatory reaction, oxidative stress, decrease in paraoxonase activity, platelet aggregation, migration, hypertrophy and proliferation of vascular smooth muscle cells. Leptin-deficient and leptin receptor-deficient mice are protected from arterial thrombosis and neointimal hyperplasia in response to arterial wall injury. Several clinical studies have demonstrated that high leptin level predicts acute cardiovascular events, restenosis after coronary angioplasty, and cerebral stroke independently of traditional risk factors. In addition, plasma leptin correlates with markers of subclinical atherosclerosis such as carotid artery intima-media thickness and coronary artery calcifications. Inhibition of leptin signaling may be a promising strategy to slow the progression of atherosclerosis in hyperleptinemic obese subjects.

Topics: Adipose Tissue; Animals; Atherosclerosis; Humans; Leptin; Obesity; Oxidative Stress; Risk Factors

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

To review the potential role of leptin, hyperleptinaemia and leptin resistance in the cardiovascular and endocrine complications of metabolic syndrome.. Review of literature listed in Medline.. Hyperleptinaemia is common in obesity and reflects increased adiposity and leptin resistance. Nevertheless, leptin resistance may not be complete as several actions of leptin, such as cardiovascular sympatho-activation, might be preserved in obese subjects known to be resistant to the metabolic effects of leptin (i.e. selective leptin resistance). Notably, the renal and sympathetic actions of leptin may play an important role in the pathogenesis of hypertension related to obesity and metabolic syndrome. Furthermore, the lipotoxic effect of leptin resistance may cause insulin resistance and beta cell dysfunction, increasing the risk of type 2 diabetes. Leptin has also been shown to possess proliferative, pro-inflammatory, pro-thrombotic, and pro-oxidative actions.. Hyperleptinaemia and leptin resistance may contribute to hypertension, impaired glucose metabolism, and pro-atherogenic state in obesity and metabolic syndrome.

Topics: Animals; Atherosclerosis; Blood Pressure; Diabetes Mellitus, Type 2; Drug Resistance; Humans; Hypertension; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity

Topics: Adipose Tissue; Animals; Atherosclerosis; Chemokines; Humans; Insulin Resistance; Interleukin 1 Receptor Antagonist Protein; Leptin

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

Bacterial and viral products, such as bacterial lipopolysaccharide (LPS), cause inducible (i) NO synthase (NOS) synthesis, which in turn produces massive amounts of nitric oxide (NO). NO, by inactivating enzymes and leading to cell death, is toxic not only to invading viruses and bacteria, but also to host cells. Injection of LPS induces interleukin (IL)-1beta, IL-1alpha, and iNOS synthesis in the anterior pituitary and pineal glands, meninges, and choroid plexus, regions outside the blood-brain barrier. Thereafter, this induction occurs in the hypothalamic regions (such as the temperature-regulating centers), paraventricular nucleus (releasing and inhibiting hormone neurons), and the arcuate nucleus (a region containing these neurons and axons bound for the median eminence). Aging of the anterior pituitary and pineal with resultant decreased secretion of pituitary hormones and the pineal hormone melatonin, respectively, may be caused by NO. The induction of iNOS in the temperature-regulating centers by infections may cause the decreased febrile response in the aged by loss of thermosensitive neurons. NO may play a role in the progression of Alzheimer's disease and parkinsonism. LPS similarly activates cytokine and iNOS production in the cardiovascular system leading to coronary heart disease. Fat is a major source of NO stimulated by leptin. As fat stores increase, leptin and NO release increases in parallel in a circadian rhythm with maxima at night. NO could be responsible for increased coronary heart disease as obesity supervenes. Antioxidants, such as melatonin, vitamin C, and vitamin E, probably play important roles in reducing or eliminating the oxidant damage produced by NO.

Topics: Aging; Animals; Atherosclerosis; Central Nervous System; Corticosterone; Gonadotropin-Releasing Hormone; Humans; Hypothalamus; Isoenzymes; Leptin; Lipopolysaccharides; Models, Biological; Neurodegenerative Diseases; Nitric Oxide; Nitric Oxide Synthase; Pineal Gland; Tumor Necrosis Factor-alpha

Despite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in patients with type 2 diabetes (DM2) and established atherosclerosis.. To investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function, coagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients with atherosclerotic vascular disease and DM2 who receive optimal medical therapy.. We conducted a prospective, double-blind, placebo-controlled, randomized, double-center study, in which thrombin generation (plasma thrombogenic potential from automated thrombogram), fibrin clot properties (plasma fibrin clot permeability; lysis time), platelet aggregation (light transmission aggregometry with adenosine diphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid profiles, leptin and adiponectin levels, as well as markers of systemic inflammation (i.e., hsCRP, IL-6, TNF-α, ICAM-1, VCAM-1, and myeloperoxidase) were determined at baseline and at 3 months after treatment with 2 g/day of n-3 PUFAs (n = 36) or placebo (n = 38). Moreover, we assessed serum fatty acids of the phospholipid fraction by gas chromatography both at baseline and at the end of the study.. Majority of patients were treated with optimal medical therapy and achieved recommended treatment targets. Despite higher serum levels of eicosapentaenoic acid (EPA) (by 204%; p < 0.001) and docosahexaenoic acid (DHA) (by 62%; p < 0.0001) in n-3 PUFA group at the end of treatment no changes in platelet aggregation, thrombin generation, fibrin clot properties or markers of systemic inflammation were observed. No intergroup differences in the insulin, HbA1c and lipid levels were found at the end of the study. There was no change in adiponectin and leptin in interventional group, however leptin increased in control group (p = 0.01), therefore after study period leptin levels were lower in the interventional group (p = 0.01). Additionally, resolvin D1 did not differ between interventional and control group.. In conclusion, our study demonstrated that in patients with long-standing, well-controlled DM2 and atherosclerotic disease the treatment with a high dose of n-3 PUFAs (namely, 1 g/day of EPA and 1 g/day of DHA for 3 months) does not improve coagulation, metabolic, and inflammatory status when measured with the specified tests. The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014.

Topics: Adiponectin; Aged; Atherosclerosis; Biomarkers; Blood Coagulation; Blood Platelets; Diabetes Mellitus, Type 2; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Glycated Hemoglobin; Humans; Inflammation; Inflammation Mediators; Insulin; Leptin; Lipids; Male; Middle Aged; Platelet Aggregation; Poland; Prospective Studies; Thrombin; Time Factors; Treatment Outcome

Resistin and the proinflammatory cytokines, such as TNF- α , IL-6, and IL-1 β , produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination) for 24 hours in vitro. Resistin, TNF- α , IL-6, and IL-1 β production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subsequent addition of high glucose significantly upregulated resistin and TNF- α mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1 β production. By comparison, exposure to dexamethasone reduced TNF- α , IL-6, and IL-1 β production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF- α , IL-6, and IL-1 β from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients.

Topics: Adult; Anti-Inflammatory Agents; Atherosclerosis; Cells, Cultured; Cytokines; Dexamethasone; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; Glucose; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemic Agents; Inflammation Mediators; Insulin; Leptin; Leukocytes, Mononuclear; Male; Obesity; Resistin; RNA, Messenger; Sweetening Agents

Leptin has nitric oxide (NO)-dependent vasodilator actions, but hyperleptinemia is an independent risk factor for cardiovascular disease.. The objective of the study was to investigate whether, in the human circulation, properties of leptin to release NO are opposed by stimulation of vasculotoxic substances, such as endothelin (ET)-1, and whether this mechanism might contribute to vascular damage in hyperleptinemic states like obesity.. Forearm blood flow responses (plethysmography) to ETA receptor antagonism (BQ-123, 10 nmol/min) and NO synthase inhibition [N(G)-monomethyl L-arginine (L-NMMA), 4 μmol/min] were assessed before and after intraarterial administration of leptin (2 μg/min) in lean controls (n = 8) and patients with obesity-related metabolic syndrome (MetS; n = 8).. Baseline plasma leptin was higher in patients than in controls (P < .001). Before infusion of leptin, the vasodilator response to BQ-123 was greater in patients than in controls (P < .001), whereas infusion of L-NMMA induced higher vasoconstriction in controls than in patients (P = .04). In lean subjects, hyperleptinemia resulted in increased vasodilator response to ETA receptor antagonism (P < .001 vs before) and enhanced vasoconstrictor effect of L-NMMA during ETA receptor blockade (P = .015 vs before). In patients with the MetS, by contrast, vascular responses to both BQ-123 and L-NMMA were not modified by exogenous leptin (both P > .05 vs before).. These findings indicate that, under physiological conditions, leptin stimulates both ET-1 and NO activity in the human circulation. This effect is absent in hyperleptinemic patients with the MetS who are unresponsive to additional leptin. In these patients, therefore, hyperleptinemia may be a biomarker of vascular dysfunction, rather than a mediator of vascular damage.

Topics: Adult; Antihypertensive Agents; Atherosclerosis; Endothelin A Receptor Antagonists; Endothelin-1; Enzyme Inhibitors; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; Obesity; omega-N-Methylarginine; Peptides, Cyclic; Plethysmography; Receptor, Endothelin A; Risk Factors; Thinness; Vasodilation

Vitamin D receptors are present in many tissues. Hypovitaminosis D is considered to be a risk factor for atherosclerosis.. This study explores the effects of vitamin D replacement on insulin sensitivity, endothelial function, inflammation, oxidative stress, and leptin in vitamin D-deficient subjects.. Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [25(OH)D] levels below 25 nmol/liter were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter. The vitamin D-deficient group received 300,000 IU im monthly for 3 months. The following parameters were evaluated before and after treatment: vitamin D metabolites, leptin, endothelial function by brachial artery flow mediated dilatation (FMD), insulin sensitivity index based on oral glucose tolerance test, and lipid peroxidation as measures of thiobarbituric acid reactive substances (TBARS).. FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls (P = 0.001) and improved after replacement therapy (P = 0.002). Posttreatment values of TBARS were significantly lower than pretreatment levels (P < 0.001). A positive correlation between FMD and 25(OH)D (r = 0.45; P = 0.001) and a negative correlation between FMD and TBARS (r = -0.28; P < 0.05) were observed. There was a significant increase in leptin levels after therapy, and the leptin levels were positively correlated with 25(OH)D levels (r = 0.45; P < 0.05).. This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D has favorable effects on endothelial function. Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis. Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter.

Topics: Adult; Atherosclerosis; Biomarkers; Blood Flow Velocity; Blood Pressure; Brachial Artery; Endothelium, Vascular; Female; Humans; Insulin Resistance; Leptin; Linear Models; Lipid Peroxidation; Male; Oxidative Stress; Risk Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Waist-Hip Ratio

Obesity represents a chronic inflammatory status and adipocytes release either cytokines or an array of adipokines such as leptin, endowed with immunomodulating and systemic activities. The involvement of cytokines in obesity as well as of the adipokine leptin is supported by the notion that weight reduction normalizes mediators of inflammation. In this framework, we will demonstrate that in obese children, subjected for a period of six months to a hypocaloric diet, reduction of major biochemical and anthropometric parameters correlates with a normalization of immune status. In fact, absolute numbers of CD4+ cells and CD4/CD8 ratio increase, while leptin values fluctuate within normal ranges, being this adipokine involved in the modulation of either innate or adaptive immune responses. In the discussion, the immune abnormalities detected in obesity will be pointed out and emphasis will be placed on the increased frequency of infectious episodes occurring in obese adolescent and adults. Finally, the infectious etiology of obesity will be illustrated in the sense that adipocytes interacting with infectious agents may cause obesity. Taken together, the bulk of available data indicate that childhood obesity should be prevented or reduced to avoid more serious complications in adulthood.

Topics: Atherosclerosis; Blood Glucose; Body Mass Index; Caloric Restriction; CD3 Complex; CD4 Lymphocyte Count; CD4-CD8 Ratio; Child; Cholesterol; Female; Humans; Insulin; Leptin; Male; Obesity; Time Factors; Treatment Outcome; Triglycerides; Waist-Hip Ratio

Obesity leads to adipocyte hypertrophy and adipokine dysregulation and is an independent risk factor for venous thromboembolism (VTE). However, the association between adipokines and VTE is not well established.. To examine whether adipokines are associated with increased risk of incident VTE.. We studied 1888 participants of the Multi-Ethnic Study of Atherosclerosis cohort who were initially free of VTE and had adipokine (adiponectin, leptin, and resistin) levels measured at either examination 2 or 3 (2002-2004 or 2004-2005, respectively). During follow-ups, VTE was ascertained through hospitalization records and death certificates by using ICD-9 and 10 codes. We used multivariable Cox proportional hazards regression to assess the association between 1 standard deviation (SD) log-transformed increments in adipokines and incident VTE.. The mean ± SD age was 64.7 ± 9.6 years, and 49.8% of participants were women. Medians (interquartile range) of adiponectin, leptin, and resistin were 17.3 (11.8-26.2) mcg/mL, 13.5 (5.6-28.2) ng/mL, and 15.0 (11.9-19.0) ng/mL, respectively. There were 78 incident cases of VTE after a median of 9.7 (5.0-12.4) years of follow-up. After adjusting for sociodemographics, smoking, and physical activity, the hazard ratios (95% CIs) per 1 SD increment of adiponectin, leptin, and resistin were 1.14 (0.90-1.44), 1.29 (1.00-1.66), and 1.38 (1.09-1.74), respectively. The association for resistin persisted after further adjustments for body mass index and computed tomography-derived total visceral adipose tissue area.. Higher resistin levels were independently associated with greater risk of incident VTE. Larger prospective cohort studies are warranted to confirm this association.

Topics: Adipokines; Adiponectin; Aged; Atherosclerosis; Female; Humans; Leptin; Male; Middle Aged; Prospective Studies; Resistin; Risk Factors; Venous Thromboembolism

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

To evaluate the relationship of genetic variability of adiponectin (ADIPOQ), leptin (LEP) and leptin receptor (LEPR) genes with glucose-insulin system and markers of subclinical atherosclerosis (ATS) in patients with newly diagnosed type 2 diabetes.. In 794 subjects we performed: 1) euglycemic hyperinsulinemic clamp to assess insulin sensitivity; 2) mathematical modelling of a 5h-OGTT to estimate β-cell function; 3) resting ECG; 4) carotid artery and lower limb artery eco-doppler sonography to identify ATS; 5) genotyping of tag-SNPs within ADIPOQ, LEP and LEPR gene.. Regression analyses showed: 1) adiponectin levels were negatively associated with BMI, waist-to-hip ratio and triglycerides and positively with HDL and insulin sensitivity (p-all<0.03); 2) leptin levels were positively associated with BMI, HDL-cholesterol and plasma triglycerides and negatively with insulin sensitivity (p-all<0.001). Two SNPs (rs1501299 and rs2241767) within ADIPOQ gene were associated with circulating levels of adiponectin. The ADIPOQ-GAACA haplotype was associated with plasma adiponectin (p=0.034; β=-0.24), ECG abnormalities (p=0.012; OR=2.76), carotid ATS (p=0.025; OR=2.00) and peripheral limb artery ATS (p=0.032; OR=1.90). The LEP-CTA haplotype showed an association with ischemic ECG abnormalities (p=0.017; OR=2.24). Finally, LEPR-GAACGG was associated with circulating leptin (p=0.005; β=-0.31) and worst β-cell function (p=0.023; β=-15.10). Omnibus haplotype analysis showed that ADIPOQ haplotypes were associated with levels of adiponectin and common carotid artery ATS, LEP with peripheral limb artery ATS, whereas LEPR haplotypes influenced circulating levels of leptin.. Results of this study reinforce knowledge on adipokines' role in regulating glucose metabolism; in particular highlighted the potential atherogenic role of leptin and the anti atherogenic role of adiponectin.

Topics: Adiponectin; Atherosclerosis; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin Resistance; Insulins; Leptin; Triglycerides

Comparison of cardiovascular risk factors, atherosclerosis, and psychological distress among adults with refractory versus well-controlled epilepsy.. The cross-sectional study consisted of two groups of 40 people each: Group I - People with well-controlled epilepsy, Group II - People with refractory epilepsy. Age- and gender-matched people of 20-50 years were recruited. People who were diabetic, smokers, hypertensive, alcoholic, pregnant, with infections, and lactating women were excluded from the study. Biochemical parameters, fasting glucose, lipid profile, fasting insulin, leptin, adiponectin, Lp[a], hsCRP, TyG INDEX, HOMA1-%S, HOMA1-IR, HOMA1-%B, QUICKI, FIRI, AIP, AC, CLTI, MLTI, CRI-I, CRI-II, and CIMT were estimated. Stress levels [PSS-10, GAD-7 & PHQ-9] were assessed based on the scoring system from the questionnaires.. The existence of metabolic syndrome, levels of triglycerides, TyG index, MDA, OSI, CIMT, AIP, and stress scores [PSS-10, GAD-7 & PHQ-9] were significantly higher in the refractory-epilepsy group in comparison to the well-controlled group. There were associations between LDL -C and CIMT as well as between GAD-7 and CIMT among all the study subjects. There were no significant differences in the levels of glucose homeostasis parameters, hsCRP, leptin, adiponectin, and Lp[a] between the two groups. Based on the ROC analysis, MDA [AUC = 0.853] and GAD-7 [AUC = 0.900] are useful in the differential diagnosis of the study groups.. People with refractory epilepsy had increased levels of vascular risk factors, atherosclerosis, and stress levels compared to people with well-controlled epilepsy. Suitable disease management and therapeutic approaches to address cardiovascular and psychological distress could be planned out among people with refractory epilepsy to improve their quality of life.

Topics: Adiponectin; Adult; Atherosclerosis; C-Reactive Protein; Cross-Sectional Studies; Drug Resistant Epilepsy; Epilepsy; Female; Glucose; Humans; Lactation; Leptin; Psychological Distress; Quality of Life; Risk Factors

Adipokines are hormones secreted from adipose tissue and are associated with cardiometabolic diseases (CMD). Functional differences between adipokines (leptin, adiponectin, and resistin) are known, but inconsistently reported associations with CMD and lack of studies in Hispanic populations are research gaps. We investigated the relationship between subclinical atherosclerosis and multiple adipokine measures.. Cross-sectional data from the Cameron County Hispanic Cohort (N = 624; mean age = 50; Female = 70.8%) were utilized to assess associations between adipokines [continuous measures of adiponectin, leptin, resistin, leptin-to-adiponectin ratio (LAR), and adiponectin-resistin index (ARI)] and early atherosclerosis [carotid-intima media thickness (cIMT)]. We adjusted for sex, age, body mass index (BMI), smoking status, cytokines, fasting blood glucose levels, blood pressure, lipid levels, and medication usage in the fully adjusted linear regression model. We conducted sexes-combined and sex-stratified analyses to account for sex-specificity and additionally tested whether stratification of participants by their metabolic status (metabolically elevated risk for CMD as defined by having two or more of the following conditions: hypertension, dyslipidemia, insulin resistance, and inflammation vs. not) influenced the relationship between adipokines and cIMT.. In the fully adjusted analyses, adiponectin, leptin, and LAR displayed significant interaction by sex (p < 0.1). Male-specific associations were between cIMT and LAR [β(SE) = 0.060 (0.016), p = 2.52 × 10. Associations between adipokines and cIMT were sex-specific, and metabolic health status influenced the relationships between adipokines and cIMT. These heterogeneities by sex and metabolic health affirm the complex relationships between adipokines and atherosclerosis.

Topics: Adipokines; Adiponectin; Atherosclerosis; Carotid Intima-Media Thickness; Cross-Sectional Studies; Female; Hispanic or Latino; Humans; Leptin; Male; Middle Aged; Resistin

The role of adipokines in causing inflammation and insulin resistance in normal weight and obese patients is generally well studied. However, there are often conflicting results regarding their levels in type 1 diabetes mellitus (T1DM) patients and their relationship to micro- and macrovascular disease. We therefore investigated which serum adipokine levels are independently associated with markers of early atherosclerosis and microvascular complications in patients with T1DM.. A cross-sectional study was performed in the Diabetes Outpatient Clinic of Hippokrateion General Hospital, Thessaloniki, Greece. Sixty T1DM patients (30 females, mean age 38.8 ± 10.6 years, mean diabetes duration 17.4 ± 9.9 years) were included. Plasma adiponectin, leptin, and resistin, carotid artery intima media thickness (cIMT), and arterial stiffness (pulse wave velocity, PWV/SpygmoCor CP System and Mobil-O-Graph 24 h PWA) were assessed.. Serum adipokine levels demonstrate similar bivariate associations with anthropometric variables in patients with T1DM to those in normal weight subjects. Although microvascular complications are associated with serum adipokine levels by bivariate analysis, only resistin, an inflammatory marker, is independently associated with arterial stiffness in patients with T1DM.

Topics: Adipokines; Adiponectin; Adult; Atherosclerosis; Carotid Intima-Media Thickness; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Humans; Leptin; Male; Middle Aged; Obesity; Pulse Wave Analysis; Resistin

In patients with systemic lupus erythematosus (SLE), a higher frequency of atherosclerotic lesions is associated with poor prognosis. Hydroxychloroquine (HCQ) has been reported to improve the lifespan and the prognosis of dyslipidaemia in patients with SLE, but the mechanism is unclear. We investigated the effect of supplemental HCQ treatment on the levels of serum cytokines associated with atherosclerosis in patients with stable SLE.. Patients with SLE who received supplemental HCQ and maintained low disease activity between January 2016 and September 2020 were included in this study. Disease activity was assessed using Safety of Estrogens in Lupus National Assessment-SLE Disease Activity Index, Cutaneous Lupus Erythematous Disease Area and Severity Index, and Lupus Low Disease Activity State. Serum complement titres, anti-dsDNA antibodies, and serum cytokines (adiponectin, resistin, and leptin) were analyzed before and after HCQ treatment.. Forty-one patients (4 males and 37 females, mean age 41.3 ± 13.2 years) were included. Serum adiponectin levels were significantly increased after 3 months of HCQ treatment compared to baseline, and serum resistin levels were significantly reduced. The change in serum resistin level after HCQ administration was correlated with a significant reduction in serum TNF-α, interleukin (IL)-6, IL-8, and IL-1RA levels.. Supplemental HCQ treatment in patients with SLE improved adipokine levels. HCQ may improve prognosis by controlling disease activity in SLE and reducing risk factors for atherosclerosis. Key Points • Hydroxychloroquine has been reported to improve the prognosis of dyslipidaemia in patients with SLE, but the underlying mechanism is unclear. • In this study, hydroxychloroquine improved adipokine levels in patients with SLE, implicating adipokines as a potential mechanism underlying the benefit of hydroxychloroquine on dyslipidaemia. • Supplemental hydroxychloroquine should be considered in patients with SLE harboring lipid abnormalities and risk factors for atherosclerosis.

Topics: Adipokines; Adiponectin; Adult; Antibodies, Antinuclear; Antirheumatic Agents; Atherosclerosis; Cytokines; Estrogens; Female; Humans; Hydroxychloroquine; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Leptin; Lipids; Lupus Erythematosus, Systemic; Male; Middle Aged; Resistin; Tumor Necrosis Factor-alpha

Diabetes mellitus (DM) is a significant predictor of atherosclerosis, cardiovascular disease, and cardiovascular mortality. It is known that atherosclerosis occurs earlier in patients with diabetes, reducing the duration of their life. Leptin as well as other inflammatory markers can contribute to the progression of atherosclerosis in patients with DM, participate in the development of a local inflammatory reaction.. Determine the cells immunophenotype of atherosclerotic plaques in patients with diabetes.. We analyzed 24 patients (20 men and 4 women), who underwent aortofemoral bypass, femoral-tibial bypass or carotid endarterectomy. During the operation, a fragment of the arterial wall with an atherosclerotic plaque was obtained for further immunohistochemical studies. Five histologic plaque characteristics (CD68+, -SMA, CD34, leptin and leptin receptor) were compared.. No difference in the expression of CD68 (p=0.922), -SMA (p=0.192), CD34 (p=0.858), leptin receptor (p=0.741) and leptin (p=0.610) in atherosclerotic plaques were observed between patients with and without DM. The lack of significant differences between the two groups was possibly due to the small number of observations with DM. In particular, when assessing the expression of selected markers in atherosclerotic plaques, patients with DM showed significantly more leptin receptors than patients without DM (2160.716 and 1205.88 respectively); and also significantly less CD68+ (0.39 and 0.98 respectively) and -SMA+ (6.5 and 13.5 respectively).. Based on the expression of CD68, -SMA, CD34, leptin receptor and leptin, no significant differences were observed in atherosclerotic plaque between patients with and without DM. At the same time, despite the limitations of the study (a small number of patients, moderate severity of DM, elderly patients in the DM group), we found a tendency in the increased number of leptin receptors and a decreased number of -SMA+, CD68+ in DM atherosclerotic plaques. Further study needed, taking into account the limitations of this work.. Обоснование. Сахарный диабет (СД) является важным предиктором развития атеросклероза, сердечно-сосудистых заболеваний и смертности от сердечно-сосудистых заболеваний. Известно, что у больных СД атеросклероз возникает раньше, сокращая продолжительность их трудовой деятельности и жизни. Лептин, как и маркеры воспаления, могут способствовать прогрессированию атеросклероза при СД, участвовать в развитии местной воспалительной реакции и патогенезе развития атеросклеротической бляшки. Цель. Изучить иммунофенотип клеток, входящих в состав атеросклеротических бляшек у пациентов с СД. Материалы и методы. Проведено наблюдательное одномоментное двухцентровое исследование, в которое включены 24 пациента (20 мужчин и 4 женщины), подвергшиеся аорто-феморальному, бедренно-берцовому шунтированию или каротидной эндартерэктомии. В ходе проведения операции получен фрагмент артериальной стенки с атеросклеротической бляшкой для дальнейшего проведения иммуногистохимического исследования: оценки экспрессии CD68+ макрофагов, -SMA (-гладкомышечный актин), CD34, лептина и рецептора лептина. Результаты. При сравнении результатов оценки экспрессии CD68 (p=0,922), -SMA (p=0,192), CD34 (p=0,858), рецептора лептина (p=0,741) и лептина (p=0,610) в атеросклеротических бляшках статистически значимых различий между группами пациентов с СД и без СД не выявлено. Отсутствие достоверных различий между двумя группами, возможно, обусловлено небольшим количеством наблюдений пациентов с СД. В частности, при оценке экспрессии выбранных маркеров в атеросклеротических бляшках у больных СД отмечено значительно больше рецепторов лептина, чем у лиц без СД (2160,716 и 1205,88 соответственно), а также значительно меньше CD68+ (0,39 и 0,98 соответственно) и -SMA+ (6,5 и 13,5 соответственно). Заключение. На основании оценки экспрессии CD68, -SMA, CD34, рецептора лептина и лептина не выявлено достоверных различий в структуре атеросклеротической бляшки у пациентов с СД и без. В то же время, несмотря на ограничения исследования (небольшое число больных, умеренная тяжесть СД, пожилой возраст пациентов в группе с нарушением углеводного обмена), мы обнаружили тенденцию в увеличении количества рецепторов лептина и уменьшении количества -SMA+, CD68+ у больных СД. Требуется дальнейшее изучение этой проблемы с учетом ограничений данной работы.

Topics: Aged; Atherosclerosis; Biomarkers; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Male; Plaque, Atherosclerotic; Receptors, Leptin

Topics: Atherosclerosis; Biomarkers; Humans; Leptin; Sleep Apnea, Obstructive; Ultrasonography

Exposure to fine particulate matter (PM

Topics: Adipose Tissue; Air Pollution; Animals; Aortic Diseases; Atherosclerosis; Diet, High-Fat; Gene Expression Regulation; Inflammation; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Particulate Matter; Superoxide Dismutase

In a condition of dysfunctional visceral fat depots, as in the case of obesity, alterations in adipokine levels may be detrimental for the cardiovascular system. The proinflammatory leptin and resistin adipokines have been described as possible links between obesity and atherosclerosis. The present study was aimed at evaluating whether proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein metabolism, is induced by leptin and resistin through the involvement of the inflammatory pathway of STAT3. In HepG2 cells, leptin and resistin up-regulated PCSK9 gene and protein expression, as well as the phosphorylation of STAT3. Upon STAT3 silencing, leptin and resistin lost their ability to activate PCSK9. The knockdown of STAT3 did not affect the expression of leptin and resistin receptors or that of PCSK9. The analysis of the human PCSK9 promoter region showed that the two adipokines raised PCSK9 promoter activity via the involvement of a sterol regulatory element motif. In healthy males, a positive association between circulating leptin and PCSK9 levels was found only when the body mass index was <25 kg/m

Topics: Atherosclerosis; Gene Expression Regulation, Enzymologic; Hep G2 Cells; Humans; Leptin; Obesity; Proprotein Convertase 9; Resistin; Response Elements; STAT3 Transcription Factor; Up-Regulation

Previously, apoE-derived ABCA1 agonist peptides have been shown to possess anti-atherosclerotic and possibly antidiabetic properties. Here we assessed the in vitro and in vivo actions of a second generation of ABCA1 peptide agonists, CS6253 and T6991-2, on glucose homeostasis. The results show that these two peptides improve glucose tolerance in a prediabetic diet-induced obesity mouse model by enhancing insulin secretion. It was further demonstrated that T6991-2 also improved glucose tolerance in leptin-deficient (ob/ob) mice. CS6253 increased insulin secretion both under basal conditions and in response to high glucose stimulation in pancreatic INS-1 β-cells rendered leptin receptor deficient with specific siRNA. Additional in vitro cell studies suggest that the CS6253 agonist attenuates hepatic gluconeogenesis and glucose transport. It also potentiates insulin-stimulated glucose uptake and utilization. These observed anti-diabetic actions suggest additional benefits of the CS6253 and T6991-2 ABCA1 peptide agonists for cardiovascular disease beyond their direct anti-atherosclerosis properties previously described.

Topics: Animals; Atherosclerosis; ATP Binding Cassette Transporter 1; Cell Line; Cell Line, Tumor; Diet, High-Fat; Disease Models, Animal; Exenatide; Gluconeogenesis; Glucose; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Resistance; Insulin Secretion; Leptin; Liver; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; Peptides; Rats; Triglycerides

Diospyros (D.) lotus has been demonstrated to have antioxidant and anti‑inflammatory properties. The purpose of the present study was to evaluate the effect of D. lotus leaf water extract (DLE) on high‑fat diet (HFD)‑induced obesity in C57BL/6 mice. The present study first investigated the effect of DLE on the lipid accumulation and triglyceride (TG) contents in 3T3‑L1 cells, and the results revealed that treatment with DLE suppressed the lipid accumulation and TG level. Subsequently, the anti‑obesity effects of DLE were investigated in vivo. Oral administration of DLE reduced the body weight gain, food efficiency ratio, and liver and visceral fat weight in mice fed with a HFD. DLE administration in these mice also reduced TG, total cholesterol, low‑density lipoprotein cholesterol, glucose, insulin and leptin levels, as well as the atherogenic index. Furthermore, DLE administration decreased hepatic steatosis, as well as serum aspartate transaminase, alanine transaminase and alkaline phosphatase levels in mice fed with HFD. It was further observed that treatment of the HFD‑fed mice with DLE prevented lipid peroxidation, while it recovered glutathione depletion and the activities of superoxide dismutase, catalase and glutathione peroxidase. In conclusion, the current study suggests that the anti‑obesity effect of DLE may provide positive insights as a potential functional food ingredient for the prevention of obesity.

Topics: 3T3-L1 Cells; Animals; Anti-Obesity Agents; Atherosclerosis; Blood Glucose; Body Weight; Diet, High-Fat; Diospyros; Feeding Behavior; Insulin; Intra-Abdominal Fat; Leptin; Lipid Metabolism; Lipid Peroxidation; Lipids; Liver; Liver Function Tests; Male; Mice; Mice, Inbred C57BL; Obesity; Oxidative Stress; Phytochemicals; Plant Extracts; Plant Leaves

Stabilin-1 (STAB1) is a scavenger receptor expressed on alternatively activated macrophages and sinusoidal endothelial cells. Its ligands include oxidized low-density lipoprotein (LDL) and the extracellular matrix glycoprotein SPARC and it is present in both human and murine atherosclerotic lesions. We aimed to investigate the effect of specific deletion of STAB1 in bone marrow-derived cells, including macrophages on atherosclerotic lesion formation in mice.. Lethally irradiated hypercholesterolemic LDL receptor knockout mice received either wildtype (WT) or STAB1 knockout (STAB1 KO) bone marrow. Bone marrow transplanted mice were fed a Western-type diet for 9 weeks to induce atherosclerotic lesion formation.. Interestingly, LDL receptor knockout mice reconstituted with STAB1 KO bone marrow showed increased body weight gain (two-way ANOVA: p < 0.001) and larger white adipocyte cell sizes (43% increase in cell area; p < 0.05) as compared to WT bone marrow transplanted mice, which correlated positively (r = 0.82; p < 0.001). This was paralleled by a significant increase in white adipose tissue relative mRNA expression levels of the adipokine leptin (+94% p < 0.05). Despite these changes, no differences in serum lipid levels, the extent of in vivo macrophage foam cell formation or circulating leukocyte concentrations were observed. Moreover, the size and composition of atherosclerotic lesions was not different between the two experimental groups.. Bone marrow-specific Stabilin-1 deletion does not affect the susceptibility for atherosclerosis in mice. However, the increased body weight gain and adipocyte cell size highlight a potential role for leukocyte STAB1 in the development of metabolic disorders.

Topics: Adipocytes, White; Adipose Tissue, White; Animals; Aortic Diseases; Atherosclerosis; Cell Adhesion Molecules, Neuronal; Diet, Western; Disease Models, Animal; Foam Cells; Hypercholesterolemia; Leptin; Male; Mice, Inbred C57BL; Mice, Knockout; Plaque, Atherosclerotic; Receptors, LDL; Weight Gain

A great debate in literature exists nowadays on the role of uric acid as a marker of cardiovascular and metabolic organ damage or a risk factor for cardiovascular and metabolic disease.. The study aimed to determine the relationship among serum uric acid and metabolic syndrome and atherosclerosis, by means of carotid intima media-thickness, in a cohort of 811 otherwise healthy overweight/obese subjects, without overt atherosclerosis not using any kind of drug.. Uric acid levels were positively related to male gender, waist circumference, BMI, systolic and diastolic pressure levels, fasting insulin, fasting glucose, HOMA-IR, triglycerides, total cholesterol, LDL cholesterol, the presence of metabolic syndrome and the number of the components of metabolic syndrome and negatively related to HDL cholesterol levels. No correlation was found between uric acid and carotid intima media thickness. At the multiple regression analysis, only waist circumference and triglycerides (positively) and HDL-cholesterol (negatively) maintained an independent association with uric acid as dependent variable, while age, female gender and uric acid showed a significant independent association with metabolic syndrome as dependent variable. Moreover, the analysis of the odd ratios showed that the risk of developing metabolic syndrome was consistent with uric acid levels ranging from 3 mg/dl to 8 mg/dl.. The presence of metabolic syndrome does not seem to provide hyperuricemia. By contrast, higher serum uric acid level may predict the risk of metabolic syndrome. Moreover, our results suggest that uric acid cannot be considered a risk factor for early atherosclerosis, at least when assessed using carotid ultrasound.

Topics: Adult; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Overweight; Uric Acid; Waist Circumference

Topics: Adipokines; Adiponectin; Adolescent; Adult; Aged; Atherosclerosis; Carotid Intima-Media Thickness; Chemokines; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Lupus Erythematosus, Systemic; Middle Aged; Resistin; Young Adult

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

Aim To assess subclinical atherosclerosis and the role of inflammatory mediators, vascular endothelial cell activation markers and adipocytokines in systemic lupus erythematosus (SLE) in the presence or absence of metabolic syndrome (MetS). Methods We studied 66 premenopausal female SLE patients (20 with MetS) and 28 female healthy controls (HCs) without history of cardiovascular disease (CVD). Subclinical atherosclerosis was screened by measuring carotid intima media thickness (CIMT). Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor α (TNFα), interleukin 6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin, leptin and visfatin were measured. Results The mean age of MetS

Topics: Adult; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Case-Control Studies; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome

Atherosclerosis is a chronic inflammatory disease that is promoted, among others, by pro-inflammatory cytokines such as IL-1β and IL-18 produced by NLRP 3 inflammasome. Development of atherosclerotic lesions is also affected by leptin. Furthermore, inflammasome's action is interfered with other inflammatory diseases, like diabetes. On the other hand, colchicine is reported to act as anti-inflammatory agent inhibiting inflammasome's action and stabilizing atherosclerotic lesions. The purpose of this study is to investigate the effect of per os colchicine on the de novo formation of atherosclerotic lesions and on the levels of IL-18, leptin and insulin in cholesterol-fed rabbits.. Twenty-three male, 2 months old New Zealand White rabbits, were seperated in 3 groups and were fed with different types of diet for 7 weeks: standard, cholesterol 1% w/w and cholesterol 1% w/w plus colchicine 2 mg/kg body weight. Blood was collected for biochemical measurements and conduction of ELISA for leptin, IL-18 and insulin. Histologic examination of stained with eosin and hematoxylin aorta specimens was performed. Aortic intimal thickness was evaluated using image analysis. The statistical analysis included non-parametric tests: a) paired-sample Wilcoxon test, b) Spearman correlation coefficient and c) Kruscal-Wallis test.. Triglerycide levels were decreased in cholesterol plus colchicine group in the end of the experiment (p < 0.05), whereas the cholesterol group had increased levels. No statistical differences were observed in the levels of IL-18, leptin and insulin between groups. Likewise, there was neither any correlation between IL-18, leptin and intima thickness nor between IL-18 and glucose and between leptin and weight. In cholesterol and colchicine group there was a strong positive correlation between IL-18 and insulin levels in the 4th week (r. Per os administration of colchicine did not influence atherosclerosis progression in cholesterol-fed rabbits, levels of IL-18, insulin and leptin. We encountered the attenuating role of colchicine on TG levels.

Topics: Administration, Oral; Animals; Aorta; Atherosclerosis; Blood Glucose; Cholesterol, Dietary; Colchicine; Insulin; Interleukin-18; Leptin; Lipid Metabolism; Male; Rabbits; Triglycerides; Tunica Intima

Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life, but the mechanism remains unclear. Adipokine imbalance in the presence of metabolic dysfunction may be a key event in promoting CVD. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma adiponectin, leptin and the leptin/adiponectin (L/A) ratio in pregnancy and at 5 years after the index pregnancy.. This population-based prospective cohort included 300 women who had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy X-ray absorptiometry, lipid analysis, and pulse wave velocity analysis. Fasting adiponectin and leptin levels were measured four times during pregnancy and at follow-up.. We found the L/A ratio higher in GDM women both during pregnancy and follow-up compared to non-GDM women. A high L/A ratio during pregnancy was associated with CV risk based on lipid ratios at follow-up, especially the TG/HDL-C ratio. Further, interaction analysis indicated that an increase in the L/A ratio of 1 unit was associated with a higher CV risk in GDM compared to normal pregnancy. Finally, low adiponectin levels independently predicted increased lipid ratios at follow-up.. Taken together, our findings suggest that high L/A ratio in pregnancy and in particularly in those with GDM are associated with an unfavorable CVD risk profile during follow-up. Future studies should investigate if a dysregulated leptin and adiponectin profile during pregnancy is associated with atherosclerotic disease during long-term follow-up.

Topics: Absorptiometry, Photon; Adiponectin; Adult; Atherosclerosis; Biomarkers; Case-Control Studies; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Leptin; Lipids; Longitudinal Studies; Pregnancy; Prognosis; Prospective Studies; Pulse Wave Analysis; Risk Assessment; Risk Factors; Time Factors

Cytochrome oxidase IV complex regulates energy production in mitochondria. Therefore, we determined the relation of COX genes with atherosclerosis in mice and pigs.. First, we compared atherosclerosis in the aortic arch of age-matched (24 weeks) C57BL/6J control (n = 10), LDL-receptor deficient (n = 8), leptin-deficient ob/ob (n = 10), and double knock-out (lacking LDL-receptor and leptin) mice (n = 12). Low aortic mitochondria-encoded cytochrome oxidase 1 in obese diabetic double knock-out mice was associated with a larger plaque area and higher propensity of M1 macrophages and oxidized LDL. Caloric restriction increased mitochondria-encoded cytochrome oxidase 1 and reduced plaque area and oxidized LDL. This was associated with a reduction of titer of anti-oxidized LDL antibodies, a proxy of systemic oxidative stress. Low of mitochondria-encoded cytochrome oxidase 1 was related to low expression of peroxisome proliferative activated receptors α, δ, and γ and of peroxisome proliferative activated receptor, gamma, co-activator 1 alpha reflecting mitochondrial dysfunction. Caloric restriction increased them. To investigate if there was a diabetic/obesity requirement for mitochondria-encoded cytochrome oxidase 1 to be down-regulated, we then studied atherosclerosis in LAD of hypercholesterolemic pigs (n = 37). Pigs at the end of the study were divided in three groups based on increasing LAD plaque complexity according to Stary (Stary I: n = 12; Stary II: n = 13; Stary III: n = 12). Low mitochondria-encoded cytochrome oxidase 1 in isolated plaque macrophages was associated with more complex coronary plaques and oxidized LDL. Nucleus-encoded cytochrome oxidase 4I1 and cytochrome oxidase 10 did not correlate with plaque complexity and oxidative stress. In mice and pigs, MT-COI was inversely related to insulin resistance.. Low MT-COI is related to mitochondrial dysfunction, oxidative stress and atherosclerosis and plaque complexity.

Topics: Animals; Aorta, Thoracic; Atherosclerosis; Caloric Restriction; Coronary Vessels; Cytochrome-c Oxidase Deficiency; Diabetes Mellitus, Experimental; Electron Transport Complex IV; Energy Metabolism; Hypercholesterolemia; Insulin Resistance; Leptin; Lipoproteins, LDL; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Mitochondria; Nuclear Receptor Coactivators; Oxidative Stress; Peroxisome Proliferator-Activated Receptors; Plaque, Atherosclerotic; Receptors, LDL; Receptors, Leptin; Swine; Swine, Miniature

Conflicting evidence concerning leptin in atherosclerosis has been published. Furthermore, dose-dependent effects of leptin on atherogenesis have not been studied.. Leptin-deficient low-density lipoprotein receptor (LDLR) knockout (LDLR(-/-);ob/ob) mice were treated with saline, 0.1, 0.5, or 3.0mg/kg body weight (BW)/d recombinant leptin over 12weeks starting at 8weeks of age. Aortic root and brachiocephalic artery (BCA) atherosclerotic lesions were analyzed by oil red O staining. Furthermore, glucose homeostasis, lipid metabolism, and liver function including tissue studies were assessed in all animals.. Leptin treatment dose-dependently decreased BW in LDLR(-/-);ob/ob mice as compared to saline. Mice in the 0.1 and 0.5mg/kgBW/d groups remained heavier (i.e. subphysiological leptin dose) and in the 3.0mg/kgBW/d group had similar weight (i.e. physiological leptin dose) as compared to non-leptin-deficient LDLR(-/-) animals. Recombinant leptin dose-dependently reduced plaque area in the aortic root and the BCA by 36% and 58%, respectively. Leptin-mediated reductions of plasma total and LDL-cholesterol (Chol) remained independent predictors for aortic root plaque area. Chol content in liver, as well as hepatic expression of key lipid and proinflammatory genes, were dose-dependently regulated by leptin. Furthermore, leptin treatment increased circulating levels and adipose tissue mRNA expression of the adipokine adiponectin.. Leptin administration within the subphysiological to physiological range diminishes atherosclerotic lesions. Leptin appears to mediate its antiatherogenic effects indirectly through reduction of hypercholesterolemia and liver steatosis, as well as upregulation of insulin-sensitizing and atheroprotective adiponectin.

Topics: Adiponectin; Animals; Anticholesteremic Agents; Atherosclerosis; Cholesterol; Fatty Liver; Hypercholesterolemia; Insulin; Leptin; Lipid Metabolism; Male; Mice; Recombinant Proteins

Peroxisome proliferator-activated receptor gamma (PPARγ) regulates multiple pathways involved in the pathogenesis of obesity and atherosclerosis. Here, we evaluated the therapeutic potential of GQ-177, a new thiazolidinedione, on diet-induced obesity and atherosclerosis. The intermolecular interaction between PPARγ and GQ-177 was examined by virtual docking and PPAR activation was determined by reporter gene assay identifying GQ-177 as a partial and selective PPARγ agonist. For the evaluation of biological activity of GQ-177, low-density lipoprotein receptor-deficient (LDLr(-/-)) C57/BL6 mice were fed either a high fat diabetogenic diet (diet-induced obesity), or a high fat atherogenic diet, and treated with vehicle, GQ-177 (20mg/kg/day), pioglitazone (20mg/kg/day, diet-induced obesity model) or rosiglitazone (15mg/kg/day, atherosclerosis model) for 28 days. In diet-induced obesity mice, GQ-177 improved insulin sensitivity and lipid profile, increased plasma adiponectin and GLUT4 mRNA in adipose tissue, without affecting body weight, food consumption, fat accumulation and bone density. Moreover, GQ-177 enhanced hepatic mRNA levels of proteins involved in lipid metabolism. In the atherosclerosis mice, GQ-177 inhibited atherosclerotic lesion progression, increased plasma HDL and mRNA levels of PPARγ and ATP-binding cassette A1 in atherosclerotic lesions. GQ-177 acts as a partial PPARγ agonist that improves obesity-associated insulin resistance and dyslipidemia with atheroprotective effects in LDLr(-/-) mice.

Topics: Adiponectin; Adipose Tissue; Animals; Aorta, Thoracic; Atherosclerosis; Bone Density; Cell Line; Cholesterol, HDL; Fibroblast Growth Factors; Glucose Transporter Type 4; Humans; Leptin; Liver; Male; Mice, Knockout; Models, Molecular; Myocardium; Obesity; PPAR gamma; Receptors, LDL; Sulfones; Thiazolidinediones

Fat radiodensity, as measured by fat attenuation on computed tomography (CT), has emerged as a potential biomarker of "fat quality." We sought to characterize the relationship between fat radiodensity and quantity in subcutaneous, visceral, and intermuscular fat depots, and its role in inflammation, insulin resistance, and metabolic syndrome (MetS).. We studied 1511 individuals from the Multi-Ethnic Study of Atherosclerosis who underwent CT for measurement of regional fat distribution and radiodensity, along with biomarker assessments and adjudication of incident metabolic syndrome (MetS). Linear, logistic and Cox regression analyses were used to measure association between fat radiodensity and (1) fat quantity, (2) biomarkers of cardiometabolic dysfunction, and (3) both prevalent and incident MetS. In each fat depot, radiodensity was strongly and inversely associated with quantity (e.g., visceral fat radiodensity vs. quantity: ρ = -0.82, P < 0.01). After adjustment for age, sex and race, lower visceral fat radiodensity was associated with greater C-reactive protein, leptin and insulin, but lower adiponectin (P < 0.01 for all). After full adjustment for cardiovascular disease risk factors, visceral (but not subcutaneous or intermuscular) fat radiodensity was associated with prevalent MetS (OR = 0.96, 95% CI = 0.93-0.99, P = 0.01). Moreover, lower visceral fat radiodensity was associated with incident MetS after the same adjustment (HR = 0.95, 95% CI 0.93-0.98, P < 0.01). However, this association became non-significant after further adjustment for visceral fat quantity.. Fat radiodensity is strongly correlated with fat quantity and relevant inflammatory biomarkers. Fat radiodensity (especially for visceral fat) may be a complementary, easily assessed marker of cardiometabolic risk.

Topics: Abdominal Fat; Adiponectin; Adiposity; Aged; Atherosclerosis; Biomarkers; C-Reactive Protein; Female; Humans; Incidence; Insulin; Intra-Abdominal Fat; Leptin; Linear Models; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Prevalence; Proportional Hazards Models; Risk Factors; Subcutaneous Fat, Abdominal; Tomography, X-Ray Computed; United States

Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE(-/-) mice showed greater hypertriglyceridemia than the obtained in ApoE(-/-) and hypercholesterolemia similar to ApoE(-/-) mice. BATIRKO;ApoE(-/-) mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-α and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations.

Topics: Adiponectin; Adipose Tissue, Brown; Adipose Tissue, White; Adiposity; Animals; Apolipoproteins E; Atherosclerosis; Biomarkers; Diabetes Mellitus, Experimental; Diabetes Mellitus, Lipoatrophic; Glucose; Insulin Resistance; Leptin; Lipid Metabolism; Male; Mice, Inbred C57BL; Mice, Knockout; Receptor, Insulin; Tumor Necrosis Factor-alpha

Among obese individuals, increased sympathetic nervous system (SNS) activity results in increased renin and aldosterone production, as well as renal tubular sodium reabsorption. This study determined the associations between adipokines and selected measures of the renin-angiotensinogen-aldosterone system (RAAS). The sample consisted of 1970 men and women from the Multi-Ethnic Study of Atherosclerosis who were free of clinical cardiovascular disease at baseline and had blood assayed for adiponectin, leptin, plasma renin activity (PRA) and aldosterone. The mean age was 64.7 years and 50% were female. The mean (s.d.) PRA and aldosterone were 1.45 (0.56) ng ml(-1) and 150.1 (130.5) pg ml(-1), respectively. After multivariable adjustment, a 1-s.d. increment of leptin was associated with a 0.55 ng ml(-1) higher PRA and 8.4 pg ml(-1) higher aldosterone (P<0.01 for both). Although adiponectin was not significantly associated with PRA levels, the same increment in this adipokine was associated with lower aldosterone levels (-5.5 pg ml(-1), P=0.01). Notably, the associations between aldosterone and both leptin and adiponectin were not materially changed with additional adjustment for PRA. Exclusion of those taking antihypertensive medications modestly attenuated the associations. The associations between leptin and both PRA and aldosterone were not different by gender but were significantly stronger among non-Hispanic Whites and Chinese Americans than African and Hispanic Americans (P<0.01). The findings suggest that both adiponectin and leptin may be relevant to blood pressure regulation via the RAAS, in that the associations appear to be robust to antihypertension medication use and that the associations are likely different by ethnicity.

Topics: Adiponectin; Aged; Aldosterone; Antihypertensive Agents; Atherosclerosis; Body Mass Index; Female; Humans; Leptin; Longitudinal Studies; Male; Middle Aged; Renin; Renin-Angiotensin System

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

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

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

To investigate the relation of epicardial adipose tissue volume (EATV) determined by dual-source CT (DSCT) cardiac angiography and EAT-derived inflammatory factors to coronary heart disease (CHD) and vulnerable plaque.. A total of 260 patients underwent cardiac computed tomography to evaluate stenosis of coronary artery, and blood samples were obtained from each patient. CHD was confirmed in 180 patients by DSA and CHD was excluded in the remaining 80 patients (NCHD). Vascular remodeling index and plaque vulnerability parameters (fatty volume, fibrous volume and calcification volume and fiber volume) were measured in CHD patients and correlation with EATV was analyzed. Epicardial adipose tissue (EAT) and intrathoracic adipose tissue (TAT) were collected from 40 CHD patients undergoing CABG surgery, and, mRNA and protein expressions of leptin and MMP9 were detected by RT-PCR and Western blot analysis.. (1) The EATV was significantly higher in the CHD group than in NCHD group ((121.2 ± 40.6) mm³ vs. (74.7 ± 18.1) mm³, P = 0.01). (2) Subgroup analysis of the CHD patients demonstrated that EATV was significantly higher in patients with positive remodeling than in patients without positive remodeling ((97.6 ± 42.0) cm³ vs. (75.5 ± 25.4) cm³, P = 0.01). Lipid plaque volume was positively correlated with EATV (r = 0.34, P = 0.002); however, fiber plaque volume was negatively correlated with EATV (r = -0.30, P = 0.008). (3) Logistic regression analysis indicated that EATV was an independent risk factor for positive vascular remodeling (OR = 2.01, 95% CI: 1.30-2.32, P = 0.01). (4) mRNA and protein expression of leptin and MMP9 in EAT was significantly upregulated in 40 CHD patients who received CABG surgery compared to 40 NCHD patients (P < 0.01). However, there was no significant difference (P > 0.05) in mRNA and protein expression of leptin and MMP9 from the SAT between CHD and NCHD patients. (5) In the CHD group, leptin and MMP9 levels in EAT and EATV were positively correlated with lipid plaque volume and fibrous plaque volume (P < 0.05).. EATV is an independent risk factors of coronary heart disease and plaque vulnerability; EAT secretion of inflammatory cytokines from CHD patients is significant increased compared to NCHD patients, EAT secretion of inflammatory cytokines are positively correlated with EATV, both of which are determinants affecting vascular remodeling. Reducing EATV might help to attenuate inflammation and plaque vulnerability and reduce the risk of coronary heart disease.

Topics: Adipose Tissue; Angiography; Atherosclerosis; Calcinosis; Constriction, Pathologic; Coronary Artery Disease; Fibrosis; Humans; Leptin; Pericardium; Plaque, Atherosclerotic; Risk Factors; Tomography, X-Ray Computed

Earlier studies differ on whether serum leptin is associated with adverse or beneficial cardiac structure. We determined the association between serum leptin with subsequent cardiac structure and function.. MESA is a multicenter longitudinal study of Black, White, Hispanic and Asian-American men and women. Cardiac MRI (CMR) was completed 6 to 8 years after leptin was measured. Left ventricular (LV) mass and volumes were indexed to body surface area. Multivariable linear regression models were constructed to assess the associations between leptin and risk factor adjusted (age, race, gender, systolic blood pressure, anti-hypertensive usage, LDL, HDL, hyperlipidemia medication usage, diabetes, diabetic medication usage, chronic kidney disease, alcohol and tobacco use, adiponectin and BMI) CMR variables.. Relative to participants in the lowest quintile of leptin concentration, participants in the highest quintile had a lower risk factor adjusted LV mass (-14 g), LV mass index (-9 g/m(2)), LV end diastolic volume index (LVEDVi) (-7 ml/m(2)), LV end systolic volume index (LVESVi) (-3 ml/m(2)) and stroke volume (-5 ml) (all p≤0.05). On regression analysis, a doubling of leptin concentration was associated with lower LV mass (-2.5 g ± 0.7 g), LV mass index (-1.7 ± 0.3g/m(2)), LVEDVi (-1.5 ± 0.4 ml/m(2)), LVESVi (-0.7 ± 0.2 ml/m(2)) and stroke volume (-1.0 ± 0.5 ml) (all p ≤ 0.05).. Higher leptin was associated with more favorable subsequent cardiac structure. Further study is needed to assess the prognostic and therapeutic implications of these observations.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Echocardiography; Ethnicity; Female; Follow-Up Studies; Heart Ventricles; Humans; Incidence; Leptin; Male; Middle Aged; Risk Factors; Stroke Volume; United States; Ventricular Function, Left; Ventricular Remodeling

To investigate the associations between selected adipokines and the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP).. As many as 1489 individuals enrolled in the Multi-Ethnic Study of Atherosclerosis were evaluated at 4 clinic visits about every 2 years. The evaluation included fasting venous blood, which was analyzed for NT-proBNP (at visits 1 and 3) and the adipokines adiponectin and leptin (at visits 2 and 3). The mean age was 64.8 ± 9.6 years and 48% were female. After multivariable adjustment, a 1-SD increment in adiponectin was associated with a 14 pg/ml higher NT-proBNP level (p < 0.01), while, compared to the 1st quartile of adiponectin, the 2nd, 3rd and 4th quartiles had 28, 45 and 67% higher NT-proBNP levels (p < 0.01 for all). For changes in NT-proBNP over the follow-up period, and after multivariable adjustment including baseline NT-proBNP, a 1-SD increment in adiponectin was associated with a 25 pg/ml absolute increase in NT-proBNP (p < 0.01), while those in the 2nd, 3rd and 4th quartiles of adiponectin were associated with increases of 5, 28 and 65 pg/ml (p = 0.74, 0.09 and <0.01, respectively). There was a significant interaction between adiponectin and sex for visit 3 NT-proBNP (p-interaction < 0.01), with significantly stronger associations in men. Leptin was not associated with NT-proBNP.. Higher adiponectin, but not leptin, is significantly associated with higher levels of NT-proBNP, as well as with greater longitudinal increases in NT-proBNP. The associations were stronger in men.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Female; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Sex Factors

Identifying psoriasis patients who present a higher risk of developing cardiovascular co-morbidities is of upmost importance. Two key adipokines, leptin and adiponectin, may play a role connecting psoriasis and its major co-morbidities.. To evaluate the potential contribution of LEPrs2167270(19 G/A), LEPRrs1137100(326 A/G) and ADIPOQrs1501299(276 G/T) gene polymorphisms in psoriasis susceptibility and their influence in epicardial adipose tissue and abdominal visceral fat volume and subclinical atherosclerosis in severe psoriasis patients.. One hundred severe psoriasis patients underwent clinical and laboratory evaluation, DNA genotyping and multi-detector computed tomography scan for epicardial adipose tissue, abdominal visceral fat and coronary artery calcification assessment. DNA control group was obtained from a previously anonymized biobank of 206 adult subjects without psoriasis.. No association was observed between the studied gene polymorphisms and psoriasis susceptibility, CAC or increased EAT or AVF volume.. The studied polymorphisms do not seem, at least in this cohort of patients, to be a genetic risk factor for the development of atherosclerosis or increased adiposity in psoriasis.

Topics: Adiponectin; Adult; Aged; Atherosclerosis; Calcinosis; Cohort Studies; Coronary Vessels; Female; Gene Expression; Genotype; Humans; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity; Pericardium; Polymorphism, Single Nucleotide; Psoriasis; Receptors, Leptin; Severity of Illness Index

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

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

Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E-deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis.

Topics: Animals; Apolipoprotein A-I; Apolipoproteins E; Atherosclerosis; Cholesterol; Cholesterol, HDL; Diet, Atherogenic; Drug Evaluation, Preclinical; Gene Expression Regulation; Genetic Therapy; Genetic Vectors; Genome-Wide Association Study; Hep G2 Cells; Humans; Hyperlipoproteinemia Type II; Kruppel-Like Transcription Factors; Leptin; Liver; Mice; Mice, Inbred C57BL; Mice, Obese; Perhexiline; Recombinant Fusion Proteins; RNA, Messenger; Sp Transcription Factors; Sterol Regulatory Element Binding Proteins

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

An increased frequency of atherosclerosis (ATH) in systemic lupus erythematosus (SLE) is well-documented but not fully explained by the presence of traditional cardiac risk factors. Several nontraditional biomarkers, including proinflammatory high-density lipoprotein (piHDL) and leptin, have been individually associated with subclinical ATH in SLE. The aim of this study was to examine whether these and other biomarkers can be combined into a risk profile, the Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular Disease in Patients with SLE (PREDICTS), that could be used to better predict future progression of ATH.. In total, 210 patients with SLE and 100 age-matched healthy control subjects (all women) participated in this prospective cohort study. The longitudinal presence of carotid plaque and intima-media thickness (IMT) were measured at baseline and followup (mean ± SD 29.6 ± 9.7 months).. At followup, carotid plaque was present in 29% of SLE patients. Factors significantly associated with plaque, determined using Salford Predictive Modeling and multivariate analysis, included age ≥48 years (odds ratio [OR] 4.1, P = 0.002), high piHDL function (OR 9.1, P < 0.001), leptin levels ≥34 ng/dl (OR 7.3, P = 0.001), plasma soluble TWEAK levels ≥373 pg/ml (OR 28.8, P = 0.004), and history of diabetes (OR 61.8, P < 0.001). Homocysteine levels ≥12 μmoles/liter were also a predictor. However, no single variable demonstrated an ideal combination of good negative predictive values (NPVs), positive predictive values (PPVs), sensitivity, and specificity. A high-risk PREDICTS profile was defined as ≥3 positive biomarkers or ≥1 positive biomarker plus a history of diabetes; for high-risk SLE patients, the PPV was 64%, NPV was 94%, sensitivity was 89%, and specificity was 79%. In multivariate analysis, SLE patients with the high-risk profile had 28-fold increased odds for the longitudinal presence of plaque (P < 0.001) and increased progression of IMT (P < 0.001).. A high-risk PREDICTS score confers 28-fold increased odds of the presence of any current, progressive, or acquired carotid plaque, both in patients with SLE and in control subjects, and is significantly associated with higher rates of IMT progression.

Topics: Adiponectin; Adult; Age Factors; Apolipoprotein A-I; Atherosclerosis; Biomarkers; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Cytokine TWEAK; Diabetes Complications; Diabetes Mellitus; Disease Progression; Female; Homocysteine; Humans; Leptin; Longitudinal Studies; Lupus Erythematosus, Systemic; Middle Aged; Multivariate Analysis; Odds Ratio; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Sensitivity and Specificity; Tumor Necrosis Factors

High-fat (HF) diets contribute to the development of cardiovascular diseases and the metabolic syndrome. This study was undertaken to investigate the beneficial effects of Vineatrol®-enriched red wines on blood lipids, oxidative stress and inflammation, and the role of some metabolic pathway regulatory proteins.. Golden Syrian hamsters received an HF diet for 13 wk, in the presence or absence of red wines supplemented with Vineatrol® (RWV) or not. The HF diet increased plasma cholesterol, triglycerides, glucose, and insulin, which were attenuated by RWV treatment. RWV protected against the HF-induced increase in liver nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and spared antioxidant enzyme activities. RWV did not reduce either liver steatosis or increased plasma leptin due to the HF diet, but greatly improved adiponectinemia. In the liver, RWV affected the inflammatory response by decreasing polymorphonuclear cell number and lowering TNF-α and IL-6 levels. Moreover, the increase in NF-κB activity in the HF group liver was prevented by RWV. Finally, RWV partially corrected low SIRT1 levels due to the HF diet but had no influence on SIRT3 or p-AMPK protein levels.. Our studies suggest that RWV is capable of reversing the atherogenic process induced by an HF diet in hamster tissues.

Topics: Adiponectin; Animals; Atherosclerosis; Biomarkers; Blood Glucose; Cholesterol; Cricetinae; Diet, High-Fat; Dietary Supplements; Fatty Liver; Insulin; Interleukin-6; Leptin; Liver; Male; Mesocricetus; Metabolic Syndrome; NADPH Oxidases; NF-kappa B; Oxidative Stress; Phenols; Sirtuin 1; Sirtuin 3; Triglycerides; Tumor Necrosis Factor-alpha; Wine

Resistin was originally identified as an adipocyte-derived factor upregulated during obesity and as a contributor to obesity-associated insulin resistance. Clinically, resistin has also been implicated in cardiovascular disease in a number of different patient populations. Our aim was to simultaneously address these phenomena.. We generated mice with modest adipocyte-specific resistin overexpression. These mice were crossed with mice deficient in the LDL receptor (Ldlr (-/-)) to probe the physiological role of resistin. Both metabolic and atherosclerotic assessments were performed.. Resistin overexpression led to increased atherosclerotic progression in Ldlr (-/-) mice. This was in part related to elevated serum triacylglycerol levels and a reduced ability to clear triacylglycerol upon a challenge. Additional phenotypic changes, such as increased body weight and reduced glucose clearance, independent of the Ldlr (-/-) background, confirmed increased adiposity associated with a more pronounced insulin resistance. A hallmark of elevated resistin was the disproportionate increase in circulating leptin levels. These mice thus recapitulated both the proposed negative cardiovascular correlation and the insulin resistance. A unifying mechanism for this complex phenotype was a resistin-mediated central leptin resistance, which we demonstrate directly both in vivo and in organotypic brain slices. In line with reduced sympathetic nervous system outflow, we found decreased brown adipose tissue (BAT) activity. The resulting elevated triacylglycerol levels provide a likely explanation for accelerated atherosclerosis.. Resistin overexpression leads to a complex metabolic phenotype driven by resistin-mediated central leptin resistance and reduced BAT activity. Hypothalamic leptin resistance thus provides a unifying mechanism for both resistin-mediated insulin resistance and enhanced atherosclerosis.

Topics: Adipose Tissue; Animals; Atherosclerosis; Diabetes Mellitus, Type 2; Female; Insulin Resistance; Leptin; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Obesity; Receptors, LDL; Resistin; Triglycerides

Metabolic syndrome was defined by IDF (International Federation for Diabetes, 2007) by abdominal obesity plus at least two of the following: high triglycerides, low HDL-cholesterol, hypertension, high levels of glucose or type II diabetes diagnosed. Obesity is associated with a high cardiovascular risk, abdominal obesity being the most aggressive form, because it secretes cytokines and hormones in comparison to subcutaneous adipose tissue. Adipocytokines secreted by adipose tissue are mediators of atherosclerosis and endothelial damage.. We studied a total of 80 subjects aged between 40 and 60 years with metabolic syndrome, in which the following adipocytokines values were determined: hs-CRP (turbidimetric method), IL-6, TNF-alpha, leptin (ELISA method), in comparison to a control group.. The values of these adipocytokines were significantly higher in the studied group compared with the control group and correlated with increased levels of glucose (patients with type II diabetes or increased tolerance test) and with hyper-triglyceridemia.. Patients with metabolic syndrome had increased levels of proatherogenic adipocytokines, particularly leptin, leptin-resistance representing the pathogenic link of obesity. The identification as early as possible of the metabolic syndrome patients allows effective monitoring and correction of cardiovascular risk factors, with the opportunity to reduce morbidity and mortality in young ages. In men, proatherogenic cytokines values presented higher values than in women, which prove the role of abdominal obesity in proatherogenic cytokines production. Although women have a higher percentage of adipose tissue, this is not primarily abdominal adipose tissue.

Topics: Adipokines; Adult; Atherosclerosis; C-Reactive Protein; Case-Control Studies; Female; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Tumor Necrosis Factor-alpha

Psoriasis patients are often susceptible to cardiovascular diseases (CVD), including atherosclerosis. Traditional markers (biochemical and inflammatory) and diagnostic tools could detect occlusive but not subclinical atherosclerosis. Carotid intima-media thickness (CIMT), has recently been recognised as a non invasive diagnostic tool for identification of premature atherosclerosis. Therefore we evaluated 80 psoriasis patients and 80 age sex matched healthy controls for serum leptin levels and apolipoprotein B/apolipoprotein A-I ratio (apoB/apoA-I ratio) in relation with CIMT of carotid artery. Carotid intima-media thickness and carotid plaques were simultaneously measured by carotid sonography. Serum concentration of leptin and apolipoprotein were measured using enzyme-linked immuno sorbent assay (ELISA) and nephelometry respectively. Raised CIMT correlated to age of onset of the disease, serum leptin and apoB/apoA-I ratio in psoriasis patients. Taking into account, values that were above the 75 percentile of the three markers (leptin, apoB/apoA-I ratio and CIMT) the odds ratio was 4.26 (2.06-8.80 CI). Leptin and apoB/apoA-I ratio showed significant cumulative association with CIMT. Results of predictive analysis supports measurement of CIMT along with estimation of serum leptin and apoB/apoA-I ratio for prediction of premature atherosclerosis in psoriasis patients.

Topics: Adult; Apolipoprotein A-I; Apolipoproteins B; Atherosclerosis; Carotid Intima-Media Thickness; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Psoriasis

Patients with psoriasis may have an increased risk of cardiovascular disease.. We sought to evaluate the potential association between subclinical atherosclerosis and psoriasis by measuring the intima-media wall thickness (IMT) of the common carotid artery (CCA) in patients with psoriasis and evaluating its correlation with serum leptin and resistin levels.. The mean IMT (MIMT) of the CCA and leptin, resistin, triglyceride (TG), and total cholesterol levels in serum were determined in 60 patients and 60 healthy sex- and age-matched control subjects.. Compared with the healthy control subjects, patients with psoriasis had significantly higher MIMT of the CCA and higher levels of serum leptin, resistin, TG, and total cholesterol. In addition, MIMT of the CCA was positively correlated with serum leptin, resistin, TG, and total cholesterol levels in patients with psoriasis.. This was a cross-sectional single-center study, and we could not evaluate additional biomarkers such as adipokine or adiponectin because of our restricted facilities.. Although serum leptin, resistin, TG, and total cholesterol levels and MIMT of the CCA were significantly increased in patients with psoriasis, MIMT of the CCA was also positively correlated with these biomarkers. Therefore, psoriasis could be an independent risk factor for subclinical atherosclerosis.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Carotid Stenosis; Case-Control Studies; Comorbidity; Female; Humans; Incidence; Leptin; Male; Middle Aged; Prognosis; Psoriasis; Resistin; Risk Assessment; Severity of Illness Index; Sex Distribution; Statistics, Nonparametric; Young Adult

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

This study investigated the relationship between aortic 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake and clinical and laboratory findings related to atherosclerosis in a general population.. 18F-FDG uptake in the ascending aorta was measured on the positron emission tomography/computed tomography (PET/CT) scans of 211 Japanese adults. The maximum target-to-background ratio (TBR) was compared with clinical and laboratory atherosclerosis findings.. By multivariate regression analysis adjusted for age and sex, TBR-ascending aorta (TBR-A) was significantly correlated with various clinical and laboratory parameters, such as body mass index, log visceral fat area, low-density lipoprotein cholesterol (LDL-C), log fasting immunoreactive insulin, log homeostasis model assessment of insulin resistance, log total adiponectin and log-leptin, in all subjects. Furthermore, by multivariate linear regression analysis adjusted for confounding factors, TBR-A was significantly correlated with LDL-C (β = 0.001, p = 0.03) and log-leptin (β = 0.336, p<0.01) in all subjects.. TBR-A was significantly correlated with LDL-C and log-leptin independent from confounding factors. Our results suggest that aortic 18F-FDG uptake is a good marker of atherosclerosis, even in a general population.

Topics: Adult; Aged; Aged, 80 and over; Aorta; Atherosclerosis; Biomarkers; Cholesterol, LDL; Female; Fluorodeoxyglucose F18; Humans; Japan; Leptin; Male; Middle Aged; Multivariate Analysis; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, Emission-Computed

To evaluate adiponectin and leptin levels in older men and women with migraine.. Fasting total and high molecular weight (HMW) adiponectin and leptin levels were evaluated in a case-cohort study of nondiabetic older migraine and nonmigraine control participants from the ongoing, longitudinal, general population, Atherosclerosis Risk in Communities Study at visit 1 (1987-1989). A standardized headache questionnaire was completed at visit 3 (1993-1995). Logistic regression models adjusted for age, sex, race, center, body mass index, and fasting glucose were used to evaluate the association of each adipocytokine with migraine.. Of the 981 participants, the mean age at baseline was 52.8 years (SE 0.3); 131 fulfilled migraine criteria. Crude, mean total adiponectin levels were greater in men and women with migraine (8.1 µg/mL, SE 0.5) as compared to those without migraine (7.0 µg/mL, SE 0.2) (p = 0.031). After adjustments, the odds of migraine were increased by 88% with each SD increase in total adiponectin in men (odds ratio [OR] 1.86; 95% confidence interval [CI] 1.15, 3.01; p = 0.011), but not in women (OR 1.05; 95% CI 0.80, 1.37; p = 0.728; p interaction = 0.029). Similar results were demonstrated for HMW adiponectin. Crude and adjusted leptin levels were not associated with migraine.. Although crude, total adiponectin levels were higher in older men and women with migraine than controls, after adjustments, the prevalence of migraine was significantly associated with total adiponectin only in older men, suggesting the association may be confounded or absent in older women. Leptin was not associated with migraine in older men or women.

Topics: Adiponectin; Atherosclerosis; Blood Chemical Analysis; Case-Control Studies; Female; Humans; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Migraine Disorders; Odds Ratio; Prevalence; Prospective Studies; Risk; Sex Factors; Surveys and Questionnaires

Hydrogen sulfide (H2S) is an important gaseous signaling molecule that functions in physiological and pathological conditions, such as atherosclerosis. H2S dilates vessels and therefore has been suggested as an anti-atherogenic molecule. Since cystathionine gamma-lyase (CSE) enzyme is responsible for producing H2S in the cardiovascular system, we hypothesized that up-regulation of CSE expression in vivo with preservation of H2S bioactivity can slow down plaque formation and, can serve as a therapeutic strategy against atherosclerosis. In this study, C57BL/6 wild type mice (WT), ApoE knockout mice (KO) and transgenic ApoE knockout mice overexpressing CSE (Tg/KO) at four weeks of age were weaned. They were then fed with either normal or atherogenic diet for 12 weeks. At week 16, serial plasma lipid levels, body weight, and blood pressure were measured prior to euthanization of the mice and the size of atherosclerotic plaques at their aortic roots was measured. Tg/KO mice showed an increase in endogenous H2S production in aortic tissue, reduced atherosclerotic plaque sizes and attenuation in plasma lipid profiles. We also showed an up-regulation in plasma glutathionine peroxidase that could indicate reduced oxidative stress. Furthermore, there was an increase in expression of p-p53 and down regulation of inflammatory nuclear factor-kappa B (NF-κB) in aorta. To conclude, alteration of endogenous H2S by CSE gene activation was associated with reduced atherosclerosis in ApoE-deficient mice. Up-regulation of CSE/H2S pathway attenuates atherosclerosis and this would be a potential target for therapeutic intervention against its formation.

Topics: Adiponectin; Animals; Aorta; Apolipoproteins E; Atherosclerosis; Blood Pressure; Body Weight; Cystathionine gamma-Lyase; Down-Regulation; Glutathione Peroxidase; Hydrogen Sulfide; Leptin; Lipids; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Myocardium; NF-kappa B; Oxidative Stress; Plaque, Atherosclerotic; Tumor Suppressor Protein p53; Up-Regulation

Plasma fractalkine (FRACT) is involved in the development of numerous inflammatory conditions including atherosclerosis. It is associated with type 2 diabetes mellitus and adipose inflammation. However, whether FRACT is associated with major risk factors for cardiovascular disease, in particular obesity, metabolic syndrome and blood lipids, is virtually unknown.. The study included a large community-based sample of 3306 middle-aged women drawn from the general UK population. Blood samples were analyzed for circulating levels of FRACT, leptin, insulin, glucose, LDL-C, HDL-C, Apo-A, ApoB and IL-6. Obesity was assessed by fat body mass (FBM) using dual-energy x-ray absorptiometry and by body mass index (BMI).. We found no association between FRACT and body composition, in particular adiposity. Obese and non obese subjects with metabolic syndrome tended to have higher levels of FRACT compared with non-obese subjects without metabolic syndrome but this did not reach statistical significance. Most importantly we report significant correlations between FRACT and circulating IL-6, Apo-B, LDL-C and insulin. The associations with IL-6 and Apo-B were particularly significant (P-value<0.001), and survived correction for multiple testing and adjustment for age and other covariates.. Higher FRACT levels correlated with elevated levels of IL-6, Apo-B, LDL-C and insulin, all known risk factors for several clinical related diseases suggesting a potential role of FRACT in inflammation and tissue injury. Variations of FRACT levels are not influenced by body composition and are not correlated with leptin indicating that fat mass alone is not responsible for elevation of FRACT seen in obese individuals.

Topics: Apolipoproteins B; Atherosclerosis; Blood Glucose; Body Composition; Body Mass Index; Chemokine CX3CL1; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Interleukin-6; Leptin; Metabolic Syndrome; Middle Aged; Regression Analysis; Risk Factors; United Kingdom

Adipokines are secreted from adipose tissue, influence energy homeostasis and may contribute to the association between obesity and hypertension. Among 1897 participants enrolled in the Multi-Ethnic Study of Atherosclerosis, we examined associations between blood pressure and leptin, tumor necrosis factor-α (TNFα), resistin and total adiponectin. The mean age and body mass index (BMI) was 64.7 years and 28.1, respectively, and 50% were female. After adjustment for risk factors, a 1-s.d.-increment higher leptin level was significantly associated with higher systolic (5.0 mm Hg), diastolic (1.9), mean arterial (2.8) and pulse pressures (3.6), as well as a 34% higher odds for being hypertensive (P<0.01 for all). These associations were not materially different when the other adipokines, as well as BMI, waist circumference or waist-to-hip ratio, were additionally added to the model. Notably, the associations between leptin and hypertension were stronger in men, but were not different by race/ethnic group, BMI or smoking status. Adiponectin, resistin and TNFα were not independently associated with blood pressure or hypertension. Higher serum leptin, but not adiponectin, resistin or TNFα, is associated with higher levels of all measures of blood pressure, as well as a higher odds of hypertension, independent of risk factors, anthropometric measures and other selected adipokines.

Topics: Adiponectin; Adiposity; Aged; Atherosclerosis; Biomarkers; Blood Pressure; Ethnicity; Female; Humans; Hypertension; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Resistin; Risk Factors; Time Factors; Tumor Necrosis Factor-alpha; United States; Up-Regulation

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular atherosclerosis independent of classical risk factors. This study investigated the influence of NAFLD on autonomic changes, which is currently unknown.. Subjects without an overt history of cardiovascular disease were enrolled during health checkups. The subjects diagnosed for NAFLD using ultrasonography underwent 5-min heart rate variability (HRV) measurements that was analyzed using the following indices: (1) the time domain with the standard deviation of N-N (SDNN) intervals and root mean square of successive differences between adjacent N-N intervals (rMSSD); (2) the frequency domain with low frequency (LF) and high frequency (HF) components; and (3) symbolic dynamics analysis. Routine blood biochemistry data and serum leptin levels were analyzed. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured.. Of the 497 subjects (mean age, 46.2 years), 176 (35.4%) had NAFLD. The HRV indices (Ln SDNN, Ln rMSSD, Ln LF, and Ln HF) were significantly decreased in the NAFLD group (3.51 vs 3.62 ms, 3.06 vs 3.22 ms, 5.26 vs 5.49 ms(2), 4.49 vs 5.21 ms(2), respectively, all P<0.05). Ln SDNN was significantly lower in the NAFLD group after adjustment for age, sex, hypertension, dyslipidemia, metabolic syndrome, body mass index, smoking, estimated glomerular filtration rate, HOMA-IR, and leptin (P<0.05). In the symbolic dynamic analysis, 0 V percentage was significantly higher in the NAFLD group (33.8% vs 28.7%, P = 0.001) and significantly correlated with linear HRV indices (Ln SDNN, Ln rMSSD, and Ln HF).. NAFLD is associated with decreased Ln SDNN and increased 0 V percentage. The former association was independent of conventional cardiovascular risk factors and serum biomarkers (insulin resistance and leptin). Further risk stratification of autonomic dysfunction with falls or cardiovascular diseases by these HRV parameters is required in patients with NAFLD.

Topics: Adult; Age Factors; Atherosclerosis; Body Mass Index; Diabetes Mellitus; Fatty Liver; Female; Glomerular Filtration Rate; Heart Rate; Humans; Hypertension; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Non-alcoholic Fatty Liver Disease; Risk Factors; Sex Factors; Ultrasonography

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

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

Conjugated linoleic acid (CLA) is found naturally in meat and dairy products, and represents a potential therapeutic functional nutrient. However, given the discrepancies in isomer composition and concentration, controversy surrounds its proposed antidiabetic, antiobesity effects. This study focused on the effects of CLA-enriched beef (composed predominantly of c9, t11-CLA) in two separate models of metabolic disease: proatherosclerotic ApoE(-/-) mice and diabetic, leptin-deficient ob/ob mice. Animals were fed CLA-enriched beef for 28 days, and markers of the metabolic syndrome and atherosclerosis were assessed. Comprehensive hepatic transcriptomic analysis was completed to understand divergent metabolic effects of CLA. CLA-enriched beef significantly reduced plasma glucose, insulin, nonesterified fatty acid and triacylglycerol and increased adiponectin levels in ob/ob mice. In contrast, plasma lipid profiles and glucose homeostasis deteriorated and promoted atherosclerosis following the CLA-enriched beef diet in ApoE(-/-) mice. Hepatic transcriptomic profiling revealed divergent effects of CLA-enriched beef on insulin signaling and lipogenic pathways, which were adversely affected in ApoE(-/-) mice. This study demonstrated clear divergence in the effects of CLA. CLA-enriched beef improved metabolic flexibility in ob/ob mice, resulting in enhanced insulin sensitivity. However, CLA-enriched diet increased expression of lipogenic genes, resulting in inefficient fatty acid storage which increases lipotoxicity in peripheral organs, and led to profound metabolic dysfunction in ApoE(-/-) mice. While CLA may have potential health effects, in some circumstances, caution must be exercised in presenting this bioactive lipid as a potential functional food for the treatment of metabolic disease.

Topics: Adipose Tissue; Animals; Apolipoproteins E; Atherosclerosis; Cattle; Diet; Disease Models, Animal; Fatty Acids, Unsaturated; Gene Expression Profiling; Gene Expression Regulation; Glucose; Insulin; Leptin; Linoleic Acids, Conjugated; Lipids; Liver; Meat Products; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese

The objective of this study was to determine potential added value of novel risk factors in predicting the development of type 2 diabetes beyond that provided by standard clinical risk factors.. The Atherosclerosis Risk in Communities (ARIC) Study is a population-based prospective cohort study in four U.S. communities. Novel risk factors were either measured in the full cohort or in a case-control sample nested within the cohort. We started with a basic prediction model, previously validated in ARIC, and evaluated 35 novel risk factors by adding them independently to the basic model. The area under the curve (AUC), net reclassification index (NRI), and integrated discrimination index (IDI) were calculated to determine if each of the novel risk factors improved risk prediction.. There were 1,457 incident cases of diabetes with a mean of >7.6 years of follow-up among 12,277 participants at risk. None of the novel risk factors significantly improved the AUC. Forced expiratory volume in 1 s was the only novel risk factor that resulted in a significant NRI (0.54%; 95% CI: 0.33-0.86%). Adiponectin, leptin, γ-glutamyl transferase, ferritin, intercellular adhesion molecule 1, complement C3, white blood cell count, albumin, activated partial thromboplastin time, factor VIII, magnesium, hip circumference, heart rate, and a genetic risk score each significantly improved the IDI, but net changes were small.. Evaluation of a large panel of novel risk factors for type 2 diabetes indicated only small improvements in risk prediction, which are unlikely to meaningfully alter clinical risk reclassification or discrimination strategies.

Topics: Adiponectin; Atherosclerosis; Case-Control Studies; Complement C3; Diabetes Mellitus, Type 2; Factor VIII; Female; Forced Expiratory Volume; Genotype; Humans; Intercellular Adhesion Molecule-1; Leptin; Male; Middle Aged; Prospective Studies; Risk Factors

Insulin clearance may decline as an early mechanism compensating for deteriorating insulin sensitivity. However, no previous studies have investigated the association between subclinical inflammation or impaired fibrinolysis and insulin clearance. We examined the association between plasminogen activator inhibitor (PAI)-1, C-reactive protein (CRP), TNF-α, leptin and fibrinogen and the progression of metabolic clearance rate of insulin (MCRI) over time.. We studied 784 non-diabetic white, Hispanic and African-American individuals in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity, acute insulin response and MCRI were determined from frequently sampled intravenous glucose tolerance tests at baseline and at 5-year follow-up. Inflammatory and fibrinolytic proteins were measured in fasting plasma at baseline.. MCRI had declined significantly by 29% at the 5-year follow-up. We observed a significant association between higher plasma PAI-1 levels and the decline in MCRI in multivariable-adjusted regression models (β = -0.045 [95% CI -0.081, -0.0091]). Higher plasma CRP and leptin levels were associated with a decline in MCRI in unadjusted models, but these associations were non-significant after adjusting for BMI and waist circumference (β = -0.016 [95% CI -0.041, 0.0083] for CRP; β = -0.044 [95% CI -0.10, 0.011] for leptin). A higher plasma TNF-α concentration was associated with a decline in MCRI in unadjusted (β = -0.071 [95% CI -0.14, -0.00087]) but not in multivariable-adjusted (β = -0.056 [95% CI -0.13, 0.017]) models. Plasma fibrinogen level was not associated with the change in MCRI.. We identified that higher plasma PAI-1 (but not CRP, TNF-α, leptin or fibrinogen) levels independently predicted the progressive decline of insulin clearance in the multiethnic cohort of the IRAS.

Topics: Atherosclerosis; Body Mass Index; Cohort Studies; Diabetic Angiopathies; Female; Fibrinogen; Follow-Up Studies; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin; Insulin Resistance; Leptin; Male; Metabolic Clearance Rate; Middle Aged; Overweight; Plasminogen Activator Inhibitor 1; Prediabetic State; Prospective Studies; Risk Factors; United States

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

To investigate whether leptin and adiponectin are associated with body fat composition in a South Asian population independent of metabolic variables.. Cross-sectional study.. 150 South Asian men and women, between the ages of 45-79 years, in the San Francisco Bay Area without pre-existing clinical cardiovascular disease.. Blood samples were obtained to measure glucose metabolism variables, lipid profiles and adipokines. Total body fat was determined using dual-energy X-ray absorptiometry. Abdominal computed tomography was used to measure subcutaneous, visceral and hepatic fat.. Average body mass index (BMI) was overweight at 26.1±4.6 kg m(-2) and did not differ by sex. However, women had significantly more total body fat (P<0.001) and subcutaneous fat (P<0.001) than men, whereas men had significantly more visceral fat (P<0.001) and hepatic fat (P=0.04) than women. Women had significantly higher levels of adiponectin (P<0.01) and leptin (P<0.01). In sex-stratified analyses, leptin was strongly associated with all-body composition measures in women (P<0.05) as well as in men (P<0.05 except for hepatic fat), whereas there was an insignificant trend towards an inverse association between adiponectin and body composition in both women and men, which was significant in combined bivariate analyses. In multivariate analyses, leptin was strongly associated with all measures of adiposity, including BMI (P<0.001), total body fat (P<0.001), visceral fat (P<0.001) and hepatic fat (P=0.01). However, adiponectin's inverse association with adiposity was significantly attenuated by high-density lipoprotein (HDL), triglycerides and insulin resistance. The association between adipokines and diabetes was markedly attenuated after adjusting for body composition.. Despite only modestly elevated BMI, South Asians have elevated levels of total and regional adiposity. Leptin is strongly associated with adiposity, whereas adiponectin's association with adiposity is attenuated by metabolic variables in South Asians. Adipokines in association with adiposity have an important role in the development of diabetes.

Topics: Adipokines; Adiponectin; Aged; Asian; Atherosclerosis; Body Composition; C-Reactive Protein; Cross-Sectional Studies; Female; Glucose Tolerance Test; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; San Francisco

Abdominal obesity is characterized by sympathetic nerve activation (SNA), probably mediated by elevated insulin and leptin levels. Resting heart rate (RHR) is a marker of sympathetic tone, and independently associated with cardiovascular events and death in various populations. We investigated and quantified the relation between visceral adipose tissue (VAT) and RHR in patients with vascular disease. In 3,723 patients with manifest vascular disease, visceral and subcutaneous fat tissue was measured with ultrasonography. RHR was obtained from an electrocardiogram (ECG). The association between quartiles of VAT and RHR was quantified using linear regression analysis with adjustments for potential confounding factors. Separate analyses were performed for men and women and for location of vascular disease. Visceral fat was categorized into sex-pooled quartiles (Q) ranging from 2.7-8.0 cm in Q1 (reference) to 9.4-20.6 cm in Q4. High visceral fat thickness was associated with increased RHR, in men (Q4 vs. Q1, β = 4.36; 95% confidence interval (CI) = 3.11-5.61) and women (β = 1.48; 95% CI = -0.70 to 3.66), after full adjustment. Waist circumference and BMI had a significant relation with RHR in men (β = 3.51; 95% CI = 2.21-4.81 and β = 2.80; 95% CI = 1.51-4.08, respectively) but these relations were smaller and not significant in women (β = 0.71; 95% CI = -1.44 to 2.85 and β = 0.24; 95% CI = -1.90 to 2.37, respectively). There was no relation between subcutaneous fat and RHR in men and women. The relation between visceral fat and RHR was similar in patients with different locations of vascular diseases. Increased visceral fat is associated with increased RHR in male and female patients with vascular disease, independent of the location.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atherosclerosis; Body Composition; Body Mass Index; Cross-Sectional Studies; Female; Heart Rate; Humans; Insulin; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity, Abdominal; Rest; Risk Factors; United States; Waist Circumference; Young Adult

Soybean is known to have an anti-obesity effect. We compared the anti-obesity effect of doenjang, a fermented soybean paste, with that of nonfermented soybeans in rats. Steamed soybeans and doenjang (steamed soybeans fermented and aged for 10 months) were sampled and freeze-dried. Male Sprague-Dawley rats were fed basal (BA) (5% fat), high fat (HF) (30% fat), HF+steamed soybeans (SOY), or HF+doenjang (DJ) diet ad libitum for 8 weeks. HF significantly increased body weight gain, liver weight, hepatic triglyceride (TG) and cholesterol levels, and epididymal fat pad weight compared with BA. Compared with HF, body weight gain and hepatic TG and cholesterol levels were significantly lower in SOY and DJ groups, but they were not significantly different from each other. DJ significantly reduced visceral fat weight and epididymal adipocyte size compared with HF, whereas SOY resulted in a mild reduction without significance. This was possibly because DJ showed lowered fatty acid synthase (FAS) activity and elevated carnitine palmitoyltransferase (CPT)-1 activity in liver tissue more than SOY. SOY and DJ did not affect serum total and high-density lipoprotein-cholesterol levels compared with HF; however, DJ significantly lowered the atherogenic index and serum leptin level. In conclusion, doenjang, a fermented soybean product, was more effective than soybeans for preventing diet-induced visceral fat accumulation, possibly because of its greater effects on CPT-1 activity stimulation and FAS activity suppression. These effects may be due in part to the higher content of aglycone isoflavones in doenjang.

Topics: Adipocytes; Animals; Anti-Obesity Agents; Atherosclerosis; Carnitine O-Palmitoyltransferase; Cholesterol; Diet, High-Fat; Dietary Fats; Fatty Acid Synthases; Fermentation; Glycine max; Intra-Abdominal Fat; Isoflavones; Leptin; Liver; Male; Obesity; Organ Size; Phytotherapy; Rats; Rats, Sprague-Dawley; Seeds; Soy Foods; Triglycerides; Weight Gain

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

The mechanisms underlying the pathogenesis of obesity-related atherosclerosis remain to be clarified. To investigate the preclinical phase, interleukin-6 (IL-6) plasma levels were analyzed together with clinical, anthropometric, inflammatory, and metabolic variables in a well-defined cohort of 677 young and middle-aged overweight/obese and normal-weight subjects. In the juvenile and adult overweight/obese study group, IL-6 levels were increased significantly compared with normal-weight, age-matched controls (P < 0.001). In both juveniles and adults, higher levels of IL-6 were observed in obese compared with overweight participants. Subjects with metabolic syndrome (MS) had significantly higher IL-6 levels than those without MS. In juveniles, leptin, and in adults, the waist-to-height ratio, turned out to be the best predictor of IL-6 plasma levels in a multiple stepwise regression model. Taken together, in every age group, interleukin-6 is associated positively with the grade of overweight. Interestingly, leptin, which is the best known adipokine, is associated predictively with interleukin-6 plasma levels only in juveniles, which may indicate an important role of this molecule in the initiation of obesity-related inflammation.

Topics: Adolescent; Adult; Age Factors; Atherosclerosis; Biomarkers; Body Height; Body Mass Index; Child; Cohort Studies; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Regression Analysis; Waist Circumference

Out study aimed to assess the serum levels of adipokines in patients with peripheral arterial occlusive disease (PAOD) caused by atherosclerosis.. Serum samples were obtained from 221 patients. One hundred and forty patients, (26 females and 114 males) met the inclusion criteria and were assigned into the case group. Eighty one patients (17 females and 64 males), were included in the control group. Circulating plasma levels of adiponectin, leptin, resistin, and TNF-α were measured using the enzyme-linked immunosorbent assay (ELISA) method.. Significant lower levels of adiponectin were present (P = 0.0061) in PAOD patients (2380.23 ± 1634.42 pg/mL) compared to the control group (3065.06 ± 1901.2 pg/mL). The mean value of leptin (2844.42 ± 3301.08 pg/mL) and resistin (2047.81±3301.08 pg/mL) patients included in the PAOD group was higher, as compared to the control group. Statistically significant difference was found between the two groups for leptin (P = 0.0332) and for resistin (P = 0.0352). No statistically significant difference for TNF-α was found between the two groups (P > 0.05).. The markers of inflammation secreted by the adipose tissue (adiponectin, leptin, resistin) showed significant differences in patients from the case group (with PAOD) compared to the control group.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adipose Tissue, White; Aged; Arterial Occlusive Diseases; Atherosclerosis; Body Mass Index; C-Reactive Protein; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Models, Biological; Models, Statistical; Resistin; Tumor Necrosis Factor-alpha

Topics: Acyltransferases; Animals; Atherosclerosis; Biochemistry; Choroideremia; Dimethylallyltranstransferase; History, 20th Century; History, 21st Century; Humans; Leptin; Lipodystrophy; Monocarboxylic Acid Transporters; Niemann-Pick Disease, Type C; Receptors, Scavenger; United States

Associations of adiponectin and leptin and their ratio with body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR) have been investigated in different ethnic groups but variability in both assays and statistical methods have made cross-study comparisons difficult. We examined associations among these variables across four ethnic groups in a single study.. Adiponectin and leptin were measured in a subset of participants from the Multi-Ethnic Study of Atherosclerosis study. We calculated associations (using both partial correlations and adjusted linear regression) in each ethnic group and then compared the magnitude of these associations across groups.. After we excluded individuals with type 2 diabetes, there were 714 white, 219 Chinese, 332 African-American, and 405 Hispanic subjects in the study sample. Associations of BMI with adiponectin and leptin differed significantly (P < .05) across the ethnic groups in regression analyses, whereas associations of HOMA-IR with adiponectin and leptin did not differ across ethnic groups. The leptin-to-adiponectin ratio was not associated with a greater amount of adiposity or HOMA-IR variance than leptin or adiponectin in any ethnic group.. Given the consistency of HOMA-IR and adipokine associations, the differing means of adiponectin and leptin across ethnic groups may help to explain ethnic differences in mean insulin resistance.

Topics: Adiponectin; Aged; Aged, 80 and over; Atherosclerosis; Blood Glucose; Body Mass Index; Cross-Sectional Studies; Ethnicity; Female; Homeostasis; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Models, Biological; United States

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

Inherent mechanisms leading to vascular smooth muscle cells (VSMC) alterations in obesitylinked type 2 diabetes (T2D) situation remain to be clarified. This study evaluates the impact of supernatant of adipocytes extracted from mice fed high-fat-diets (HFD) on the proliferation and apoptosis of VSMC.. Adipocytes were extracted from visceral white fat pads of male and female C57Bl6 mice showing different stages of metabolic alterations after 20 weeks of vegetal or animal HFD feeding. These cells were stimulated or not with insulin or glucose to condition VSMC media. After 24h of stimulation with adipocyte supernatants (AdS), VSMC proliferation and sustainability were assessed in the absence and presence of AdS. CD36 and insulin receptor mRNA levels were also evaluated.. Proliferation and viability of VSMC were significantly modulated by the nature of the AdS used and the gender of mice from which adipocytes have been extracted. The most extensive effects on VSMC were triggered by adipocytes from males fed animal HFD and females fed vegetal HFD. These effects were concurrent with increased leptin concentration and decreased adiponectin levels in AdS. In addition, adipocytes of HFD-fed mice increased caspase-3 activity and apoptosis in VSMC. Significant up-regulation of CD36 mRNA was also found in these cells.. Adipocytes of HFD-fed mice induce VSMC alterations. These changes involved mouse gender, most probably correlated to the diet-induced adipocyte secretion profile. Greater sensitivity to AdS effects in VSMC raises concerns about the more frequent cardiovascular events associated with obesity in the presence of T2D, which impairs adipocyte activity.

Topics: Adipocytes; Adipokines; Animal Feed; Animals; Apoptosis; Atherosclerosis; Caspase 3; CD36 Antigens; Cell Proliferation; Cells, Cultured; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Female; Glucose; Leptin; Lipids; Male; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; RNA, Messenger

We evaluated the effect of the intake of a grapevine-shoot phenolic extract (Vineatrol 30) on early atherosclerosis in hamsters fed a hyperlipidic diet. Golden Syrian hamsters received for 13 weeks either a standard diet, a high-fat (HF) diet, or the HF diet plus Vineatrol 30 at 0.04, 0.2, or 1.0 mg/(kg body weight/d). We measured plasma lipids and glucose, insulin, leptin and adiponectin, as well as liver TNF-α and IL-6 levels. Oxidative stress was assessed by measuring plasma paraoxonase activity (PON) and liver superoxide anion production (O(2)(•-)). The aortic fatty streak area (AFSA) was also determined. In comparison with HF group, we demonstrated that the highest dose of Vineatrol 30 was capable of decreasing AFSA (67%), insulinemia (40%), and leptinemia (8.7%), which were increased by the HF diet. We also showed increased O(2)(•-) production (35%) and a rise in levels of the liver proinflammatory cytokines TNF-α (22%) and IL-6 (21%), accompanied by a fall in PON activity (56%) due to the HF diet versus the standard diet. In contrast, except plasma adiponectin levels that are not changed, Vineatrol 30 treatment lowered AFSA (67%), O(2)(•-) production (36%), insulin resistance (42%), leptinemia (9%), liver TNF-α (18%) and IL-6 (15%), while it rose PON activity (29%). These findings demonstrate the preventive effects of polyphenols present in Vineatrol 30 in managing cardiovascular, metabolic, and inflammatory risk factors.

Topics: Adiponectin; Animals; Aryldialkylphosphatase; Atherosclerosis; Blood Glucose; Cricetinae; Disease Models, Animal; Dose-Response Relationship, Drug; Insulin; Interleukin-6; Leptin; Lipids; Male; Mesocricetus; Oxidative Stress; Phenols; Tumor Necrosis Factor-alpha

Studies investigating serum ghrelin level in atherosclerosis yielded contradictory results. Interaction of ghrelin with adipocytokines is obscure in cardiovascular diseases. We undertook this study to determine which molecules influence ghrelin level and to see whether post-myocardial infarction (MI) patients have decreased ghrelin levels.. In this cross-sectional study, acyl-ghrelin concentration was determined by radioimmunoassay in sera of 171 patients (ages 62 ± 6 years, mean ± SD) with previous MI and 81 age-matched referent subjects. We evaluated the associations of ghrelin with insulin, adiponectin, leptin, resistin, fetuin-A and tumor necrosis factor-alpha (TNF-α).. Patients had lower ghrelin levels compared to referent subjects (240.55 ± 59.33 vs. 337.96 ± 30.75 pg/mL, p <0.001) even after excluding diabetic and obese patients (240.63 ± 54.08 vs. 337.96 ± 30.75, p <0.001). In multivariate analysis, insulin (β = -0.327, p <0.001) and adiponectin (β = 0.301, p <0.001) determined ghrelin level (R(2) = 0.199, p <0.001). There was no association between ghrelin and TNF-α levels. In discriminant analysis using ghrelin, adiponectin, leptin, fetuin-A, resistin and TNF-α, the structure matrix revealed ghrelin and TNF-α as strongest predictors for belonging to the patient group (0.760 and -0.569, respectively). Using these two parameters, 89.7% of cases were correctly classified. Subjects with high TNF-α/ghrelin ratio had 11.25 times higher chance for belonging to the patient group (95% CI 5.80-21.80; χ(2) (1) = 215.6, p <0.001). Acylated ghrelin levels are decreased in patients with coronary atherosclerosis, independently of body weight and the presence of type 2 diabetes mellitus. Ghrelin level is determined by elevated insulin and decreased adiponectin levels. Ghrelin alone or in combination with TNF-α may prove to be a novel indicator of coronary atherosclerosis.

Topics: Adiponectin; Aged; alpha-2-HS-Glycoprotein; Atherosclerosis; Blood Glucose; Body Weight; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Ghrelin; Humans; Insulin; Leptin; Male; Middle Aged; Myocardial Infarction; Resistin; Tumor Necrosis Factor-alpha

The impact of leptin deficiency and its replacement in T1D remain unclear in the context of dyslipidemia and atherosclerosis. The current study has investigated the physiologic role of leptin in lipid metabolism and atherosclerosis in T1D.. The present study has employed Ins2(+/Akita):apoE(-/-) mouse model that spontaneously develops T1D, hypercholesterolemia, and atherosclerosis. At age 13 weeks, diabetic Ins2(+/Akita):apoE(-/-) mice showed leptin deficiency by ~92% compared with nondiabetic Ins2(+/+):apoE(-/-) mice. From 13 weeks to 25 weeks of age, diabetic Ins2(+/Akita):apoE(-/-) mice were treated with low-dose leptin (at 0.4 μg/g body weight daily). Leptin treatment diminished food intake by 22-27% in diabetic mice without affecting body weight and lean mass throughout the experiment. Importantly, leptin therapy substantially reduced plasma cholesterol concentrations by ~41%, especially in LDL fractions, in diabetic Ins2(+/Akita):apoE(-/-) mice. Moreover, leptin therapy decreased atherosclerotic lesion in diabetic mice by ~62% comparable to that seen in nondiabetic mice. In addition, leptin restored repressed expression of hepatic sortilin-1, a receptor for LDL clearance, and reversed altered expression of several hepatic genes involved in lipogenesis and cholesterol synthesis characteristic of diabetic mice. These findings were accompanied by normalization of reduced hepatic expression of Irs1 and Irs2 mRNA as well as their protein levels, and improved hepatic insulin-receptor signaling.. The present findings suggest that leptin administration may be useful to improve dyslipidemia and reduce atherosclerosis-related cardiovascular disease in human subjects with T1D.

Topics: Adaptor Proteins, Vesicular Transport; Animals; Apolipoproteins E; Atherosclerosis; Cholesterol; Diabetes Mellitus, Type 1; Disease Models, Animal; Disease Progression; Eating; Gene Expression Regulation; Hypercholesterolemia; Injections, Intraperitoneal; Insulin; Insulin Receptor Substrate Proteins; Leptin; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Recombinant Proteins; RNA, Messenger; Time Factors

The association between nutritional status, antioxidant human paraoxonase-1 (PON1) activity and low grade inflammation in hemodialized (HD) patients with chronic kidney disease (CKD) is unclear. The aim of this study was to determine PON1 paraoxonase and lactonase activities, ADMA, adiponectin and leptin concentrations, and to clarify the relationship between paraoxonase activity and a set of cardiovascular risk factors in malnourished, normal weight and obese HD patients; 114 HD patients with end-stage renal failure were enrolled.. Leptin levels were significantly higher and PON1 paraoxonase activities were significantly lower in obese patients compared to the other groups. Plasma adiponectin concentration was significantly lower in obese subjects compared to malnourished patients. Paraoxonase activity was negatively correlated with CRP level in HD and malnourished patients. Furthermore, we found significant inverse correlation between paraoxonase activity and BMI in the whole patient group. In multiple regression analysis, PON1 lactonase activity, CRP level and leptin concentration proved to be independent predictors of paraoxonase activity.. Despite the previous findings of reverse epidemiology for the mortality rate of HD patients, further studies are needed to clarify the effects of nutritional state on atherosclerosis in obese and malnourished patients with end-stage renal failure.

Topics: Adiponectin; Aged; Aryldialkylphosphatase; Atherosclerosis; Biomarkers; C-Reactive Protein; Comorbidity; Humans; Kidney Failure, Chronic; Leptin; Malnutrition; Middle Aged; Nutritional Status; Obesity; Regression Analysis; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors

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

To determine the role of hyperleptinemia on caveolin-1 expression and leptin signaling.. Endothelial cells are critical to atherosclerosis development; therefore we investigated hyperleptinemia in cultured vascular endothelial cells. Dose-dependent effect of leptin on caveolin-1 expression was determined by Western blot analysis. Also, the consequence of increased caveolin-1 expression on leptin signaling was investigated by adenovirus mediated caveolin-1 overexpression. The effect of increased caveolin-1 expression on leptin-dependent activation of ERK1/2 and eNOS was determined by Western blot analysis.. Leptin upregulates caveolin-1 protein expression in a dose dependent manner and increased caveolin-1 expression impairs leptin signaling.. Leptin increases caveolin-1 protein expression which impairs leptin signaling in vascular endothelial cells. Our study identifies an additional leptin mediated proatherogenic mechanism and a novel caveolin-1 dependent leptin feedback mechanism which may have implications for development of peripheral leptin resistance in the endothelium.

Topics: Adenoviridae; Atherosclerosis; Blotting, Western; Caveolin 1; Cells, Cultured; Endothelial Cells; Genetic Vectors; Human Umbilical Vein Endothelial Cells; Humans; Leptin; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Nitric Oxide Synthase Type III; Signal Transduction; Time Factors; Transfection; Up-Regulation

The inflammatory status of atherosclerotic lesions is a major factor triggering acute cardiovascular events. Growing evidence has shown that adipocyte fatty acid-binding protein (A-FABP) has an important role in the development of atherosclerosis.. The objective of the study was to determine the association between circulating A-FABP levels with vascular inflammation as measured using [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), which is a novel imaging technique for noninvasive measurement of atherosclerotic inflammation.. This was a cross-sectional study.. Eighty-seven men without previously diagnosed cardiovascular disease or diabetes participated in the study.. We measured the serum A-FABP, adiponectin, and leptin levels as well as other cardiovascular risk factors. Vascular inflammation in the carotid arterial wall, as indicated by the target to background ratio (TBR), was analyzed using FDG-PET.. The circulating A-FABP and leptin levels had positive correlations with maximum TBR values (r = 0.38, P < 0.001; and r = 0.28, P = 0.010, respectively), whereas the adiponectin levels had a negative correlation (r = -0.31, P = 0.004). The maximum TBR levels exhibited an additive linear increment according to the rise in tertiles of the A-FABP levels in subjects with and without metabolic syndrome. Multiple regression analysis showed that serum A-FABP levels were independently associated with maximum TBR after adjustment for other cardiovascular risk factors (P = 0.006).. Circulating A-FABP, adiponectin, and leptin levels were shown to be associated with vascular inflammation, as measured using FDG-PET. Specifically, the A-FABP level was an independent risk factor for vascular inflammation in Korean men without cardiovascular disease or diabetes.

Topics: Adult; Atherosclerosis; Biomarkers; Carotid Arteries; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Fatty Acid-Binding Proteins; Fluorodeoxyglucose F18; Hemodynamics; Humans; Leptin; Lipids; Male; Metabolic Syndrome; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Risk Factors; Tunica Intima; Ultrasonography; Vasculitis

The objective of the study was to determine the effects of oxidized linoleic acid (Ox-LA) on plasma leptin and to determine the relationship between plasma leptin levels and atherosclerosis in animals treated with Ox-LA. Low-density lipoprotein (LDL) receptor knockout (LDL r(-/-)) mice were fed a high fat diet with or without Ox-LA for 11 weeks. Plasma leptin levels in the high fat group consuming Ox-LA were significantly higher (14,052 ± 601 pg/mL vs. 10,950 ± 541 pg/mL; P < .01) compared to the group receiving the high fat diet alone. There was a highly significant correlation between the plasma leptin levels and aortic atherosclerotic lesions. From this we conclude that chronic exposure to dietary Ox-LA increases the plasma levels of leptin in LDL r(-/-) mice on a high fat diet. Considering our previous finding that dietary Ox-LA increased atherosclerosis, the current findings emphasize the need to reduce dietary intake of oxidized fat.

Topics: Animals; Aorta; Atherosclerosis; Cholesterol, Dietary; Cholesterol, LDL; Leptin; Linoleic Acid; Lipid Peroxidation; Lipoproteins, LDL; Male; Mice; Mice, Knockout; Obesity; Oxidative Stress; Receptors, LDL; Triglycerides

Few studies have investigated if exercise by itself has anti-atherosclerotic effects, without combining interventions with a low-fat diet. We studied the effects of exercise as a stand-alone intervention on preexisting atheromata by measuring not only plaque size but also the levels of plaque-destabilizing matrix-metalloproteinase (MMP) activity in vivo.. We used near-infrared fluorescent (NIRF) molecular imaging with an MMP-2/9 activatable NIRF probe to visualize the inflammatory protease activity within preexisting atheromata of 17-week-old ApoE(-/-) mice on: (a) normal chow diet (NCD), (b) Western diet (WD), and (c) WD with treadmill exercise for 10 weeks. We also measured tissue levels of aortic lipid peroxidation (LPO) and plasma levels of glucose/lipid/cytokine profiles. Exercise did not attenuate growth of preexisting atheromatous plaques. However, exercise strongly decreased proteolytic activity in plaques for animals on WD, with levels decreasing almost to NCD levels. Exercise was associated with decreased aortic LPO levels and increased blood adiponectin/leptin levels; however, exercise did not affect WD-consumption/weight-gain or improve blood glucose/lipid profiles.. Exercise training reduced aortic MMP activity in mice with preexisting atheromata, even though they remained on a high fat diet and plaque-growth was not attenuated.

Topics: Adiponectin; Analysis of Variance; Animals; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Blood Glucose; Body Weight; Cytokines; Disease Models, Animal; Down-Regulation; Exercise Therapy; Immunohistochemistry; Infrared Rays; Leptin; Lipid Peroxidation; Lipids; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Knockout; Microscopy; Molecular Imaging; Plaque, Atherosclerotic

Obesity is a risk factor for atherosclerotic vascular disease. Altered adipokine secretion, including increased production of nicotinamide phosphoribosyltransferase (Nampt) and retinol binding protein 4 (RBP4) may link adipose tissue dysfunction to cardiovascular complications.. We determined Nampt and RBP4 serum concentrations in 193 consecutive patients with carotid stenosis prior to carotid endarterectomy (CEA) in relation to recently experienced ischemic events, markers of atherosclerosis and obesity, as well as anthropometric and clinical characteristics.. Nampt but not RBP4 was significantly higher in symptomatic patients who experienced an ischemic event within 6 months before surgery compared to asymptomatic patients (p=0.001). In multivariate regression analysis Nampt was the only independent predictor of symptomatic carotid stenosis. Nampt correlated with peripheral leukocyte blood count (p<0.0001) and with the number of macrophages/foam cells within carotid plaques (p=0.042). However, Nampt and RBP4 serum concentrations did not correlate with the maximum percentage of carotid stenosis.. Our data suggest circulating Nampt as an independent predictor of recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between Nampt and carotid atherosclerosis severity.

Topics: Adiponectin; Aged; Asymptomatic Diseases; Atherosclerosis; Carotid Stenosis; Endarterectomy, Carotid; Female; Humans; Ischemia; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Obesity; Retinol-Binding Proteins, Plasma

Postmortem studies have demonstrated that morbidly obese subjects, surprisingly, have less coronary atherosclerosis than obese subjects. However, the reasons for this apparent protection from atherosclerosis are not yet clear. Thromboxane A2, a marker of platelet activation, is greater in obese subjects than in lean subjects, and this might be a clue to their increased cardiovascular risk. However, data on thromboxane A2 in morbidly obese subjects are lacking; therefore, we hypothesized that lower levels of thromboxane A2 in morbidly obese subjects might play a role in their lower atherothrombotic burden. We measured the serum levels of thromboxane B2 (TxB2), a stable metabolite of thromboxane A2, high-sensitivity C-reactive protein (hs-CRP) and leptin in 17 lean subjects (body mass index [BMI] 22.9 ± 1.6 kg/m(2)), 25 obese subjects (BMI 32.6 ± 2.4 kg/m(2)), and 23 morbidly obese subjects (BMI 48.6 ± 7.1 kg/m(2)), without insulin resistance, diabetes, or overt cardiovascular disease. The serum TxB2 levels were lower in the lean subjects than in the obese subjects (p = 0.046) and in the morbidly obese subjects than in the lean and obese subjects (p = 0.015 and p <0.001, respectively). In contrast, the hs-CRP and leptin levels were greater in the obese than in the lean subjects (hs-CRP, p <0.001; leptin, p <0.001) and in the morbidly obese subjects than in the lean subjects (p <0.001 for both). Leptin was also higher in the morbidly obese subjects than in the obese subjects (p <0.001). TxB2 negatively correlated with leptin and BMI. hs-CRP correlated with leptin, and both also correlated with waist circumference, BMI, and homeostasis model assessment of insulin-resistance. In conclusion, insulin-sensitive morbidly obese subjects had lower levels of TxB2 than the obese subjects and lean subjects, suggesting that reduced platelet activation could play a role in the paradoxical protection of morbidly obese subjects from atherosclerosis, despite the greater levels of leptin.

Topics: Adult; Atherosclerosis; Body Mass Index; C-Reactive Protein; Female; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Thromboxane A2; Thromboxane B2

Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I (apoA-I) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-β-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.

Topics: Adult; Aged; Antibodies; Aryldialkylphosphatase; Atherosclerosis; Case-Control Studies; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Renal Dialysis; Risk Factors; Young Adult

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

Patients with systemic lupus erythematosus (SLE) are at increased risk of atherosclerosis, even after accounting for traditional risk factors. High levels of leptin and low levels of adiponectin are associated with both atherosclerosis and immunomodulatory functions in the general population.. To examine the association between these adipokines and subclinical atherosclerosis in SLE, and also with other known inflammatory biomarkers of atherosclerosis.. Carotid ultrasonography was performed in 250 women with SLE and 122 controls. Plasma leptin and adiponectin levels were measured. Lipoprotein a (Lp(a)), oxidised phospholipids on apoB100 (OxPL/apoB100), paraoxonase, apoA-1 and inflammatory high-density lipoprotein (HDL) function were also assessed.. Leptin levels were significantly higher in patients with SLE than in controls (23.7±28.0 vs 13.3±12.9 ng/ml, p<0.001). Leptin was also higher in the 43 patients with SLE with plaque than without plaque (36.4±32.3 vs 20.9±26.4 ng/ml, p=0.002). After multivariate analysis, the only significant factors associated with plaque in SLE were leptin levels in the highest quartile (≥29.5 ng/ml) (OR=2.8, p=0.03), proinflammatory HDL (piHDL) (OR=12.8, p<0.001), age (OR=1.1, p<0.001), tobacco use (OR=7.7, p=0.03) and hypertension (OR=3.0, p=0.01). Adiponectin levels were not significantly associated with plaque in our cohort. A significant correlation between leptin and piHDL function (p<0.001), Lp(a) (p=0.01) and OxPL/apoB100 (p=0.02) was also present.. High leptin levels greatly increase the risk of subclinical atherosclerosis in SLE, and are also associated with an increase in inflammatory biomarkers of atherosclerosis such as piHDL, Lp(a) and OxPL/apoB100. High leptin levels may help to identify patients with SLE at risk of atherosclerosis.

Topics: Adipokines; Adult; Atherosclerosis; Biomarkers; Body Mass Index; Carotid Artery, Common; Epidemiologic Methods; Female; Humans; Inflammation Mediators; Leptin; Lipids; Lupus Erythematosus, Systemic; Middle Aged; Oxidation-Reduction; Ultrasonography

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

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

Dietary flaxseed has cardioprotective effects that may be achieved through its rich content of the omega-3 fatty acid, alpha linolenic acid (ALA). Because ALA can be stored in adipose tissue, it is possible that some of its beneficial actions may be due to effects it has on the adipose tissue. We investigated the effects of dietary flaxseed both with and without an atherogenic cholesterol-enriched diet to determine the effects of dietary flaxseed on the expression of the adipose cytokines leptin and adiponectin. Rabbits were fed one of four diets: a regular (RG) diet, or a regular diet with added 0.5% cholesterol (CH), or 10% ground flaxseed (FX), or both (CF) for 8 weeks. Levels of leptin and adiponectin expression were assessed by RT-PCR in visceral adipose tissue. Consumption of flaxseed significantly increased plasma and adipose levels of ALA. Leptin protein and mRNA expression were lower in CH animals and were elevated in CF animals. Changes in leptin expression were strongly and positively correlated with adipose ALA levels and inversely correlated with levels of en face atherosclerosis. Adiponectin expression was not significantly affected by any of the dietary interventions. Our data demonstrate that the type of fat in the diet as well as its caloric content can specifically influence leptin expression. The findings support the hypothesis that the beneficial cardiovascular effects associated with flaxseed consumption may be related to a change in leptin expression.

Topics: Adiponectin; Administration, Oral; alpha-Linolenic Acid; Animals; Aorta, Thoracic; Atherosclerosis; Cholesterol; Dietary Fats; Epididymis; Fatty Acids; Flax; Intra-Abdominal Fat; Leptin; Male; Rabbits; Triglycerides

The epidemic of obesity sweeping developed nations is accompanied by an increase in atherosclerotic cardiovascular diseases. Dyslipidemia, diabetes, hypertension, and obesity are risk factors for cardiovascular disease. However, delineating the mechanism of obesity-accelerated atherosclerosis has been hampered by a paucity of animal models. Similar to humans, apolipoprotein E-deficient (apoE(-/-)) mice spontaneously develop atherosclerosis over their lifetime. To determine whether apoE(-/-) mice would develop obesity with accelerated atherosclerosis, we fed mice diets containing 10 (low fat (LF)) or 60 (high fat (HF)) kcal % from fat for 17 weeks. Mice fed the HF diet had a marked increase in body weight and atherosclerotic lesion formation compared to mice fed the LF diet. There were no significant differences between groups in serum total cholesterol, triglycerides, or leptin concentrations. Plasma concentrations of the acute-phase reactant serum amyloid A (SAA) are elevated in both obesity and cardiovascular disease. Accordingly, plasma SAA concentrations were increased fourfold (P < 0.01) in mice fed the HF diet. SAA was associated with both pro- and antiatherogenic lipoproteins in mice fed the HF diet compared to those fed the LF diet, in which SAA was primarily associated with the antiatherogenic lipoprotein high-density lipoprotein (HDL). Moreover, SAA was localized with apoB-containing lipoproteins and biglycan in the vascular wall. Taken together, these data suggest male apoE-deficient mice are a model of metabolic syndrome and that chronic low level inflammation associated with increased SAA concentrations may mediate atherosclerotic lesion formation.

Topics: Adiponectin; Analysis of Variance; Animals; Apolipoproteins E; Atherosclerosis; Blood Glucose; Blotting, Western; Body Weight; Chemokine CCL2; Chromatography, High Pressure Liquid; Diet; Dietary Fats; Disease Progression; Energy Intake; Enzyme-Linked Immunosorbent Assay; Image Processing, Computer-Assisted; Interleukin-6; Leptin; Lipids; Liver; Male; Mice; Mice, Knockout; Obesity; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha

A prothrombotic state in obesity may be partially responsible for the higher incidence of atherosclerotic complications. However the factors responsible for this prothrombotic state, linked with high levels of plasminogen activator inhibitor-1 (PAI-1), are not fully known. Leptin is elevated in obesity and studies have shown a positive correlation between leptin and PAI-1 levels in human subjects, along with a negative correlation with tissue-type plasminogen activator (tPA). We tested the hypothesis that leptin induces PAI-1 and inhibits tPA expression using human coronary artery endothelial cells (HCAEC) in culture as these cells play an important role in atherosclerosis. We demonstrate that leptin induces the transcription and translation of PAI-1 in HCAEC. The leptin dependent upregulation of PAI-1 mRNA and protein was comparable to insulin-induced PAI-1 expression. We show leptin concentration (0-150 ng/ml) dependent increases in PAI-1 mRNA and protein after 6 and 12h of leptin administration, respectively. Increased intracellular PAI-1 expression correlates with increased PAI-1 activity in conditioned media and inhibition of specific ERK1/2 pathway by treatment with PD98059 (20-40 microM) inhibits leptin dependent PAI-1 expression. However no changes in tPA expression were seen with time or increasing concentrations of leptin. Also leptin treatment did not alter total tPA concentration or tPA activity in conditioned media. In conclusion, our study shows that leptin upregulates the expression of PAI-1 in vascular endothelial cells via activation of ERK1/2 but does not regulate tPA expression. These studies demonstrate a novel mechanism for the prothrombotic role of leptin in development of atherosclerosis.

Topics: Atherosclerosis; Cells, Cultured; Endothelium, Vascular; Flavonoids; Humans; Leptin; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Obesity; Plasminogen Activator Inhibitor 1; Protein Kinase Inhibitors; Thrombosis; Up-Regulation

Adipokines are protein products of adipose tissue with paracrine and endocrine actions, which have been implicated in the pathogenesis of cardiovascular disease. Locally produced adipokines, especially by periadventitial adipose tissue, may affect vascular physiology and pathology. We investigated the expression of adiponectin, visfatin, leptin and novel adipokines chemerin and vaspin in human periaortic and epicardial adipose tissue, as well as their correlation to aortic and coronary atherosclerosis.. Standard immunohistochemical staining for the adipokines was performed on samples of human periaortic, pericoronary and apical epicardial adipose tissue. Atherosclerotic lesions of the adjacent vascular wall were assessed using the AHA classification.. Adipokines were expressed in periadventitial and apical epicardial adipose tissue and - except for adiponectin - in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Aortic atherosclerosis was positively correlated with chemerin, vaspin, visfatin and leptin periaortic fat expression. Coronary atherosclerosis was positively correlated with chemerin and visfatin pericoronary fat expression. Adipose tissue adiponectin expression was negatively correlated to atherosclerosis in both locations. Expression of adipokines in apical epicardial fat was not associated with atherosclerosis.. Our results show: a) a different expression pattern of adiponectin, visfatin, leptin, chemerin and vaspin in periaortic, pericoronary and apical epicardial adipose tissue, b) a correlation of these adipokines with either aortic or coronary atherosclerosis or both in a pattern characteristic for each adipokine and suggest that locally produced adipokines might differently affect the atherosclerotic process in different locations.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adolescent; Adult; Aged; Aged, 80 and over; Atherosclerosis; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Pericardium; Receptors, Chemokine; Serpins

Adiposity is associated with arterial stiffness, and both adiposity and arterial stiffness independently predict morbidity and mortality. Because adipocytes account for most adipokine production, the objectives of this study were to examine the influence of adipokines such as leptin, adiponectin, and resistin on the relationship between abdominal adiposity and arterial stiffness.. This is a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging (BLSA). Adiposity was measured as kilograms of abdominal adipose tissue using dual-energy X-ray absorptiometry (DXA). Arterial stiffness was assessed as carotid-femoral pulse wave velocity (PWV). Leptin, adiponectin, and resistin were assayed in fasting serum samples. The influence of adipokines on the relationship between adiposity and arterial stiffness by adipokines was examined using standard mediation pathway analysis.. Among 749 participants ages 26-96 years (mean age 67, 52% men, 27% black), abdominal adiposity was positively associated with PWV (relative ratio (RR) = 1.04, P = 0.02), after adjusting for potential confounders but was attenuated and no longer significant after adjusting for leptin (RR = 0.99, P = 0.77). The relationship between adiposity and PWV was not substantially influenced by adiponectin (RR = 1.03, P = 0.06) or resistin (RR = 1.05, P = 0.010). Leptin (RR = 1.02, P < 0.001), resistin (RR = 0.92, P < 0.0001), and adiponectin (RR = 0.97, P = 0.004), but not abdominal adiposity (RR = 1.00, P = 0.94), retained significant associations with PWV when adjusting for each other and confounders.. Our findings are consistent with the hypothesis that leptin explains, in part, the observed relationship between abdominal adiposity and arterial stiffness. Adiponectin, leptin, and resistin are independent correlates of PWV.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Arteries; Atherosclerosis; Carotid Arteries; Cross-Sectional Studies; Elasticity; Female; Femoral Artery; Humans; Leptin; Male; Middle Aged; Obesity, Abdominal; Regional Blood Flow; Resistin; Risk Factors

Adipocytes are nowadays recognised as cells able to produce and secrete a large variety of active substances termed adipokines, which exert direct effects on vascular cells. Among these adipokines, leptin has been proposed to play a role in the pathophysiology of acute coronary syndromes, as well as in increasing cardiovascular risk. At the moment, however, the mechanisms linking leptin to cardiovascular disease are not completely understood. This study investigates the effects of leptin, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk or measurable in patients with acute coronary syndromes, on tissue factor (TF) and cellular adhesion molecules (CAMs) expression in human coronary endothelial cells (HCAECs). We demonstrate that leptin induces transcription of mRNA for TF and CAMs by real-time PCR. In addition, we show that this adipokine promotes surface expression of TF and CAMs that are functionally active since we observed increased procoagulant activity and leukocyte adhesion on cell surface. Leptin effects appear modulated by eNOS-production of oxygen free radicals through the activation of the transcription factor, nuclear factor(NF)-kappaB, since L-NAME, Superoxide Dismutase and NF-kappaB inhibitors suppressed CAMs and TF expression. Data of the present study, although in vitro , indicate that leptin may exert direct effects on human coronary endothelial cells by promoting CAMs and TF expression and support the hypothesis that this adipokines, besides being involved in the pathophysiology of obesity, might play a relevant role as an active mediator linking obesity to cardiovascular disease.

Topics: Acute Coronary Syndrome; Atherosclerosis; Cell Adhesion Molecules; Cells, Cultured; Coronary Thrombosis; Coronary Vessels; Endothelial Cells; Enzyme Inhibitors; Humans; Leptin; NF-kappa B; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type III; Reactive Oxygen Species; Thromboplastin

Topics: Adipokines; Adiponectin; Arteries; Atherosclerosis; Carotid Arteries; Elasticity; Femoral Artery; Humans; Leptin; Obesity, Abdominal; Regional Blood Flow; Resistin; Risk Factors

Atherosclerosis is accelerated in people with systemic lupus erythematosus, and the presence of dysfunctional, pro-inflammatory high-density lipoproteins is a marker of increased risk. We developed a mouse model of multigenic lupus exposed to environmental factors known to accelerate atherosclerosis in humans - high-fat diet with or without injections of the adipokine leptin. BWF1 mice were the lupus-prone model; BALB/c were non-autoimmune controls. High-fat diet increased total serum cholesterol in both strains. In BALB/c mice, non-high-density lipoprotein cholesterol levels increased; they did not develop atherosclerosis. In contrast, BWF1 mice on high-fat diets developed increased quantities of high-density lipoproteins as well as elevated high-density lipoprotein scores, indicating pro-inflammatory high-density lipoproteins; they also developed atherosclerosis. In the lupus-prone strain, addition of leptin increased pro-inflammatory high-density lipoprotein scores and atherosclerosis, and accelerated proteinuria. These data suggest that environmental factors associated with obesity and metabolic syndrome can accelerate atherosclerosis and disease in a lupus-prone background.

Topics: Animals; Atherosclerosis; Diet; Dietary Fats; Disease Models, Animal; Female; Humans; Leptin; Lipoproteins, HDL; Lupus Erythematosus, Systemic; Metabolic Syndrome; Mice; Mice, Inbred BALB C; Mice, Inbred NZB; Obesity; Risk Factors

Topics: Adult; Atherosclerosis; Biomarkers; Blood Glucose; Body Fat Distribution; CD40 Ligand; Female; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Middle Aged; Oxidative Stress; Peptic Ulcer; Prognosis

Fetuin-A, also known as alpha2-Heremans Schmid glycoprotein, is an abundant plasma protein synthesized predominantly in the liver. Fetuin-A inhibits insulin receptor autophosphorylation, which is mediated by its intrinsic tyrosine kinase activity. In this study, we examined the association between the serum fetuin-A level and insulin resistance in Japanese men.. We recruited 300 unrelated Japanese men without known chronic diseases, such as diabetes mellitus, or a history of regular drug use, and who underwent health examinations. From a 75-g oral glucose tolerance test, the study population included 194 individuals with normal glucose tolerance, 91 with impaired glucose tolerance and/or impaired fasting glucose, and 15 with diabetes mellitus. Serum fetuin-A concentrations were measured using an ELISA kit.. Serum fetuin-A concentrations were positively correlated with fasting insulin levels (r = 0.269, p<0.001), HOMA-IR (r = 0.274, p<0.001) and LDL-cholesterol (r = 0.172, p<0.01), and negatively correlated with HDL-cholesterol concentrations (r = -0.191, p<0.001). Fetuin-A concentrations were also positively correlated with serum leptin (r = 0.150, p<0.01) and negatively with adiponectin concentrations (r = -0.208, p<0.001). Stepwise regression analyses confirmed that the fetuin-A concentration was independently associated with the fasting insulin level and HOMA-IR, as were body mass index, triglyceride, LDL-cholesterol, leptin and adiponectin concentrations.. Our data suggest that increased serum fetuin-A levels constitute an independent marker of insulin resistance and an atherogenic lipid profile in Japanese men.

Topics: Adiponectin; Adiposity; Adult; Aged; alpha-2-HS-Glycoprotein; Asian People; Atherosclerosis; Biomarkers; Blood Proteins; C-Reactive Protein; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin Resistance; Japan; Leptin; Lipids; Male; Middle Aged

To investigate the factors that influence visceral fat accumulation in adolescence, we performed a medical examination of high school students and assessed abdominal fat thickness and fatty change of the liver.. A cohort of 374 Japanese high school students aged 15-16 years (193 boys and 181 girls) in public high schools in Chiba prefecture were enrolled. Anthropometric parameters, blood cell count, blood chemistry and adipocytokine levels were measured. Preperitoneal fat thickness (PFT) and echoic contrast of the liver were measured by ultrasonography.. Anthropometric parameters, systolic blood pressure, blood cell count, ALT, AST, FBS, gamma-GTP, HDL-C, LpL, UA, adiponectin, resistin and leptin levels differed between sexes. Multivariate regression analysis revealed that leptin was the most appropriate marker for PFT in both sexes (p<0.0001). Visceral obesity, categorized as PFT exceeding 8 mm, was observed in 9.6% of all students. Boys with visceral obesity showed apparent liver dysfunction, hyperlipidemia, hyperinsulinemia, and high leptin and low adiponectin levels. Overall, 16.6% of boys and 30.4% of girls showed hepatorenal echo contrast positivity. Boys with visceral obesity and fatty liver had more risk factors for atherosclerosis.. Physical examination of high school students is important for early detection of atherosclerosis.

Topics: Adolescent; Asian People; Atherosclerosis; Biomarkers; Female; Humans; Intra-Abdominal Fat; Leptin; Liver; Male; Obesity; Risk Factors; Sex Factors; Ultrasonography

Hyperleptinemia and oxidative stress play a major role in the development of cardiovascular diseases in obesity. This study aimed to investigate whether there is a relationship between plasma levels of leptin and phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and its potential relevance in the vascular remodeling in obese patients.. The study was performed in 164 obese and 94 normal-weight individuals (controls). NADPH oxidase activity was evaluated by luminescence in phagocytic cells. Levels of leptin were quantified by ELISA in plasma samples. Carotid intima-media thickness (cIMT) was measured by ultrasonography. In addition, we performed in-vitro experiments in human peripheral blood mononuclear cells and murine macrophages.. Phagocytic NADPH oxidase activity and leptin levels were enhanced (P < 0.05) in obese patients compared with controls. NADPH oxidase activity positively correlated with leptin in obese patients. This association remained significant in a multivariate analysis. cIMT was higher (P < 0.05) in obese patients compared with controls. In addition, cIMT also correlated positively with leptin and NADPH oxidase activity in obese patients. In-vitro studies showed that leptin induced NADPH oxidase activation. Inhibition of the leptin-induced NADPH oxidase activity by wortmannin and bisindolyl maleimide suggested a direct involvement of the phosphatidylinositol 3-kinase and protein kinase C pathways, respectively. Finally, leptin-induced NADPH oxidase activation promoted macrophage proliferation.. These findings show that phagocytic NADPH oxidase activity is increased in obesity and is related to preclinical atherosclerosis in this condition. We also suggest that hyperleptinemia may contribute to phagocytic NADPH oxidase overactivity in obesity.

Topics: Animals; Atherosclerosis; Carotid Arteries; Case-Control Studies; Cell Line; Cell Proliferation; Female; Humans; In Vitro Techniques; Leptin; Macrophages; Male; Mice; Middle Aged; NADPH Oxidases; Obesity; Oxidative Stress; Phagocytes; Superoxides; Tunica Intima

The objectives of this study were to use magnetic resonance (MR) molecular imaging to 1) characterize the aortic neovascular development in a rat model of atherosclerosis and 2) monitor the effects of an appetite suppressant on vascular angiogenesis progression.. The James C. Russell:LA corpulent rat strain (JCR:LA-cp) is a model of metabolic syndrome characterized by obesity, insulin resistance, hyperlipidemia, and vasculopathy, although plaque neovascularity has not been reported in this strain. MR molecular imaging with alpha(nu)beta(3)-targeted nanoparticles can serially map angiogenesis in the aortic wall and monitor the progression of atherosclerosis.. Six-week old JCR:LA-cp (+/?; lean, n = 5) and JCR:LA-cp (cp/cp; obese, n = 5) rats received standard chow, and 6 obese rats were fed the appetite suppressant benfluorex over 16 weeks. Body weight and food consumption were recorded at baseline and weeks 4, 8, 12, and 16. MR molecular imaging with alpha(nu)beta(3)-targeted paramagnetic nanoparticles was performed at weeks 0, 8, and 16. Fasted plasma triglyceride, cholesterol, and glucose were measured immediately before MR scans. Plasma insulin and leptin levels were assayed at weeks 8 and 16.. Benfluorex reduced food consumption (p < 0.05) to the same rate as lean animals, but had no effect on serum cholesterol or triglyceride levels. MR (3-T) aortic signal enhancement with alpha(nu)beta(3)-targeted nanoparticles was initially equivalent between groups, but increased (p < 0.05) in the untreated obese animals over 16 weeks. No signal change (p > 0.05) was observed in the benfluorex-treated or lean rat groups. MR differences paralleled adventitial microvessel counts, which increased (p < 0.05) among the obese rats and were equivalently low in the lean and benfluorex-treated animals (p > 0.05). Body weight, insulin, and leptin were decreased (p < 0.05) from the untreated obese animals by benfluorex, but not to the lean control levels (p < 0.05).. Neovascular expansion is a prominent feature of the JCR:LA-cp model. MR imaging with alpha(nu)beta(3)-targeted nanoparticles provided a noninvasive assessment of angiogenesis in untreated obese rats, which was suppressed by benfluorex.

Topics: Animals; Aorta; Appetite Depressants; Atherosclerosis; Body Weight; Cholesterol; Disease Models, Animal; Eating; Fenfluramine; Insulin; Integrin alphaVbeta3; Leptin; Magnetic Resonance Angiography; Male; Metabolic Syndrome; Nanoparticles; Neovascularization, Pathologic; Obesity; Rats; Time Factors; Triglycerides

Leptin is a hormone expressed by the leptin gene, primarily in adipocytes, controlling food intake and energy expenditure. The effects of leptin are mediated by its receptor (LEPR) located in the central nervous system and other tissues, including adipocytes and endothelial cells. The aim of this study was to characterize two polymorphisms of LEPR, Lys109Arg (rs1137100) and Gln223Arg (rs1137101), as risk factors for early atherosclerosis. This connection has not been studied before.. This study was performed in the randomly selected, middle-aged control subjects (n=526) from our well-defined OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. Analysis of covariance (ANCOVA) was performed to study the associations between genotypes, intima media thickness (IMT) measurements, and risk factors for atherosclerosis.. Subjects with the genotype Lys109Arg had the lowest body mass index (BMI) (P = 0.035), whereas Arg109Arg homozygotes had the highest total cholesterol (P=0.021) when adjusted for sex and age. Gln223Arg associated independently with systolic blood pressure (P=0.036). There were no differences in leptin concentrations between the genotypes. The adjusted (sex, age, BMI, smoking status, low-density lipoprotein cholesterol, systolic blood pressure, and fasting blood glucose) means for the IMT measurements were lowest in the Arg109 and Arg223 homozygotes (P=0.042 and P=0.041, ANCOVA, respectively).. The variations in the LEPR gene are independently associated with early atherosclerosis and some of its risk factors. These variations could possibly affect leptin signaling and thereby modify the effects of leptin on the atherosclerotic process.

Topics: Adipocytes; Arginine; Atherosclerosis; Blood Pressure; Body Mass Index; Endothelial Cells; Female; Glutamine; Humans; Leptin; Male; Middle Aged; Models, Genetic; Polymorphism, Genetic; Random Allocation; Receptors, Leptin; Risk Factors

Leptin, a 16-kDa cytokine that is released mainly by the adipose tissue, is known to affect a wide assortment of processes, ranging from energy homeostasis to angiogenesis and the immune response. In the present study, the effect of leptin on atherosclerosis-related properties of human monocytes was investigated. methods: Monocytes were isolated from whole blood obtained from healthy donors who had normal body mass index values. Pharmacological inhibition of specific signaling proteins was implemented. Fluorescence spectrometry and immunofluorescence techniques, as well as ELISA methods, were utilized. Leptin dose response curves were determined for each type of experiment.. Leptin (160 ng/ml) was found to augment monocyte adhesion to laminin-1 and its migration through this glycoprotein, which is one of the main components of the extracellular matrix. Additionally, leptin increased CD36-receptor surface expression, as well as moderately oxidized low-density lipoprotein (oxLDL(3)) uptake levels.. Leptin amplifies the pro-atheromatic properties of human monocytes through a complex signaling net which involves the Na(+)/H(+) exchanger isoform-1, the actin cytoskeleton, phosphoinositide 3-kinase, certain conventional isoforms of protein kinase C and NADPH oxidase.

Topics: Atherosclerosis; Cation Transport Proteins; CD36 Antigens; Cell Adhesion; Cell Movement; Dose-Response Relationship, Drug; Humans; Laminin; Leptin; Lipoproteins, LDL; Monocytes; NADPH Oxidases; Phosphatidylinositol 3-Kinases; Signal Transduction; Sodium-Hydrogen Exchanger 1; Sodium-Hydrogen Exchangers

Obesity and type 2 diabetes increase the risk of atherosclerosis. It is unknown to what extent this reflects direct effects on the arterial wall or secondary effects of hyperlipidaemia.. The effect of obesity and type 2 diabetes on the development of atherosclerosis and inflammation, in the absence or presence of hyperlipidaemia, was assed in wild-type (n = 36) and human apolipoprotein B (apoB) transgenic mice (n = 27) that were fed normal chow or 60% fat for 12 months.. Fat-feeding caused obesity, glucose intolerance and elevated plasma leptin and soluble vascular cell adhesion molecule-1 (sVCAM-1) in both wild-type and apoB transgenic mice. In wild-type mice, plasma very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were unaffected by fat-feeding. ApoB transgenic mice had mildly elevated plasma LDL-C (approximately 1 mmol L(-1)), which was slightly increased by fat-feeding. Sixty-four per cent of fat-fed wild-type mice vs. 7% of chow-fed wild-type mice had lipid-staining intimal lesions in the aortic root (P = 0.002). Eighty-six per cent of fat-fed apoB transgenic mice had lipid-staining lesions and the median lesion area was 8.0 times higher than in fat-fed wild-type mice (P = 0.001). Intracellular adhesion molecule-1 staining of the aortic endothelium was most pronounced in the fat-fed apoB transgenic mice.. Our findings suggest that diet-induced type 2 diabetes causes early atherosclerosis in the absence of dyslipidaemia, and that even a moderate level of LDL-C markedly augments this effect.

Topics: Animals; Arteritis; Atherosclerosis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dietary Fats; Disease Models, Animal; Female; Humans; Hyperlipidemias; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Random Allocation; Risk Factors; Statistics as Topic; Time Factors; Vascular Cell Adhesion Molecule-1

Malnutrition-inflammation-atherosclerosis syndrome (MIA) in haemodialysis (HD) patients is a common clinical condition characterized by increased mortality rate. The aim of this study was to analyze the frequency of MIA components in a selected population of HD patients with and without diabetic nephropathy.. The frequency of MIA components was analysed in 49 patients with an over 10-year history of diabetes before initiation of HD (DM group) and 49 non-diabetic HD patients (non-DM group).. The chance for occurrence of atherosclerosis (odds ratio = 3.26) was markedly higher in DM than non-DM subjects. The most frequent MIA component in DM and non-DM subjects was atherosclerosis (67.3% and 40.8%, respectively). Atherosclerosis frequently coexisted with inflammation in both groups (51.5% in DM and 20.0% in non-DM) and less frequently with malnutrition. The frequency of inflammation was only slightly higher in DM, while of malnutrition was similar. Patients with atherosclerosis in the DM group had significantly higher serum concentrations of interleukin-6 than the ones in the non-DM group: 11 (6-24) versus 5 (2-9) pg/mL, respectively (P = 0.002).. We can conclude that: (i) atherosclerosis is more common in HD patients with diabetic nephropathy; and (ii) this fact may explain the poor outcome of these patients and indicates the challenge in diagnostic and therapeutic management.

Topics: Aged; Atherosclerosis; Diabetic Nephropathies; Female; Humans; Inflammation; Leptin; Male; Malnutrition; Middle Aged; Renal Dialysis; Serum Albumin

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

Serum amyloid A (SAA) is a sensitive marker of inflammation and its elevation has been implicated in obesity and in cardiovascular disease, yet data on its regulation in young adults or on its role in early atherosclerosis is scarce. We investigated which factors explain the variation in SAA and analysed whether SAA could be associated with preclinical atherosclerosis.. Serum amyloid A levels were measured in participants of the Cardiovascular Risk in Young Finns Study (n = 2280, n = 1254 women, n = 1026 men). Correlates and determinants of SAA were analysed and the effect of SAA on subclinical atherosclerosis, measured as intima-media thickness (IMT) and carotid artery compliance, was evaluated with risk-factor adjusted models.. Serum amyloid A correlated directly and independently of BMI with C-reactive protein (CRP), waist circumference and leptin in both sexes, with total cholesterol, LDL cholesterol and ApolipoproteinA1 (ApoA1) in women and with triglycerides, insulin levels and insulin resistance in men. Use of combined oral contraceptives and intrauterine device was also associated with SAA levels. Determinants for SAA included CRP, leptin and ApoA1 in women, and CRP, leptin and HDL cholesterol in men. SAA levels correlated with carotid compliance in both sexes and with IMT in men, yet SAA had no independent effect on IMT or carotid compliance in multivariable analysis.. Serum amyloid A was associated with several metabolic risk factors but was not an independent predictor of IMT or carotid artery compliance. Further longitudinal studies will show whether SAA holds a prognostic value as a risk marker, analogously to CRP.

Topics: Adolescent; Adult; Apolipoprotein A-I; Atherosclerosis; Biomarkers; C-Reactive Protein; Carotid Arteries; Child; Child, Preschool; Cholesterol; Cholesterol, LDL; Cross-Sectional Studies; Female; Humans; Leptin; Logistic Models; Longitudinal Studies; Male; Metabolic Syndrome; Risk Assessment; Serum Amyloid A Protein; Sex Factors; Tunica Intima; Ultrasonography; Vascular Resistance

The adipocytokine leptin has been proposed to increase cardiovascular risk in both obese and diabetic individuals. In the current study, therefore, we used apoE-deficient mice to examine the effects of leptin on both lesion size and calcification.. Mice were treated with once daily intraperitoneal injections of leptin (125 microg/mouse/d) for 2 months. The mice were then euthanized, and sections of the aortic root and thoracic aorta analyzed histomorphometrically. Measurements of lesion size and surface area occupied by atherosclerotic lesions did not reveal any differences between nontreated and leptin-treated animals. However, von Kossa staining of the aortic root demonstrated an 8.3+/-2.0-fold increase in lesion calcification as well as a 2.5+/-0.6-fold increase in valvular calcification in those animals treated with leptin. In addition, the percent total lesion area demonstrating ALP-positive staining was 5.4+/-2.1-fold greater in leptin-treated mice when compared to nontreated control mice. This increase in ALP staining was also accompanied by an increase in the expression of the osteoblast-specific markers, osteocalcin, and osteopontin.. Based on these observations, we conclude that leptin may increase cardiovascular risk by promoting osteogenic differentiation and thus vascular calcification.

Topics: Alkaline Phosphatase; Animals; Aorta; Aortic Valve; Apolipoproteins E; Atherosclerosis; Body Weight; Calcinosis; Cattle; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Female; Humans; Leptin; Lipids; Mice; Mice, Knockout; Myocytes, Smooth Muscle; Osteoblasts; Osteocalcin; Osteopontin; Recombinant Proteins; Risk Factors

To determine the effect of Helicobacter pylori (H. pylori) eradication on blood levels of soluble CD40 ligand, leptin, oxidative stress and body composition in patients with dyspepsia infected with H. pylori.. The infection of H. pylori was based on the presence of both (14)C urea breath test (UBT) and histology. Patients were given triple eradication therapy for 14 days and at 3 months after the treatment, (14)C UBT was reinstituted. Fasting glucose, leptin, body composition, soluble CD40 ligand, total oxidant status (TOS) were studied before and at 3 months after the treatment.. In 33 subjects, H. pylori infection was successfully eradicated. sCD40L, and TOS levels were significantly decreased after H. pylori eradication. The percentage of body fat and body fat mass significantly decreased whereas the fat free mass (FFM) increased after eradication. However, eradication of the organism yielded no differences in leptin levels.. These findings suggest that H. pylori eradication reduces the sCD40L and oxidative stress, fat mass with a significant increase in fat free mass. Thus, eradication of H. pylori infection not only improves ulcer healing, but may also reduce the presumed atherosclerosis risk.

Topics: Adult; Anti-Bacterial Agents; Atherosclerosis; Body Fat Distribution; CD40 Ligand; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Oxidative Stress; Peptic Ulcer; Prospective Studies; Risk Factors; Young Adult

Topics: Animals; Atherosclerosis; Cell Division; Endothelial Cells; Humans; Ischemia; Leptin

Obesity is an effect of interaction of genetic and environmental factors. It leads to development of serious complications, like insulin resistance, diabetes type 2, arterial hypertension and atherosclerosis. The adipose tissue is a place where many adipokines, mainly leptin and adiponectin, are produced and released. Adiponectin, which blood level is decreased in obesity is considered to have antidiabetic and antiatherogenic effect. While leptin, which blood level is increased in obesity, is associated with regulation of appetite, energy expenditure, lipids and carbohydrates metabolism, cellular differentiation and puberty. The aim of this research was estimation of leptin to adiponectin ratio (Lep/AdipoR) in the blood of patients who came from obese families. The study was carried out on 80 patients (43 female and 37 male). The antropometric examination with proportional contents of adipose tissue, oral glucose tolerance test (OGTT) and oral postprandial lipaemia test (OPLT) were performed. The fasting level of leptin (Elisa), adiponectin (Elisa) and von Willebrand factor (Elisa) lipidogram were performed. During OGTT blood was sampled in intervals of 30 minutes up to 2 hours, to measure glucose and insulin concentration. In fasting state and then every 2 hours after consumption of a high-fat meal (OPLT), (0, 2 hours, 4 hours, 6 hours, and 8 hours) blood was sampled for: trigliceride, glucose, free fatty acids and insulin concentration. The insulin resistance ratio (HOMA-IR) was calculated for each patient according to the formula: [insulin (mU/ml) x glucose (mmol/l)]/22.5. Adiponectin blood level was higher in the examined women than in men. It (regardless to the sex) was decreased with decrease of body mass index (BMI). Blood level of leptin (also higher in women) was positively corelated with BMI. In the group of patients with low level of adiponectin in serum (below 5mg/ml in men and 10 mg/ml in women) the highest con- centration of glucose and insulin in successive time points of OGTT and the highest HOMA-IR value (4.79 in men and 4.38 in women) were observed. In patients with high level of leptin in serum (over 20 ng/ml), the highest concentration of insulin, especially in 2 hours of the test (101.75 micromol/ l), and the highest HOMA-IR value (4.30 during OPLT ) were found. The Lep/AdipoR in the blood was significantly higher in obese patients in comparison to people with normal BMI. Lep/AdipoR had high correlation factor with BMI (r = 0.6267, p

Topics: Adiponectin; Adipose Tissue; Atherosclerosis; Female; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; ROC Curve

Both experimental and epidemiological studies suggest that leptin is one of the molecules responsible for accelerated atherosclerosis in obese humans. To confirm the notion, we studied whether leptin accelerates atherosclerosis in apoE(-/-) mice. Leptin deficient hyperlipidemic mice (ob/ob;apoE(-/-) mice) developed significantly less atherosclerosis than apoE(-/-) mice, when fed an atherogenic diet for 16 weeks from 8 weeks of age. Histological analysis revealed that most of the atherosclerotic lesions in ob/ob;apoE(-/-) mice remained as fatty streaks, while those in apoE(-/-) mice were mainly fibrous plaques. The decrease in atherosclerosis was not due to changes in the serum levels of cholesterol, TNF-alpha, or adiponectin. Exogenous leptin significantly increased atherosclerotic areas in apoE(-/-) mice, even though it decreased food intake and body weight. Our findings support the notion that leptin accelerates atherosclerosis.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Diet, Atherogenic; Disease Models, Animal; Leptin; Male; Mice; Mice, Knockout; Obesity

Previous studies have demonstrated that macrophage-derived apolipoprotein E (apoE) reduces atherosclerotic lesion formation in lean apoE-deficient ((-/-)) mice. apoE has also been demonstrated to play a role in adipocyte differentiation and lipid accumulation. Because the prevalence of obesity has grown to epidemic proportions, we sought to determine whether macrophage-derived apoE could impact atherosclerotic lesion formation or adipose tissue expansion and inflammation in obese apoE(-/-) mice. To this end, we transplanted obese leptin-deficient (ob/ob) apoE(-/-) mice with bone marrow from either ob/ob;apoE(-/-) or ob/ob;apoE(+/+) donors. There were no differences in body weight, total body adipose tissue, or visceral fat pad mass between recipient groups. The presence of macrophage-apoE had no impact on adipose tissue macrophage content or inflammatory cytokine expression. Recipients of apoE(+/+) marrow demonstrated 3.7-fold lower plasma cholesterol (P < 0.001) and 1.7-fold lower plasma triglyceride levels (P < 0.01) by 12 wk after transplantation even though apoE was present in plasma at concentrations <10% of wild-type levels. The reduced plasma lipids reflected a dramatic decrease in very low density lipoprotein and a mild increase in high-density lipoprotein levels. Atherosclerotic lesion area was >10-fold lower in recipients of ob/ob;apoE(+/+) marrow (P < 0.005). Similar results were seen in leptin receptor-deficient (db/db) apoE(-/-) mice. Finally, when bone marrow transplantation was performed in 4-mo-old ob/ob;apoE(-/-) and db/db;apoE(-/-) mice with preexisting lesions, recipients of apoE(+/+) marrow had a 2.8-fold lower lesion area than controls (P = 0.0002). These results demonstrate that macrophage-derived apoE does not impact adipose tissue expansion or inflammatory status; however, even very low levels of macrophage-derived apoE are capable of reducing plasma lipids and atherosclerotic lesion area in obese mice.

Topics: Adipose Tissue; Animals; Apolipoproteins E; Atherosclerosis; Blotting, Western; Body Composition; Bone Marrow Transplantation; Dyslipidemias; Leptin; Lipids; Lipoproteins; Macrophages; Mice; Mice, Knockout; Obesity; Reverse Transcriptase Polymerase Chain Reaction

Anxiety has been shown to be associated with cardiovascular disease. Atherosclerosis is responsible for the vast majority of cardiovascular events. Recent evidence is accumulating to show that insulin resistance (IR) plays a central role in determining the clinical manifestations of established atherosclerotic lesions. The current preliminary study aimed to investigate the associations between trait anxiety, IR, and atherosclerotic progression in healthy elderly subjects with normal fasting glucose and without metabolic syndrome. Thirty-five healthy elderly subjects (19 males and 16 females, mean age 64.5+/-4.7 years) were enrolled in this study. Trait anxiety was measured using a questionnaire corresponding to the trait anxiety scale taken from the State and Trait Anxiety Inventory. The homeostasis model assessment (HOMA-R) and plasma leptin-to-adiponectin ratio (L/A ratio), which are convenient IR indexes calculated from fasting blood sampling, were examined. As measurements of atherosclerotic progression, we performed two ultrasound methods, namely brachial artery flow-mediated dilation (FMD), an endothelial function assessment quantitatively reflecting the endothelium-dependent vasodilation responses following hyperemia, and measurement of carotid intima-media thickness (IMT). The severity of trait anxiety was positively associated with HOMA-R and L/A ratio, and negatively associated with the percent change of brachial artery FMD (%FMD). HOMA-R and L/A ratio were positively associated with carotid IMT, and L/A ratio was negatively associated with %FMD. These data showed the associations between trait anxiety, IR indexes and endothelial dysfunction or atherosclerotic progression. This pilot study, with a cross-sectional design, supports the promising role of IR for clarifying the pathophysiological mechanism by which anxiety contributes to an increasing risk of atherosclerosis.

Topics: Adiponectin; Aged; Anxiety; Atherosclerosis; Blood Pressure; Body Mass Index; Brachial Artery; Carotid Arteries; Cross-Sectional Studies; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Middle Aged; Pilot Projects; Regional Blood Flow

Plasma leptin is often elevated in obese individuals, and previous studies have suggested leptin as a factor that links obesity and atherosclerosis. Because macrophages play a key role in atherogenesis and are responsive to leptin, we hypothesized that leptin increases aortic root lesion formation, in part, through macrophage leptin receptor (LepR). Three different bone marrow transplantation studies were conducted in which bone marrow, with or without LepR, was transplanted into lethally irradiated 1) LDL receptor-deficient (LDLR(-/-)) mice with moderate hyperleptinemia due to Western diet (WD) feeding, 2) LDLR(-/-) mice with WD feeding plus pharmacologically induced hyperleptinemia (daily injection of 125 microg leptin), or 3) obese, hyperleptinemic, LepR-deficient LDLR(-/-) (LepR(db/db);LDLR(-/-)) mice. Minor differences in plasma parameters such as cholesterol, triglycerides, and insulin were observed in some groups; however, a consistent trend for the role of LepR on these parameters was not detected. In each of the studies, macrophage LepR expression did not have an effect on aortic root atherosclerotic lesion formation. These results suggest that nonhematopoietic cells may have a more significant role than macrophages in leptin-mediated effects on aortic root lesion formation.

Topics: Animals; Aortic Diseases; Atherosclerosis; Bone Marrow Transplantation; Diet; Female; Half-Life; Leptin; Macrophages; Male; Mice; Mice, Knockout; Obesity; Receptors, LDL; Receptors, Leptin

Fat inflammation may play an important role in comorbidities associated with obesity such as atherosclerosis.. To first establish feasibility of fat transplantation, epididymal fat pads were harvested from wild-type C57BL/6J mice and transplanted into leptin-deficient (Lep(ob/ob)) mice. Fat transplantation produced physiological leptin levels and prevented obesity and infertility in Lep(ob/ob) mice. However, the transplanted fat depots were associated with chronically increased macrophage infiltration with characteristics identical to those observed in fat harvested from obese animals. The inflammation in transplanted adipose depots was regulated by the same factors that have been implicated in endogenous fat inflammation such as monocyte chemoattractant protein-1. To determine whether this inflamed adipose depot could affect vascular disease in mice, epididymal fat depots were transplanted into atherosclerosis-prone apolipoprotein E-deficient ApoE(-/-) mice. Plasma from ApoE(-/-) mice receiving fat transplants contained increased leptin, resistin, and monocyte chemoattractant protein-1 compared with plasma from sham-operated ApoE(-/-) mice. Furthermore, mice transplanted with visceral fat developed significantly more atherosclerosis compared with sham-operated animals, whereas transplants with subcutaneous fat did not affect atherosclerosis despite a similar degree of fat inflammation. Treatment of transplanted ApoE(-/-) mice with pioglitazone decreased macrophage content of the transplanted visceral fat pad and reduced plasma monocyte chemoattractant protein-1. Importantly, pioglitazone also reduced atherosclerosis triggered by inflammatory visceral fat but had no protective effect on atherosclerosis in the absence of the visceral fat transplantation.. Our results indicate that visceral adipose-related inflammation accelerates atherosclerosis in mice. Drugs such as thiazolidinediones might be a useful strategy to specifically attenuate the vascular disease induced by visceral inflammatory fat.

Topics: Adiponectin; Animals; Apolipoproteins E; Atherosclerosis; Inflammation; Intra-Abdominal Fat; Leptin; Macrophages; Mice; Mice, Inbred C57BL; Pioglitazone; Thiazolidinediones

The relationship of visceral adiposity with adipocytokines and low-density lipoprotein (LDL) particle distribution and oxidation in Asian metabolically obese, normal-weight (MONW) individuals has not been evaluated. We aimed to investigate the association between visceral adiposity and adipocytokines and cardiovascular disease (CVD) risk factors in MONW Korean women with normal glucose tolerance.. We examined the metabolic characteristics of 135 non-obese (BMI <25 kg/m(2)) women aged 25-64 years. Twenty-five women (BMI <25 kg/m(2) and visceral fat adiposity (VFA) > or =100 cm(2)) were classified as MONW and 25 women (BMI <25 kg/m(2) and VFA <100 cm(2)), pair-matched for age, weight, height, and menopausal status, as control group. Plasma lipid profiles and adipocytokines were evaluated in these two groups.. MONW subjects had higher systolic (P < 0.05) and diastolic blood pressure (P < 0.005) and higher concentrations of triacylglycerol (TG) (P < 0.005), insulin (P < 0.01), and free fatty acid (FFA) (P < 0.05) than control subjects. There was no significant difference between two groups in LDL-cholesterol (LDL-C) concentrations; however, MONW subjects had smaller LDL particles (P < 0.01) and higher concentrations of oxidized LDL (ox-LDL) (P < 0.05) compared with controls. Moreover, MONW subjects had higher concentrations of tumor necrosis factor-alpha (TNF-alpha) (P < 0.05), interleukin-6 (IL-6) (P < 0.05) and leptin (P < 0.05), and lower plasma adiponectin concentrations (P < 0.05). Higher intake of saturated fat with lower ratio of polyunsaturated fatty acids (PUFAs) to saturated fatty acids (SFA) and lower fiber intake than normal subjects were found in MONW women.. We found an unfavorable inflammatory profile and a more atherogenic LDL profile in MONW female subjects even in the absence of a known CVD risk factors. Moreover, MONW consumed more saturated fat and less fiber than the control group.

Topics: Adiponectin; Adult; Atherosclerosis; Blood Pressure; Body Weight; Cholesterol, LDL; Energy Intake; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; Female; Humans; Insulin; Intra-Abdominal Fat; Leptin; Lipoproteins, LDL; Middle Aged; Obesity; Particle Size; Risk Factors; Triglycerides

Little is known about the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms and the presence of insulin resistance and the early evolution of atherosclerosis in nondiabetic subjects with cardiovascular disease (CAD) and stent implantation. The present study was performed in an attempt to better understand whether metabolic, endothelial, and angiographic findings characteristic of subjects with cardiovascular disease and in-stent restenosis are related to NOS3 variants. This is a case-control study performed from 2002 to 2006. All subjects admitted to the study were recruited in the Nord-Centre of Italy, most from Milan and its surrounding towns. Measures of glucose tolerance, insulin sensitivity, markers of endothelial dysfunction, forearm vasodilation, and adipokine levels were determined and associated to the frequency of two single-nucleotide polymorphisms of NOS3, i.e., Glu298Asp (rs1799983, G/T) and rs753482 (intron 18 A/C). A total of 747 subjects, not known to have diabetes, were evaluated: 333 subjects had asymptomatic CAD, 106 subjects had unstable angina and were evaluated for in-stent restenosis 6 mo after stent placement, and 308 were control subjects. The presence of TT and CC minor alleles was significantly greater in case groups compared with control subjects. At phenotypic level, subjects with the polymorphisms were characterized by hyperinsulinemia and reduced reactive hyperemia, whereas increased leptin and decreased adiponectin levels were present in subjects with restenosis in the presence of reduced minimal lumen diameter and length of stenosis almost doubled. Hyperinsulinemia, endothelial dysfunction, and a more atherogenic profile seem to be peculiar features of subjects with asymptomatic CAD and restenosis carrying NOS3 gene variants.

Topics: Adiponectin; Aged; Atherosclerosis; Blood Glucose; Coronary Angiography; Coronary Artery Disease; Diabetes Complications; DNA; Female; Forearm; Gene Frequency; Genotype; Glucose Tolerance Test; Glycated Hemoglobin; Graft Occlusion, Vascular; Haplotypes; Humans; Hyperinsulinism; Leptin; Lipids; Male; Middle Aged; Nitric Oxide Synthase Type III; Polymorphism, Genetic; Regional Blood Flow

Cellular and animal studies suggest that leptin has proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis. To investigate this hypothesis, we examined the effect of genetic variability at the leptin receptor (LEPR) locus on the plasma levels of fibrinogen and CRP--two markers of inflammation and susceptibility to atherosclerosis.. Linkage disequilibrium analysis of 71 single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian individuals, variability in block #4 was significantly associated with plasma fibrinogen (p=0.005), accounting for 3% of its variance (r2=0.030). The same block was also associated with CRP levels (p=0.049, r2=0.022). The effect was strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10% higher in minor allele homozygotes than in major allele homozygotes and intermediate in heterozygotes (p=0.015). At rs1805096, it was 5% higher (p=0.007) and CRP 32% higher (p=0.011) in major allele homozygotes than in minor allele carriers. This pattern of association was also evident in the haplotype analysis.. Association of leptin receptor variability with inflammatory traits supports the hypothesis that leptin may play a role in atherogenesis.

Topics: Adipose Tissue; Adult; Atherosclerosis; C-Reactive Protein; Female; Fibrinogen; Humans; Inflammation; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Cell Surface; Receptors, Leptin; White People

Topics: Abdominal Fat; Acanthosis Nigricans; Adolescent; Atherosclerosis; Bone Diseases, Endocrine; Child; Fatty Liver; Ghrelin; Humans; Hyperandrogenism; Hypertension; Insulin; Insulin Resistance; Leptin; Obesity; Peptide Hormones; Phenotype; Satiation; Sleep Apnea Syndromes

Topics: Aged; Atherosclerosis; C-Reactive Protein; Female; Humans; Leptin; Male; Middle Aged; Risk Factors

Our goal was to elucidate mechanisms of the inhibitory effect of rosuvastatin on the accumulation of plaque oxidized low density lipoproteins (oxLDL) and on plaque volume, without lowering cholesterol, in mice with combined leptin and LDL-receptor deficiency (DKO).. Twelve-week old DKO mice were treated with rosuvastatin (10 mg kg(-1) day(-1), s.c.) or placebo or no treatment for 12 weeks. The effect on blood variables, aortic plaque volume and composition and gene expression in the aorta and in THP-1 cells was assessed.. Rosuvastatin lowered free fatty acids (FFA), triglycerides, and increased insulin sensitivity, without affecting cholesterol. Rosuvastatin lowered the plaque volume, inhibited macrophage, lipid and oxLDL accumulation, and decreased the oxLDL-to-LDL ratio of plaques in the aortic arch. It increased superoxide dismutase 1 (SOD1), CD36, LXR-alpha, ABCA-1 and PPAR-gamma RNA expression in aortic extracts. SOD1 was the strongest inverse correlate of oxLDL. In THP-1 macrophages and foam cells, expression of SOD1 was lower than in THP-1 monocytes. Rosuvastatin restored expression of SOD1 in THP-1 macrophages and foam cells.. Rosuvastatin restored SOD1 expression in THP-1 macrophages and foam cells in vitro and in the aorta of DKO mice. The latter was associated with less oxLDL accumulation within atherosclerotic plaques and inhibition of plaque progression. This effect was obtained at a dose not affecting cholesterol levels but improving insulin sensitivity. SOD1 is a potentially important mediator of the prevention of oxLDL accumulation within atherosclerotic plaques.

Topics: Animals; Aorta; Atherosclerosis; Blood Glucose; Body Weight; Cell Line; Dyslipidemias; Fluorobenzenes; Gene Expression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Leptin; Lipids; Lipoproteins, LDL; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; PPAR gamma; Pyrimidines; Receptors, LDL; Reverse Transcriptase Polymerase Chain Reaction; Rosuvastatin Calcium; Sulfonamides; Superoxide Dismutase

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

Obesity and hyperlipidaemia are found very frequently after kidney transplantation (Tx) and may represent independent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored, a total of 68 obese transplant patients [body mass index (BMI) > 30 kg/m2] with dyslipidaemia over a period of 24 months. We compared the findings of a new therapeutic regimen 1 year (start of the study) and 2 years after renal transplantation. Based on a Subjective Global Assessment Scoring Sheet, we started at the end of the first year with an individualized hypoenergic-hypolipidaemic diet (IHHD). Subsequently, after corticoid withdrawal, IHHD was supplemented regularly with statins (atorvastatin 10-20 mg/day)) and followed-up for 2 years. All patients were on a regimen of cyclosporin A or tacrolimus and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (p < 0.025) and an increase of the adiponectin level (p < 0.01). Long-term therapy was associated with a significant decrease in serum leptin (p < 0.01) and lipid metabolism parameters (p < 0.01). Inulin clearance, mean systolic and diastolic blood pressure, proteinuria, lipoprotein(a) and apo-lipoprotein E isoforms did not differ significantly. Based on our results, we assume that obesity and hyperlipidaemia after renal transplantation can be treated effectively by modified immunosuppression (corticosteroid withdrawal), statins and long-term diet (IHHD). The increased level of adiponectin may be a marker of reducing atherosclerotic and chronic allograft nephropathy processes.

Topics: Adiponectin; Atherosclerosis; Body Mass Index; Diet, Reducing; Hyperlipidemias; Kidney Transplantation; Leptin; Obesity; Prospective Studies

Type 2 diabetes is a heterogeneous syndrome characterized by defective insulin secretion and/or insulin resistance. In distinct from Caucasian populations, Japanese type 2 diabetic patients are divided into two categories: one with insulin resistance and the other with normal insulin sensitivity. This unique feature allows us to explore the factors responsible for the evolution of insulin resistance in Japanese type 2 diabetic patients. In this article, we describe the factors responsible for insulin resistance in Japanese type 2 diabetic patients and discuss the relationships between these factors and atherosclerosis. Japanese type 2 diabetic patients with insulin resistance had significantly higher concentrations of triglyceride, remnant-like particle cholesterol, subcutaneous and visceral abdominal fat areas, leptin, high sensitive C-reactive protein (hs-CRP), and soluble E-selectin and lower concentration of adiponectin when compared to those with normal insulin sensitivity. There were, however, no significant difference in tumor necrosis factor (TNF)-alpha and soluble TNF receptors between the two groups. Serum triglyceride was positively correlated to visceral abdominal fat area, while serum leptin was positively correlated with subcutaneous abdominal fat area. In contrast, serum adiponectin was negatively correlated to visceral abdominal fat area. High sensitive CRP was positively correlated to BMI, triglyceride, and leptin, but was negatively correlated to adiponectin. Tumor necrosis factor-alpha and soluble TNF receptors, however, were not associated with any of these factors. Thus, it may be hypothesized that Japanese type 2 diabetic patients are divided into two categories: one with normal insulin sensitivity and the other with insulin resistance. The former group has a low cardiovascular risk factor, whereas the latter one has a markedly increased cardiovascular disease risk factor. Furthermore, abdominal fat related insulin resistance seems to be associated with insulin resistance in Japanese type 2 diabetic patients. In this section, we would like to focus on the factors contributing to insulin resistance and discuss the association of these factors with atherosclerosis in Japanese type 2 diabetic patients.

Topics: Adiponectin; Atherosclerosis; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Insulin Resistance; Japan; Leptin; Triglycerides

The role of leptin in the pathomechanism of atherosclerosis, through its free radical generating ability is established. Its effect however, on the regulation of intracellular cholesterol synthesis has not been studied. The aim of the present study was to elucidate whether leptin influences endogenous cholesterol synthesis in monocytes. Furthermore, leptin signaling to HMG CoA reductase in control and hypercholesterolemic monocytes were compared. The in vitro effect of leptin was studied on freshly isolated human monocytes obtained from healthy control volunteers and patients with hypercholesterolemia. Our results can be summarized as follows: (1) Leptin is able to increase endogenous cholesterol synthesis in human monocytes in vitro. (2) The cholesterol synthesis increasing effect of the hormone is more pronounced in hypercholesterolemic monocytes with high basal cholesterol biosynthesis. (3) The leptin-induced Ca(2+) signal was involved in the enhancement of HMG CoA reductase activation in monocytes from both controls and hypercholesterolemic patients. (4) In control monocytes the Ca(2+) signal originated from intracellular pools, whereas in patients, Ca(2+)-influx and protein kinase C activation were found to be responsible for the leptin-effect. Mevalonate cycle inhibiting fluvastatin and 25-hydroxycholesterol decreased cholesterol production in leptin-stimulated monocytes. Our present study provides the first proof of the cholesterol synthesis enhancing effect of leptin through a statin-sensitive pathway in circulating monocytes. Furthermore our results suggest that leptin can be involved in the pathomechanism of atherosclerotic plaque formation also through its effect on cholesterol biosynthesis in monocytes.

Topics: Acetates; Area Under Curve; Atherosclerosis; Calcium; Calcium Signaling; Carbon Radioisotopes; Case-Control Studies; Cholesterol; Demography; Female; Humans; Hypercholesterolemia; Inositol 1,4,5-Trisphosphate; Leptin; Male; Middle Aged; Monocytes

To investigate the effects of variation in the leptin [LEP (19A>G)] and melanocortin-4 receptor [MC4R (V103I)] genes on obesity-related traits in 13 405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study.. We tested the association between the single-locus and multilocus genotypes and obesity-related measures [body mass index (BMI), body weight (BW), waist-hip ratio, waist circumference and leptin levels], adjusted for age, physical activity level, smoking status, diabetic status, prevalence of coronary heart disease, hypertension, stroke or transient ischaemic attack.. AA and white female carriers of the MC4R I103 allele exhibited significantly lower BW than non-carriers of this allele (p < 0.05 and p < 0.01 respectively). AA female carriers of both the LEP A19 allele and the MC4R I103 allele were 63% [odds ratio (OR) = 0.37, 95% confidence interval (CI) (0.18-0.78)] less likely to be obese, and white female carriers of the same two alleles were 46% [OR = 0.54, 95% CI (0.32-0.91)] less likely to be obese, than non-carriers of the variant alleles. Female carriers of both the LEP A19 and MC4R I103 alleles had significantly lower BW (p < 0.05), BMI (p < 0.05) and plasma leptin (p < 0.01) than the non-carriers of both the alleles. Carriers of the two variant alleles had lower BMI over the 9-year course of the ARIC study and significantly lower weight gain from age 25 years. No significant joint effect of these two variants was observed in males.. These results suggest that variation within the LEP and MC4R genes is associated with reduced risk for obesity in females.

Topics: Atherosclerosis; Body Mass Index; Body Size; Caspase 10; DNA Primers; Female; Genetic Variation; Genotype; Humans; Leptin; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Racial Groups; Risk Factors; Sex Characteristics

There is increasing evidence of an association between leptin and increased cardiovascular risk. Higher leptin levels are associated with increased levels of C-reactive protein (CRP), which itself elicits proatherogenic effects in the vascular endothelium. We tested the hypothesis that leptin induces CRP expression in human coronary artery endothelial cells (HCAECs).. We confirmed the presence of both long and short isoforms of the leptin receptor in cultured HCAECs. Leptin but not IFNalphaA/D nor tumor necrosis factor (TNF) alpha, induced expression of CRP. A dose dependent increase of CRP mRNA and protein was observed with increasing concentration of leptin (0 to 400 ng/mL). This increased CRP expression was attenuated in the presence of anti-leptin receptor antibodies and also by inhibition of ERK1/2 by PD98059 (20 to 40 micromol/L). Time (0 to 60 minutes) and leptin concentration (0 to 200 ng/mL)-dependence of ERK1/2 phosphorylation were evident in response to leptin treatment. Leptin also elicited ROS generation. Inhibition of ROS by catalase (200 microg/mL) prevented ERK1/2 phosphorylation and CRP mRNA transcription.. Leptin induces CRP expression in HCAECs via activation of the leptin receptor, increased ROS production, and phosphorylation of ERK1/2. These studies suggest a mechanism for the proatherogenic effects of leptin.

Topics: Atherosclerosis; C-Reactive Protein; Cells, Cultured; Coronary Vessels; Endothelial Cells; Humans; Leptin; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Reactive Oxygen Species; Receptors, Cell Surface; Receptors, Leptin; Signal Transduction

The aim of the present study was to investigate the relationships between metabolic syndrome and atherosclerosis in 57 Japanese type 2 diabetic patients. Metabolic syndrome was diagnosed based on the criteria raised by the Japan Internal Medicine Society. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment. Ultrasonographically measured carotid atherosclerosis, brachial-ankle pulse wave velocity (ba-PWV), and ankle brachial index (ABI) were used to assess the degree of atherosclerosis. Of 57 patients, 25 were diagnosed as having metabolic syndrome. The patients with metabolic syndrome had significantly higher levels of waist circumference, insulin, insulin resistance index of homeostasis model assessment, systolic and diastolic blood pressures, and serum triglycerides, and lower concentrations of adiponectin. However, there was no significant difference in age, sex, glycosylated hemoglobin (hemoglobin A1c), fasting glucose, leptin, and tumor necrosis factor system activities including tumor necrosis factor alpha between the 2 groups. Furthermore, no significant difference was observed in the degree of carotid atherosclerosis (intimal-medial thickness in plaque-free segments: 0.72+/-0.03 vs 0.72+/-0.02 mm, P=.435; carotid stenosis in plaque segments: 6.6%+/-3.0% vs 6.6%+/-1.7%, P=.497), ba-PWV (1676+/-56 vs 1654+/-44, P=.380), and ABI (1.16+/-0.01 vs 1.15+/-0.01, P=.245) between the 2 groups. From these results, it can be suggested that metabolic syndrome, an insulin-resistant state, is not associated with carotid atherosclerosis, ba-PWV, or ABI in Japanese type 2 diabetic patients.

Topics: Adult; Aged; Atherosclerosis; Blood Glucose; Body Mass Index; Brachial Artery; Carotid Arteries; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Resistance; Japan; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Regional Blood Flow; Tumor Necrosis Factor-alpha; Ultrasonography

Obesity is a major risk factor for atherosclerosis and is associated with increased cardiovascular morbidity and mortality. However, the precise molecular pathways responsible for this close association remain poorly understood.. In this study, we report that leptin-deficiency (ob/ob) in low-density lipoprotein receptor knockout (ldlr(-/-)) mice induces an unexpected 2.2- to 6-fold reduction in atherosclerotic lesion development, compared with ldlr(-/-) mice having similar total cholesterol levels. Ldlr(-/-)/ob/ob mice show reduced T cell helper type 1 (Th1) response, enhanced expression of Foxp3, the specification transcription factor of regulatory T (Treg) cells, and improved Treg cell function. Leptin receptor-deficient (db/db) mice display marked increase in the number and suppressive function of Treg cells. Supplementation of Treg-deficient lymphocytes with Treg cells from db/db mice in an experimental model of atherosclerosis induces a significant reduction of lesion size and a marked inhibition of interferon (INF)-gamma production, compared with supplementation by Treg cells from wild-type mice.. These results identify a critical role for leptin/leptin receptor pathway in the modulation of the regulatory immune response in atherosclerosis, and suggest that alteration in regulatory immunity may predispose obese individuals to atherosclerosis.

Topics: Adoptive Transfer; Animals; Apolipoproteins E; Atherosclerosis; CD28 Antigens; Cell Proliferation; Cells, Cultured; Dietary Fats; Disease Models, Animal; Female; Forkhead Transcription Factors; Immunity, Cellular; Interferon-gamma; Leptin; Lipids; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; Receptors, Leptin; Signal Transduction; T-Lymphocytes, Regulatory; Th1 Cells

Topics: Adoptive Transfer; Animals; Apolipoproteins E; Atherosclerosis; CD28 Antigens; Cell Proliferation; Cytokines; Disease Models, Animal; Forkhead Transcription Factors; Immunity, Cellular; Leptin; Lipids; Mice; Mice, Knockout; Obesity; Receptors, Leptin; Signal Transduction; T-Lymphocytes, Regulatory; Th1 Cells

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

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

Increased oxidative stress has been associated with obesity-related disorders. In this study, we investigated how oxidative stress, in different ways of exposure, regulates gene expression of various adipokines in 3T3-L1 adipocytes. Exposure to 100-500microM H(2)O(2) for 10min, as well as exposure to 5-25mU/ml glucose oxidase for 18h, similarly decreased adiponectin, leptin, and resistin mRNAs, and increased plasminogen activator inhibitor-1 mRNA. Secretion levels of adipokines were also changed by oxidative stress in parallel with mRNA expression levels. Although a peak increase in plasminogen activator inhibitor-1 mRNA was achieved between 4 and 8h after exposure to H(2)O(2) for 10min, significant decreases in adiponectin and resistin mRNA were observed after 16h, while leptin mRNA was decreased earlier. Our results suggest that oxidative stress, even of short duration, has a significant impact on the regulation of various adipokine gene expressions favoring atherosclerosis.

Topics: 3T3-L1 Cells; Acetylcysteine; Adipocytes; Adiponectin; Animals; Atherosclerosis; Gene Expression Regulation; Glucose Oxidase; Hydrogen Peroxide; Leptin; Mice; Oxidative Stress; Peptide Hormones; Plasminogen Activator Inhibitor 1; Resistin; RNA, Messenger

Obesity is an independent risk factor for coronary heart disease, whereas the underlying mechanisms have not been fully elucidated. Adipocytes may produce various adipokines with favorable and unfavorable cardiovascular effects. The dysregulated secretion of adipokines by adipocytes may contribute to obese associated atherosclerosis. Adipocytes can also function as phagocytes to uptake and degrade oxidized low-density lipoprotein (Ox-LDL), suggesting that adipocytes possibly involve in clearance of Ox-LDL in blood. The dysfunctional adipocytes might be implicated in the atherogenesis. Some cardioprotective drugs mediate their cardiovascular benefits partly through their direct beneficial effects on adipocytes. Therefore, we hypothesized that adipocytes might be potential target for the treatment of atherosclerosis.

Topics: Adipocytes; Adipose Tissue; Animals; Atherosclerosis; Cardiotonic Agents; Humans; Leptin; Lipoproteins, LDL; Models, Biological; Receptors, Oxidized LDL

Recent evidence suggested that leptin-induced oxidative stress in human endothelial cells in vivo and increased oxidative stress in human essential hypertension may further contribute to both the development of atherosclerosis and other cardiovascular diseases. We investigated the association of plasma leptin levels with plasma lipid peroxidation and nitric oxide metabolites (NOx) in obese hypertensive atherosclerosis model.. Plasma leptin, lipid peroxidation and NOx levels were determined in age-matched non-obese normotensive female subjects (n = 30), obese normotensive female subjects (n = 45), and obese hypertensive female subjects (n = 50). Plasma leptin levels were determined by immunoradiometric method. Lipid peroxidation was determined as thiobarbituric acid reactive substances (TBARS) using spectrophotometric method. NOx levels were determined using enzymatic method.. We found that plasma leptin and TBARS levels were increased in obesity, and obese hypertensives have significantly higher plasma leptin and TBARS levels than obese normotensives (p <0.001 and p <0.001). Obese hypertensives have significantly lower plasma NOx levels than obese normotensives (p <0.001). In univariate and multivariate regression analysis, plasma leptin levels were significantly correlated with TBARS (p <0.01 and p <0.01) in obese subjects. Plasma TBARS were also inversely correlated with NOx in hypertensive obese subjects (r = -0.412, p <0.01).. Our results have shown that elevated leptin levels may be associated with increased oxidative stress and free-radical-induced decreased NOx levels. Therefore, hyperleptinemia may be an important contributor to the generation of hypertension in obesity.

Topics: Atherosclerosis; Female; Humans; Hypertension; Leptin; Lipid Peroxidation; Middle Aged; Nitric Oxide; Obesity; Oxidative Stress

High-density lipoprotein (HDL) has significant anti-atherogenic properties, whereas the underlying mechanisms are complex and have not been completely elucidated. Adipocytes produce a variety of adipokines with cardiovascular effects. The dysregulated secretion of adipokines by adipocytes may contribute to the increased risk of atherosclerosis associated with obesity. Clinical evidences indicate that higher plasma HDL-C levels are associated with a favourable adipokines secretion profile, suggesting that HDL might improve the dysregulated adipokines secretion. HDL may diminish lipid accumulation in adipocytes through phosphorylation of PPARgamma and inhibition of aP2 expression, which possibly account for the favourable effects of HDL on adipokines secretion. Therefore, we hypothesize that HDL might exert several beneficial effects on adipocytes, which may relate to its anti-atherogenic properties.

Topics: Adipocytes; Adipokines; Adipose Tissue; Adult; Aged; Atherosclerosis; Cholesterol, HDL; Coronary Disease; Female; Humans; Leptin; Lipoproteins, HDL; Male; Middle Aged; Risk Factors

Rare mutations in the leptin (LEP) gene cause severe obesity. Common polymorphisms of LEP have been associated with obesity, but their association with cardiovascular disease has been little studied. We have examined the impact of both common and rare polymorphisms of the LEP gene on blood pressure (BP), subclinical atherosclerosis as measured by carotid intima-medial thickness (CIMT), and body mass index (BMI) in a large family study.. Five polymorphisms spanning LEP were typed in 1428 individuals from 248 nuclear families. BP, CIMT, BMI, and plasma leptin were measured.. The polymorphisms typed captured all common haplotypes present at LEP. There was strong association between a rare polymorphism in the 3' untranslated region of LEP (C538T) and both pulse pressure (p = 0.0001) and CIMT (p = 0.008). C/T heterozygotes had a 22% lower pulse pressure and a 17% lower CIMT than C/C homozygotes. The polymorphism accounted for 3-5% of the population variation in pulse pressure and CIMT. There was no association between any LEP polymorphism and either BMI or plasma leptin level.. This large family study shows that the rare T allele at the C538T polymorphism of LEP substantially influences pulse pressure and CIMT, but does not appear to exert this effect through actions on plasma leptin level or BMI. This suggests that autocrine or paracrine effects in vascular tissue may be important physiological functions of leptin. This study also provides evidence that rare polymorphisms of particular genes may have substantial effects within the normal range of certain quantitative traits.

Topics: Atherosclerosis; Blood Pressure; Body Mass Index; Family Health; Gene Frequency; Genes; Genotype; Humans; Leptin; Middle Aged; Polymorphism, Single Nucleotide; Tunica Intima; Tunica Media; Ultrasonography

The direct role of leptin in vascular disease remains controversial. The objective of this study was to examine the effects of leptin treatment on atherosclerosis and thrombosis in atherosclerotic-prone mice.. Sixteen-week-old, male apolipoprotein E-deficient mice were treated with injections of recombinant leptin (125 microg per day IP; n=10) or vehicle (n=10) for 4 weeks. Leptin treatment resulted in reduced epididymal fat (352+/-30.7 versus 621+/-61.5 mg; P=0.005) and fasting insulin (0.57+/-0.25 versus 1.7+/-0.22 ng/mL; P=0.014). Despite these metabolic benefits, leptin treatment resulted in an increase in atherosclerosis (8.0+/-0.95% versus 5.4+/-0.59% lesion surface coverage; P<0.05). Leptin treatment also resulted in a shortened time to occlusive thrombosis after vascular injury (21+/-2.1 versus 34.6+/-5.4 minutes; P=0.045).. These studies indicate that exogenous leptin promotes atherosclerosis and thrombosis and support the concept that elevations of leptin may increase the risk for cardiovascular disease.

Topics: Adiposity; Animals; Apolipoproteins E; Atherosclerosis; Body Weight; Cholesterol; Cytokines; Fasting; Fluorescent Dyes; Insulin; Leptin; Male; Mice; Mice, Mutant Strains; Recombinant Proteins; Rose Bengal; Thrombosis; Triglycerides

Topics: Adiponectin; Aged; Aging; Atherosclerosis; Biomarkers; Blood Pressure; Body Mass Index; Carotid Arteries; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diet, Diabetic; Female; Humans; Leptin; Male; Pulse; Regression Analysis; Severity of Illness Index; Sulfonylurea Compounds; Tunica Intima

To investigate the effects of leptin on expression of acyl-coenzymeA: cholesterol acyl-transferases-1 (ACAT-1) in monocyte-macrophage differentiation, human monocytic cells (THP-1) were cultured in RPMI 1640 and made to differentiate into macrophages under the incubation with phorbol myristate acetate (PMA) for 48 h. The cells were divided into 4 groups according to different intervention factors as follows: MCs cultured in RPM11640 medium with 10% FBS for 48 h served as MC group (control group), MCs cultured in medium with serum-free RPM11640 containing 5% BSA, 100 nmol/L PMA for 48 h as MP group, MCs cultured in RPMI1640 medium with 10% FBS, 10 micromol/ml leptin for 48 h as leptin-MC group, and MCs cultured in medium with serum-free RPMI1640 containing 5% BSA. 100 nmol/L PMA, and 10 micromol/ml leptin for 48 h as leptin-MP group. Immunocytochemistry, reverse transcription polymerase chain reaction (RT-PCR) and Western blot were performed, respectively, to observe the effects of leptin on expression of ACAT-1 in the monocyte-macrophage differentiation. Our results showed that expression of ACAT-1 protein and mRNA in MP-group is two times that in MC-group (P<0.05), and the expression of ACAT-1 protein and mRNA increased by up to 4 folds in leptin-MP group-as compared with that of MC group (P<0.01). Thus, our results support the idea that expression of ACAT-1 increases more in cultured human macrophages than in monocytes, and leptin can significantly promote ACAT-1 expression. It was concluded that high expression of ACAT-1 may accelerate the development of human atherogenesis, and leptin might participate in atherogenesis by increasing expression of ACAT-1.

Topics: Atherosclerosis; Cell Differentiation; Cells, Cultured; Humans; Leptin; Macrophages; Monocytes; Sterol O-Acyltransferase; Tetradecanoylphorbol Acetate