leptin and Metabolic-Syndrome

Microbiota dysbiosis and metabolic syndrome, consequences of a non-adequate diet, generate a feedback pathogenic state implicated in Alzheimer's disease development. The lower production of short chain fatty acids (SCFAs) under dysbiosis status leads to lipid homeostasis deregulation and decreases Angptl4 release and AMPK activation in the adipose tissue, promoting higher lipid storage (adipocyte hypertrophy) and cholesterol levels. Also, low SCFA generation reduces GPR41 and GPR43 receptor activation at the adipose tissue (increasing leptin release and leptin receptor resistance) and intestinal levels, reducing the release of GLP-1 and YPP. Therefore, lower satiety sensation and energy expenditure occur, promoting a weight gaining environment mediated by higher food intake and lipid storage, developing dyslipemia. In this context, higher glucose levels, together with higher free fatty acids in the bloodstream, promote glycolipotoxicity, provoking a reduction in insulin released, insulin receptor resistance, advanced glycation products (AGEs) and type 2 diabetes. Intestinal dysbiosis and low SCFAs reduce bacterial biodiversity, increasing lipopolysaccharide (LPS)-producing bacteria and intestinal barrier permeability. Higher amounts of LPS pass to the bloodstream (endotoxemia), causing a low-grade chronic inflammatory state characterized by higher levels of leptin, IL-1β, IL-6 and TNF-α, together with a reduced release of adiponectin and IL-10. At the brain and neuronal levels, the generated insulin resistance, low-grade chronic inflammation, leptin resistance, AGE production and LPS increase directly impact the secretase enzymes and tau hyperphosphorylation, creating an enabling environment for β-amyloid senile plaque and tau tangled formations and, as a consequence, Alzheimer's initiation, development and maintenance.

Topics: Alzheimer Disease; Diabetes Mellitus, Type 2; Dietetics; Dysbiosis; Humans; Insulin Resistance; Leptin; Lipopolysaccharides; Metabolic Syndrome; Microbiota

This study focused to systematically extract, summarize and analyse the data on the effect of lifestyle modification on leptin resistance and quality of life in metabolic syndrome.. The systematic search was done using PubMed, Cochrane Database, EMBASE, Science Direct, CINAHL, Springer link, Web of Science from 2000-2018. English language articles and quantitative studies focusing on leptin resistance and quality of life were included. Random effect analysis was adopted to pool data and estimate 95% CI. The meta-analysis was done separately for leptin resistance and quality of life which included a total of 9 studies on both RCTs and Non-RCTs.. The meta-analysis of RCTs reported insignificant effect of lifestyle modification on leptin resistance in metabolic syndrome when compared to comparison group (-5.94(-14.28, 2.41). Two clinical trials showed a significant effect with pooled data (5.52(2.14, 8.91). Meta-analysis of RCTs focusing on quality of life showed significant effect on mental component (4.89 (0.16, 9.62) of quality of life (2.36 (-3.67, 8.39) when compared to comparison group.. This meta-analysis suggested that lifestyle modification has a potential to improve leptin resistance and mental component of quality of life in metabolic syndrome. However, more clearly defined studies are required to come to a stronger conclusion.

Topics: Exercise; Humans; Leptin; Life Style; Metabolic Syndrome; Quality of Life

Far beyond the compelling proofs supporting that the metabolic syndrome represents a risk factor for diabetes and cardiovascular diseases, a growing body of evidence suggests that it is also a risk factor for different types of cancer. However, the involved molecular mechanisms underlying this association are not fully understood, and they have been mainly focused on the individual contributions of each component of the metabolic syndrome such as obesity, hyperglycemia, and high blood pressure to the development of cancer. The Receptor for Advanced Glycation End-products (RAGE) axis activation has emerged as an important contributor to the pathophysiology of many clinical entities, by fueling a chronic inflammatory milieu, and thus supporting an optimal microenvironment to promote tumor growth and progression. In the present review, we intend to highlight that RAGE axis activation is a crosswise element on the potential mechanistic contributions of some relevant components of metabolic syndrome into the association with cancer.

Topics: Adiponectin; Adipose Tissue; Animals; Disease Progression; Gene Expression Regulation; Humans; Hyperglycemia; Hypertension; Inflammation; Insulin-Like Growth Factor I; Leptin; Ligands; Metabolic Syndrome; Mice; Neoplasms; Obesity; Peroxisome Proliferator-Activated Receptors; Rats; Receptor for Advanced Glycation End Products; Signal Transduction; Vascular Endothelial Growth Factor A; Wnt Proteins

Metabolic syndrome (MetS) is a complex of diseases that lead to mortality due to the development of cardiovascular problems. Quercetin, as an important flavonoid, has various properties such as decreasing blood pressure, anti-hyperlipidemia, anti-hyperglycemia, anti-oxidant, antiviral, anticancer, anti-inflammatory, anti-microbial, neuroprotective, and cardio-protective effects. In this review article, we collected original articles from different sources such as Google Scholar, Medline, Scopus, and Pubmed, which is related to the effect of quercetin on the improvement of the signs of MetS, including elevated glucose level, hyperlipidemia, obesity, and blood pressure. According to these data, quercetin may also have a role in the management of metabolic disorders via different mechanisms such as increasing adiponectin, decreasing leptin, anti-oxidant activity, reduction of insulin resistance, the elevation of insulin level, and blocking of calcium channel. We have attempted to make some recommendations on the quercetin application in patients. However, it needs to do further clinical trials and more investigations to show the real clinical value of quercetin on metabolic syndrome.

Topics: Adiponectin; Humans; Leptin; Metabolic Syndrome; Obesity; Quercetin

Numerous rodent studies have evaluated the effects of maternal stress (MS) on later in life susceptibility to Metabolic Syndrome (MetS) intermediate phenotypes with varying results. The aim of this study was to quantitatively synthesize the available data on the effects of MS on offspring obesity, estimated indirectly by body mass (BM), body fat (BF) and plasma leptin; systolic blood pressure (SBP); plasma glucose (and insulin) and blood lipid concentrations.. Literature was screened and summary estimates of the effect of MS outcomes were calculated by using random-effects models. Data on the effects of exogenous corticosteroid administration (or inhibition of 11β-HSD2) during pregnancy in rodents was analysed separately to characterize the direct phenotypic effects of prenatal corticosteroid excess (PCE).. We conducted 14 separate meta-analyses and synthesized relevant data on outcomes scarcely reported in literature. Both MS and PCE were associated with low birth weight without rapid catch-up growth resulting in decreased body mass later in life. Our analysis also revealed significant and contradictory effects on offspring adiposity. Little evidence was found for effects on glucose metabolism and blood lipids. We identified increased SBP in offspring exposed to PCE; however, there is not enough data to draw any conclusion about effects of MS on SBP.. Neonatal weight proved to be decreased in offspring prenatally exposed to stress or corticosteroids, but laboratory rodents in the absence of a challenging environment did not show catch-up growth. The available evidence is inconclusive regarding the effect on adiposity revealing clear methodological and knowledge gaps. This meta-analysis also confirmed a significant positive association between PCE and SBP. Nevertheless, additional studies should address the association with MS.

Topics: Adipose Tissue; Adiposity; Animals; Birth Weight; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Female; Insulin; Leptin; Lipids; Metabolic Syndrome; Mice; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Risk Factors; Rodentia; Stress, Psychological; Triglycerides

Metabolic syndrome (MetS) has been associated with osteoarthritis (OA). Leptin, which is one of the markers of MetS, has been associated with OA pathophysiology. This study aimed to provide an update on the association between MetS and OA and on the potential role of leptin in OA. In this review, we summarized the current knowledge of the association between MetS and OA and updated the evidence on the potential role of leptin in OA. Clinical studies have investigated the epidemiologic association between MetS or its components and OA. Results suggested strong epidemiologic associations between MetS and OA, especially in the Asian population. Animal studies also indicated that metabolic dysregulation may lead to OA pathogenesis. The systemic role of MetS in OA pathophysiology is associated with obesity-related inflammation, the beneficial role of n-3 polyunsaturated fatty acids and deleterious role of cholesterol, physical inactivity, hypertension-induced subchondral ischemia, dyslipidemia-induced ectopic lipid deposition in chondrocytes, hyperglycemia-induced local effects of oxidative stress and advanced glycation end-products, low-grade systemic inflammation, and obesity-related adipokines by inducing the expression of proinflammtory factors. Leptin levels in serum/plasma and synovial fluid were associated with joint pain, radiographic progression, bone formation biomarkers, cartilage volume, knee OA incidence, and total joint arthroplasty in OA patients. Elevated leptin expression and increased effect of leptin on infrapatellar fat pad, synovium, articular cartilage, and bone were also involved in the pathogenesis of OA. Current knowledge indicates a convincing epidemiologic association between MetS and OA, especially in the Asian population. Animal studies have also shown that metabolic dysregulation may lead to OA pathogenesis. Accumulating evidence suggests that leptin may play a potential role in OA pathogenesis. Therefore, leptin and its receptor may be an emerging target for intervention in metabolic-associated OA.

Topics: Adipokines; Animals; Chondrocytes; Humans; Inflammation; Leptin; Metabolic Syndrome; Obesity; Osteoarthritis

Epidemiological evidence indicates the presence of dysregulated homeostatic biological pathways in depressed patients, such as increased inflammation and disrupted energy-regulating neuroendocrine signaling (e.g., leptin, insulin). Alterations in these biological pathways may explain the considerable comorbidity between depression and cardiometabolic conditions (e.g., obesity, metabolic syndrome, diabetes) and represent a promising target for intervention. This review describes how immunometabolic dysregulations vary as a function of depression heterogeneity by illustrating that such biological dysregulations map more consistently to atypical behavioral symptoms reflecting altered energy intake/expenditure balance (hyperphagia, weight gain, hypersomnia, fatigue, and leaden paralysis) and may moderate the antidepressant effects of standard or novel (e.g., anti-inflammatory) therapeutic approaches. These lines of evidence are integrated in a conceptual model of immunometabolic depression emerging from the clustering of immunometabolic biological dysregulations and specific behavioral symptoms. The review finally elicits questions to be answered by future research and describes how the immunometabolic depression dimension could be used to dissect the heterogeneity of depression and potentially to match subgroups of patients to specific treatments with higher likelihood of clinical success.

Topics: Depression; Humans; Leptin; Metabolic Syndrome; Obesity; Weight Gain

Hyperinsulinemia and insulin resistance were proposed more than 30 years ago to be important contributors to elevated blood pressure (BP) associated with obesity and the metabolic syndrome, also called syndrome X. Support for this concept initially came from clinical and population studies showing correlations among hyperinsulinemia, insulin resistance, and elevated BP in individuals with metabolic syndrome. Short-term studies in experimental animals and in humans provided additional evidence that hyperinsulinemia may evoke increases in sympathetic nervous system (SNS) activity and renal sodium retention that, if sustained, could increase BP. Although insulin infusions may increase SNS activity and modestly raise BP in rodents, chronic insulin administration does not significantly increase BP in lean or obese insulin-resistant rabbits, dogs, horses, or humans. Multiple studies in humans and experimental animals have also shown that severe insulin resistance and hyperinsulinemia may occur in the absence of elevated BP. These observations question whether insulin resistance and hyperinsulinemia are major factors linking obesity/metabolic syndrome with hypertension. Other mechanisms, such as physical compression of the kidneys, activation of the renin-angiotensin-aldosterone system, hyperleptinemia, stimulation of the brain melanocortin system, and SNS activation, appear to play a more critical role in initiating hypertension in obese subjects with metabolic syndrome. However, the metabolic effects of insulin resistance, including hyperglycemia and dyslipidemia, appear to interact synergistically with increased BP to cause vascular and kidney injury that can exacerbate the hypertension and associated injury to the kidneys and cardiovascular system.

Topics: Animals; Humans; Hyperinsulinism; Hypertension; Insulin Resistance; Kidney; Leptin; Metabolic Syndrome; Obesity; Renin-Angiotensin System; Sodium; Sympathetic Nervous System

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

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

Leptin and adiponectin are two adipokines currently used as biomarkers for diagnostic orientation and phenotyping in syndromes of lipodystrophy and severe insulin resistance. The level of these biomarkers also has an impact on the therapeutic management of the patients. These aspects, as well as our experience as a reference center, are described in this brief overview.

Topics: Adiponectin; Biomarkers; Humans; Insulin Resistance; Leptin; Lipodystrophy; Metabolic Syndrome; Phenotype; Severity of Illness Index

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

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

Nowadays, it is well-known that the deregulation of epigenetic machinery is a common biological event leading to the development and progression of metabolic disorders. Moreover, the expression level and actions of leptin, a vast adipocytokine regulating energy metabolism, appear to be strongly associated with epigenetics. Therefore, the aim of this review was to summarize the current knowledge of the epigenetic regulation of leptin as well as the leptin-induced epigenetic modifications in metabolic disorders and associated phenomena. The collected data indicated that the deregulation of leptin expression and secretion that occurs during the course of metabolic diseases is underlain by a variation in the level of promoter methylation, the occurrence of histone modifications, along with miRNA interference. Furthermore, leptin was proven to epigenetically regulate several miRNAs and affect the activity of the histone deacetylases. These epigenetic modifications were observed in obesity, gestational diabetes, metabolic syndrome and concerned various molecular processes like glucose metabolism, insulin sensitivity, liver fibrosis, obesity-related carcinogenesis, adipogenesis or fetal/early postnatal programming. Moreover, the circulating miRNA profiles were associated with the plasma leptin level in metabolic syndrome, and miRNAs were found to be involved in hypothalamic leptin sensitivity. In summary, the evidence suggests that leptin is both a target and a mediator of epigenetic changes that develop in numerous tissues during metabolic disorders.

Topics: Adipogenesis; Animals; Diabetes, Gestational; DNA Methylation; Epigenesis, Genetic; Female; Fetal Development; Histone Code; Humans; Hypothalamus; Leptin; Metabolic Diseases; Metabolic Syndrome; MicroRNAs; Obesity; Pregnancy

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

Metabolic syndrome poses a major threat on human health affecting the quality of life. Adipose tissue is an important organ which plays a crucial role in the pathogenesis of metabolic syndrome. Adipocytokines secreted by the adipose tissue plays a critical role in storage, food intake, energy expenditure, lipid and glucose metabolism. Leptin is primarily involved in regulating food intake, body weight and energy homeostasis through neuroendocrine functions. Contemporary research suggests that leptin also influences insulin sensitivity and lipid metabolism. High leptin concentrations are directly associated with the obesity subsequent development of metabolic disease sequelae such as insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidation of the mechanism of action of leptin would help to develop novel therapeutic approaches for there metabolic disorders like obesity and diabetes. This review provides an updated 'state-of-the-art' about the leptin and its role in the pathophysiology of metabolic syndrome at the molecular level.

Topics: Animals; Biomarkers; Ethnicity; Humans; Leptin; Metabolic Syndrome; Models, Biological; Receptors, Leptin

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

Obesity is currently the most extended metabolic disturbance worldwide favoring the development of cardiometabolic alterations such as type 2 diabetes, hypertension, and dyslipidemia. Obesity and the metabolic syndrome (MS) are characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Consequently, the adiponectin/leptin ratio has been suggested as a maker of adipose tissue dysfunction. This emerging biomarker correlates with insulin resistance better than adiponectin or leptin alone, or even HOMA and is decreased with increasing number of metabolic risk factors having been proposed as a predictive marker for the MS. Moreover, the adiponectin/leptin ratio is negatively correlated with markers of low-grade chronic inflammation. In this sense, an increase in this ratio has been related with reduced atherosclerosis risk as well as with a decreased risk of some types of cancer in epidemiological studies. In this commentary we propose new cutoffs to estimate obesity- and MS-associated cardiometabolic risk according to the adiponectin/leptin ratio and discuss different therapeutic strategies to increase this promising biomarker of metabolic risk.

Topics: Adiponectin; Adipose Tissue; Animals; Humans; Inflammation; Leptin; Metabolic Syndrome; Obesity

Metabolic syndrome, a risk factor of cardiovascular disease, is more common in patients with psoriasis than in the general population. Circulating adipokine concentrations are altered in patients with psoriasis and are suggested to represent the pathophysiological link between psoriatic lesions and metabolic alterations.. To perform a systematic review of the literature for studies that investigated possible differences in circulating levels of leptin, adiponectin or resistin in patients with psoriasis before and after any treatment intervention, and to meta-analyse the best evidence available.. A search was conducted in three databases (PubMed, Central and Embase). Eligible for the review were studies that assessed leptin, adiponectin or resistin concentrations in patients with psoriasis before and after any topical or systemic treatment.. After treatment, blood concentrations of leptin were similar to those before treatment [standardized mean difference (SMD) 0·06, 95% confidence interval (CI) -0·09 to 0·20], with no heterogeneity among studies (I. There is no evidence that treatment for psoriasis modifies leptin and adiponectin concentrations. However, treatment intervention reduces resistin concentrations, a finding that is expected to be of clinical importance.

Topics: Adiponectin; Dermatologic Agents; Humans; Leptin; Metabolic Syndrome; Psoriasis; Resistin; Treatment Outcome

Metabolic syndrome (MS) is one of the leading risk factors for the development of some common cancers (endometrial cancer, postmenopausal breast cancer, colorectal cancer). Currently, a drug-induced metabolic syndrome related with androgen deprivation therapy in patients with prostate cancer represents a serious medical problem. Not only MS, or its individual components, but MS variants with different levels of leptin, adiponectin, visfatin, resistin are associated with tumor invasion, metastasis and survival rates in patients with MS-associated malignancies.

Topics: Disease Progression; Genetic Variation; Humans; Leptin; Metabolic Syndrome; Neoplasm Invasiveness; Nicotinamide Phosphoribosyltransferase; Risk Factors

One-third of men with obesity or type 2 diabetes have subnormal free testosterone concentrations. The lower free testosterone concentrations are observed in obese men at all ages, including adolescents at completion of puberty. The gonadotropin concentrations in these males are inappropriately normal; thus, these patients have hypogonadotropic hypogonadism (HH). The causative mechanism of diabesity-induced HH is yet to be defined but is likely multifactorial. Decreased insulin and leptin signaling in the central nervous system are probably significant contributors. Contrary to popular belief, estrogen concentrations are lower in men with HH. Men with diabesity and HH have more fat mass and are more insulin resistant than eugonadal men. In addition, they have a high prevalence of anemia and higher mortality rates than eugonadal men. Testosterone replacement therapy results in a loss of fat mass, gain in lean mass, and increase in insulin sensitivity in men with diabesity and HH. This is accompanied by an increase in insulin-signaling genes in adipose tissue and a reduction in inflammatory mediators that interfere with insulin signaling. There is also an improvement in sexual symptoms, anemia, LDL cholesterol, and lipoprotein (a). However, testosterone therapy does not consistently affect HbA

Topics: Diabetes Mellitus, Type 2; Humans; Hypogonadism; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Prevalence; Testosterone

Numerous rodent studies have evaluated the effects of a maternal high-fat diet (HFD) on later in life susceptibility to Metabolic Syndrome (MetS) with varying results. Our aim was to quantitatively synthesize the available data on effects of maternal HFD around gestation on offspring's body mass, body fat, plasma leptin, glucose, insulin, lipids and systolic blood pressure (SBP). Literature was screened and summary estimates of the effect of maternal HFD on outcomes were calculated by using fixed- or random-effects models. 362 effect sizes from 68 studies together with relevant moderators were collected. We found that maternal HFD is statistically associated with higher body fat, body weight, leptin, glucose, insulin and triglycerides levels, together with increased SBP in offspring later in life. Our analysis also revealed non-significant overall effect on offspring's HDL-cholesterol. A main source of variation among studies emerged from rat strain and lard-based diet type. Strain and sex -specific effects on particular data subsets were detected. Recommendations are suggested for future research in the field of developmental programming of the MetS. Despite significant heterogeneity, our meta-analysis confirms that maternal HFD had long-term metabolic effects in offspring.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Diet, High-Fat; Female; Insulin; Leptin; Male; Metabolic Syndrome; Phenotype; Pregnancy; Publication Bias; Rats, Sprague-Dawley; Rats, Wistar; Triglycerides

Antipsychotics (APs) are associated with metabolic syndrome, with increases in leptin proposed as an underlying mechanism of AP-induced weight gain. Currently available meta-analyses on this topic have limited their populations of interest to those diagnosed with schizophrenia. The purpose of this meta-analysis is to explore the relationship between leptin levels and AP use across multiple psychiatric diagnoses, and also in healthy controls.. Systematic electronic searches were conducted using PubMed and OVID: Medline. Longitudinal studies were included if showing leptin levels before and after AP use. We included participants with any psychiatric disorders and mentally healthy participants, if exposed to AP use. The differences in leptin levels were evaluated using Hedges' g with a random effects model.. Forty-two studies were found (36 schizophrenia, 2 bipolar disorder, 1 anorexia nervosa, and 3 healthy controls), encompassing 66 study arms and 1,156 participants. The meta-analysis showed that regardless of diagnoses, leptin levels increase with AP use (Hedges' g = 0.811, p ≤ .001).. Leptin increases induced by APs are present across all diagnoses. More comprehensive research is needed to understand the relationship between AP use and leptin levels across multiple diagnoses.

Topics: Anorexia Nervosa; Antipsychotic Agents; Bipolar Disorder; Humans; Leptin; Metabolic Syndrome; Schizophrenia

Aging is associated with dysregulation of glucose and lipid metabolism. Various factors that contribute to the dysregulation include both modifiable (e.g. obesity, insulin resistance) and non-modifiable risk factors (age-associated physiologic changes). Although there is no linear relationship between aging and prevalence of non-alcoholic fatty liver disease, current data strongly suggests that advanced age leads to more severe histological changes and poorer clinical outcomes. Hepatic lipid accumulation could lead to significant hepatic and systemic consequences including steatohepatitis, cirrhosis, impairment of systemic glucose metabolism and metabolic syndrome, thereby contributing to age-related diseases. Insulin, leptin and adiponectin are key regulators of the various physiologic processes that regulate hepatic lipid metabolism. Recent advances have expanded our understanding in this field, highlighting the role of novel mediators such as FGF 21, and mitochondria derived peptides. In this review, we will summarize the mediators of hepatic lipid metabolism and how they are altered in aging.

Topics: Adiponectin; Aging; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Glucose; Humans; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Liver; Liver Cirrhosis; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Signal Transduction

The brain leptin signaling system has a key role in regulation of feeding behavior, peripheral metabo- lism, functions of the nervous and endocrine systems, and disturbances in this system lead to metabolic disorders, including metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). This system is activa- ted by leptin produced by adipocytes and then penetrates into brain through the blood-brain barrier, where leptin binds to leptin receptors OBRb. This leads to activation of tyrosine kinase JAK2, which phosphory- lates tyrosine-containing sites located in the cytoplasmic domain of the receptor, resulting in stimulation of activity of phosphatidylinositol-3-kinase, the transcription factors STAT3 and STAT5, phosphatase SHP2, and mitogen-activated protein kinase. Decrease in number of functionally active leptin receptors and disturbances in the downstream components of leptin cascades in neuronal cells lead to development of leptin resistance. Since the leptin system in hypothalamic neurons is closely linked to the insulin, mela- nocortin, dopaminergic and other signaling systems, leptin resistance induces a lot of functional disorders in the CNS and on the periphery. The restoration of the brain leptin system functions is one of the promi- sing approaches to treatment and prevention of metabolic disorders, including MS and DM2. The review analyzes data on structural and functional organization of the leptin signaling system, its functional, interaction with other brain signaling systems, the causes and effects of central leptin resistance, as well as the approaches to restore the functions of the hypothalamic leptin system in MS and DM2. Key words: leptin, leptin resistance, hypothalamus, JAK2-kinase, leptin receptor, diabetes mellitus, metabolic syndrome, melanocortin system, phosphatase inhibitor.

Topics: Animals; Brain; Diabetes Mellitus, Type 2; Humans; Leptin; Metabolic Syndrome; Nerve Tissue Proteins; Signal Transduction

The human prostate gland is an endocrine organ where dysregulation of various hormonal factors may play a pivotal role in the pathogenesis of prostate cancer. There is emerging epidemiological data to support the role of components of metabolic syndrome, namely, obesity, hypercholesterolaemia, diabetes and hyperinsulinaemia on the development and/or the progression of prostate cancer. Although the exact mechanisms behind the relationship between metabolic syndrome and prostate cancer remain largely unknown, various in vitro and animal experiments of metabolic syndrome models have been shown to promote survival, mitogenesis, metastasis and treatment resistance pathways, through various adaptive responses such as intracellular steroidogenesis and lipogenesis. Also, in a large proportion of men with metabolic syndrome, alteration in levels of hormones such as testosterone, leptin and adiponectin has been shown to contribute towards the aggression of prostate cancer. Whilst the exact bio-pathophysiological mechanisms between metabolic syndrome and prostate cancer are yet to be fully elucidated, medications that target specific components of metabolic syndrome have further provided evidence for the inter-relationship between metabolic syndrome, its components and prostate cancer. Emerging in vitro and molecular data is likely to bring us closer to utilizing this knowledge to target particular cancer survival pathways and improving outcomes for men with prostate cancer.

Topics: Adiponectin; Animals; Disease Progression; Genetic Predisposition to Disease; Humans; Leptin; Male; Metabolic Syndrome; Prostatic Neoplasms; Testosterone

To conduct a systematic review and meta-analysis of relevant randomized clinical trials (RCTs) to ascertain the effect size of orlistat in modulating plasma levels of adipokines, ghrelin and C-reactive protein (CRP).. Medline, SCOPUS, Web of Science and Google Scholar databases were searched. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of duration of treatment, percentage change in body mass index (BMI) and baseline BMI values as potential confounders of the estimated effect size.. Meta-analysis suggested a significant increase in plasma levels of adiponectin [weighted mean difference (WMD): 19.18%, 95% confidence interval (CI): 5.80, 32.57, p = 0.005] and significant reductions in plasma levels of leptin (WMD: -13.24%, 95% CI: -20.69, -5.78, p = 0.001) and CRP (WMD: -11.52%, 95% CI: -16.55, -6.49, p < 0.001) following treatment with orlistat. In meta-regression, changes in plasma concentrations of adiponectin, leptin and CRP were associated with duration of treatment, but not with either change in BMI or baseline BMI values.. Orlistat is effective in increasing plasma concentrations of adiponectin and decreasing those of leptin and CRP.

Topics: Adiponectin; Anti-Obesity Agents; Body Weight; C-Reactive Protein; Ghrelin; Humans; Lactones; Leptin; Metabolic Syndrome; Orlistat; Randomized Controlled Trials as Topic

Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic syndrome and this panel can aid in early detection and management of metabolic syndrome in high risk populations, such as in West Virginia.. A literature review was conducted using PubMed, Science Direct, and Google Scholar to search for markers related to metabolic syndrome. Biomarkers searched included adipokines (leptin, adiponectin), neuropeptides (ghrelin), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-10), markers of antioxidant status (OxLDL, PON-1, uric acid), and prothrombic factors (PAI-1).. According to the literature, the concentrations of pro-inflammatory cytokines (IL-6, TNF-α), markers of pro-oxidant status (OxLDL, uric acid), and prothrombic factors (PAI-1) were elevated in metabolic syndrome. Additionally, leptin concentrations were found to be elevated in metabolic syndrome as well, likely due to leptin resistance. In contrast, concentrations of anti-inflammatory cytokines (IL-10), ghrelin, adiponectin, and antioxidant factors (PON-1) were decreased in metabolic syndrome, and these decreases also correlated with specific disorders within the cluster.. Based on the evidence presented within the literature, the aforementioned biomarkers correlate significantly with metabolic syndrome and could provide a minimally-invasive means for early detection and specific treatment of these disorders. Further research is encouraged to determine the efficacy of applying these biomarkers to diagnosis and treatment in a clinical setting.

Topics: Adipokines; Adiponectin; Biomarkers; Humans; Inflammation; Interleukin-10; Leptin; Metabolic Syndrome; Plasminogen Activator Inhibitor 1; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; West Virginia

Experimental and clinical studies have clearly shown the role of the sympathetic nervous system in the pathophysiology of several cardiovascular and non-cardiovascular diseases. This short review will be aimed at focusing and discussing the new information collected on two specific clinical conditions such as obesity and metabolic syndrome. The paper will briefly describe the four main mechanisms that represent the common link between these two pathophysiological conditions and that through the sympathetic nervous system contribute to increase the cardiovascular risk.

Topics: Animals; Baroreflex; Biomarkers; Blood Pressure; Cardiovascular System; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity, Abdominal; Oxidative Stress; Prognosis; Renin-Angiotensin System; Risk Factors; Sympathetic Nervous System

Obesity is one of the major risk factors of metabolic syndrome, such as hypertension, hyperlipidemia, and diabetes. Leptin exerts an anti-obesity effect through the Ob-Rb leptin receptor, which is mainly expressed on hypothalamic neuronal cells. Recent evidence indicated that one of the mechanisms of obesity may be the development of leptin resistance. In the present review, we discuss the mechanisms of leptin resistance in obesity, focusing on endoplasmic reticulum (ER) stress. We previously found that flurbiprofen is a candidate drug for attenuating ER stress and the subsequent development of leptin resistance. We will discuss a possible pharmacological strategy for treating obesity by ameliorating ER stress.

Topics: Drug Discovery; Endoplasmic Reticulum Stress; Flurbiprofen; Humans; Hypothalamus; Leptin; Metabolic Syndrome; Obesity; Receptors, Leptin; Risk Factors

Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

Topics: Animals; Antihypertensive Agents; Clinical Trials as Topic; Diagnostic Techniques, Cardiovascular; Forecasting; Heart Rate; Humans; Hyperinsulinism; Hypertension; Hypertension, Renal; Insulin Resistance; Kidney; Kidney Diseases; Leptin; Melanocortins; Metabolic Syndrome; Multicenter Studies as Topic; Neuroimaging; Norepinephrine; Obesity; Sympathectomy; Sympathetic Fibers, Postganglionic; Sympathetic Nervous System; Vasoconstriction

Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include (1) physical compression of the kidneys by fat in and around the kidneys, (2) activation of the renin-angiotensin-aldosterone system, and (3) increased sympathetic nervous system activity. Activation of the renin-angiotensin-aldosterone system is likely due, in part, to renal compression, as well as sympathetic nervous system activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for sympathetic nervous system activation in obesity have not been fully elucidated but may require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation. Unless effective antiobesity drugs are developed, the effect of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase.

Topics: Aldosterone; Animals; Antihypertensive Agents; Dyslipidemias; Heart Conduction System; Hemodynamics; Humans; Hypertension; Insulin Resistance; Intra-Abdominal Fat; Kidney; Leptin; Metabolic Syndrome; Models, Animal; Models, Cardiovascular; Natriuresis; Obesity; Organ Specificity; Parasympathetic Nervous System; Pressure; Prevalence; Pro-Opiomelanocortin; Receptors, Leptin; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sodium; Sympathetic Nervous System

To summarize recent primary publications and discuss the impact these finding have on current understanding on the development of hypoventilation in obesity hypoventilation syndrome (OHS), also known as Pickwickian syndrome.. As a result of the significant morbidity and mortality associated with OHS, evidence is building for pre-OHS intermediate states that can be identified earlier and treated sooner, with the goal of modifying disease course. Findings of alterations in respiratory mechanics with obesity remain unchanged; however, elevated metabolism and CO2 production may be instrumental in OHS-related hypercapnia. Ongoing positive airway pressure trials continue to demonstrate that correction of nocturnal obstructive sleep apnea and hypoventilation improves diurnal respiratory physiology, metabolic profiles, quality of life, and morbidity/mortality. Finally, CNS effects of leptin on respiratory mechanics and chemoreceptor sensitivity are becoming better understood; however, characterization remains incomplete.. OHS is a complex multiorgan system disease process that appears to be driven by adaptive changes in respiratory physiology and compensatory changes in metabolic processes, both of which are ultimately counter-productive. The diurnal hypercapnia and hypoxia induce pathologic effects that further worsen sleep-related breathing, resulting in a slowly progressive worsening of disease. In addition, leptin resistance in obesity and OHS likely contributes to blunting of ventilatory drive and inadequate chemoreceptor response to hypercarbia and hypoxemia.

Topics: Animals; Humans; Hypoxia; Leptin; Metabolic Syndrome; Obesity Hypoventilation Syndrome; Quality of Life; Sleep Apnea, Obstructive

Every cell reserves fatty acids in cytozol in drops of lipids in the form of non-polar triglycerides for itself andfor oxidation in mitochondria. The specialized visceral fatty cells ofomentum and adipocytes ofsubcutaneous fat are the cells absorbing saturated and mono unsaturated fatty acids in form of triglycerides in apoB-48 chylomicrons, apoB-100 lipoproteins of low and very low density. They deposit their physiological time and liberate fatty acids in intercellular medium in the form ofpolar unesterified fatty acids bound by albumin. According phylogenetic theory of general pathology, in biological function of trophology (nutrition) fatty cells sequentially implement biological reaction of exotrophy (external nutrition), deposition and endotrophy (internal nutrition). The humoral regulator offeedback in visceral fatty cells is leptin acting in autocrine way, in paracrin cenosises of cells and on the level of organism. The biological role of leptin is in preventing a) deposition of surplus amount of non-polar triglycerides in fatty cells; b) formation of endoplasmic "stress"; c) death of fatty cells in apoptosis way, formation of corpuscles of apoptosis and failure of biological function of endoecology; d) formation of biological reaction of inflammation in visceral fatty tissue; e) high level of unsaturated fatty acids in intercellular medium and f) development of metabolic syndrome. The leptin prevents aphysiological deposit ofnon-polar triglycerides in insulin-dependent cells that are not intended to deposit non-polar triglycerides and also in β-cells of islands. The main cause of high level ofleptin in blood plasma is overeating offood physiological by content of nutrients.

Topics: Adipocytes; Adiponectin; Adipose Tissue, Brown; Chylomicrons; Fatty Acids; Gene Expression Regulation; Humans; Hyperphagia; Intra-Abdominal Fat; Leptin; Lipid Metabolism; Metabolic Syndrome; Mitochondria; Signal Transduction; Triglycerides

For billions years, two phylogenetically, functionally and regulatory different pools of fatty cells - visceral fatty acids and adipocytes coexist in vivo. Their becoming occurred at different degrees of phylogenesis. The phylogenetically earlier pool of visceral fatty acids is meant to supply with fatty acids-substrates for gaining energy by those cells which implement biological function of nutrition (trophology), homeostasis, endoecology biological function of adaptation and continuation of species. They have no receptors to phylogenetically later insulin. The adipocytes, later in phylogenesis, implement one biological function - the function of locomotion and they are as insulin-dependent as skeletal myocytes, cardiomyocytes, adipocytes and periportal hepatocytes. The difference in regulation is traced on all levels of "biological perfection " - autocrine (cellular) level, in humoral regulated paracrin cenosises of cells and on the level of organism. In biological function of trophology, paracrin cenosises of visceral fatty acids and adipocytes implement subsequently three biological reactions: exotrophy, deposit of fatty acids and endotrophy. In conditions of humoral regulation of three functionally different biological reactions in paracrin cenosises synthesis of so many humoral mediators is required. The humoral mediators of mechanism of feedback at autocrine level, in paracrin cenosises and at the level of organism are leptin of visceral fatty acids and adiponectin of adipocytes. At the level of organism, phylogenetically earlier paracrin cenosises of fatty cells are regulated by endocrine system. The phylogenetically later paracrin cenosises are regulated by insulin and nuclei of hypothalamus. The metabolic syndrome is a pathology of phylogenetically earlier insulin-independent visceral fatty acids. The obesity is a pathology of phylogenetically later pool of insulin-dependent adipocytes.

Topics: Adipocytes; Adiponectin; Adipose Tissue, Brown; Autocrine Communication; Fatty Acids; Gene Expression Regulation; Humans; Intra-Abdominal Fat; Leptin; Lipid Metabolism; Metabolic Syndrome; Mitochondria; Paracrine Communication; Phylogeny; Signal Transduction

The insulin signaling system of the brain has a key role in the regulation of fundamental cell processes in neurons and controls metabolic processes in the CNS and periphery. In hypothalamic neurons insulin signaling system interacts closely with the other signaling systems regulated by leptin, melanocortin peptides, dopamine, serotonin, and is the key component of the hypothalamic signaling network, which integrates and transforms the central and peripheral signals. The disturbances in the brain insulin system lead to central insulin resistance, which is one of the primary causes of type 2 diabetes mellitus (DM), metabolic syndrome and Alzheimer's disease. The early restoration of the functions of this system provides an effective approach to prevent and treat type 2 DM and neurodegenerative diseases associated to it. In this review the literature data and own results on structural functional organization of the brain insulin signaling system, causes and functional consequences of central insulin resistance, abnormalities of insulin signaling in the CNS and approaches to its restoration in type 2 DM are analyzed and discussed.

Topics: Alzheimer Disease; Diabetes Mellitus, Type 2; Dopamine; Humans; Hypoglycemic Agents; Hypothalamus; Insulin; Insulin Resistance; Leptin; Melanocortins; Metabolic Syndrome; Neurons; Serotonin; Signal Transduction

Since identification in 1994 of leptin, a hormone produced by adipocytes, adipose tissue has become the subject of intensive research. These studies contributed to the discovery that adipocytes have the ability to synthesize and secrete biologically active substances called "adipokines". Adipokines include a variety of cytokines, peptide hormones and enzymes that play a role in a wide variety of biological functions. For example, they are involved in the regulation of appetite, energy homeostasis, vascular hemostasis, blood pressure, inflammatory and immune processes and play a role in the metabolism of carbohydrates and fats. In obese patients, the secretion of adipokines is frequently abnormal. These changes may predispose to the development of insulin resistance, hypertension and inflammation. Therefore, adipokines are the subject of ongoing clinical trials. The family of adipokines is increasing by the newly discovered peptides. This paper presents the current state of knowledge about retinol binding protein 4 (RBP-4), fasting-induced adipose factor/angiopoietin-like protein 4 (FIAF/ANGPTL4), fibroblast growth factor-21 (FGF21), dipeptidyl peptidase-4 (DPP-4), irisin and their potential role in the pathogenesis of metabolic disorders associated with obesity. The knowledge of the role of newly discovered adipokines may help in the treatment of metabolic syndrome.

Topics: Adipocytes; Adipokines; Adipose Tissue; Humans; Insulin Resistance; Leptin; Metabolic Diseases; Metabolic Syndrome; Obesity

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

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

The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases.

Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Humans; Leptin; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Resistin; Rheumatic Diseases

Clozapine is, and will remain in the coming years, an irreplaceable drug in psychiatry which has elective indication in treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. Unfortunately, the drug is largely underused for many and serious side effects. Only a good knowledge of these side effects and of the main strategies to prevent their occurrence or minimize their impact can allow overcoming the underutilization of this valuable therapy. The article describes the clinical and epidemiological features of the non-motor side effects of clozapine including blood dyscrasias, constipation, diabetes, enuresis, fever, hepatitis, hypersalivation, ileus, myocarditis, nephritis, priapism, seizures, serositis, weight gain and metabolic syndrome. The paper suggests several strategies, supported by scientific evidence, in the management of these side effects. The neuropsychiatric side effects of clozapine are not discussed in this review.

Topics: Antipsychotic Agents; Clozapine; Diabetes Mellitus, Type 2; Electroencephalography; Humans; Leptin; Metabolic Syndrome; Paraproteinemias; Receptor, Serotonin, 5-HT2C; Seizures; Weight Gain

Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream and exerts biological effects on pancreatic beta cells and adipose tissue. Undercarboxylated osteocalcin is the hormonally active isoform and stimulates insulin secretion and enhances insulin sensitivity in adipose tissue and muscle. Insulin and leptin, in turn, act on bone tissue, modulating the osteocalcin secretion, in a traditional feedback mechanism that places the skeleton as a true endocrine organ. Further studies are required to elucidate the role of osteocalcin in the regulation of glucose and energy metabolism in humans and its potential therapeutic implications in diabetes, obesity and metabolic syndrome.

Topics: Adipose Tissue; Animals; Bone and Bones; Diabetes Mellitus, Type 2; Energy Metabolism; Glucose; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Leptin; Metabolic Syndrome; Muscles; Obesity; Osteocalcin

Metabolic syndrome, hypernutrition syndrome is a phylogenetically determined sequence of symptoms having common pathogenesis. Etiologically, it is due to excessive intake of adequate food. Enterocytes and omental adipose cells form an early phylogenetically unified and paracrinically regulated community that alternately realize exo- and endotrophic biological reactions. Visceral obesity high level of non-esterified fatty acids (FA), formation of plasma FA pool and their integration into the endothelial membrane, and enlargement of enterocytes are the main cause of increased hydrodynamic pressure. Toll-like receptors perceive albumin associates containing a supraphysiological number of FA as aliens and initiate the inflammatory reaction. Lipid-overloaded cells undergo "endoplasmic stress", abnormal protein synthesis (folding), and apoptosis-like death. Visceral fat serves as phylogenetically early FA depot for the realization of biological functions of homeostasis, trophology endoecology, and adaptation; it is anatomically confined and regulated at the level of paracrine communities. The subcutaneous depot realizes the phylogenetically late locomotor function; its size is not anatomically restricted. Visceral adipose cells have no receptors for phylogenetically late insulin (INS). Cells of the subcutaneous FA depot are specialized adipocytes having INS and GLUT4 receptors. They are regulated by the phylogenetically late humoral mechanisms at the total body level. Leptin initiates in vivo humoral, hypothalamic regulation of the size of INS-insensitive visceral adipose cells quantitatively programmed in ontogenesis; also, it prevents "endoplasmic stress" and apoptosis, regulates food consumption. Leptin initiates switching FA storage from the visceral adipocyte pool to the subcutaneous one. Adiponectin is a phylogenetically late humoral inducer of regulation of the optimal in vivo number of cells from the hypothalamus level. It is biologically predetermined to regulate the number (proliferation) of INS-dependent adipocytes in subcutaneous fat.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Apoptosis Regulatory Proteins; Eating; Endoplasmic Reticulum Stress; Fatty Acids; Humans; Leptin; Metabolic Syndrome

Matrix metalloproteinases (MMPs) play an important role during physiological tissue remodeling in embryonic development and angiogenesis, as well as in pathophysiological conditions such as obesity and development and vulnerability of atherosclerotic plaque. Moreover, MMP circulating levels have emerged as potential biomarkers of cardiovascular disease. MMP expression and activity are regulated by different factors such as insulin resistance and obesity. Expanded fat tissue has been demonstrated to be an active organ, where MMPs also exert a role in adipogenesis, angiogenesis, and proliferation of extracellular matrix (ECM). However, the lack of association between adipose tissue and plasma levels of some MMPs, specifically MMP-2 and MMP-9, suggests that this tissue is not a major contributor to circulating gelatinases. MMPs are also co-expressed or co-repressed in response to inflammatory adipocytokines, like adiponectin and leptin. Adiponectin may also play a protective role in plaque rupture through selectively increasing the tissue inhibitor of metalloproteinase (TIMP) expression. Leptin induces the expression of MMP-2 activators as well as the expression of MMP-2, MMP-9, and TIMP-1 in different human cells. Furthermore, sex hormones also participate in MMP regulation. In postmenopausal women, hormone replacement therapy produces an increase in MMP activity, leading to a breakdown in ECM homeostasis and accelerated progression of vascular pathologies. Besides, in men, an inverse relationship between testosterone levels and MMP-2 activity has been described. It is still necessary to go forward in the study of MMPs in different metabolic situations to corroborate their role as vulnerable plaque biomarkers.

Topics: Adiponectin; Adipose Tissue; Animals; Gonadal Steroid Hormones; Humans; Leptin; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Metabolic Syndrome; Myocardium; Obesity; Risk Factors

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

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

The more common sporadic form of Alzheimer disease (SAD) and the metabolic syndrome are two highly prevalent pathological conditions of Western society due to incorrect diet, lifestyle, and vascular risk factors. Due to the increasing aging of populations, prevalence of AD in western industrialized countries will rise in the near future and, thus, new knowledge in the area of molecular biology and epigenetics will probably help to reverse the neurodegenerative process. Recent data have suggested metabolic syndrome as an independent risk factor for SAD. Furthermore, biological plausibility for this relationship has been framed within the metabolic cognitive syndrome concept, and some authors designed SAD as a brain diabetes or diabetes 3. Then, impaired signaling of insulin and from some adipokines involved in the so called adipoinsular axis, like leptin, ghrelin or amylin could give a metabolic basis to explain the origin and progression of SAD. Thus, dipokines like leptin, ghrelin and amylin, or their mimetic compounds, could contribuite to inhibit apoptosis and inflammation processes and, thus, generate protective responses in the nervous system. Moreover, these adipokines might promote the activation of a cognitive process which may retard or even partially reverse selected aspects of Alzheimer's disease or ageing memory loss.

Topics: Adipokines; Alzheimer Disease; Animals; Brain; Diabetes Complications; Energy Metabolism; Ghrelin; Glucose; Humans; Islet Amyloid Polypeptide; Leptin; Metabolic Syndrome

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

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

Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance. Patients who gain weight during VPA therapy can develop dyslipidemia and metabolic syndrome that are associated with long-term vascular complications such as hypertension and atherosclerosis. Moreover, an elevation in the levels of uric acid and homocysteine, together with oxidative stress, may contribute to atherosclerotic risk in patients under long-term therapy with VPA. The aim of this review is to discuss the metabolic and endocrine effects of VPA chronic treatment in patients with epilepsy.

Topics: Anticonvulsants; Epilepsy; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Metabolic Syndrome; Valproic Acid; Weight Gain

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

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

Metabolic syndrome has been described as the association of insulin resistance, hypertension, hyperlipidemia and obesity. Its prevalence increased dramatically, mainly in developed countries. Animal models are essential to understand the pathophysiology of this syndrome. This review presents the murine models of metabolic syndrome the most often used in pharmacological studies. The most common metabolic syndrome models exhibit a non-functional leptin pathway, or metabolic disorders induced by high fat diets. In a first part, and after a short introduction on leptin, its receptor and mechanism of action, we provide a detailed description of each model: SHROB, SHHF, JCR:LA-cp, Zucker, ZDF, Wistar Ottawa Karlsburg W, and Otsuka Long-Evans Tokushima Fatty rats, ob/ob, db/db, agouti yellow and Mc4R KO mice. The second part of this review is dedicated to metabolic syndrome models obtained by high fat feeding.

Topics: Animals; Diet; Disease Models, Animal; Humans; Leptin; Metabolic Syndrome; Receptors, Leptin

Obesity and the accompanying metabolic syndrome are among the most important causes of cardiovascular pathologies associated with endothelial dysfunction, such as arterial hypertension and atherosclerosis. This detrimental effect of obesity is mediated, in part, by excessive production of the adipose tissue hormone leptin. Under physiological conditions leptin induces endothelium-dependent vasorelaxation by stimulating nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Leptin activates endothelial NO synthase (eNOS) through a mechanism involving AMP-activated protein kinase (AMPK) and protein kinase B/Akt, which phosphorylates eNOS at Ser(1177) , increasing its activity. Under pathological conditions, such as obesity and metabolic syndrome, the NO-mediated vasodilatory effect of leptin is impaired. Resistance to the acute NO-mimetic effect of leptin is accounted for by chronic hyperleptinaemia and may result from different mechanisms, such as downregulation of leptin receptors, increased levels of circulating C-reactive protein, oxidative stress and overexpression of suppressor of cytokine signalling-3. In short-lasting obesity, impaired leptin-induced NO production is compensated by EDHF; however, in advanced metabolic syndrome, the contribution of EDHF to the haemodynamic effect of leptin becomes inefficient. Resistance to the vasodilatory effects of leptin may contribute to the development of arterial hypertension owing to unopposed stimulation of the sympathetic nervous system by this hormone.

Topics: Animals; Blood Pressure; Endothelium, Vascular; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Vasodilation

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic 'bodyweight/appetite/satiety set point,' resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer's disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer's disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer's disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders.

Topics: Adipokines; Cannabinoid Receptor Modulators; Ceramides; Humans; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Metabolic Syndrome; Nervous System Diseases; Risk Factors

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

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

Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy) or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.

Topics: Body Mass Index; Child; Comorbidity; Energy Metabolism; Growth Hormone; Humans; Hypothalamus; Leptin; Life Style; Metabolic Syndrome; Obesity; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiotherapy; Risk Factors; Survivors; Weight Gain

Obesity and the metabolic syndrome (MS) are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although rare cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to nonalcoholic fatty liver disease (NAFLD). Moreover, MS and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with MS to improve the screening guidelines and develop prophylactic treatments in this setting.

Topics: Adiponectin; Carcinoma, Hepatocellular; Diabetes Complications; Disease Progression; Fatty Liver; Hepatitis C, Chronic; Humans; Leptin; Liver Neoplasms; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Risk Factors

The spectrum of adipose tissue diseases ranges from obesity to lipodystrophy, and is accompanied by insulin resistance syndrome, which promotes the occurrence of type 2 diabetes, dyslipidemia and cardiovascular complications. Lipodystrophy refers to a group of rare diseases characterized by the generalized or partial absence of adipose tissue, and occurs with or without hypertrophy of adipose tissue in other sites. They are classified as being familial or acquired, and generalized or partial. The genetically determined partial forms usually occur as Dunnigan syndrome, which is a type of laminopathy that can also manifest as muscle, cardiac, neuropathic or progeroid involvement. Gene mutations encoding for PPAR-gamma, Akt2, CIDEC, perilipin and the ZMPSTE 24 enzyme are much more rare. The genetically determined generalized forms are also very rare and are linked to mutations of seipin AGPAT2, FBN1, which is accompanied by Marfan syndrome, or of BANF1, which is characterized by a progeroid syndrome without insulin resistance and with early bone complications. Glycosylation disorders are sometimes involved. Some genetically determined forms have recently been found to be due to autoinflammatory syndromes linked to a proteasome anomaly (PSMB8). They result in a lipodystrophy syndrome that occurs secondarily with fever, dermatosis and panniculitis. Then there are forms that are considered to be acquired. They may be iatrogenic (protease inhibitors in HIV patients, glucocorticosteroids, insulin, graft-versus-host disease, etc.), related to an immune system disease (sequelae of dermatopolymyositis, autoimmune polyendocrine syndromes, particularly associated with type 1 diabetes, Barraquer-Simons and Lawrence syndromes), which are promoted by anomalies of the complement system. Finally, lipomatosis is currently classified as a painful form (adiposis dolorosa or Dercum's disease) or benign symmetric multiple form, also known as Launois-Bensaude syndrome or Madelung's disease, which are sometimes related to mitochondrial DNA mutations, but are usually promoted by alcohol. In addition to the medical management of metabolic syndrome and the sometimes surgical treatment of lipodystrophy, recombinant leptin provides hope for genetically determined lipodystrophy syndromes, whereas modifications in antiretroviral treatment and tesamorelin, a GHRH analog, is effective in the metabolic syndrome of HIV patients. Other therapeutic options will undoubtedly be developed, depen

Topics: Adipocytes; Adipogenesis; Adipokines; Adipose Tissue; Anti-HIV Agents; Cardiomyopathies; Genes, Recessive; Humans; Insulin Resistance; Leptin; Lipodystrophy; Lipomatosis; Magnetic Resonance Imaging; Metabolic Syndrome; Mutation; Physical Examination; Skin; Syndrome

Nearly 35% of adults and 20% of children in the United States are obese, defined as a body mass index ≥ 30 kg/m(2). Obesity, which is accompanied by metabolic dysregulation often manifesting in the metabolic syndrome, is an established risk factor for many cancers. Within the growth-promoting, proinflammatory environment of the obese state, cross talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, cytokines, and other mediators that may enhance cancer risk and progression. This review synthesizes the evidence on key biological mechanisms underlying the obesity-cancer link, with particular emphasis on obesity-associated enhancements in growth factor signaling, inflammation, and vascular integrity processes. These interrelated pathways represent possible mechanistic targets for disrupting the obesity-cancer link.

Topics: Adiponectin; Cell Communication; Humans; Inflammation; Insulin; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Neoplasms; Obesity; Receptor, IGF Type 1; Receptor, Insulin; Signal Transduction; Vascular Endothelial Growth Factor A

Topics: Adipokines; Adiponectin; Adipose Tissue; Adult; Aged; Animals; Chronic Disease; Clinical Trials as Topic; Cytokines; Diabetes Mellitus, Type 2; Exercise; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin; Serpins

The purpose of this review was to highlight, in relation to the currently accepted pathophysiology of non-alcoholic fatty liver disease (NAFLD), the known exercise habits of patients with NAFLD and to detail the benefits of lifestyle modification with exercise (and/or physical activity) on parameters of metabolic syndrome. More rigorous, controlled studies of longer duration and defined histopathological end-points comparing exercise alone and other treatment are needed before better, evidence-based physical activity modification guidelines can be established, since several questions remain unanswered.

Topics: Diet; Exercise; Fatty Liver; Hormones; Humans; Insulin Resistance; Leptin; Life Style; Lipids; Liver; Metabolic Syndrome; Motor Activity; Non-alcoholic Fatty Liver Disease; Obesity; Practice Guidelines as Topic; Treatment Outcome

Obesity is the most critical factor in the pathology of metabolic syndrome (MetS), and is associated with an increased risk of depression. The imbalance of hormones and neural peptides which are involved in energy regulation are observed in obesity. It becomes evident that these hormones and neural peptides also affect mood. Leptin plays a pivotal role in energy regulation mainly acting in the hypothalamus of the brain. Although obese humans and rodents usually have high circulating levels of leptin, leptin neither reduces food intake nor increases energy expenditure. This paradoxical situation in obesity has been termed "leptin resistance", which is considered to be a central dogma for obesity. Based on these observations, we examined the functional significance of leptin in the regulation of the depressive state in diet-induced obese (DIO) mice. Our recent study demonstrated that DIO mice showed severe depressive behavior without response to the antidepressant effect of leptin, which is, in part, due to the impairment of leptin action in the hippocampus (Yamada, et al., Endocrinology, 2011). MetS and CNS dysfunction might have common pathological bases vulnerable to these disorders. Our future direction is to investigate a new treatment strategy of MetS by analyzing CNS dysfunction associated with obesity.

Topics: Animals; Central Nervous System Diseases; Depression; Disease Models, Animal; Humans; Leptin; Metabolic Syndrome; Obesity

Increased evidence suggests that obesity-related glomerulopathy and chronic kidney diseases should be identified as isolated complications of obesity. It is questioned if the numerous adipose tissue productions could play a role in the initiation/maintenance of such kidney diseases. This review will provide a sum-up of recent advances on fat cell metabolism and adipose tissue physiology. The adipose tissue behaves as an endocrine organ with multiple activities. It is secreting hormones (leptin, adiponectin, apelin) and numerous factors with autocrine, paracrine and systemic effects. These secretions are coming from adipocytes themselves or from cells present in the stroma-vascular fraction of the adipose tissue. When expanding, the adipose tissue of the obese is infiltrated by immune cells such as macrophages and lymphocytes; the role of which is not fully clarified. An attempt will be done to delineate if alterations of lipid storage/fatty acid release or of the secretion potencies of adipose tissue could contribute to kidney lipotoxicity and other chronic kidney diseases described in the obese.

Topics: Adipocytes; Adiponectin; Adipose Tissue, White; Apelin; Biomarkers; Body Mass Index; Cytokines; Evidence-Based Medicine; Glomerulonephritis; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Obesity; Renal Insufficiency, Chronic

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

Obesity is a highly prevalent health problem in Western countries that leads to many important diseases such as type 2 diabetes and metabolic syndrome being now considered an inflammatory chronic disease. Adipocytes are no longer considered passive cells storing fat since they are major producers of inflammatory cytokines during obesity. Adipocytes and macrophages share many biological properties including the synthesis of similar molecules regulating inflammation. Fatty acid levels are elevated in obesity and induce inflammatory pathways by yet a mostly unknown mechanism, leading to the development of insulin and leptin resistance. Recent studies suggest that these effects could be mediated through the activation of toll-like receptors (TLR). TLR signalling pathways might contribute to the development of obesity-associated insulin resistance, thus representing a connection between innate immunity and metabolism. Here, we summarize the recent evidence for the important role that TLRs play in adipose tissue, obesity and insulin resistance.

Topics: Adipocytes; Adipose Tissue; Animals; Cytokines; Diabetes Mellitus, Type 2; Humans; Inflammation; Insulin Resistance; Leptin; Macrophages; Metabolic Syndrome; Obesity; Signal Transduction; Toll-Like Receptors

Topics: Animals; Energy Metabolism; Homeostasis; Humans; Leptin; Metabolic Syndrome

Topics: Adiponectin; Complement Factor D; Humans; Leptin; Metabolic Syndrome

Topics: Adiponectin; Animals; Humans; Leptin; Metabolic Syndrome; Obesity; Receptors, Leptin

Topics: Animals; Drug Therapy, Combination; Humans; Islet Amyloid Polypeptide; Leptin; Metabolic Syndrome; Mice; Obesity

Obesity is associated with metabolic syndrome, a cluster of symptoms including diabetes, hyperlipidemia, hypertension and arteriosclerosis, which can cause serious health problems. Accumulating evidence suggests that endoplasmic reticulum stress (ER stress) is associated with metabolic syndrome. Leptin is an anti-obesity hormone, which is secreted from adipose tissue. Circulating leptin acts at the brain hypothalamus and reduces food intake. As most forms of obesity indicate a state of leptin resistance, elucidation of the mechanisms of leptin resistance would be an important subject. We and other groups have recently suggested that leptin resistance may be derived from ER stress. These results raised the possibility that attenuating ER stress would be effective treatment for the disease. In the present review article, recent understanding of the mechanisms of the development of obesity and the potential novel therapeutic approaches targeting ER stress are discussed.

Topics: Adipose Tissue; Animals; Drug Design; Eating; Endoplasmic Reticulum Stress; Humans; Hypothalamus; Leptin; Life Style; Metabolic Syndrome; Mice; Molecular Targeted Therapy; Obesity; STAT3 Transcription Factor

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

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

In the 20th century industrialized nations have become afflicted with an unprecedented pandemic of increased adiposity. In the United States, the epicenter of the epidemic, over 2/3 of the population, is overweight and 1 of every 6 Americans carries the diagnosis of metabolic syndrome. Although genes determine susceptibility to environmental factors, the epidemic is clearly due to increased consumption of calorie-dense, highly lipogenic foods, coupled with a marked decrease in physical exertion resulting from modern technologies. If this lifestyle continues, morbid consequences are virtually inevitable. They include type II diabetes and a cluster of disorders known as "the metabolic syndrome" usually appearing in middle age. The morbid consequences of the chronic caloric surplus are buffered before middle age by the partitioning of these calories as fat in the adipocyte compartment which is specifically designed to store triglycerides. Leptin has been proposed as the major hormonal regulator of the partitioning of surplus calories. However, multiple factors can determine the storage capacity of the fat tissue and when it is exceeded ectopic lipid deposition begins. The organs affected in metabolic syndrome include skeletal muscle, liver, heart and pancreas, which are now known to contain abnormal levels of triglycerides. While neutral fat is probably harmless, it is an index of ectopic lipid overload. Fatty acid derivatives can interfere with the function of the cell and ultimately lead to its demise through lipoapoptosis, the consequences of which are gradual organ failure.

Topics: Animals; Homeostasis; Humans; Leptin; Lipid Metabolism; Metabolic Syndrome; Obesity

Leptin is a hormone secreted by adipose tissue in direct proportion to amount of body fat. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Persons with congenital deficiency are obese, and treatment with leptin results in dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese persons are resistant to the weight-reducing effects of leptin. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. Current studies investigate the role of leptin in weight-loss management because persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight. Leptin deficiency is also evident in patients with diet- or exercise-induced hypothalamic amenorrhea and lipoatrophy. Replacement of leptin in physiologic doses restores ovulatory menstruation in women with hypothalamic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy. The applications of leptin continue to grow and will hopefully soon be used therapeutically.

Topics: Adipose Tissue; Amenorrhea; Animals; Atrophy; Energy Metabolism; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Neurosecretory Systems; Obesity; Recombinant Proteins; Weight Loss

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

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

Once considered divine retribution for sins, comorbidities of obesity (metabolic syndrome) are today attributed to obesity-induced metabolic defects. Here, we propose that obesity and hyperleptinemia protect lipid-intolerant nonadipose organs against lipotoxic lipid spillover during sustained caloric surplus. Metabolic syndrome is ascribed to lipotoxicity caused by age-related resistance to antilipotoxic protection by leptin.

Topics: Adipose Tissue; Energy Intake; Humans; Hyperphagia; Leptin; Lipids; Metabolic Syndrome; Obesity

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, whose pathogenesis begins with the accumulation of liver fat and is followed by the development of necro-inflammation and fibrosis. Recent evidence indicates that adipocytokines, polypeptides secreted by the adispose tissue, might play an important role in the pathogeneic process and progression of NAFLD. In this review, we explore the role of leptin, and in part of other adipocytokines, in the interference with hepatic injury associated with fatty infiltration, in the modulation of steatosis and fibrosis, in both experimental models of the disease and in the clinical practice. We also discuss the potential use of leptin as non-invasive marker for differentiating simple fatty liver from NAFLD, and the possible novel therapeutic strategies aimed at interfering with the leptin axis to dampen chronic liver inflammation and NAFLD.

Topics: Adipokines; Animals; Biomarkers; Drug Delivery Systems; Fatty Liver; Humans; Inflammation; Leptin; Liver Cirrhosis; Metabolic Syndrome

Metabolic syndrome (MetS) is a constellation of metabolic derangements and underlying factors that significantly increases the risk for developing type 2 diabetes and cardiovascular diseases. MetS is a low-grade inflammatory condition, with systemic inflammation and inflammation of central abdominal fat as contributors. Systemic inflammation in MetS is thought to involve C-reactive protein and some proinflammatory cytokines; the nuclear factor-kappaB pathway also is believed to play a role. Inflammation of central adipose tissue leads to adipokine production, followed by secretion of adipokines into the general circulation to contribute to the overall inflammatory condition. The molecular mechanisms that contribute to this inflammation are still somewhat unclear, but several serine/threonine kinases are known to be involved. Dietary components may also contribute to central adiposity and the inflammation seen in MetS.

Topics: Abdominal Fat; Adipokines; Adiponectin; Adiposity; C-Reactive Protein; Cytokines; Diet; Humans; Inflammation; Insulin Resistance; Interleukins; Leptin; Life Style; Metabolic Syndrome; NF-kappa B; Nutritional Status; Oxidative Stress; Risk Factors; Serine; Threonine; Tumor Necrosis Factor-alpha

Recent upsurge in research has uncovered distinct circuitries that regulate appetite, energy expenditure and fat accrual under the supervision of hormonal feedback signalling of adipocyte leptin and gastric ghrelin in the hypothalamic integration of energy homeostasis. A host of messenger molecules of diverse chemical composition and origin mediate the crosstalk between the three circuitries. Leptin is now recognized as the mandatory afferent signal in maintenance of weight homeostasis. Leptin insufficiency in the hypothalamus due to diminished transport of leptin across the blood-brain barrier (BBB) imposed by environmental causes, such as consumption of energy-enriched diets and diminished energy expenditure, orchestrates unregulated fat accrual and the attendant disease cluster of metabolic syndrome. Bioavailability of leptin selectively in the hypothalamic targets with the aid of gene therapy successfully averted the environmentally induced metabolic afflictions and normalized lifespan. Thus, sustenance of optimal sufficiency in leptin signalling solely in the hypothalamus is a novel strategy to combat the worldwide epidemic of obesity and metabolic syndrome.

Topics: Animals; Appetite; Body Weight; Energy Metabolism; Ghrelin; Homeostasis; Humans; Hypothalamus; Leptin; Metabolic Syndrome; Neurosecretory Systems; Obesity; Signal Transduction

Obesity is associated with an increased risk and worsened prognosis for many types of cancer, but the mechanisms underlying the obesity-cancer progression link are poorly understood. Several energy balance-related host factors are known to influence tumor progression and/or treatment responsiveness after cancer develops, and these have been implicated as key contributors to the complex effects of obesity on cancer outcome. These host factors include leptin, adiponectin, steroid hormones, reactive oxygen species associated with inflammation, insulin, insulin-like growth factor-1, and sirtuins. Each of these host factors is considered in this article in the context of energy balance and cancer progression. In addition, future research directions in this field are discussed, including the importance of study designs addressing energy balance across the life course, the development and application of highly relevant animal models, potential roles of cancer stem cells in the response to energy balance modulation, and emerging pharmacologic approaches that target energy balance-related pathways.

Topics: Adiponectin; Adrenal Cortex Hormones; Disease Progression; Energy Metabolism; Gonadal Steroid Hormones; Humans; Inflammation; Insulin; Insulin-Like Growth Factor I; Leptin; Metabolic Syndrome; Neoplasms; Oxidative Stress; Sirtuin 1

Obesity has been recognized as an important risk factor for many serious medical conditions. The association of obesity with an increased risk of many cancers is of enormous economic importance to the health industry.The metabolic syndrome and visceral obesity have an increasing prevelance and incidence in the general population.The actual prevelance of the metabolic syndrome is 24% in US population and between 24,6% and 30.9% in Europe. Recent evidence from epidemiologic and basic research studies, as well as clinical and intervention studies, supports the emerging hypothesis that metabolic syndrome may be an important etiologic factor for the onset of cancer. In addition, increased body weight has recently been shown to be associated with an increased risk of cancers at multiple specific sites. The close interaction between cancer cells and adipocytes is an intriguing issue in tumor biology. In nowdays, several metabolic markers are implicated in the development and progression of several malignancies. This review describes the emerging data concerning the role of metabolic markes in tumor cell growth and relates them to their future clinical prospects.

Topics: Adiponectin; Animals; Fatty Acids, Nonesterified; Ghrelin; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Neoplasms; Obesity

Adipocytokines, such as adiponectin, TNF-alpha, and leptin, are cytokines secreted by visceral adipocytes, and they are associated with metabolic syndrome. Adiponectin is one of the adipocytokines, and is a protein comprised of 244 amino acids. It is known as ACRP30, GBP28, and AdipoQ. Adiponectin is secreted by adipocytes, has three different isoforms, including trimers (low-molecular weight: LMW), hexamers (middle-molecular-weight: MMW), and higher-order oligomeric (high-molecular-weight: HMW) structures, and affects the biological activity. Adiponectin is a clinically relevant parameter measured routinely in subjects at risk of type 2 diabetes and metabolic syndrome. We investigated the adiponectin levels using a number of ELISA assay kits.

Topics: Adipokines; Adiponectin; Biomarkers; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Ghrelin; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Plasminogen Activator Inhibitor 1; Reagent Kits, Diagnostic; Resistin; Risk; Tumor Necrosis Factor-alpha

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

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

The risk factors for hepatocellular carcinoma (HCC) development have been established, and include chronic hepatitis B and C, heavy alcohol consumption, and aflatoxins. In fact, 5%-30% of patients with HCC still lack a readily identifiable risk factor. It has been reported that the majority of ''cryptogenic'' HCC may be attributed to nonalcoholic fatty liver disease, the hepatic presentation of the metabolic syndrome (MS). Obesity is associated with the development of the MS. Recently, adipose tissue has been considered as an endocrine organ because of its capacity to secrete a variety of cytokines, which are collectively known as the adipokines. Leptin, the product of the obese gene, is mainly produced by adipose tissue. Since leptin was first characterized in 1994, accumulated literature has demonstrated the involvement of this adipokine in several areas of human physiology. After binding to its receptor, leptin initiates a cascade of signaling events and subsequent cellular effects. In addition to being the regulatory mediator of energy homeostasis, several in vitro studies have demonstrated the fibrogenic role of leptin in the liver. Furthermore, the deregulated expression of leptin and its receptor have been demonstrated to be associated with a variety of metabolic disorders as well as human cancers. Most importantly, direct evidence supporting the inhibitory and/or activating role of leptin in the process of carcinogenesis and progression of human HCC has been accumulating rapidly. This review aims to provide important insights into the potential mechanisms of leptin in the development of HCC. Hopefully, further investigations will shed light on a new therapeutic target in HCC.

Topics: Aflatoxins; Carcinoma, Hepatocellular; Fatty Liver; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Leptin; Liver Neoplasms; Metabolic Syndrome; Receptors, Leptin; Risk Factors; Signal Transduction

Obesity is characterized by increased concentration of leptin and disturbance of the feedback between hyperleptinaemia and enhanced appetite. The hyperleptinaemia is often combined with hyperglycaemia and arterial hypertension and seems to be a predictor of acute cardiovascular events. Leptin inhibitors might be used in the future for therapy in case of the metabolic syndrome.

Topics: Animals; Appetite; Humans; Hyperglycemia; Hypertension; Leptin; Metabolic Syndrome

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

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

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

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

To highlight the metabolic or inflammatory components, deregulated in or pathogenic for the metabolic syndrome, that may, directly or indirectly, modulate hepatic fibrogenesis.. Advanced glycation end products signal profibrogenetic transformation of hepatic stellate cells. Altered adipocytokines favor insulin resistance and steatosis. They participate to the proinflammatory status of the metabolic syndrome. Among them, leptin has been shown to directly enhance fibrogenesis, whereas adiponectin has shown antifibrotic properties. The renin-angiotensin system, a component of arterial hypertension, is activated in the diseased liver, and there is convincing evidence that blockade of angiotensin II signaling attenuates fibrosis. Endocannabinoids, whose hepatic production and signaling capability are increased with insulin resistance and obesity, signal profibrotic response via the preponderant receptor, cannabinoid receptor 1, whereas antifibrotic and anti-inflammatory signals are rather generated via stimulation of cannabinoid receptor 2. Finally, recent data demonstrate that modulation of innate immunity, particularly modulation of natural killer and natural killer T cells, has potential roles in the resolution of steatohepatitis and fibrosis.. Several features associated with the metabolic syndrome can undoubtedly modulate liver fibrosis. More studies are needed to identify those that are prominent determinants of fibrosis in the metabolic syndrome and the benefit of their targeting for fibrosis prevention and treatment.

Topics: Adiponectin; Glycation End Products, Advanced; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Liver Cirrhosis; Metabolic Syndrome

Changes in maternal diet at different stages of reproduction can have pronounced influences on the health and well-being of the resulting offspring, especially following exposure to an obesogenic environment. The mechanisms mediating adaptations in development of the embryo, placenta, fetus and newborn include changes in the maternal metabolic environment. These changes include reductions in a range of maternal counter-regulatory hormones such as cortisol, leptin and insulin. In the sheep, for example, targeted maternal nutrient restriction coincident with the period of maximal placental growth has pronounced effects on the development of the kidney and adipose tissue. As a consequence, the response of these tissues varies greatly following adolescent-onset obesity and ultimately results in these offspring exhibiting all the symptoms of the metabolic syndrome earlier in young adult life. Leptin administration to the offspring after birth can have some long-term differential effects, although much higher amounts are required to cause a response in small compared with large animal models. At the same time, the responsiveness of the offspring is gender dependent, which may relate to the differences in leptin sensitivity around the time of birth. Increasing maternal food intake during pregnancy, either globally or of individual nutrients, has little positive impact on birth weight but does impact on liver development. The challenge now is to establish which components of the maternal diet can be sustainably modified in order to optimise the maternal endocrine environment through pregnancy, thus ensuring feto-placental growth is appropriate in relation to an individual's gender and body composition.

Topics: Adipose Tissue; Animals; Diet; Female; Fetus; Humans; Kidney; Leptin; Liver; Metabolic Syndrome; Models, Animal; Obesity; Pregnancy; Prenatal Nutritional Physiological Phenomena; Sex Factors

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

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

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

Obesity is the most serious long-term health risk currently facing America's adolescents. Weight gain during adolescence carries a higher risk for adult obesity and the metabolic syndrome. This review highlights early adolescence as a particularly high-risk time for weight gain due to the synergy of naturally occurring metabolic changes along with increasing behavioral risk factors. One of the first potential health effects of abnormal weight gain during this period is earlier puberty, usually manifested as thelarche. The obesity epidemic is clearly implicated in the national trend toward earlier thelarche, although the data are not as strong in relation to menarche. Leptin activation of the hypothalamic-pituitary axis, combined with insulin resistance, and increased adiposity may result in the higher estrogen levels that are linked to breast development. Young adolescents also experience a sharp decline in their level of physical activity, worsening nutritional habits, and other important psychosocial and developmental risk factors that may contribute to obesity and estrogen-dependent disease in later life, including polycystic ovary syndrome and breast cancer. Unfortunately, the very psychosocial factors that contribute to abnormal weight gain during early adolescence make prevention and treatment in this population particularly challenging. Therefore, intervening prior to pubertal onset becomes even more important given the risk factors present once puberty begins.

Topics: Adolescent; Adult; Breast Neoplasms; Estrogens; Female; Humans; Hypothalamo-Hypophyseal System; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Puberty; Risk Factors; Weight Gain

The epidemic of obesity in the United States and around the world is intensifying in severity and scope and has been implicated as an underlying mechanism in systemic hypertension. Obese hypertensive individuals characteristically exhibit volume congestion, relative elevation in heart rate, and high cardiac output with concomitant activation of the renin-angiotensin-aldosterone system. When the metabolic syndrome is present, insulin resistance and hyperinsulinemia may contribute to hypertension through diverse mechanisms. Blood pressure can be lowered when weight control measures are successful, using, for example, caloric restriction, aerobic exercise, weight loss drugs, or bariatric surgery. A major clinical challenge resides in converting short-term weight reduction into a sustained benefit. Pharmacotherapy for the obese hypertensive patient may require multiple agents, with an optimal regimen consisting of inhibitors of the renin-angiotensin-aldosterone system, thiazide diuretics, beta-blockers, and calcium channel blockers if needed to attain contemporary blood pressure treatment goals.

Topics: Antihypertensive Agents; Bariatric Surgery; Blood Pressure; Drug Therapy, Combination; Hemodynamics; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Renin-Angiotensin System; Risk Reduction Behavior; Sympathetic Nervous System; Weight Loss

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

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

It has been suggested that sympathetic hyperactivity is found in patients with metabolic syndrome (MS) by measuring turnover rate of catecholamines and/or muscle sympathetic nerve firing rate. Increased leptin associated with MS stimulates sympathetic outflow from the hypothalamus, which may be one of causes of sympathetic hyperactivity. Insulin increased in association with insulin resistant in MS increases sodium reabsorption in the kidney leading to sodium retention. Increased intra-cranial sodium ions are known to augment sympathetic nervous system activity via stimulation of epithelial sodium channels, mineralocorticoid receptors, the renin-angiotensin-aldosterone system and endogenous digitalislike factors in the brain. This mechanism may be true in patients with essential hypertension, particularly in those who are sensitive to sodium loading.

Topics: Brain; Catecholamines; Humans; Hypertension; Insulin Resistance; Kidney; Leptin; Metabolic Syndrome; Receptors, Mineralocorticoid; Renin-Angiotensin System; Sodium; Sodium Channels; Sympathetic Nervous System

Multidisciplinary research from my and my colleagues' laboratory has shown that disruption at various levels of leptin signaling to the interactive hypothalamic network of neuropeptide Y (NPY) and cohorts contributes to the antecedent pathophysiologic sequelae of the disease cluster of the metabolic syndrome. Disruptions in NPY signaling due to high or low abundance of NPY and cognate receptors dysregulate the homeostatic milieu to promote hyperinsulinemia, hyperglycemia, fat accrual, and overt diabetes. Hyperleptinemia induced by consumption of energy-rich diets inhibits leptin transport across the blood-brain barrier and thereby produces leptin insufficiency in the hypothalamus. Sustained leptin insufficiency results in loss of hypothalamic restraint on pancreatic insulin secretion and diminished glucose metabolism and energy expenditure. This chain of events culminates in hyperinsulinemia, hyperglycemia, and diabetes. Our recent studies have shown that increasing the supply of leptin centrally by gene therapy reinstates the restraint on hypothalamic NPY signaling and ameliorates diabetes and the attendant disease cluster of the metabolic syndrome. Thus, newer therapies that would enhance leptin transport across the blood-brain barrier in a timely manner or reinstate leptin restraint on NPY signaling through central leptin gene therapy or pharmacologically with leptin mimetics are likely to curtail the pathophysiologic sequelae of diabetes and related ailments of the metabolic syndrome.

Topics: Animals; Diabetes Mellitus; Hypothalamus; Leptin; Metabolic Syndrome; Mice; Neuropeptide Y; Rats

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

Despite the early recognition of the strong association between obstructive sleep apnoea (OSA) and obesity, and OSA and cardiovascular problems, sleep apnoea has been treated as a "local abnormality" of the respiratory track rather than as a "systemic illness". In 1997, we first reported that the pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNFalpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. In subsequent studies, it was shown that IL-6, TNFalpha, and insulin levels were elevated in sleep apnoea independently of obesity and that visceral fat was the primary parameter linked with sleep apnoea. Further studies showed that women with the polycystic ovary syndrome (PCOS) were much more likely than controls to have sleep-disordered breathing (SDB) and daytime sleepiness, suggesting a pathogenetic role of insulin resistance in OSA. Additional accumulated evidence that supports the role of obesity and the associated metabolic aberrations in the pathogenesis of sleep apnoea and related symptoms include: obesity without sleep apnoea is associated with daytime sleepiness; the protective role of gonadal hormones as suggested by the increased prevalence of sleep apnoea in post-menopausal women and the significantly reduced risk for OSA in women on hormonal therapy; partial effects of continuous positive airway pressure (CPAP) in obese patients with apnoea on hypercytokinemia, insulin resistance indices, and visceral fat; and that the prevalence of the metabolic syndrome in the U.S. population from the Third National Health and Nutrition Examination Survey (1988-1994) parallels the prevalence of symptomatic sleep apnoea in general random samples. Furthermore, the beneficial effect of a cytokine antagonist on EDS and apnoea in obese, male apnoeics and that of exercise and weight loss on SDB and EDS in general random or clinical samples, supports the hypothesis that cytokines and insulin resistance are mediators of EDS and sleep apnoea in humans. Finally, our recent finding that in obese, hypothalamic CRH neuron is hypoactive, provides additional evidence on the potential central neural mechanisms for depressed ventilation and consequent development of sleep apnoea in obese individuals. In conclusion, accumulating evidence provides support to our thesis that obesity via inflammation, insulin resistance, visceral adiposity, and

Topics: Adiposity; Female; Humans; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Models, Biological; Obesity; Polycystic Ovary Syndrome; Sleep Apnea Syndromes

Nonalcoholic fatty liver disease (NAFLD) spans a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to cirrhosis. Simple steatosis is the substrate upon which the more serious entities in the spectrum develop; it is the first "hit" in the multistep pathogenesis of NASH, which is considered the hepatic manifestation of the metabolic syndrome. Demonstration of the existence of regulatable fatty acid transport mechanisms has contributed to clarifying the role of fatty acid disposition in obesity, the various components of NAFLD, and the metabolic syndrome. Hepatic steatosis is closely linked to obesity. This linkage is based on the fact that obesity results in marked enlargement of the intraabdominal visceral fat depots. The eventual development of insulin resistance leads to continuous lipolysis within these depots, releasing fatty acids into the portal circulation, where they are rapidly translocated to the liver and reassembled into triglycerides. Reactive oxygen species, generated in the liver from oxidation of fatty acids, are precipitating factors in the cascade of events leading from simple steatosis to NASH. Dysregulation of fatty acid disposition, with ectopic lipid accumulation in other tissues, is a major contributing factor to other components of the metabolic syndrome. Bariatric surgery is an effective treatment for severe obesity, but its role in the management of the various forms of fatty liver disease is unclear. Our review of the literature that includes both initial and follow-up liver biopsies suggests that most obese patients with simple steatosis and NASH who undergo bariatric surgery will achieve improvement in hepatic histology, but that occasional patients, especially those who lose weight very rapidly, may show worsening of either fibrosis or steatohepatitis.

Topics: Abdominal Fat; Adipocytes; Animals; Bariatric Surgery; Comorbidity; Diabetes Mellitus, Type 2; Fatty Acids; Fatty Liver; Gastrointestinal Hormones; Humans; Insulin Resistance; Leptin; Lipolysis; Liver; Metabolic Syndrome; Obesity; Obesity, Morbid

The metabolic syndrome represents a major public health burden because of its high prevalence in the general population and its association with cardiovascular disease and type 2 diabetes. Accumulated evidence based on biochemical, neurophysiologic, and indirect measurements of autonomic activity indicate that visceral obesity and the metabolic syndrome are associated with enhanced sympathetic neural drive and vagal impairment. The mechanisms linking metabolic syndrome with sympathetic activation are complex and not completely understood, and cause-effect relationships need further clarification from prospective trials. Components of the metabolic syndrome that may directly or indirectly enhance sympathetic drive include hyperinsulinemia, leptin, nonesterified fatty acids, proinflammatory cytokines, angiotensinogen, baroreflex impairment, and obstructive sleep apnea. beta-Adrenoceptor polymorphisms have also been associated with adrenoceptor desensitization, increased adiposity, insulin resistance, and enhanced sympathetic activity. Because chronic sympathetic activation contributes to hypertension and its target-organ damage, sympathoinhibition remains an important goal in the therapeutic management of the metabolic syndrome.

Topics: Adipokines; Cytokines; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Risk Assessment; Sensitivity and Specificity; Sleep Apnea, Obstructive; Sympathetic Nervous System

Recently more and more evidences have emerged about the oncogenic effect of type 2 diabetes and metabolic syndrome. Among these evidences epidemiological data are in first line. There is a causal relationship according to gender, ethnicity and geographic situation between different tumors and type 2 diabetes/metabolic syndrome as well. Supposed pathomechanisms are obesity, cytokines, secreted excessively in adipose tissue, permanent and postprandial hyperglycemia, hyperinsulinism and insulin resistance, other growth factors, like proinsulin, insulin like growth factor-1, reactive oxygen species, angiogenesis, inflammation, and the multiple effects of inflammatory cytokines. It proved to be evident that both peroxisome-proliferator-activated receptors and the regulatory ubiquitin proteasome system have significant role in insulin sensitivity and in co-ordinating cell proliferation and angiogenesis. These mechanisms in metabolic syndrome are risk factors towards atherosclerosis and cancer diseases as well. This newly emerged knowledge may open new pathways in treating and preventing the above-mentioned pathologic processes.

Topics: Adiponectin; Adipose Tissue; Animals; Cell Proliferation; Cytokines; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hyperinsulinism; Inflammation; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Metabolic Syndrome; Neoplasms; Neovascularization, Pathologic; Obesity; Peroxisome Proliferator-Activated Receptors; Reactive Oxygen Species; Risk Factors; Ubiquitins; Vascular Endothelial Growth Factor A

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

Many adverse effects of atypical antipsychotic treatment are associated with antagonism of monoamine receptors; however, data indicate that important metabolic effects, such as hypertriglyceridemia and impairment in glucose/insulin homeostasis, may not be related to these mechanisms, leading investigators to explore alternative hypotheses. Promising candidates include a possible impact of antipsychotics on peptide hormonal regulators of metabolic control such as leptin, ghrelin, and adiponectin. The purpose of this review is to summarize recent data on changes in these hormones during atypical antipsychotic treatment.. A Medline search was performed for papers published from January 1999 to January 2007 using key words antipsychotic, atypical antipsychotic, and individual atypical antipsychotic drug names cross-referenced with leptin, ghrelin, and adiponectin.. The bulk of the published work focused on changes in body weight and serum leptin, with far less data on ghrelin, and adiponectin, and nonweight metabolic changes. Leptin changes were directly related to a medication's weight gain liability, with no added antipsychotic effects on leptin signaling. Conflicting results emerged for the other markers, but all three long-term studies on ghrelin showed increased levels in patients on atypical antipsychotics with weight gain liabilities.. Leptin increases during antipsychotic treatment are a result of weight gain rather than a direct impact of atypical antipsychotics on leptin physiology. Preliminary long-term data show increased ghrelin levels, but this finding must be replicated. The association with antipsychotic effects on glucose and lipid metabolism and these hormones remains virtually unstudied. Future research should indicate whether ghrelin and other peptide hormones may be useful predictors of weight gain or metabolic changes in patients on antipsychotics.

Topics: Adiponectin; Adult; Animals; Antipsychotic Agents; Body Mass Index; Body Weight; Cross-Sectional Studies; Female; Ghrelin; Humans; In Vitro Techniques; Leptin; Male; Metabolic Syndrome; Obesity; Pharmacogenetics; Prospective Studies; Rats; Schizophrenia

In recent years there is increasing evidence of an interaction between metabolic syndrome and testicular function. Metabolic syndrome, in particular obesity, affects testicular function by reducing total testosterone and sex hormone-binding globulin levels, as well as having a detrimental effect on spermatogenesis. On the other hand, hypogonadism further increases insulin resistance, which is the main pathophysiological feature of metabolic syndrome. There are implications that testosterone replacement can improve not only testicular function, but also parameters of the metabolic syndrome. Although the exact pathophysiological mechanisms remain unclear, leptin, resistin and ghrelin appear to play crucial roles in the interaction between metabolic syndrome and testicular function. All of this evidence supports the notion that the metabolic syndrome is a complex clinical entity characterized by pathophysiological mechanisms that affect the endocrine system as a whole; for these reasons it has been proposed to rename it 'metabolic-neuroendocrine syndrome'.

Topics: Ghrelin; Humans; Hypothalamo-Hypophyseal System; Leptin; Male; Metabolic Syndrome; Resistin; Spermatogenesis; Testis; Testosterone

The relentless rise in the prevalence of obesity predicts an exponential increase in the incidence of obesity-related complications. Medical and surgical treatments are necessary to prevent and treat obese co-morbidities, thereby avoiding disability and premature death. Interventions for obesity should be evaluated not by weight loss alone but against the new incidence in obesity-related co-morbidities, their remission or improvement. In combination with lifestyle measures, currently available pharmacological therapies -- rimonabant, orlistat and sibutramine -- achieve 5-10% weight loss, although a return to baseline is the norm after cessation of medication. All these agents demonstrate approximately 0.5% reduction in HbA1c in diabetic subjects; orlistat also reduces the new incidence of type 2 diabetes. Modest improvement in lipid profiles and reduced calculated cardiovascular risk is observed, but data on improvement of other co-morbidities are sparse. In contrast, surgical procedures that restrict food ingestion and/or curtail the absorptive surface area of the gut consistently achieve substantial weight loss, typically 20-35%, effect resolution of co-morbid conditions and improve quality of life. Although mortality is low, complications and hospitalisation are not uncommon after bariatric surgery. Intriguingly, surgical patients experience a reduction in appetite and report changes in food preference. Accentuation of the normal gastrointestinal hormonal response to food intake and possible changes in vagal afferent signalling are proposed to induce satiety. Increased understanding of body weight homeostasis and appetite regulation has provided an impressive list of potential targets for drug development, with the promise that single or combination therapy may ultimately challenge the supremacy of bariatric surgery.

Topics: Adipose Tissue; Amyloid; Anticonvulsants; Antidepressive Agents; Anxiety; Appetite Regulation; Bariatric Surgery; Body Mass Index; Bupropion; Cholecystokinin; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Depression; Diabetes Mellitus, Type 2; Female; Fluoxetine; Fructose; Ghrelin; Humans; Intra-Abdominal Fat; Islet Amyloid Polypeptide; Isoxazoles; Lactones; Leptin; Metabolic Syndrome; Metformin; Obesity; Obesity, Morbid; Orlistat; Oxyntomodulin; Peptide YY; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Sertraline; Sleep Apnea, Obstructive; Surgical Procedures, Operative; Topiramate; Zonisamide

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

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

After an initial attempt by the WHO to define metabolic syndrome (MS) on a pathophysiologically oriented approach requiring the assessment of insulin resistance markers, the NCEP-ATPIII and more recently the IDF proposed more clinically oriented criteria to help, toward a preventive medicine goal, to identify patients who are likely to have features of the MS and be at increased risk of type 2 diabetes and cardio vascular disease. The notion of MS is built around abnormalities of the metabolism of lipids and carbon hydrates, a rise of blood pressure, and visceral obesity of abdominal localization. These parameters report only partially on mechanisms leading to the development of the MS. The physiopathology of MS is partially understood even today and likely results from the combination of environmental, genetic and epigenetic factors. Abdominal visceral obesity, a state of low-grade chronic inflammation and insulin resistance are the main processes susceptible to explain the various constituents of this syndrome.

Topics: Environment; Exercise; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; Models, Biological; Nutritional Status; Psoriasis

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

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

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

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

Recently the definition, the pathophysiology and even the clinical utility of metabolic syndrome (MS) have been discussed. The risk induced by each component of the metabolic syndrome is higher than the risk induced by MS alone. MS alone is, in fact, a weaker predictor of cardiovascular disease than diabetes. New criteria to define the metabolic syndrome have been proposed, as adipokines, CRP and PAI-1. IGFBP-1 is related to hyperinsulinemia/insulin resistance and to the risk of diabetes and fatal ischemic heart disease development. IGF/IGFBP system could be a link between insulin resistance and cardiovascular disease. RBP-4 can attenuate insulin signalling in skeletal muscle and induce hepatic gluconeogenesis. The belief that insulin-resistance is the main cause of MS could change in favour of the adipose tissue dysfunction. The most common cause of a reduced capacity of the adipose tissue to store fats is the increased dietary intake, also present in lipodistrophy, type 1 diabetes mellitus and polycystic ovarian syndrome. The adipose tissue production of adipokines and cytokines (such as IL-6, TNF-alpha and TGF-beta) and the excessive lipid flux towards muscles, heart and liver (Ectopic fat storage syndrome) contribute to the MS genesis and to an increased cardiovascular risk. The comprehension of adipose tissue dysfunction mechanisms offers new possibilities of prevention and therapy.

Topics: Adiponectin; Adipose Tissue; C-Reactive Protein; Humans; Insulin Resistance; Insulin-Like Growth Factor Binding Proteins; Interleukin-6; Leptin; Metabolic Syndrome; Plasminogen Activator Inhibitor 1; Retinoblastoma Protein; Terminology as Topic

Obesity is associated with significant morbidity and mortality and is increasing in prevalence worldwide. Associated conditions include insulin resistance (IR), diabetes, hypertension and dyslipidaemia; a clustering of these has recently been termed as metabolic syndrome. Weight gain is a major predictor of the metabolic syndrome with waist circumference being a more sensitive indicator than body mass index as it reflects both abdominal subcutaneous adipose tissue and visceral adipose tissue (VAT). VAT has more metabolic activity and secretes a number of hormones and pro-inflammatory cytokines which are linked with the metabolic abnormalities listed above. Central obesity also increases the risk of obstructive sleep apnoea syndrome (OSAS), where the sleep disordered breathing may also independently lead to/or exacerbate IR, diabetes and cardiovascular risk. The contribution of OSAS to the metabolic syndrome has been under-recognized. The putative mechanisms by which OSAS causes or exacerbates these other abnormalities are discussed. We propose that activation of nuclear factor kappa B by stress hypoxia and/or by increased adipokines and free fatty acids released by excess adipose tissue is the final common inflammatory pathway linking obesity, OSAS and the metabolic syndrome both individually and, in many cases, synergistically.

Topics: Adiponectin; Diabetes Mellitus, Type 2; Humans; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; NF-kappa B; Obesity; Risk Factors; Sleep Apnea Syndromes

Depending on the definitions used, up to 10% of all live-born neonates are small for gestational age (SGA). Although the vast majority of these children show catch-up growth by 2 yr of age, one in 10 does not. It is increasingly recognized that those who are born SGA are at risk of developing metabolic disease later in life. Reduced fetal growth has been shown to be associated with an increased risk of insulin resistance, obesity, cardiovascular disease, and type 2 diabetes mellitus. The majority of pathology is seen in adults who show spontaneous catch-up growth as children. There is evidence to suggest that some of the metabolic consequences of intrauterine growth retardation in children born SGA can be mitigated by ensuring early appropriate catch-up growth, while avoiding excessive weight gain. Implicitly, this argument questions current infant formula feeding practices. The risk is less clear for individuals who do not show catch-up growth and who are treated with GH for short stature. Recent data, however, suggest that long-term treatment with GH does not increase the risk of type 2 diabetes mellitus and the metabolic syndrome in young adults born SGA.

Topics: Adult; Animals; Body Height; Child; Child Development; Fetal Development; Growth Disorders; Growth Hormone; Humans; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Metabolic Syndrome; Models, Biological

There is ample discussion of the relevance of the metabolic syndrome, the definition criteria, and predictive power. Nevertheless, along with the increasing prevalence of childhood obesity, the prevalence of the metabolic syndrome in obese children is reported at 30%, irrespective of the definition applied. Because children are otherwise relatively free of co-morbidities, they constitute an interesting population in which to study the sequence of events of obesity-related pathology. The adipocytokines appear to be important in this respect. Leptin was initially suggested as a promising "antiobesity" hormone. New concepts indicate that, in humans, leptin and its soluble receptor may be more important in states of energy deficiency rather than a predictor of the metabolic syndrome. Adiponectin, on the other hand, is not only related to obesity and insulin resistance, but appears to be the strongest predictor for metabolic syndrome, even in children. In newborns and infants, both adipocytokines occur in high concentrations, even though this cannot completely explain the increased risk for ensuing metabolic disease later in life. Finally, low-grade systemic inflammation may underlie the clustering of metabolic risk factors, but their role in children remains to be specified. Overall factors from the adipose tissue may constitute not only markers but also mediators of metabolic sequelae of obesity.

Topics: Adiponectin; Adipose Tissue; Biomarkers; Birth Weight; Child; Child, Preschool; Cytokines; Fatty Liver; Humans; Infant; Infant, Newborn; Leptin; Metabolic Syndrome; Prognosis

Topics: Adiponectin; Angiotensin II Type 1 Receptor Blockers; Antioxidants; Drug Design; Fatty Acids, Nonesterified; Fatty Liver; Humans; Hypolipidemic Agents; Insulin Resistance; Leptin; Metabolic Syndrome; Receptors, Adiponectin; Receptors, Cell Surface; Tumor Necrosis Factor-alpha

The increasing prevalence of the metabolic syndrome in numerous populations throughout the world is currently of major concern, and presents a huge global health problem. The link between low birth weight and the subsequent development of obesity, disrupted glucose homeostasis and hypertension is now well established, and there is extensive evidence supporting these associations in both epidemiological and experimental studies. Alterations in the secretion of, and responses to, the circulating hormones insulin and leptin are likely candidates in terms of disease development. The aim of current research is to define how the central and peripheral pathways in which these signals exert their effects may be disrupted following poor early growth, and how this disruption contributes to the development of metabolic disease. The present review aims to outline the existing evidence whereby alterations in early growth may programme an individual to be at increased risk of the metabolic syndrome. The development of central appetite and expenditure circuits and of peripheral metabolic tissues, are likely to play a key role in the long-term regulation of energy balance.

Topics: Animals; Appetite Regulation; Birth Weight; Disease Models, Animal; Energy Intake; Energy Metabolism; Genetic Predisposition to Disease; Humans; Leptin; Metabolic Syndrome; Nutritional Physiological Phenomena; Obesity; Risk Factors

An imbalance between pro- and anti-inflammatory molecules occurs in metabolic syndrome X. High-energy diet, saturated fats and trans-fats during perinatal period could suppress Delta(6) and Delta(5) desaturases both in the maternal and fetal tissues, resulting in a decrease in the concentrations of long-chain polyunsaturated fatty acids (LCPUFAs): arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that have a negative feedback control on inflammation. EPA, DHA and AA augment endothelial nitric oxide synthesis, potentiate insulin action both in the peripheral tissues and brain and alter leptin production. LCPUFAs are essential for brain growth and development and synaptogenesis and modulate the action of several neurotransmitters and hypothalamic peptides. This suggests that metabolic syndrome X could be a disorder of the brain due to suboptimal LCPUFAs during perinatal period that triggers low-grade systemic inflammation, implying that perinatal strategies are needed to prevent its development.

Topics: Animals; Appetite Regulation; Arachidonic Acid; Brain; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Dopamine; Eicosapentaenoic Acid; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Aminobutyric Acid; Humans; Hypothalamus, Middle; Infant, Newborn; Inflammation; Insulin; Leptin; Metabolic Syndrome; N-Methylaspartate; Neurons; Qa-SNARE Proteins; Receptor, Insulin; Receptors, Retinoic Acid; Serotonin; Synapses

The metabolic syndrome is a long-term process, explained by the interaction of genetic and environmental factors, that starts early in life and is involved in the pathophysiology of a large percentage of cases with type 2 diabetes and atherosclerosis. A number of clinical studies have demonstrated the importance of fat distribution and especially the contribution of visceral fat accumulation to the development of metabolic disorders. Visceral adipose tissue can be studied through different imaging techniques. The accumulation of visceral adipose tissue, as opposed to subcutaneous fat, increases the risk of developing metabolic disease and cardiovascular diseases (CVD). Visceral adipocytes secrete a variety of cytokines known as adipocytokines suggesting that adipose tissue is an endocrine organ that may affect the function of other organs. Weight loss, particularly a reduction in waist circumference, improves insulin sensitivity, lipid profile, and serum adipocytokines, reducing the risk of developing chronic disease and CVD. Waist circumference is a required component of metabolic syndrome under the International Diabetes Federation (IDF) criteria, rather than an optional component as used by other previous classifications. Studies have shown that using a lower waist circumference threshold within the context of metabolic syndrome increases the prevalence, but decreases the risk of mortality and type 2 diabetes. It is possible that waist circumference acts as a marker for other risk factors. These findings reinforce the notion that reductions in visceral adipose tissue should be a primary aim of strategies designed to reduce health risks associated with metabolic syndrome.

Topics: Abdominal Fat; Adiponectin; Adipose Tissue; Animals; Homocysteine; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Metabolic Syndrome; Waist-Hip Ratio

The metabolic syndrome represents a constellation of co-morbidities that include central adiposity, insulin resistance, dyslipidemia and hypertension, which results from an elevated prevalence of obesity. An increased abdominal adiposity is observed in upper-body obesity with preferential accumulation of fat in the visceral depot, which renders these individuals more prone to metabolic and cardiovascular problems. The pathophysiology of the metabolic syndrome seems to be closely associated to an elevated efflux of free fatty acids from the visceral fat compartment and a dysregulation of the expression of adipose tissue-derived factors (also termed "adipokines"). Weight reduction and increased physical activity represent the main approach to tackle the "diabesity" epidemic. Nonetheless, taking advantage of the different biochemical and molecular characteristics of visceral and subcutaneous adipose tissue may open up novel pharmacological strategies to combat the metabolic and cardiovascular derangements accompanying the metabolic syndrome.

Topics: Adiponectin; Adiposity; Animals; Cytokines; Humans; Insulin; Intra-Abdominal Fat; Leptin; Lipolysis; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Subcutaneous Fat; Tumor Necrosis Factor-alpha

The metabolic syndrome is an emerging global epidemic characterized by clustering of metabolic abnormalities leading to increased cardiovascular risk: glucose intolerance or type 2 diabetes, dyslipidemia, hypertension, and "central" obesity. Scientists are decoding and piecing together the molecular texture underlying the metabolic syndrome: insulin resistance and dyslipidemia stand out as central pathophysiological events. In this picture, the liver rises as the leading organ in the maintenance of metabolic fitness; it serves as the first relay station for processing dietary information, and encloses the whole biochemical machinery for both glucose and lipid storage and disposal. In addition, the liver is a target of the different endocrine molecules secreted by pancreatic beta-cells and adipose tissue. Evidence collected in animal models supports the central role of the liver in the metabolic syndrome. While specific bereft of insulin sensitivity in skeletal muscle and adipose tissue fails to induce diabetes at certain extent, this is constantly the outcome in case of hepatic insulin resistance. Also, dyslipidemia is currently interpreted as the result of increased flux of free fatty acids to the liver with ensuing misbalance of lipoprotein synthesis and removal. In this review we bring together recent advances in the field of lipid sensing nuclear receptors, adipokines and other molecules responsible for metabolic fitness, and provide a putative coherent frame to conceive the pathophysiology of the metabolic syndrome.

Topics: Adiponectin; Animals; Carbohydrate Metabolism; Disease Models, Animal; Dyslipidemias; Humans; Insulin Resistance; Leptin; Lipid Metabolism; Liver; Metabolic Syndrome; PPAR alpha; PPAR gamma

Leptin, a hormone produced by adipocytes in proportion to fat stores, signals the sufficiency of energy reserves to the brain to control feeding and metabolism. Leptin represents a vital link between metabolic and neuroendocrine pathways, and adequate circulating leptin levels are required to permit the expenditure of energy on reproduction, growth, and other energy-intensive endocrine outputs. Leptin mediates its effects by acting upon a distributed network of CNS neurons that express the signaling form of the leptin receptor (LRb). Nutritional status early in development influences a lifelong metabolic program that modulates risk for diabetes, obesity and other elements of the metabolic syndrome. Recent evidence has demonstrated a number of important roles for leptin in the regulation of neural development and metabolic programming. In this review, we discuss leptin action, the neural circuits on which leptin acts, and our nascent understanding of how early leptin exposure may influence neural development and the predisposition to metabolic diseases.

Topics: Animals; Brain; Humans; Leptin; Metabolic Syndrome; Models, Biological; Neurosecretory Systems; Receptors, Leptin; Signal Transduction

Upper body obesity and the related metabolic disorder type 2 diabetes have been identified as risk factors for breast cancer, and associated with late-stage disease and a poor prognosis. Components of the metabolic syndrome, including visceral adiposity, insulin resistance, hyperglycemia and hyperinsulinemia, with or without clinically manifest diabetes mellitus, low serum high-density lipoprotein cholesterol and hypertension have all been related to increased breast cancer risk. The biochemical mechanisms include extraglandular oestrogen production, reduced sex hormone-binding globulin with consequent elevation of the bioactive plasma free oestradiol and increased insulin biosynthesis, all of which exert mitogenic effects on both untransformed and neoplastic breast epithelial cells. Obesity, type 2 diabetes and the metabolic syndrome also have in common an increased production of leptin and a decreased production of adiponectin by adipose tissue, with consequent elevations and reductions, respectively, in the circulating levels of these two adipokines. These changes in plasma leptin and adiponectin, acting through endocrine and paracrine mechanisms, have been associated in several studies with an increase in breast cancer risk and, perhaps, to more aggressive tumours; studies in vitro showed that leptin stimulates, and adiponectin inhibits, tumour cell proliferation and the microvessel angiogenesis which is essential for breast cancer development and progression.

Topics: Adiponectin; Body Composition; Breast Neoplasms; Diabetes Mellitus, Type 2; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Obesity; Risk Factors

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

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

Unique genetic traits appear to play a role in the increased rates of hypertension (HTN), glucose dysregulation/diabetes (T2DM), and obesity in persons of African descent. Indeed, with increasing rates of westernization/urbanization and concomitant increases in obesity and T2DM, a similar predisposition to the cardiometabolic syndrome and cardiovascular disease (CVD) can be seen in Africans compared with persons of African descent, with CVD reaching epidemic proportions in many areas of Africa. In addition, the complex relationships of metabolic abnormalities that are unique to individuals of African descent have also been demonstrated in Africans. These include: (1) a dissociation of HTN to insulin resistance; (2) relative favorable lipid profile in the setting of increasing rates of CVD; (3) low levels of visceral adiposity in the setting of obesity and insulin resistance; and (4) a dissociation of insulin sensitivity and adiponectin when compared with Caucasians. Although not well understood, these unique relationships suggest that conventional parameters for CVD do not apply to Africans of persons of African descent.

Topics: Adiponectin; Africa; Diabetes Mellitus, Type 2; Dyslipidemias; Genetic Predisposition to Disease; Humans; Hypertension; Insulin Resistance; Leptin; Life Style; Metabolic Syndrome; Obesity; Risk Factors

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

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

Although obesity has been consistently linked to an increased risk of several malignancies, including cancers of the colon, gallbladder, kidney, and pancreas, its role in prostate cancer etiology remains elusive. Data on the association between obesity and prostate cancer incidence are inconsistent, and in some studies obesity is associated with an increase in risk of high-grade prostate cancer but with a decrease in risk of low-grade tumors. In contrast, obesity has been consistently associated with an increased risk of prostate cancer aggressiveness and mortality. The differential effects of obesity on subtypes of prostate cancer suggest etiologic heterogeneity in these tumors and complex interactions between androgen metabolism and several putative risk factors, including insulin resistance, diabetes, inflammation, and genetic susceptibility, on prostate cancer risk. Data on the role of abdominal obesity, insulin resistance, and metabolic syndrome in prostate cancer etiology are limited. Obesity has been shown to be associated with a state of low-grade chronic inflammation, and insulin resistance and the metabolic syndrome are associated with adverse metabolic profiles and with higher circulating concentrations of inflammation-related markers, including leptin, interleukin-6, and tumor necrosis factor-, many of which have been shown to enhance tumor growth. Thus, whether obesity and metabolic syndrome modulate the risk of prostate cancer through chronic inflammation needs to be investigated further. Given that the prevalence of obesity and metabolic syndrome is increasing worldwide and that the world population is aging, the roles of obesity and metabolic syndrome in prostate carcinogenesis warrant further clarification.

Topics: Abdominal Fat; Body Mass Index; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Obesity; Prostatic Neoplasms; Risk Factors; Somatomedins

Millions of people worldwide suffer from type 2 diabetes mellitus. There are two major factors that play a role in its pathogenesis: insulin resistance and impaired secretion of insulin by beta-cells. Impaired insulin action is closely linked to the phenomenon of obesity. The adipose tissue releases free fatty acids but also hormones and cytokines such as leptin, adiponectin, resistin, TNF-alpha and others. All those particles modify insulin action. This review article summarizes contemporary opinions on the role of obesity in the generation of resistance to insulin and subsequently impaired glucose tolerance as well as overt type 2 diabetes mellitus.

Topics: Adiponectin; Adipose Tissue; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Resistin; Tumor Necrosis Factor-alpha

An interactive network comprised of neuropeptide Y (NPY) and cohorts is obligatory in the hypothalamic integration of appetite and energy expenditure on a minute-to-minute basis. High or low abundance of NPY and cognate receptors dysregulates the homeostatic milieu engendering hyperphagia, decreased energy expenditure, obesity and attendant metabolic syndrome cluster of dyslipidemia, glucose intolerance, insulin resistance and hyperinsulinemia, risk factors for type II diabetes and cardiovascular diseases. Increasing the supply of the endogenous repressor hormone leptin locally in the hypothalamus with the aid of leptin gene therapy, blocked age-related and dietary obesities, and the sequential development of dyslipidemia, hyperglycemia, and insulin resistance. Thus, sustained repression of NPY signaling with increased leptin selectively in the hypothalamus can avert environmental obesity and the risks of metabolic diseases.

Topics: Animals; Dyslipidemias; Genetic Therapy; Humans; Hypothalamus; Insulin Resistance; Leptin; Metabolic Syndrome; Neuropeptide Y; Obesity

Recent epidemiology demonstrates higher rate of obesity and metabolic syndrome in offspring with undernutrition in utero. IUGR babies with intrauterine undernutrition grow rapidly to catch up with normal growth course. Leptin is an adipocyte derived satiety factor that regulates food intake and energy expenditure. We demonstrated in mice model with maternal food restriction during pregnancy that premature leptin surge during neonatal catch up growth of the offspring lead them to impaired leptin sensitivity and obesity in adulthood.

Topics: Animals; Disease Models, Animal; Eating; Energy Intake; Female; Fetal Growth Retardation; Humans; Leptin; Malnutrition; Metabolic Syndrome; Obesity; Pregnancy; Pregnancy Complications

Topics: Adipocytes; Adiponectin; Animals; Diet, Atherogenic; Energy Metabolism; Exercise; Humans; Insulin Resistance; Leptin; Life Style; Metabolic Syndrome; Obesity; Tumor Necrosis Factor-alpha

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

Obese women are characterized by similar comorbidities to men, particularly type 2 diabetes mellitus and cardiovascular diseases. Moreover, they also develop some specific problems, including fertility-related disorders and some hormone-dependent forms of cancer. The relationship between excess body fat and reproductive disturbances appears to be stronger for early-onset obesity. Early onset of obesity, particularly during adolescence, favours the development of menses irregularities, chronic oligo-anovulation and infertility in adulthood. Moreover, obesity in women can increase the risk of miscarriage and impair the outcome of assisted reproductive technologies. The main factor implicated in the association between obesity and fertility-related disorders is insulin excess, which accompanies insulin resistance. Hyperinsulinaemia may be directly responsible for the development of androgen excess, through its effects in reducing sex hormone-binding globulin synthesis and circulating concentrations, and in stimulating ovarian androgen production rates. Androgen excess, in turn, represents one of the major factors leading to altered ovarian physiology and associated ovulatory disturbances. Obesity-associated hyperleptinaemia may represent an additional factor involved in anovulation, not only through the induction of insulin resistance, but also through a direct impairment of ovarian function.

Topics: Androgens; Animals; Female; Humans; Hyperinsulinism; Infertility, Female; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Reproduction

Adipose tissue contains various types of cells that include preadipocytes and adipocytes. Studies have emphasized that (i) preadipocytes secrete factors involved in their own differentiation and (ii) adipocytes acquire the ability to communicate systemically with other organs (brain, liver, skeletal muscle) and locally with other cells (preadipocytes, endothelial cells and monocytes/macrophages). Adipocytes secrete proteins exhibiting either beneficial (leptin, adiponectin) or deleterious effects (angiotensinogen). Associated to the effect of secretory products from macrophages (cytokines), a disturbance in the balance between these various secreted factors leads to the development of a metabolic syndrome.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Angiotensinogen; Cell Communication; Humans; Leptin; Macrophages; Metabolic Syndrome

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Humans; Hypertension; Insulin Resistance; Leptin; Life Style; Metabolic Syndrome; Obesity; Sympathetic Nervous System

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

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

Obesity is a very common disease worldwide, resulting from a disturbance in the energy balance. The metabolic syndrome is also a cluster of abnormalities with basic characteristics being insulin resistance and visceral obesity. The major concerns of obesity and metabolic syndrome are the comorbidities, such as type 2 diabetes, cardiovascular disease, stroke, and certain types of cancers. Sympathetic nervous system (SNS) activity is associated with both energy balance and metabolic syndrome. Sympathomimetic medications decrease food intake, increase resting metabolic rate (RMR), and thermogenic responses, whereas blockage of the SNS exerts opposite effects. The contribution of the SNS to the daily energy expenditure, however, is small ( approximately 5%) in normal subjects consuming a weight maintenance diet. Fasting suppresses, whereas meal ingestion induces SNS activity. Most of the data agree that obesity is characterized by SNS predominance in the basal state and reduced SNS responsiveness after various sympathetic stimuli. Weight loss reduces SNS overactivity in obesity. Metabolic syndrome is characterized by enhanced SNS activity. Most of the indices used for the assessment of its activity are better associated with visceral fat than with total fat mass. Visceral fat is prone to lipolysis: this effect is mediated by catecholamine action on the sensitive beta(3)-adrenoceptors found in the intraabdominal fat. In addition, central fat distribution is associated with disturbances in the hypothalamo-pituitary-adrenal axis, suggesting that a disturbed axis may be implicated in the development of the metabolic syndrome. Furthermore, SNS activity induces a proinflammatory state by IL-6 production, which in turn results in an acute phase response. The increased levels of inflammatory markers seen in the metabolic syndrome may be elicited, at least in part, by SNS overactivity. Intervention studies showed that the disturbances of the autonomic nervous system seen in the metabolic syndrome are reversible.

Topics: Eating; Energy Metabolism; Humans; Leptin; Metabolic Syndrome; Obesity; Sympathetic Nervous System; Weight Gain; Weight Loss

Adipose tissue is not simply a depot of energy, but is an active endocrine organ. The adipokines play an important role in the pathogenesis of metabolic syndrome. The proinflammatory adipokines secreted from expanded visceral adipose tissue directly induce insulin resistance and vascular injuries. A better understanding of the endocrine function of adipose tissue may lead to more rational therapy for metabolic syndrome.

Topics: Adiponectin; Adipose Tissue; Drug Design; Leptin; Metabolic Syndrome; Resistin; Tumor Necrosis Factor-alpha

Atherosclerosis is a chronic inflammatory disease characterized by infiltration of blood vessels by lipids and leukocytes. There is a growing body of evidence that among risk factors that promote atherosclerosis, the metabolic syndrome is a powerful and prevalent predictor of cardiovascular events. The systemic inflammatory process associated with the metabolic syndrome has numerous deleterious effects that promote plaque activation, which is responsible for clinical events. Interactions between the innate immune system with lipid-derived products seem to play a major role in the pathophysiology of atherosclerosis in relation with the metabolic syndrome. The multiple links among adipose tissue, the vascular wall, and the immune system are the topics of this review, which examines the roles of oxidized low-density lipoprotein, inflammatory cytokines, and adipokines in triggering and perpetuating a danger signal response that promotes the development of atherosclerosis. Furthermore, therapeutic options that specifically target the metabolic syndrome components are reviewed in light of recent developments.

Topics: Adipose Tissue; C-Reactive Protein; Cholesterol, LDL; Coronary Artery Disease; Coronary Disease; Endothelium, Vascular; Genetic Predisposition to Disease; Humans; Immunity; Leptin; Metabolic Syndrome; Peroxisome Proliferator-Activated Receptors; PPAR alpha; PPAR delta; Receptors, Scavenger; Resistin; Risk Factors; Toll-Like Receptors

Topics: Appetite Regulation; Humans; Hypothalamus; Leptin; Metabolic Syndrome; Signal Transduction

Topics: Adipose Tissue; Humans; Hypothalamus; Leptin; Metabolic Syndrome; Receptors, Cell Surface; Receptors, Leptin

Topics: Adipose Tissue; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Tumor Necrosis Factor-alpha

Topics: Animals; Brain; Hypothalamus; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Mice

Topics: Animals; Humans; Leptin; Metabolic Syndrome; Mice; Mice, Transgenic; Obesity

Topics: Adiponectin; Humans; Leptin; Metabolic Syndrome; Mutation

Topics: Adiponectin; Arteriosclerosis; Biomarkers; Humans; Leptin; Metabolic Syndrome

The metabolic syndrome, an emerging public health problem, represents a constellation of cardiovascular risk factors. It has been suggested that the presence of obstructive sleep apnea (OSA) may increase the risk of developing some of the features of the metabolic syndrome, including hypertension, insulin resistance, and type 2 diabetes. In this article, we discuss the parallels between the metabolic syndrome and obstructive sleep apnea and describe possible OSA-related factors that may contribute to the metabolic syndrome, specifically the roles of obesity, hypertension, dyslipidemia, sex hormones, inflammation, vascular dysfunction, leptin, insulin resistance, and sleep deprivation.

Topics: Female; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Risk Factors; Sleep Apnea, Obstructive

In this review, we propose that actions of the lipid-lowering, apoptosis-inhibiting effects of certain "longevity genes" oppose the life-shortening consequences of lipotoxicity and lipoapoptosis. We note that lipotoxicity occurs whenever leptin action is deficient, or whenever satiety is overridden, as in forced or voluntary overfeeding ("supersizing"). The role of hyperleptinemia, we suggest, is to extend survival during famine by permitting the storage of surplus calories in adipocytes without concomitant injury to nonadipose tissues from ectopic lipid deposits. It achieves this lipid partitioning by (1) restraining the level of overnutrition so as not to exceed the available adipocyte storage space and (2) enhancing oxidation of any ectopic lipid overflow: The mechanisms of lipoapoptosis are discussed, and the possibility that metabolic syndrome is the human equivalent of rodent lipotoxicity is suggested.

Topics: Adipocytes; Animals; Apoptosis; Humans; Hyperphagia; Leptin; Lipids; Lipodystrophy; Longevity; Metabolic Syndrome; Proto-Oncogene Proteins c-bcl-2; Starvation

Fatty tissue synthesizes and secretes a wide range of products that may be directly involved in the pathogenesis of the complications associated with obesity. These so-called adipokines may trigger or sustain a chronic inflammatory process. By manipulating the secretory function of fat cells, it might in future be possible to prevent the development of the metabolic and cardiovascular complications of obesity. Current data already suggest that weight reduction and certain substances with an anti-inflammatory action reduce the risk for the metabolic and cardiovascular complications of obesity. To date, however, the evidence available is only indirect, and is insufficient to definitively establish causal relationships between certain secretory products of adipocytes and the comorbidities of adiposity. Further clinical studies are needed.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Coronary Disease; Diabetes Mellitus, Type 2; Humans; Hypertension; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Metabolic Syndrome; Obesity; Plasminogen Inactivators; Risk Factors; Thromboembolism; Weight Loss

The metabolic syndrome currently reaches epidemic proportions in the Western industrialized world. Its hallmarks obesity, type 2 diabetes mellitus, and atherosclerosis are closely associated, and we are just beginning to understand the reasons for this relationship: adipose tissue-derived proteohormones (adipocytokines), under normal weight conditions, guarantee homeostasis of glucose and lipid metabolism, but their dysregulated production in the obese state promotes insulin resistance, inflammation, as well as atherosclerotic events. This review will focus on the current understanding of the adipocytokines' molecular role in metabolism and metabolic disease.

Topics: Adipocytes; Adiponectin; Adult; Cytokines; Developed Countries; Homeostasis; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Obesity; Prevalence

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

Recent studies reveal that sleep loss in humans leads to metabolic disorders. A new study reports the development of metabolic syndrome in mice with altered circadian timing brought about by a mutation in a gene that functions in the biological clock. An intriguing and unanswered question is the relation between a healthy biological clock and normal appetite and weight regulation.

Topics: Animals; Appetite; Circadian Rhythm; CLOCK Proteins; Feeding Behavior; Humans; Leptin; Mammals; Metabolic Syndrome; Mice; Obesity; Sleep; Sleep Wake Disorders; Trans-Activators; Weight Gain

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

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

For a long time it has been known that obesity (adiposity) is linked to insulin resistance. Recently, many investigators have reported that adipocytes secrete a variety of bioactive molecules, termed adipokines (adipocytokines), including TNFalpha, IL-6, leptin, adiponectin, resistin and so on. These adipokines play pivotal roles in energy homeostasis by affecting insulin sensitivity, glucose and lipid metabolisms, food intake, the coagulation system and inflammation. This review provides a summary of these adipose tissue-secreting biomolecules and discusses their feasibilities as drug targets for the treatment of metabolic syndrome.

Topics: Adipocytes; Adiponectin; Animals; Cytokines; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Plasminogen Activator Inhibitor 1; Resistin; Tumor Necrosis Factor-alpha

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

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

Topics: Biomarkers; Cushing Syndrome; Diabetes Mellitus, Lipoatrophic; Diagnostic Techniques, Endocrine; Enzyme-Linked Immunosorbent Assay; Feeding and Eating Disorders; Gonadal Disorders; Humans; Leptin; Metabolic Syndrome; Obesity; Radioimmunoassay; Reagent Kits, Diagnostic; Receptors, Cell Surface; Receptors, Leptin; Reference Values; Specimen Handling

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

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

The insulin resistance (metabolic) syndrome (IRS), also known as syndrome X, is characterized by a clustering of factors associated with cardiovascular risk (obesity, impaired glucose metabolism, hypertension, and dyslipidemia). As reported from the third National Health and Nutrition Examination survey, the IRS is present in approximately 24% of adults in the United States and is strongly associated with coronary heart disease, stroke, type 2 diabetes, and all-cause mortality. Of equal importance, it is now clear that the origins of the IRS extend back into childhood (the IRS is found in approximately 4-10% of children and adolescents) and that the high prevalence of adult IRS is strongly linked to the development of cardiovascular risk during childhood and tracking of the components of the IRS into adulthood. The goal of this review is to present a summary of the currently available information on the IRS in the pre-adult age group with reference to adult studies only when necessary for clarification. The review will specifically summarize insulin resistance in childhood; the important influence of obesity and, in particular, visceral fat, on insulin resistance and the IRS; differences between ethnic groups; relations to adipocytokines, inflammatory factors and oxidative stress; relations of hypertension and lipids to insulin resistance; familial factors; endocrine complications; and potential therapeutic effects from diet and physical activity. Despite the lesser amount of basic and clinical information on childhood IRS in comparison to information available from adult studies, there can now be little doubt that the adverse associations among risk factors comprising the IRS begin in childhood. The challenge is to identify etiologic relations and develop intervention strategies designed to reduce the increasing prevalence of type 2 diabetes and cardiovascular disease.

Topics: Adolescent; C-Reactive Protein; Child; Humans; Hypertension; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipoproteins, VLDL; Metabolic Syndrome; Obesity; Oxidative Stress; Risk Factors

In this review article, the crucial roles of adipocytes in the development of so-called metabolic syndrome and vascular disease are reviewed, focusing on adipocyte-derived bioactive substances, adipocytokines. Recent progress in adipocyte biology shows that adipocytes are not merely energy-storing cells but that they secrete a variety of hormones cytokines, growth factors, and other bioactive substances. To search for novel adipocytokines by the large-scale random sequence analysis of expressed genes in adipocytes, we identified an adipose-specific collagen-like molecule, adiponectin. This novel adipocytokine has plural biofunctions, such as antidiabetic, antiatherosclerotic, and antiinflammatory functions. Adiponectin plasma levels decrease with the accumulation of visceral adipose tissue. In this review, we discuss the link of adiponectin to visceral adiposity, insulin resistance, and vascular diseases.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Arteriosclerosis; Diabetes Mellitus; Gene Expression Profiling; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Mice; Mice, Knockout; Models, Biological; Obesity; Organ Specificity; Proteins; Subcutaneous Tissue; Viscera

The development of atherosclerotic cardiovascular disease is a common comorbidity in patients with the metabolic syndrome, a concurrence of cardiovascular risk factors in one individual. While multiple growth factors and adipokines are identified in atherosclerotic lesions, as well as neurotrophins implicated in both cardiac ischemia and lipid and glucose metabolism, the potential role of neurotrophins in human coronary atherosclerosis and in the metabolic syndrome still remains to be elucidated. Here we describe and discuss our results that represent a novel attempt to study the cardiovascular and metabolic biology of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and mast cells (MC). The local amount of NGF, the immunolocalization of p75 neurotrophin receptor (p75NTR) and the number of MC were correlatively examined in coronary vascular wall and in the surrounding subepicardial adipose tissue, obtained from autopsy cases in humans with advanced coronary atherosclerosis. We also analyzed the plasma levels of NGF, BDNF and leptin and the number of MC in biopsies from abdominal subcutaneous adipose tissue in patients with a severe form of the metabolic syndrome. The results demonstrate that NGF levels are decreased in atherosclerotic coronary vascular tissue but increased in the subepicardial adipose tissue, whereas both tissues express a greater number of MC and a stronger p75NTR immunoreactivity, compared to controls. Metabolic syndrome patients display a significant hyponeurotrophinemia and an increased number of adipose MC; the later correlates with elevated plasma leptin levels. In effect, we provide the first evidence for (i) an altered presence of NGF, p75NTR and MC in both coronary vascular and subepicardial adipose tissue in human coronary atherosclerosis, and (ii) a significant decrease in plasma NGF and BDNF levels and an elevated amount of plasma leptin and adipose MC in metabolic syndrome patients. Together our findings suggest that neuroimmune mediators such as NGF, BDNF, leptin and MC may be involved in the development of cardiovascular disease and related disorders.

Topics: Animals; Brain-Derived Neurotrophic Factor; Coronary Artery Disease; Coronary Vessels; Humans; Leptin; Mast Cells; Metabolic Syndrome; Nerve Growth Factor; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor; Serine Endopeptidases

Obesity is a common problem in much of the western world today in that is linked directly with several disease processes, notably, hypertension. It is becoming clear that the adipocyte is not merely an inert organ for storage of energy but that it also secretes a host of factors that interact with each other and may result in elevated blood pressure. Of particular importance is the putative role of leptin in the causation of hypertension via an activation of the sympathetic nervous system and a direct effect on the kidneys, resulting in increased sodium reabsorption leading to hypertension. Obesity per se may have structural effects on the kidneys that may perpetuate hypertension, leading to an increased incidence of end-stage renal disease that results in further hypertension. Adipose tissue may elaborate angiotensin from its own local renin-angiotensin system. The distribution of body fat is considered important in the genesis of the obesity-hypertension syndrome, with a predominantly central distribution being particularly ominous. Weight loss is the cornerstone in the management of the obesity-hypertension syndrome. It may be achieved with diet, exercise, medications, and a combination of these measures. Anti-obesity medications that are currently undergoing clinical trials may play a promising role in the management of obesity and may also result in lowering of blood pressure. Antihypertensives are considered important components in the holistic approach to the management of this complex problem.

Topics: Adipose Tissue; Aldosterone; Animals; Body Mass Index; Humans; Hypertension; Inflammation; Insulin Resistance; Kidney; Leptin; Metabolic Syndrome; Neuropeptides; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Thrombosis

Topics: Adipocytes; Animals; Arteriosclerosis; Cell Differentiation; Humans; Hypertension; Insulin Resistance; Leptin; Ligands; Lipid Metabolism; Macrophage Activation; Metabolic Syndrome; Neovascularization, Pathologic; Receptors, Cytoplasmic and Nuclear; Thiazolidinediones; Transcription Factors; Vascular Endothelial Growth Factor A

The incidence of obesity has increased sharply in recent years, making it one of the most urgent public health concerns worldwide. The hormone leptin is the central mediator in a negative feedback loop regulating energy homeostasis. Leptin administration leads to reduced food intake, increased energy expenditure, and weight loss. Leptin also mediates unique metabolic effects, specifically depleting lipid from liver and other peripheral tissues. While elucidation of leptin's role has permitted a more detailed view of the biology underlying energy homeostasis, most obese individuals are leptin resistant. A more complete understanding of the molecular components of the leptin pathway is necessary to develop effective treatment for obesity and the Metabolic Syndrome. We review here studies on the identification of one such component, stearoyl-CoA desaturase-1 (SCD-1), as a gene specifically repressed by leptin and discuss the role of this process in mediating the metabolic effects of leptin. Data indicate that pharmacologic manipulation of SCD-1 may be of benefit in the treatment of obesity, diabetes, hepatic steatosis, and other components of the Metabolic Syndrome.

Topics: Animals; Body Weight; Fatty Liver; Humans; Leptin; Liver; Metabolic Syndrome; Obesity; Stearoyl-CoA Desaturase

Topics: Fatty Liver; Female; Hepatitis; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Oxidative Stress; Risk Factors; Tumor Necrosis Factor-alpha

Topics: Animals; Eating; Energy Metabolism; Humans; Hypothalamus; Leptin; Metabolic Syndrome; Mutation; Obesity; Osteogenesis; Receptors, Cell Surface; Receptors, Leptin; Risk Factors

Topics: Adipose Tissue; Adult; Aged; Aging; Androgens; Body Composition; Cholesterol; Growth Hormone; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Triglycerides

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

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

The obesity crisis in the United States has been associated with an alarming increase in the prevalence of the metabolic syndrome (MSX) disease cluster. Here we review evidence that the MSX reflects a failure of a system of intracellular lipid homeostasis that prevents lipotoxicity in the organs of overnourished individuals by confining the lipid overload to cells specifically designed to store large quantities of surplus calories, the white adipocytes. Normally, early in obesity, adipocytes increase leptin and adiponectin secretion, hormones that enhance oxidation of surplus liquids in nonadipose tissues by activating AMP-activated protein kinase and reducing the activity and expression of lipogenic enzymes. These events combine to lower malonyl coenzyme A. Deficiency of and/or unresponsiveness to leptin prevents these protective events and results in ectopic accumulation of lipids. Increased de novo ceramide formation is probably the most damaging lipid and is a cause of lipoapoptosis, abetted by a decline in tissue Bcl-2. Pancreatic beta-cells and myocardiocytes are cellular victims of the process, leading to non-insulin-dependent diabetes and lipotoxic cardiomyopathy. The MSX is particularly prevalent in visceral obesity, probably because visceral adipocytes make less leptin than sc adipocytes. Cushing's syndrome, the lipodystrophy associated with protease inhibitor therapy of AIDS, polycystic ovarian disease, as well as diet-induced visceral obesity, all have a high waist/hip ratio, and all exhibit MSX. Increased lipid content in the heart and skeletal muscle organs of such patients is now under study.

Topics: Body Mass Index; Dietary Fats; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity

Approximately two-thirds of the US population are overweight, which means that insulin resistance is probably the most common metabolic abnormality in the USA. I propose three novel concepts concerning the causes and consequences of insulin resistance that challenge current thinking. First, there is the evidence that resistance to insulin-stimulated glucose metabolism is not a primary event in obesity, but is secondary to lipid accumulation resulting from full responsiveness to insulin-stimulated lipogenic activity. Second, resistance to insulin-stimulated glucose metabolism, now considered detrimental to health, might be a protective mechanism that reduces lipid-induced damage to tissue by excluding glucose from cells, thus decreasing glucose-derived lipogenesis. Third, I suggest that lipid-induced insulin resistance and the accompanying metabolic syndrome are secondary to leptin resistance, resulting in breakdown in the normal partitioning of surplus lipids in the adipocyte compartment.

Topics: Adipose Tissue; Animals; Blood Glucose; Humans; Insulin Resistance; Leptin; Lipid Metabolism; Metabolic Syndrome; Obesity; Rats

Large longitudinal studies showed the epidemiological link between obesity and hypertension. During last years, multiple possible mechanisms involved in this association were identified. Adipose tissue has an important role in the genesis of hypertension in obese patients through several pathways: insulin resistance, leptin, renin-angiotensin-aldosteron system and mediators of inflammation (TNF-alpha, IL-6). Adipocyte may be the major player in the development of insulin resistance and hypertension, elements of the metabolic syndrome, responsible for the cardiovascular complications.

Topics: Adipocytes; Cytokines; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Renin-Angiotensin System

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

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

Topics: Animals; Bezafibrate; Biguanides; Fatty Acids, Nonesterified; Humans; Hyperglycemia; Hyperinsulinism; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Leptin; Life Style; Metabolic Syndrome; Pioglitazone; Thiazoles; Thiazolidinediones; Tumor Necrosis Factor-alpha

I review evidence that leptin is a liporegulatory hormone that controls lipid homeostasis in nonadipose tissues during periods of overnutrition. When adipocytes store excess calories as triacylglycerol (TG), leptin secretion rises so as to prevent accumulation of lipids in nonadipose tissues, which are not adapted for TG storage. Whenever leptin action is lacking, whether through leptin deficiency or leptin resistance, overnutrition causes disease of nonadipose tissues with generalized steatosis, lipotoxicity, and lipoapoptosis. Examples of such disorders of liporegulation include generalized lipodystrophies, mutations of leptin and leptin receptor genes, and diet-induced obesity. Lipotoxicity of pancreatic beta-cells, myocardium, and skeletal muscle leads, respectively, to type 2 diabetes, cardiomyopathy, and insulin resistance. In humans this constellation of abnormalities is referred to as the metabolic syndrome, a major health problem in the United States. When lipids overaccumulate in nonadipose tissues during overnutrition, fatty acids enter deleterious pathways such as ceramide production, which, through increased nitric oxide formation, causes apoptosis of lipid-laden cells, such as beta-cells and cardiomyocytes. Lipoapoptosis can be prevented by caloric restriction, by thiazolidinedione treatment, and by administration of nitric oxide blockers. There is now substantial evidence that complications of human obesity may reflect lipotoxicity similar to that described in rodents.

Topics: Adipose Tissue; Animals; Homeostasis; Humans; Leptin; Lipids; Metabolic Syndrome; Myocardium; Obesity; Risk Factors

Topics: Adiponectin; Cholesterol; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucose; Humans; Leptin; Metabolic Syndrome; Obesity; Obesity, Morbid

OSA is associated with metabolic syndrome (MS), but it is unclear whether OSA treatment with CPAP can revert MS.. Does OSA treatment with CPAP per se have effects on the MS reversibility and the associated metabolic, adiposity and vascular parameters?. The TREATOSA-MS trial is a randomized placebo-controlled trial that enrolled adult patients with a recent diagnosis of MS and moderate or severe OSA (apnea-hypopnea index [AHI], ≥ 15 events/h) to undergo therapeutic CPAP or nasal dilator strips (placebo group) for 6 months. Before and after each intervention, we measured anthropometric variables, BP, glucose, and lipid profile. To control potential-related mechanisms and consequences, we also measured adiposity biomarkers (leptin and adiponectin), body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic fat), and endothelial function.. Despite the higher rate of MS reversibility after CPAP therapy as compared with placebo, most patients retained this diagnosis. The lack of significant or relevant effects on adiposity biomarkers and depots supports the modest role of OSA in modulating MS.. ClinicalTrials.gov; No.: NCT02295202; URL: www.. gov.

Topics: Adiponectin; Adult; Continuous Positive Airway Pressure; Female; Humans; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Sleep Apnea, Obstructive

Metabolic syndrome (MetS) is characterised by metabolic abnormalities that increase the risk of developing type 2 diabetes mellitus and cardiovascular disease. Altered levels of circulating ghrelin, several adipokines and inflammatory markers secreted from adipose tissue, such as leptin, adiponectin, tumor necrosis factor alpha, are observed in overweight and obese individuals. We assessed the effect of supplementation with low doses of a cod protein hydrolysate (CPH) on fasting and postprandial levels of acylated ghrelin, as well as fasting levels of adiponectin, leptin and inflammatory markers in subjects with MetS. A multicentre, double-blinded, randomized controlled trial with a parallel group design was conducted. Subjects received a daily supplement of CPH (4 g protein,

Topics: Adiponectin; Adult; Biomarkers; Dietary Supplements; Female; Fish Proteins; Ghrelin; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Middle Aged; Protein Hydrolysates; Satiation

Metformin treatment (1000-2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR). We aimed to ascertain if long-term treatment (24 months) with lower doses of metformin (850 mg/day) normalizes the endocrine-metabolic abnormalities, improves body composition, and reduces the carotid intima-media thickness (cIMT) in pre-puberal and early pubertal children with obesity.. A pilot double-blind, placebo-controlled trial was conducted on 18 pre-puberal and early pubertal (Tanner stage I-II) children with obesity and risk markers for metabolic syndrome. Patients were randomly assigned (1:1) to receive metformin (850 mg/day) or placebo for 24 months. Clinical, biochemical (insulin, lipids, leptin, and high-sensitivity C-reactive protein [hsCRP]), and imaging (body composition [dual-energy X-ray absorptiometry and magnetic resonance imaging]) parameters as well as cIMT (ultrasonography) were assessed at baseline and at 6, 12, and 24 months.. The 12-month treatment tend to cause a reduction in weight standard deviation scores (SDS), BMI-SDS, leptin, leptin-to-high-molecular-weight (HMW) adiponectin ratio, hsCRP, cIMT, fat mass, and liver fat in metformin-treated children compared with placebo. The effect of metformin on the reduction of BMI-SDS, leptin, leptin-to-HMW adiponectin ratio, hsCRP, and liver fat seemed to be maintained after completing the 24 months of treatment. No changes in insulin sensitivity (HOMA-IR) or adverse effects were detected.. In this pilot study, metformin treatment in pre-puberal and early pubertal children with obesity seemed to improve body composition and inflammation markers. Our data encourage the development of future fully powered trials using 850 mg/day metformin in young children, highlighting its excellent tolerance and potential long-term benefits.

Topics: Adolescent; Body Mass Index; Body Weight; C-Reactive Protein; Carotid Intima-Media Thickness; Child; Double-Blind Method; Female; Humans; Hyperinsulinism; Insulin; Leptin; Male; Metabolic Syndrome; Metformin; Obesity; Pilot Projects; Spain; White People

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

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

The metabolic syndrome is highly prevalent in patients with schizophrenia. We previously found that blood C-reactive protein (CRP), interleukin-6 (IL-6), and leptin levels were predictors of current metabolic syndrome in schizophrenia. In the present study, we investigated whether baseline levels of total and differential white blood cell (WBC) counts, inflammatory markers, and adipokines predicted incident metabolic syndrome in schizophrenia.. For subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial who did not have metabolic syndrome at baseline (n = 726), WBC counts, inflammatory markers, and adipokines were investigated as predictors of incident metabolic syndrome over 12 months of antipsychotic treatment. Cox proportional hazards regression models, controlling for multiple potential confounding factors, were used to investigate these associations.. 39% of subjects (n = 280) had incident metabolic syndrome over 12 months. After controlling for potential confounders, baseline blood IL-6 (HR = 1.12, 95% CI 1.01-1.24, p = 0.031) and leptin (HR = 1.12, 95% CI 1.01-1.24, p = 0.038) were significant predictors of incident metabolic syndrome, and there was a trend-level association with CRP (HR = 1.09, 95% CI 1.00-1.19, p = 0.059).. Our findings provide additional evidence that measurement of inflammatory markers and adipokines are germane to the clinical care of patients with schizophrenia. Specifically, these markers may identify-prior to treatment-patients with schizophrenia at heightened risk for incident adverse cardiometabolic effects of antipsychotics. Given the tremendous burden of cardiovascular disease morbidity and mortality in schizophrenia, vigilant screening for and treatment of metabolic risk factors in this patient population are warranted.

Topics: Adipokines; Adult; Antipsychotic Agents; C-Reactive Protein; Female; Humans; Inflammation; Interleukin-6; Leptin; Leukocyte Count; Male; Metabolic Syndrome; Middle Aged; Schizophrenia

Metabolic syndrome (MetS) is associated with diabetes mellitus and cardiovascular diseases. Our previous study indicated that people with MetS showed a decrease in waist circumference and a decreasing trend in blood pressure after 1-year yoga. This study investigated the effect of yoga on MetS people with high-normal blood pressure by exploring modulations in proinflammatory adipokines (leptin, chemerin, visfatin, and plasminogen activator inhibitor-1 or PAI-1) and an anti-inflammatory adipokine (adiponectin). A total of 97 Hong Kong Chinese individuals aged 57.6 ± 9.1 years with MetS and high-normal blood pressure were randomly assigned to control (n = 45) and yoga groups (n = 52). Participants in the control group were not given any intervention but were contacted monthly to monitor their health status. Participants in the yoga group underwent a yoga training program with three 1-hour yoga sessions weekly for 1 year. The participants' sera were harvested and assessed for adipokines. Generalized estimating equation (GEE) was used to examine the interaction effect between 1-year time (pre vs post), and intervention (control vs yoga). GEE analyses revealed significant interaction effects between 1-year time and yoga intervention for the decreases in leptin and chemerin and the increase in adiponectin concentration in the sera examined. These results demonstrated that 1-year yoga training decreased proinflammatory adipokines and increased anti-inflammatory adipokine in adults with MetS and high-normal blood pressure. These findings support the beneficial role of yoga in managing MetS by favorably modulating adipokines.

Topics: Adipokines; Aged; Chemokines; Female; Humans; Hypertension; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Plasminogen Activator Inhibitor 1; Risk Factors; Yoga

Equine metabolic syndrome (EMS), like human metabolic syndrome, comprises a collection of clinical signs related to obesity, insulin dysregulation and susceptibility to secondary inflammatory disease. Although the secondary conditions resulting from EMS can be life-threatening, diagnosis is not straightforward and often complicated by the presence of other concurrent conditions like pituitary pars intermedia dysfunction (PPID). In order to better characterize EMS, we sought to describe the variation within, and correlations between, typical physical and endocrine parameters for EMS. Utilizing an unsupervised statistical approach, we evaluated a population of Arabian horses using a physical examination including body measurements, as well as blood plasma insulin, leptin, ACTH, glucose, and lipid values. We investigated the relationships among these variables using principle component analysis (PCA), hierarchical clustering, and linear regression. Owner-assigned assessments of body condition were one full score (on a nine-point scale) lower than scores assigned by researchers, indicating differing perception of healthy equine body weight. Rotated PCA defined two factor scores explaining a total of 46.3% of variation within the dataset. Hierarchical clustering using these two factors revealed three groups corresponding well to traditional diagnostic categories of "Healthy", "PPID-suspect", and "EMS-suspect" based on the characteristics of each group. Proxies estimating up to 93.4% of the composite "EMS-suspect" and "PPID-suspect" scores were created using a reduced set of commonly used diagnostic variables, to facilitate application of these quantitative scores to horses of the Arabian breed in the field. Use of breed-specific, comprehensive physical and endocrinological variables combined in a single quantitative score may improve detection of horses at-risk for developing EMS, particularly in those lacking severe clinical signs. Quantification of EMS without the use of predetermined reference ranges provides an advantageous approach for future studies utilizing genomic or metabolomics approaches to improve understanding of the etiology behind this troubling condition.

Topics: Animals; Blood Glucose; Body Weight; Female; Horse Diseases; Horses; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Phenotype

Chemerin has been suggested as a potential link between obesity and associated comorbidities in humans. Therefore, we studied the relationships between chemerin, parameters of fat mass, and Metabolic Syndrome (MetS) in obese children before and after weight reduction.. We determined chemerin, bioactive leptin (bioLep), BMI-SDS, waist circumference (WC), body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index HOMA, and blood pressure in 88 obese children participating in a lifestyle intervention at baseline and 1 year later. Furthermore, we determined chemerin concentrations in 23 normal-weight children.. Obese children demonstrated significantly (p < 0.001) higher chemerin concentrations compared to normal-weight children (96.2 ± 23.0 versus 63.1 ± 12.4 ng/ml). The chemerin concentrations were not related to age or gender. Prepubertal children had higher (p = 0.024) chemerin concentrations than pubertal children (71.0 ± 13.4 versus 58.0 ± 8.9 ng/ml). Weight loss was associated with a decrease of chemerin (-14.0 ± 22.0 ng/ml; p < 0.001) and an improvement of all parameters of the MetS. Chemerin was significantly related to BMI-SDS, WC, and bioLep in cross-sectional and longitudinal analyses. Chemerin and its changes were significantly related to insulin, HDL-cholesterol, triglycerides and their changes in multiple linear regression analyses adjusted to age, gender, pubertal stage, leptin and BMI.. Since chemerin was related to parameters of central fat mass and MetS both in cross-sectional and longitudinal analyses these findings suggest an impact of chemerin on factors of the MetS in obese children.

Topics: Biomarkers; Blood Glucose; Body Mass Index; Chemokines; Child; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Longitudinal Studies; Male; Metabolic Syndrome; Pediatric Obesity; Treatment Outcome; Triglycerides; Waist Circumference; Weight Loss; Weight Reduction Programs

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

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

Low-grade inflammation is associated with obesity and the metabolic syndrome (MetS). Preclinical evidence suggests that resveratrol (RSV) has beneficial metabolic and anti-inflammatory effects that could have therapeutic implications.. To investigate effects of long-term RSV treatment on inflammation and MetS.. A randomized, placebo-controlled, double-blind, parallel group clinical trial conducted at Aarhus University Hospital.. Middle-aged community-dwelling men (N = 74) with MetS, 66 of whom completed all visits (mean ± standard error of the mean): age, 49.5 ± 0.796 years; body mass index, 33.8 ± 0.44 kg/m2; waist circumference, 115 ± 1.14 cm.. Daily oral supplementation with 1000 mg RSV (RSVhigh), 150 mg RSV, or placebo for 16 weeks.. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), circulating lipids, and inflammatory markers in circulation and adipose/muscle tissue biopsy specimens; glucose metabolism; and body composition including visceral fat and ectopic fat deposition.. RSV treatment did not lower circulating levels of hs-CRP, interleukin 6, or soluble urokinase plasminogen activator receptor in plasma, and inflammatory gene expression in adipose and muscle tissues also remained unchanged. RSV treatment had no effect on blood pressure, body composition, and lipid deposition in the liver or striated muscle. RSV treatment had no beneficial effect on glucose or lipid metabolism. RSVhigh treatment significantly increased total cholesterol (P < 0.002), low-density lipoprotein (LDL) cholesterol (P < 0.006), and fructosamine (P < 0.013) levels compared with placebo.. RSV treatment did not improve inflammatory status, glucose homeostasis, blood pressure, or hepatic lipid content in middle-aged men with MetS. On the contrary, RSVhigh significantly increased total cholesterol, LDL cholesterol, and fructosamine levels compared with placebo.

Topics: Absorptiometry, Photon; Adipose Tissue; Antioxidants; Blood Glucose; Blood Pressure; Blotting, Western; Body Composition; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Fructosamine; Humans; Insulin; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Leptin; Liver; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Metabolic Syndrome; Middle Aged; Muscle, Skeletal; Quadriceps Muscle; Real-Time Polymerase Chain Reaction; Receptors, Urokinase Plasminogen Activator; Resveratrol; Stilbenes; Triglycerides

Previous experimental studies have suggested curcumin as a safe phytochemical that can improve insulin resistance through effects on adiponectin and leptin. This study aimed to investigate the effect of curcumin on circulating adiponectin and leptin concentrations in patients with metabolic syndrome.. In this pilot, randomized, double-blind, placebo-controlled trial, subjects who met the criteria of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria were randomly assigned to curcumin (n = 59; 1000 mg/d) or a placebo (n = 58) for 8 wk. Serum adiponectin and leptin concentrations were determined before and after intervention. The pooled effect size for the impact of curcumin supplementation on serum adiponectin and leptin levels was also estimated using random-effects metaanalysis.. Eight-week supplementation with curcumin was associated with a significant increase in serum adiponectin levels (P < 0.001) and a reduction in serum leptin concentrations (P < 0.001). Serum leptin:adiponectin ratio was also improved by curcumin (P < 0.001). These beneficial effects of curcumin remained significant after adjustment for changes in serum lipids and glucose concentrations and baseline differences in body mass index and serum levels of glucose and glycated hemoglobin as potential confounders of treatment response. Metaanalysis suggested that curcumin supplementation can increase adiponectin levels by 76.78% (95% CI: 6.14-147.42; P = 0.0330), and reduce leptin by 26.49% (95% CI: -70.44 to 17.46), however this latter effect size did not reach statistical significance (P = 0.238).. Curcumin can improve serum levels of adiponectin and leptin in patients with metabolic syndrome. This trial was registered at the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/) under Trial No. UMIN000018339.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Pilot Projects

To explore the effect and mechanism of electroacupuncture (EA) for Z syndrome without organic lesion (metabolic syndrome combined with obstructive sleep apnea hypopnea syndrome).. Fifty-eight patients with Z syndrome were divided into three groups according to mild,moderate and severe degree. Acupuncture and EA were used at Daimai (GB 26), Zhongwan (CV 12), Xiawan (CV 10), Zusanli ST 36), Qihai (CV 6) and Huaroumen (ST 24), etc., once a day and five times a week. The treatment of ten times was a course, and two courses were acquired continuously. Sleep respiration monitoring (PSG) was done before EA and in one week after treatment respectively. Triacylglycerol (TG) fasting blood glucose (FBG) fasting insulin (INS) and serum leptin (Lep) were tested before and after treatment in the three groups.. After treatment apnea hypopnea index (AHI) and the percentage of the time of arterial oxygen saturation (SaO₂) less than 90% taken in the total sleep time (SLT 90%) were improved apparently than those before treatment in the three groups (all P < 0.05). The levels of TG, FPG, INS and Lep were decreased after treatment in all groups (all P < 0.05).. EA can improve AHI and nocturnal hypoxia of Z syndrome, and the mechanism may be related to decreasing the indices of metabolism syndrome and leptin.

Topics: Acupuncture Therapy; Adult; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Sleep; Sleep Apnea, Obstructive; Treatment Outcome; Triglycerides; Young Adult

The evidence for a link between sleep duration and cardiovascular risk is accumulating in youths, but no study has yet investigated the relationship between sleep duration and change of cardiac structure. In this study, we recruited 559 youths aged 14-28 years from the cohort of Beijing Child and Adolescent Metabolic Syndrome Study. Questionnaire, color Doppler echocardiography, oral glucose tolerance test and blood biomarkers analyses were performed. We found that sleep duration was negatively correlated with body mass index, waist circumstance, and HbA1c (all P < 0.05), but not with adiponectin and leptin. Meanwhile, participants with shorter sleep duration (≤7 h) had larger interventricular septal diastolic thickness, left ventricular (LV) end-diastolic diameter, LV posterior wall thickness, LV mass (LVM), and LV mass index (LVMI), compared to participants in 7-9 h/night or >9 h/night group. Findings remained significant after adjustment for the major confounding factors (P < 0.05). Multivariate regression modeling revealed that each additional hour of sleep was associated with smaller LVM (β: -3.483, P < 0.0001) and LVMI (β: -0.815, P < 0.0001). Our findings suggest that short sleep has a possible direct effect on cardiac remodeling, occurring already at young ages.

Topics: Adiponectin; Adolescent; Adult; Body Mass Index; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Leptin; Male; Metabolic Syndrome; Risk Factors; Sleep; Waist Circumference

Hypoxic and hypobaric conditions may augment the beneficial influence of training on cardiovascular risk factors. This pilot study aimed to explore for effects of a two-week hiking vacation at moderate versus low altitude on adipokines and parameters of carbohydrate and lipid metabolism in patients with metabolic syndrome.. Fourteen subjects (mean age: 55.8 years, range: 39 - 69) with metabolic syndrome participated in a 2-week structured training program (3 hours of guided daily hiking 4 times a week, training intensity at 55-65% of individual maximal heart rate; total training time, 24 hours). Participants were divided for residence and training into two groups, one at moderate altitude (1,900 m; n = 8), and the other at low altitude (300 m; n = 6). Anthropometric, cardiovascular and metabolic parameters were measured before and after the training period.. In study participants, training overall reduced circulating levels of total cholesterol (p = 0.024), low-density lipoprotein cholesterol (p = 0.025) and adiponectin (p < 0.001). In the group training at moderate altitude (n = 8), lowering effects on circulating levels were significant not only for total cholesterol, low-density-lipoprotein cholesterol and adiponectin (all, p < 0.05) but also for triglycerides (p = 0.025) and leptin (p = 0.015), whereas in the low altitude group (n = 6), none of the lipid parameters was significantly changed (each p > 0.05). Hiking-induced relative changes of triglyceride levels were positively associated with reductions in leptin levels (p = 0.006). As compared to 300 m altitude, training at 1,900 m showed borderline significant differences in the pre-post mean reduction rates of triglyceride (p = 0.050) and leptin levels (p = 0.093).. Preliminary data on patients with metabolic syndrome suggest that a 2-week hiking vacation at moderate altitude may be more beneficial for adipokines and parameters of lipid metabolism than training at low altitude. In order to draw firm conclusions regarding better corrections of dyslipidemia and metabolic syndrome by physical exercise under mild hypobaric and hypoxic conditions, a sufficiently powered randomized clinical trial appears warranted.. ClinicalTrials.gov ID NCT02013947 (first received November 6, 2013).

Topics: Adiponectin; Adult; Aged; Altitude; Blood Pressure; Cholesterol; Exercise Therapy; Female; Heart Rate; Humans; Hypoxia; Insulin; Leptin; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Pilot Projects; Triglycerides; Walking

This study aimed to analyze the influence of H. pylori infection on insulin resistance and metabolic syndrome (MS) by multivariate analysis of a community-based cohort study. From January 2013 to February 2014,811 subjects were enrolled in a community-based cohort study from the northeastern region of Taiwan. All subjects received a demographic survey and blood tests, including an H. pylori antibody test, liver biochemistry tests, lipid profiles, sugar/insulin levels for Homeostatic model assessment (HOMA-IR index), and measurements of adipokines and inflammatory cytokines. A total of 264 men and 547 women were included in this study. The mean age was 59.2 ± 12.7 years. Subjects seropositive for H. pylori antibodies exhibited higher rates of hypertension, an increased incidence of a HOMA-IR index > 2.5 and a higher level of tumor necrosis factor-α than those without H. pylori antibodies. We found a significant difference in the presence of H. pylori antibodies between subjects with MS and those without MS (76.7% vs. 53.7%, p = 0.007) among subjects < 50 y/o. A HOMA-IR index >2.5, H. pylori antibody presence and leptin were predictors for MS in subjects < 50 y/o. The estimated odds ratio of MS for a subject with H. pylori antibodies was 3.717 (95% CI = 1.086-12.719) times that of a subject without H. pylori antibodies. In addition, no difference in H. pylori antibody status was detected for MS prediction in subjects that were ≧ 50 y/o (p = 0.861). In conclusion, subjects with H. pylori antibodies had a higher incidence of a HOMA-IR >2.5 than those without H pylori antibodies. For subjects aged < 50 y/o, the H. pylori antibody was a predictor for MS.

Topics: Age Factors; Aged; Antibodies, Bacterial; Case-Control Studies; Female; Helicobacter Infections; Helicobacter pylori; Humans; Hypertension; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Taiwan

Limited studies have shown that Coleus forskohlii extract may aid in weight management. This randomized, double blind placebo-controlled clinical study assessed the effects of supplementation with C. forskohlii extract on key markers of obesity and metabolic parameters in overweight and obese individuals. Thirty participants completed the trial and they were randomly assigned to receive either 250 mg of C. forskohlii extract (n = 15) or a placebo twice daily for 12 weeks. All participants were advised to follow a hypocaloric diet throughout the study. Body weight, body mass index (BMI), waist and hip circumference, and waist to hip ratio, were monitored fortnightly. Dietary intake was assessed at the baseline and weeks 4, 8 and 12. Appetite was assessed using visual analogue scales and blood samples were analyzed for plasma lipids, ghrelin, leptin, glucose and insulin at the baseline and end of the intervention. Significant reductions to waist and hip circumference (p = 0.02; p = 0.01, respectively) were recorded in both experimental and placebo groups after the 12 week intervention. Furthermore, high density lipoprotein-cholesterol (HDL-C) was significantly increased (p = 0.01) in both groups. The experimental group showed a favorable improvement in insulin concentration and insulin resistance (p = 0.001; 0.01 respectively) compared to the placebo group. These findings suggest that C. forskohlii extract in conjunction with a hypocaloric diet may be useful in the management of metabolic risk factors.

Topics: Adult; Aged; Appetite; Blood Glucose; Body Mass Index; Body Weight; Cholesterol, HDL; Diet, Reducing; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Energy Intake; Female; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Plant Extracts; Plectranthus; Risk Factors; Waist Circumference; Waist-Hip Ratio; Young Adult

The aim of this study was to evaluate the effects of pistachio nuts as an adjunct to diet and exercise on body composition, metabolic, inflammatory, and oxidative stress parameters in Asian Indians with metabolic syndrome.. In this 24-wk randomized control trial, 60 individuals with the metabolic syndrome were randomized to either pistachio (intervention group) or control group (diet as per weight and physical activity profile, modulated according to dietary guidelines for Asian Indians) after 3 wk of a diet and exercise run in. In the first group, unsalted pistachios (20% energy) were given daily. A standard diet and exercise protocol was followed for both groups. Body weight, waist circumference (WC), magnetic resonance imaging estimation of intraabdominal adipose tissue and subcutaneous abdominal adipose tissue, fasting blood glucose (FBG), fasting serum insulin, glycosylated hemoglobin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), adiponectin, free fatty acids (FFAs), tumor necrosis factor (TNF)-α, leptin, and thiobarbituric acid reactive substances (TBARS) were assessed before and after the intervention.. Statistically significant improvement in mean values for various parameters in the intervention group compared with control group were as follows: WC (P < 0.02), FBG (P < 0.04), total cholesterol (P < 0.02), low-density lipoprotein cholesterol (P < 0.006), hs-CRP (P < 0.05), TNF-α (P < 0.03), FFAs (P < 0.001), TBARS (P < 0.01), and adiponectin levels (P < 0.001).. A single food intervention with pistachios leads to beneficial effects on the cardiometabolic profile of Asian Indians with metabolic syndrome.

Topics: Adiponectin; Adiposity; Adult; Asian People; Blood Glucose; Body Composition; Body Weight; C-Reactive Protein; Cholesterol, LDL; Diet; Exercise; Fasting; Fatty Acids; Female; Hemoglobins; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Nuts; Oxidative Stress; Patient Compliance; Pistacia; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha

There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%).. Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome.. This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy.. Metreleptin (0.06-0.24 mg/kg/d) was administered for 24 months in lipodystrophy.. Serum triglycerides and HDL-C were measured.. At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = -0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C.. The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition.

Topics: Adolescent; Adult; Child; Cholesterol, HDL; Female; Humans; Insulin Resistance; Leptin; Lipid Metabolism; Lipodystrophy; Male; Metabolic Syndrome; Middle Aged; Obesity; Treatment Outcome; Triglycerides; Young Adult

Progressive midlife weight gain is associated with multiple adverse health outcomes and may represent an early manifestation of insulin resistance in a distinct subset of women. Emerging data implicate hyperinsulinema as a proximate cause of weight gain and support strategies that attenuate insulin secretion.. To assess a previously reported novel hypocaloric carbohydrate modified diet alone (D), and in combination with metformin (M) and metformin plus low-dose rosiglitazone (MR), in diverse women with midlife weight gain (defined as >20lbs since the twenties), normal glucose tolerance, and hyperinsulinemia.. 46 women, mean age 46.6±1.0, BMI 30.5±0.04 kg/m2, 54.5% white, 22.7% black, 15.9% Hispanic, at 2 university medical centers.. A dietary intervention designed to reduce insulin excursions was implemented in 4 weekly nutritional group workshops prior to randomization.. Change in 6-month fasting insulin. Pre-specified secondary outcomes were changes in body weight, HOMA-IR, metabolic syndrome (MS) measures, leptin, and adiponectin.. Six-month fasting insulin declined significantly in the M group: 12.5 to 8.0 µU/ml, p = .026. Mean 6-month weight decreased significantly and comparably in D, M, and MR groups: 4.7, 5.4, and 5.5% (p's.049, .002, and.032). HOMA-IR decreased in M and MR groups (2.5 to 1.6 and 1.9 to 1.3, p's = .054, .013). Additional improvement in MS measures included reduced waist circumference in D and MR groups and increased HDL in the D and M groups. Notably, mean fasting leptin did not decline in a subset of subjects with weight loss (26.15±2.01 ng/ml to 25.99±2.61 ng/ml, p = .907. Adiponectin increased significantly in the MR group (11.1±1.0 to 18.5±7.4, p<.001) Study medications were well tolerated.. These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies.. ClinicalTrials.gov NCT00618072.

Topics: Blood Glucose; Body Mass Index; Body Weight; Diet, Carbohydrate-Restricted; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Patient Compliance; Risk Factors; Treatment Outcome

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

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

Weight loss helps reduce the symptoms of the metabolic syndrome (MetS) in the obese, but weight regain after active weight loss is common. The changes and predictive role of circulating adipokines and sex hormones for weight regain in men during dietary intervention, and also the effect of basal MetS status on weight regain, were investigated.. Twenty-four men who continued to lose weight (WL) and 24 men who regained weight (WR) during the 6-month follow-up period after weight loss were selected from the Diogenes Study. Their circulating concentrations of leptin, adiponectin, retinol-binding protein 4 (RBP4), luteinizing hormone, prolactin, progesterone, total and free testosterone, and sex hormone-binding globulin (SHBG) were measured at baseline, after 8-week low-calorie diet-induced active weight loss, and after a subsequent 26-week ad libitum weight maintenance diet, and analyzed together with anthropometrical and physiological parameters.. Overweight and obese men with MetS at baseline had higher risk to regain weight (odds ratio = 2.8, P = 0.015). High baseline RBP4, low total testosterone, and low SHBG are predictors of weight loss regain (different between WR and WL with P = 0.001, 0.038, and 0.044, respectively).. These variables may play roles in the link between MetS and weight loss regain.

Topics: Adiponectin; Adult; Caloric Restriction; Follow-Up Studies; Humans; Leptin; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Retinol-Binding Proteins, Plasma; Sex Hormone-Binding Globulin; Testosterone; Weight Gain; Weight Loss

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

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

Recent data suggest excess circulating aldosterone promotes cardiometabolic decline. Weight loss may lower aldosterone levels, but little longitudinal data is available in normotensive adults. We aimed to determine whether, independent of changes in sodium excretion, reductions in serum aldosterone are associated with favorable changes in obesity-related factors in normotensive overweight/obese young adults. We studied 285 overweight/obese young adult participants (body mass index ≥ 25 and<40 kg m⁻², age 20-45 years) in a clinical trial examining the effects of a 1-year diet and physical activity intervention with or without sodium restriction on vascular health. Body weight, serum aldosterone, 24-h sodium and potassium excretion and obesity-related factors were measured at baseline, 6, 12 and 24 months. Weight loss was significant at 6 (7%), 12 (6%) and 24 months (4%; all P<0.0001). Decreases in aldosterone were associated with decreases in C-reactive protein, leptin, insulin, homeostasis assessment of insulin resistance, heart rate, tonic cardiac sympathovagal balance and increases in adiponectin (all P<0.05) in models adjusting for baseline age, sex, race, intervention arm, time since baseline, and sodium and potassium excretion. Weight loss and reductions in thigh intermuscular fat (intermuscular adipose tissue area; IMAT) were associated with decreases in aldosterone in the subgroup (n=98) with metabolic syndrome (MetS) at baseline (MetS × weight loss, P=0.04; MetS × change in IMAT, P=0.04). Favorable changes in obesity-related factors are associated with reductions in aldosterone in young adults with no risk factors besides excess weight, an important finding, given aldosterone's emergence as an important cardiometabolic risk factor.

Topics: Adiponectin; Adiposity; Adult; Aldosterone; Blood Pressure; C-Reactive Protein; Diet, Sodium-Restricted; Female; Follow-Up Studies; Ghrelin; Humans; Insulin Resistance; Leptin; Life Style; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Motor Activity; Obesity; Overweight; Potassium; Sodium

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

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

CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor involved in adipogenesis and energy homeostasis. Caloric restriction reduces CEBPA protein expression in patients with metabolic syndrome (MetS). A previous report linked rs12691 SNP in CEBPA to altered concentration of fasting triglycerides. Our objective was to assess the effects of rs12691 in glucose metabolism in Metabolic Syndrome (MetS) patients.. Glucose metabolism was assessed by static (glucose, insulin, adiponectin, leptin and resistin plasma concentrations) and dynamic (disposition index, insulin sensitivity index, HOMA-IR and acute insulin response to glucose) indices, performed at baseline and after 12 weeks of 4 dietary interventions (high saturated fatty acid (SFA), high monounsaturated fatty acid (MUFA), low-fat and low-fat-high-n3 polyunsaturated fatty acid (PUFA)) in 486 subjects with MetS. Carriers of the minor A allele of rs12691 had altered disposition index (p = 0.0003), lower acute insulin response (p = 0.005) and a lower insulin sensitivity index (p = 0.025) indicating a lower insulin sensitivity and a lower insulin secretion, at baseline and at the end of the diets. Furthermore, A allele carriers displayed lower HDL concentration.. The presence of the A allele of rs12691 influences glucose metabolism of MetS patients.

Topics: Adiponectin; Adult; Aged; Alleles; Blood Glucose; Body Mass Index; Body Weight; CCAAT-Enhancer-Binding Proteins; Dietary Fats; Dietary Supplements; DNA; Fasting; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Female; Genotype; Humans; Insulin; Insulin Resistance; Insulin Secretion; Leptin; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Polymorphism, Single Nucleotide; Resistin; Triglycerides

Complement C1q tumor necrosis factor-related protein 1 (CTRP1), a recently identified adipokine, was found to stimulate aldosterone production. Obesity and metabolic syndrome are frequently associated with elevated levels of aldosterone. Therefore, it would be interesting to investigate whether the secretion of CTRP1 in human serum is associated with obesity as well as with hypertension.. This study evaluated serum CTRP1 concentrations in healthy individuals and patients with metabolic syndrome.. Serum samples from 61 healthy individuals and 46 patients with metabolic syndrome were measured for CTRP1 by enzyme-linked immunosorbent assay (ELISA).. Correlation analyses showed that serum CTRP1 in healthy individuals did not correlate with BMI, leptin, TG, HDL-CH, and LDL-CH; however, in patients with metabolic syndrome, CTRP1 correlated with glucose, HbA1c and BMI. CTRP1 level was significantly higher in subjects with metabolic syndrome compared to healthy subjects.. Our results support the hypothesis that adipokine CTRP1 is associated with metabolic syndrome and obesity compared to healthy individuals.

Topics: Adult; Aged; Animals; Biomarkers; Blood Glucose; Body Mass Index; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Female; Glycated Hemoglobin; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Pilot Projects; Proteins; Reference Values; Triglycerides

Dysfunction of adipose tissue is one of the major factors leading to insulin resistance. Altered adipokine concentration is an early sign of adipose tissue dysfunction. The aim of this study was to assess the impact of exercise intervention on adipokine profile, glycemic control, and risk factors of the metabolic syndrome (MeS) in men with impaired glucose regulation (IGR).. Overweight and obese men with IGR (n =144) aged 40-65 years were studied at baseline and at 12 weeks in a randomized controlled multicenter intervention study. BMI varied from 25.1 to 34.9. The subjects were randomized into one of three groups: 1) a control group (C; n =47), 2) a Nordic walking group (NW; n =48), or 3) a resistance training group (RT; n =49).. Leptin concentrations decreased in the NW group compared to both other groups. Both types of exercise intervention significantly decreased serum chemerin concentrations compared to the C group. In the NW group also body fat percentage, fatty liver index (FLI), and total and LDL cholesterol concentrations decreased compared to the RT group.. Nordic walking intervention seems to decrease chemerin and leptin levels, and subjects in this intervention group achieved the most beneficial effects on components of MeS.

Topics: Adult; Aged; Blood Glucose; Chemokines; Exercise; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Risk Factors; Walking

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

Resistant maltodextrin (RMD) is a soluble dietary fiber ingredient whose physiological functions are well recognized in Foods for Specified Health Use (FOSHU) for maintaining healthy intestinal regularity, blood glucose levels, and serum lipids. However, its efficacy on combined health risks--metabolic syndrome--was not studied yet. In this study the efficacy of RMD on humans with metabolic syndrome was investigated. A randomized double-blind placebo-controlled parallel-group trial was conducted. Thirty subjects with metabolic syndrome were randomly allocated into 2 groups and took either tea containing 9 g of RMD (treatment group) or placebo tea at three mealtimes daily for 12 wk. Blood was collected and body fat was scanned periodically. In the RMD treatment group, waist circumference, visceral fat area, fasting blood glucose, HOMA-R and serum triacylglycerol (TG) were significantly decreased compared to baseline, and significant time-by-treatment interaction was observed for waist circumference, visceral fat area, HOMA-R and serum TG (p=0.044, p=0.012, p=0.032, and p=0.049, respectively). The change ratio of visceral fat area showed negative statistical correlation with the baseline value (p=0.033), suggesting that efficacy of RMD was emphasized in the subjects having a larger visceral fat area. After the 12-wk RMD treatment, the total number of metabolic syndrome risk factors decreased to 20 from 32 with 2 subjects having no risks, while that of the placebo group decreased to 25 from 32. These findings suggest that continuous ingestion of RMD may improve the risk factors of metabolic syndrome by reducing visceral fat and improving glucose and lipid metabolism.

Topics: Aged; Asian People; Blood Glucose; Body Composition; Cholesterol; Double-Blind Method; Female; Humans; Image Processing, Computer-Assisted; Insulin; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Polysaccharides; Risk Factors; Triglycerides

Leptin is a key hormone of weight regulation that modulates food intake. Since the elaboration of the leptin action mechanism, several studies tried to establish the relationship between obesity and the common polymorphisms of leptin (LEP) and leptin receptor (LEPR) genes, but results were controversial. We studied the association of G2548A of the LEP gene and Q223R of LEPR gene polymorphisms with obesity and metabolic syndrome (MetS). We recruited 169 nonobese volunteers (body mass index [BMI] < 30 kg/m(2)) and 160 obese ones (BMI ≥ 30 kg/m(2)). Glucose, insulin, and lipids were measured. BMI, homeostasis model assessment-insulin resistance (HOMA-IR), and daily energy intake were calculated. After adjustment to confounders parameters, 2548AA was found to increase the MetS (p=0.043) and obesity risk (p=0.019) in the studied population. After stratification according to the degree of obesity, the odds ratio [OR] of 2548AA was associated with moderate obesity (p=0.048) and morbid obesity (p=0.048). The LEPR 223RR genotype was associated with obesity in the studied population (OR=1.74, p=0.037) and only in the overweight (OR=1.8, p=0.049). Subjects with 2548AA had significantly higher BMI, daily energy intake, total cholesterol (TC), waist circumference (WC), insulinemia, and low high-density lipoprotein-cholesterol (HDL-C) levels. With regard to 223RR, we noted a significantly higher daily energy intake, BMI, TC, glycemia, insulinemia, HOMA-IR index, and low HDL-C levels. Haplotype model AR (2548A+223R) and AQ (2548A+223Q) increased the risk of obesity (OR=3.36, p<0.001; OR=2.56, p=0.010, respectively). When we added daily energy intake in adjustment, these significant associations disappeared. In addition, the AR and AQ increased the MetS risk. This significant association persisted after we had added daily energy intake in adjustment. This study showed that LEP G2548A and LEPR Q223R polymorphisms and haplotype combination were associated with MetS and obesity risk in Tunisian volunteers.

Topics: Adult; Amino Acid Substitution; Blood Glucose; Body Mass Index; Cholesterol; Energy Intake; Female; Haplotypes; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Polymorphism, Genetic; Receptors, Leptin; Risk Factors; Tunisia

Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied.. To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss.. A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings.. After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks.. Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components.. Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged.. Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet.. clinicaltrials.gov Identifier: NCT00315354.

Topics: Adult; Cholesterol, HDL; Cross-Over Studies; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Energy Metabolism; Female; Glycemic Index; Humans; Hydrocortisone; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Nutritive Value; Obesity; Overweight; Plasminogen Activator Inhibitor 1; Triglycerides; Weight Loss; Young Adult

The aim of the study was to compare the baseline and the 18-month follow-up for weight and metabolic characteristics of superobese (SO) (body mass index [BMI] ≥50 kg/m(2)) and morbidly obese (MO) (BMI <50 kg/m(2)) adolescents who participated in a prospective longitudinal study of gastric banding delivered in an adolescent multidisciplinary treatment program.. Clinical information was extracted from an institutional review board-approved database of bariatric adolescents. Fasting cytokine and acute phase protein serum levels were analyzed by enzyme-linked immunosorbent assay. Liver histopathologies were assessed using the Kleiner's classification score.. Other than BMI, MO (n = 11) and SO (n = 7) patients have similar degree of insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease. Serum C-reactive protein (10.2 ± 5.6 SO vs 4 ± 3.9 μg/mL MO [P < .02]) and leptin (71 ± 31 SO vs 45 ± 28 MO ng/mL [P = .04]) were more elevated in SO patients. Although weight loss is similar (30 ± 19 kg MO vs 28 ± 12 kg SO, P = .8 at 18 months; mean percent change in BMI, 22.8% ± 11.6% vs 20.5% ± 10.3% SO, P = .2), SO patients has less resolution of insulin resistance and dyslipidemia but experienced significantly improved health-related quality of life.. The SO adolescents demonstrate equivalent short-term weight loss and improved quality of life but delayed metabolic response to a gastric banding-based weight loss treatment program compared with MO patients, illustrating the importance of early referral for timely intervention of MO patients.

Topics: Acute-Phase Proteins; Adolescent; Biomarkers; Body Mass Index; Cross-Sectional Studies; Cytokines; Dyslipidemias; Enzyme-Linked Immunosorbent Assay; Fatty Liver; Follow-Up Studies; Gastroplasty; Humans; Insulin Resistance; Laparoscopy; Leptin; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity, Morbid; Prospective Studies; Treatment Outcome; Weight Loss; Weight Reduction Programs

The objective of this study was to test whether "Dietary Guidelines for Chinese Residents" have beneficial effects on anthropometric and metabolic variables, adipokines and inflammatory markers in metabolic syndrome patients.. A multi-stage sampling method was applied to select metabolic syndrome patients in two districts of Shanghai. Two hundred and seventy-two metabolic syndrome patients were divided into control and intervention groups according to their district. Nutrition education guided by "Dietary Guidelines for Chinese Residents" was performed in the intervention group for one year.. Nutrition-related knowledge, attitudes and behavior were improved in the intervention group. Potassium intake and food to total energy ratio for grain, vegetable and fruit increased while sodium intake as well as fat to total energy ratio decreased in the intervention group compared to the control group (p<0.05). Correspondently, the intervention group significantly improved its waist circumference, waist to hip ratio, high-density lipoprotein cholesterol, adiponectin, leptin and tumor necrosis factor-α compared to the control group (p<0.05). Waist circumference changes from baseline to end of the study in the intervention and the control groups were -3.9±0.3 and -2.3±0.4 cm respectively. There was a significant difference between the two groups (p=0.004). Means of waist circumference, waist to hip ratio, leptin and tumor necrosis factor-α were lower, and high density lipoprotein-cholesterol was higher in the intervention group than the control group (p<0.05).. This study confirmed "Dietary Guidelines for Chinese Residents" had beneficial effects on anthropometric, lipids, adipokines and inflammatory markers in metabolic syndrome patients.

Topics: Adipokines; Adiponectin; Adult; Aged; Anthropometry; Biomarkers; Blood Pressure; China; Diet; Exercise; Female; Health Knowledge, Attitudes, Practice; Humans; Inflammation; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Nutrition Policy; Nutritional Physiological Phenomena; Patient Education as Topic; Tumor Necrosis Factor-alpha

Estrogen sulfotransferase (EST) catalyzes the inactivation of estrone and estradiol in numerous tissues. Animal studies suggest that EST modulates glucose and lipid metabolism in adipose tissue, but it is unknown whether EST is expressed in human adipose tissue and, if so, how its expression relates to features of the metabolic syndrome.. Cross-sectional data from 16 obese men and women with metabolic dysregulation were collected as part of a larger randomized trial at an academic medical center.. Participants underwent assessment of body composition, oral glucose tolerance testing, measurement of serum hormones and inflammatory markers, and sc fat biopsy to assess adipose expression of TNF-α, suppressor of cytokine signaling 3 (SOCS3), leptin, adiponectin, and EST.. EST expression was detectable in sc adipose tissue from both men and women. Log(10) EST mRNA was not significantly associated with age, race, sex or menopausal status, or circulating levels of estrogen or testosterone. In univariate analysis, log(10) EST mRNA was significantly associated with visceral adipose tissue area (r = 0.57, P = 0.02) as well as adipose tissue expression of TNF-α (r = 0.94, P < 0.0001) and SOCS3 mRNA (r = 0.93, P < 0.0001). The associations between EST expression and TNF-α and SOCS3 held in multivariate modeling controlling for age, race, sex and menopausal status, and visceral adiposity. EST expression was not significantly associated with the adipose tissue levels of leptin or adiponectin expression.. EST is expressed in abdominal sc adipose tissue of both obese males and females in association with expression of TNF-α and SOCS3, suggesting potential roles in inflammation. Further studies are needed to determine the specific metabolic roles of EST expression in human adipose tissue.

Topics: Adiponectin; Adult; Body Composition; Cross-Sectional Studies; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Subcutaneous Fat; Sulfotransferases; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Tumor Necrosis Factor-alpha

The reason for weight loss at high altitudes is largely unknown. To date, studies have been unable to differentiate between weight loss due to hypobaric hypoxia and that related to increased physical exercise. The aim of our study was to examine the effect of hypobaric hypoxia on body weight at high altitude in obese subjects. We investigated 20 male obese subjects (age 55.7 +/- 4.1 years, BMI 33.7 +/- 1.0 kg/m(2)). Body weight, waist circumference, basal metabolic rate (BMR), nutrition protocols, and objective activity parameters as well as metabolic and cardiovascular parameters, blood gas analysis, leptin, and ghrelin were determined at low altitude (LA) (Munich 530 m, D1), at the beginning and at the end of a 1-week stay at high altitude (2,650 m, D7 and D14) and 4 weeks after returning to LA (D42). Although daily pace counting remained stable at high altitude, at D14 and D42, participants weighed significantly less and had higher BMRs than at D1. Food intake was decreased at D7. Basal leptin levels increased significantly at high altitude despite the reduction in body weight. Diastolic blood pressure was significantly lower at D7, D14, and D42 compared to D1. This study shows that obese subjects lose weight at high altitudes. This may be due to a higher metabolic rate and reduced food intake. Interestingly, leptin levels rise in high altitude despite reduced body weight. Hypobaric hypoxia seems to play a major role, although the physiological mechanisms remain unclear. Weight loss at high altitudes was associated with clinically relevant improvements in diastolic blood pressure.

Topics: Altitude; Atmospheric Pressure; Basal Metabolism; Blood Pressure; Body Mass Index; Body Weight; Energy Intake; Exercise; Humans; Hypoxia; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Weight Loss

LeptiCore is a proprietary combination of various ingredients which have been shown to have properties which could be beneficial to weight loss in obese and overweight human subjects. This study evaluates the effect of Lepticore on bodyweight as well as parameters associated with obesity and metabolic syndrome.. The study was an 8 week randomized, double-blind, placebo-controlled design involving 92 obese (mean BMI > 30 kg/m2) participants (37 males; 55 females; ages 19-52; mean age = 30.7). The participants were randomly divided into three groups: placebo (n = 30), LeptiCore formula A (low dose) (n = 31) and LeptiCore formula B (high dose) (n = 31). Capsules containing the placebo or active formulations were administered twice daily before meals with 300 ml of water. None of the participants followed any specific diet nor took any weight-reducing medications for the duration of the study. A total of 12 anthropomorphic and serological measurements were taken at the beginning of the study and after 2, 4, 6, and 8 weeks of treatment.. Compared to the placebo group, the two active groups showed statistically significant differences on all 12 variables by week 8. These included four anthropomorphic variables (body weight, body fat, waist and hip size) and eight measures of serological levels (plasma total cholesterol, LDL, HDL, triglycerides, blood glucose, serotonin, leptin, C-reactive protein). The two active groups also showed significant intra-group differences on all 12 variables between study onset and week 8.. The LeptiCore formulation at both the low and high dosages appears to be helpful in the management of fat gain and its related complications. The higher dosage resulted in significantly greater reductions in body weight and triglyceride, blood glucose, and C-reactive protein levels, as well as increased serotonin levels.

Topics: Adult; Anthropometry; Antioxidants; Body Weight; C-Reactive Protein; Double-Blind Method; Fatty Acids; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Placebos; Polysaccharides

Metabolic syndrome, a constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease, is one of the fastest growing disease entities in the world. Weight loss is thought to be a key to improving all aspects of metabolic syndrome. Research studies have suggested benefits from diets rich in vegetables and fruits in helping individuals reach and achieve healthy weights.. To evaluate the effects of a ready to serve vegetable juice as part of a calorie-appropriate Dietary Approaches to Stop Hypertension (DASH) diet in an ethnically diverse population of people with Metabolic Syndrome on weight loss and their ability to meet vegetable intake recommendations, and on their clinical characteristics of metabolic syndrome (waist circumference, triglycerides, HDL, fasting blood glucose and blood pressure).A secondary goal was to examine the impact of the vegetable juice on associated parameters, including leptin, vascular adhesion markers, and markers of the oxidative defense system and of oxidative stress.. A prospective 12 week, 3 group (0, 8, or 16 fluid ounces of low sodium vegetable juice) parallel arm randomized controlled trial. Participants were requested to limit their calorie intake to 1600 kcals for women and 1800 kcals for men and were educated on the DASH diet. A total of 81 (22 men & 59 women) participants with Metabolic Syndrome were enrolled into the study. Dietary nutrient and vegetable intake, weight, height, leptin, metabolic syndrome clinical characteristics and related markers of endothelial and cardiovascular health were measured at baseline, 6-, and 12-weeks.. There were significant group by time interactions when aggregating both groups consuming vegetable juice (8 or 16 fluid ounces daily). Those consuming juice lost more weight, consumed more Vitamin C, potassium, and dietary vegetables than individuals who were in the group that only received diet counseling (p < 0.05).. The incorporation of vegetable juice into the daily diet can be a simple and effective way to increase the number of daily vegetable servings. Data from this study also suggest the potential of using a low sodium vegetable juice in conjunction with a calorie restricted diet to aid in weight loss in overweight individuals with metabolic syndrome.

Topics: Adult; Aged; Beverages; Biomarkers; Blood Pressure; Counseling; Diet Records; Diet, Sodium-Restricted; Female; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Sodium, Dietary; Texas; Vegetables; Weight Loss

We investigated the effects of daily palatinose intake on the risk factors of metabolic syndrome in sedentary non-obese Japanese adults.. Japanese adults (40 females and 10 males, age: 53 +/- 9 years, range: 31-72 years old) were randomized into two groups for a double-blind, placebo-controlled intervention study and given either 40 g/day palatinose-blended sugar (PS group) or 40 g/day sucrose (S group) in their diet for 12 weeks.. After the intervention, the insulin resistance index (HOMA-IR) had significantly decreased only in the PS group; the inter-group difference was significant at P = 0.006. Although the S group showed a significant increase in the leptin concentration and the systolic blood pressure, the PS group showed no significant changes; the inter-group differences were significant at P = 0.018 and P = 0.037, respectively.. Palatinose intake possibly improves insulin sensitivity when compared with sucrose intake.

Topics: Adult; Aged; Blood Pressure; Dietary Sucrose; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Isomaltose; Leptin; Male; Metabolic Syndrome; Middle Aged; Risk Factors; Sedentary Behavior; Sucrose

Insulin resistance ameliorates after bariatric surgery, yet there is still a need for data on the acute effect of Roux-en-Y gastric bypass (RYGBP) on insulin sensitivity.. The objective of the study was to describe the acute effect of RYGBP on insulin sensitivity, measured by both the euglycemic-hyperinsulinemic clamp and homeostasis model assessment insulin resistance index (HOMA-IR).. Evaluations were conducted before and 1 month after RYGBP at State University of Campinas (São Paulo, Brazil).. Patients included 19 premenopausal women with metabolic syndrome aged 35.3 (6.7) yr, body mass index 45.50 (3.74) kg/m2 [mean (sd)]. Six had mild type 2 diabetes, seven impaired glucose tolerance, and six normal glucose tolerance.. The volunteers underwent RYGBP either alone or combined with omentectomy. Euglycemic-hyperinsulinemic clamp, HOMA-IR, nonesterified fatty acids, leptin, ultrasensitive C-reactive protein, adiponectin, and IL-6 were assessed at baseline and 4.5 (0.9) wk postoperatively.. Fasting glucose decreased [99.2 (13.1) to 83.6 (8.1) mg/dl, P<0.01] along with a reduction in fasting insulin [30.4 (17.0) to 11.4 (6.3) mU/liter, P<0.01]. M value did not improve postoperatively [25.82 (6.30) to 22.02 (6.05) micromol/kgFFM.min] despite of a decrease in body weight [114.8 (14.5) to 102.3 (14.5) kg, P<0.001]. This finding was discordant to the observation of an improvement in HOMA-IR [3.85 (2.10) to 1.42 (0.76), P<0.01]. Nonesterified fatty acids increased. Leptin and C-reactive protein decreased. IL-6 and adiponectin remained unchanged.. A month after RYGBP, fasting glucose metabolism improves independent of a change in peripheral insulin sensitivity.

Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Nonesterified; Female; Gastric Bypass; Glucose Clamp Technique; Humans; Insulin Resistance; Interleukin-6; Leptin; Metabolic Syndrome; Obesity, Morbid; Statistics, Nonparametric; Treatment Outcome

To assess the additional effect of sudden visceral fat reduction by omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in patients with grade III obesity (G-III O) undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB).. Twenty-two patients were randomized into two groups, LRYGB alone or with omentectomy. Levels of interleukin-6, C-reactive protein, tumor necrosis factor-alpha, leptin, adiponectin, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, as well as clinical characteristics, were evaluated before surgery and at 1, 3, 6, and 12 months after surgery. Results were compared between groups.. Baseline characteristics were comparable in both groups. Mean operative time was significantly higher in the group of patients who underwent omentectomy (P < 0.001). Median weight of the omentum was 795 +/- 341 g. In one patient, a duodenal perforation occurred at the time of omentectomy. BMI, blood pressure, glucose, total cholesterol, LDL, and triglycerides significantly improved in both groups at 1, 3, 6, and 12 months of follow-up when compared with basal values. However, there were no consistent statistically significant differences among the groups in terms of metabolic syndrome components, acute-phase reactants, and inflammatory mediators.. Omentectomy does not have an ancillary short-term significant impact on the components of metabolic syndrome and does not induce important changes in the inflammatory mediators in patients undergoing LRYGB. Operative time is more prolonged when omentectomy is performed.

Topics: Acute-Phase Proteins; Adiponectin; Adult; Blood Glucose; C-Reactive Protein; Female; Gastric Bypass; Humans; Inflammation Mediators; Interleukin-6; Intra-Abdominal Fat; Laparoscopy; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity, Morbid; Omentum; Pilot Projects; Prospective Studies; Tumor Necrosis Factor-alpha; Weight Loss

Men with the metabolic syndrome (MetS) have low plasma testosterone (T) levels. The aim of this study was to establish whether the normalization of plasma T improves the features of the MetS.. A randomized, placebo-controlled, double-blinded, phase III trial of 184 men suffering from both the MetS and hypogonadism.. One hundred and eighty-four men, aged 35-70, with the MetS and hypogonadism (baseline total T level <12·0 nm or calculated free T level <225 pm.), recruited in the outpatient andrology and urology clinic, Research Center for Endocrinology in Moscow, Russia.. Treatment for 30 weeks with either parenteral T undecanoate (n = 113; TU; 1000 mg IM) or placebo (n = 71), administered at baseline, and after 6 and 18 weeks. One hundred and five (92·9%) men receiving TU and 65 (91·5%) receiving placebo completed the trial.. Body weight, body mass index (BMI), waist circumference (WC), hip circumference, waist-to-hip ratio, insulin, leptin, glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, C-reactive protein (CRP), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor-alpha (TNF-α).. There were significant decreases in weight, BMI and WC in the TU vs placebo group. Levels of leptin and insulin also decreased, but there were no changes in serum glucose or lipid profile. Of the inflammatory markers, IL-1β, TNF-α and CRP decreased, while IL-6 and IL-10 did not change significantly.. Thirty weeks of T administration normalizing plasma T in hypogonadal men with the MetS improved some components of the MetS and a number of inflammatory markers.

Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Humans; Hypogonadism; Inflammation; Insulin; Interleukin-10; Interleukin-6; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Testosterone; Tumor Necrosis Factor-alpha; Waist Circumference; Waist-Hip Ratio

Metabolic syndrome (MetS) is prevalent among antipsychotic-treated patients; however, in psychiatric clinics, scarce resources often limit the feasibility of monitoring all 5 criteria that are necessary for diagnosing MetS. As one goal of the MetS definition is to facilitate the clinical identification of insulin-resistant individuals, other biomarkers of insulin resistance have been explored. However, there are relatively few data from antipsychotic-treated patients, especially on the association between these markers and the clinical MetS diagnosis.. We analyzed data from 196 psychiatric patients over age 40 years enrolled in an ongoing study of antipsychotic-related metabolic effects that began in August 2005. In addition to anthropometric measures and MetS criteria, levels of certain metabolism-related peptides (ghrelin, adiponectin, peptide YY, leptin, and insulin) were measured. The utility of these clinical and metabolic markers to identify individuals with MetS was evaluated by constructing receiver operating characteristic curves. Optimal cutoff values were calculated for markers with the greatest area under the curve on the basis of sensitivities and specificities for MetS diagnosis.. Ninety-nine subjects (50.5%) met MetS criteria. The receiver operating characteristic analysis found that waist circumference, triglyceride to high-density lipoprotein (TG:HDL) ratio, and body mass index had the greatest area under the curve. The waist circumference cutoff value of 40 inches, TG:HDL ratio of 2.6, and body mass index of 28 kg/m² yielded sensitivities and specificities of 73% and 80%, 74% and 78%, and 75% and 74%, respectively, for MetS diagnosis.. Waist circumference, TG:HDL cholesterol ratio, or body mass index could be used as screens for identifying possible MetS in antipsychotic-treated patients to prompt complete investigation into all MetS criteria.. clinicaltrials.gov Identifier: NCT00245206.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Biomarkers; Body Mass Index; Female; Ghrelin; Humans; Insulin; Leptin; Lipoproteins, HDL; Male; Metabolic Syndrome; Middle Aged; Peptide YY; ROC Curve; Triglycerides; Waist Circumference

Leptin is an adipocyte secreted hormone and an important regulator of neuroendocrine, metabolic, and immune function. Both r-metHuLeptin and IGF1 administration result in reduced central adipose tissue in subjects with highly active antiretroviral therapy-induced metabolic syndrome (HAART-MS) but whether the effects of leptin are mediated through increasing IGF levels remains unknown.. To assess whether r-metHuLeptin improves the HAART-MS by regulating circulating IGF and IGFBPs, we first conducted a cross-sectional study of 118 men and women with HIV infection and >6 months of exposure to antiretroviral medications to examine any association between circulating IGF1 and leptin levels. We also performed a randomized, double-blinded, placebo-controlled, crossover trial of recombinant human leptin (r-metHuLeptin) administration to seven HIV positive men with lipoatrophy and leptin deficiency (leptin <3 ng/ml) related to antiretroviral medication use.. In the observational study, leptin levels were inversely associated with circulating IGF1 levels after adjusting for age and gender (r=0.27 P=0.002), but this inverse association became non-significant after adjustment for % body fat and exercise. In the interventional leptin study, leptin levels increased significantly during r-metHuLeptin treatment (from 1.34+/-0.20 ng/ml at baseline to 17+/-5.05 ng/ml after 8 weeks P=0.046) and metabolic parameters improved including reduced fasting insulin levels and reduced homeostasis model assessment-insulin resistance (HOMA-IR). Despite the increase in circulating leptin levels, there was no change in IGF1, IGF2, free IGF1, or IGF-binding proteins during the 2-month treatment period.. The effects of r-metHuLeptin in patients with HAART-MS are not mediated through increasing IGF or IGFBP levels.

Topics: Acquired Immunodeficiency Syndrome; Adipose Tissue; Adult; Antiretroviral Therapy, Highly Active; Cross-Over Studies; Cross-Sectional Studies; Drug Therapy, Combination; Female; HIV-1; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Male; Metabolic Syndrome; Middle Aged; Placebos

Adipose tissue is an active endocrine organ that secretes signaling molecules involved in the regulation of insulin sensitivity, food intake and inflammation. Apelin is a peptide secreted by adipose tissue that has been shown to modulate cardiovascular tone in animals. The aim of this study was to measure abdominal fat, blood pressure and circulating apelin, adiponectin, leptin, ghrelin, TNF-alpha and IL-6 levels in patients with the metabolic syndrome after a diet-induced weight loss.. 35 obese individuals with the metabolic syndrome underwent an 8-week very-low-calorie diet (VLCD) and a 6-month weight maintenance period (WM) with 120mg orlistat or placebo administered 3 times daily. VLCD and WM (-15.1+/-1.0kg) decreased mean arterial pressure (MAP), insulin, leptin, triglycerides and visceral and subcutaneous adipose tissue. Moreover, adiponectin increased in response to the weight loss. However, the overall changes in plasma apelin, TNF-alpha and IL-6 were non-significant. A correlation between plasma apelin and TNF-alpha was observed at baseline (0.41, p<0.05), and the minor changes in plasma apelin levels were associated with changes in BMI during VLCD and MAP and TNF-alpha during VLCD and WM periods.. Despite reductions in BMI, body adiposity, MAP and enhancement of glucose metabolism and adiponectin in response to weight loss, no significant changes in plasma apelin, TNF-alpha and IL-6 were observed. However, apelin significantly correlated with TNF-alpha and MAP. These results suggest that apelin may not be that strongly correlated with the fat mass as an adipokine like the more abundant adipokines adiponectin or leptin and it might be involved in the regulation of inflammation and cardiovascular tone.

Topics: Adiponectin; Adipose Tissue; Anti-Obesity Agents; Apelin; Biomarkers; Blood Glucose; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Female; Ghrelin; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Interleukin-6; Lactones; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Placebos; Tumor Necrosis Factor-alpha; Weight Loss

Topics: Adult; Antipsychotic Agents; Cross-Sectional Studies; Female; Ghrelin; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Schizophrenia; Sex Factors

Some epidemiologic studies have suggested inverse relations between intake of dairy products and components of the metabolic syndrome.. The objective was to investigate the effects of an increased intake of dairy products in persons with a habitually low intake on body composition and factors related to the metabolic syndrome.. Middle-aged overweight subjects (n = 121) with traits of the metabolic syndrome were recruited in Finland, Norway, and Sweden and randomly assigned into milk or control groups. The milk group was instructed to consume 3-5 portions of dairy products daily. The control group maintained their habitual diet. Clinical investigations were conducted on admission and after 6 mo.. There were no significant differences between changes in body weight or body composition, blood pressure, markers of inflammation, endothelial function, adiponectin, or oxidative stress in the milk and the control groups. There was a modest unfavorable increase in serum cholesterol concentrations in the milk group (P = 0.043). Among participants with a low calcium intake at baseline (<700 mg/d), there was a significant treatment effect for waist circumference (P = 0.003) and sagittal abdominal diameter (P = 0.034). When the sexes were analyzed separately, leptin increased (P = 0.045) and vascular cell adhesion molecule-1 decreased (P = 0.001) in women in the milk group.. This study gives no clear support to the hypothesis that a moderately increased intake of dairy products beneficially affects aspects of the metabolic syndrome. The apparently positive effects on waist circumference and sagittal abdominal diameter in subjects with a low calcium intake suggest a possible threshold in relation to effects on body composition.

Topics: Adult; Aged; Calcium, Dietary; Cholesterol; Dairy Products; Deficiency Diseases; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Female; Finland; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Norway; Overweight; Sex Factors; Sweden; Vascular Cell Adhesion Molecule-1; Waist Circumference

Ghrelin has been proposed to be a regulator of energy balance, and its dysregulation may be important in obesity. The aims of this study were (i) to compare short- and long-term changes in circulating ghrelin concentration after increasing energy expenditure vs. its changes after decreasing energy intake, (ii) to determine factors associated with changes in ghrelin level, and (iii) to assess relationships of ghrelin concentration with metabolic syndrome (MetS) in prepubescent obese children.. Randomized controlled trial.. About 100 obese children aged 7-9 years.. After baseline testing, children were randomly assigned to two interventional groups, either receiving dietary recommendations or engaging in physical training classes for 6 months. Ghrelin, insulin, leptin, fasting blood sugar, lipid profile and anthropometric indexes, as well as energy intake and expenditure were measured.. Of the participants, 92 completed the 6-month trial, and 87 returned for the 1-year follow-up. Except ghrelin level, other biochemical variables had no significant change at 12- vs. 6-month follow-up. In both groups, ghrelin showed a progressive increase in the periods of time with significant reduction of overweight and negative energy balance; while after the end of the trial, when children regained weight, it decreased toward baseline levels. Baseline ghrelin had strong negative correlation with measures of central obesity. The odds of having the MetS were 12% lower in the middle and 37% lower in the highest tertile of ghrelin level. As the number of MetS components increased, there was a progressive decrease in ghrelin and quantitative insulin sensitivity check index (QUICKI), with a progressive increase in serum insulin, HOMA-R and leptin levels.. Ghrelin increases in response to overweight reduction and negative energy balance resulting from either an exercise intervention or reduction in food intake in prepubescent obese children. It is unlikely to regulate long-term energy balance in young obese children.

Topics: Body Composition; Child; Diet Therapy; Exercise Therapy; Female; Follow-Up Studies; Ghrelin; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Obesity; Puberty; Time Factors; Weight Loss

Our objective was to assess alterations in metabolic risk factors, body weight, fat mass and hormonal parameters following 6 weeks of lifestyle intervention with increased physical activity and either a meal-replacement regimen or a low calorie diet.. 90 overweight or obese subjects (age 47 +/- 7.5 years, weight 90.6 +/- 11.3 kg, BMI 31.5 +/- 2.3) were included in this randomized controlled clinical trial. Subjects in the fat-restricted low-calorie-diet group (LCD-G; n = 30) received 2 dietary counseling sessions and instructions on how to increase physical activity. Subjects in the meal-replacement-diet group (MRD-G; n = 60) received the same lifestyle education and were instructed to replace 2 daily meals by a low-calorie high soy-protein drink.. Subjects in the MRD-G lost significantly more weight (6.4 vs. 3.1 kg, p < 0.01) and fat mass (5.1 vs. 2.8 kg, p < 0.01) than the LCD-G. Most metabolic risk parameters were reduced in both the MRD-G and the LCD-G; however, subjects in the MRD-G showed a higher reduction in waist circumference (6.1 vs. 1.8 cm, p < 0.01) and a larger decrease in triglycerides (-19.6 vs. +12.5 mg/dl, p < 0.01). The prevalence of the metabolic syndrome was reduced in subjects in the MRD-G only (-12%, p < 0.05) compared to an unchanged risk score in the LCD-G. The reductions in leptin (18.2 vs. 6.97 ng/ml) and insulin (4.92 vs. 0.58 microU/ml) were only significant in the MRD-G (p < 0.01).. Our data suggest that even over a short period of time, a meal-replacement diet is more effective in reducing metabolic risk factors, insulin, and leptin, and in improving anthropometric measures than a fat-restricted low-calorie diet.

Topics: Blood Glucose; Body Composition; Body Mass Index; Diet, Reducing; Energy Metabolism; Exercise; Female; Food, Formulated; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Soybean Proteins; Weight Loss

The lipid-lowering drug niacin has attracted renewed interest because it raises HDL-cholesterol and because it has recently been found to slow down the progression of intima media thickness in patients with coronary heart disease. Since niacin acts on adipocytes, we investigated its impact on adipokines and on some functions attributed to adipokines.. In a randomized, placebo-controlled, double-blind study 30 men with the metabolic syndrome were treated for 6 weeks with 1500 mg extended-release niacin (n=20) or a placebo (n=10). Adiponectin increased by 56% (p<0.001) and leptin by 26.8% (p<0.012). Resistin, TNF-alpha, IL-6, and high sensitive CRP remained unchanged. In spite of the increase in adiponectin there was no improvement in endothelial function. The HOMA index actually deteriorated by 42% (p<0.014).. Short-term treatment with extended-release niacin causes a pronounced increase in adiponectin but fails to improve atheroprotective functions attributed to adiponectin, such as insulin sensitivity, anti-inflammation and endothelial function.

Topics: Adipocytes; Adiponectin; Delayed-Action Preparations; Double-Blind Method; Endothelial Cells; Humans; Hypolipidemic Agents; Leptin; Male; Metabolic Syndrome; Middle Aged; Niacin; Pilot Projects

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

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

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

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

In this study, the Authors assessed some insulin counter-regulatory factors, fibrinogen and C-reactive protein after olanzapine administration, and the effect of metformin on these variables, 37 patients with chronic schizophrenia were given olanzapine (10 mg/day for 14 weeks). Nineteen patients received metformin (850-2550 mg/day) and 18 received placebo in a randomized, double-blind protocol. The following variables were quantified before and after olanzapine: cortisol, leptin, tumor necrosis factor-alpha, glucagon, growth hormone, fibrinogen and C-reactive protein. Results were correlated with the changes in body weight and the insulin resistance index. We have reported elsewhere that metformin did not prevent olanzapine-induced weight gain, and the insulin resistance index significantly decreased after metformin and placebo; Baptista T, et al. Can J Psychiatry 2006; 51: 192-196. Cortisol, tumor necrosis factor-alpha and fibrinogen levels significantly decreased in both groups. Glucagon significantly increased after metformin (P=0.03). Leptin tended to increase after placebo (P=0.1) and displayed a small nonsignificant reduction after metformin. The C-reactive protein did not change significantly in any group. Contrarily to most published studies, olanzapine was associated with decreased insulin resistance. Decrements in cortisol, fibrinogen and tumor necrosis factor-alpha levels point to an improvement in the metabolic profile. The trend for leptin to increase after placebo, but not after metformin in spite of similar weight gain suggests a beneficial effect of this antidiabetic agent.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; C-Reactive Protein; Double-Blind Method; Female; Fibrinogen; Glucagon; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Metformin; Middle Aged; Olanzapine; Schizophrenia; Sex Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

In a prior study, we have shown that tumor necrosis factor (TNF)-alpha neutralization improves inflammatory markers and total adiponectin in patients with the metabolic syndrome, without improving insulin sensitivity. In this study, we sought to extend our understanding of the effects of TNF-alpha neutralization in this human model of obesity by investigating the responses of high-molecular-weight (HMW) adiponectin, resistin, leptin, and muscle adiposity to etanercept in patients with the metabolic syndrome. Fifty-six men and women with the metabolic syndrome enrolled in a double-blind randomized placebo-controlled trial. Circulating concentrations of total and HMW adiponectin, resistin, and leptin were determined at baseline and after 4 wk of treatment with etanercept. Muscle adiposity was measured by computed tomography (CT). Although etanercept increased total adiponectin concentration, the HMW form, which is thought to mediate insulin sensitivity, was unchanged. Thus the ratio of HMW to total adiponectin decreased following etanercept treatment compared with placebo (-0.03 +/- 0.03 vs. 0.06 +/- 0.03, P = 0.02). Resistin tended to decrease in the etanercept-treated group compared with placebo (-0.6 +/- 0.7 vs. 1.2 +/- 0.7 ng/ml, P = 0.06), whereas leptin was not altered. Etanercept decreased muscle attenuation on CT [-0.61 +/- 0.64 Hounsfield units (HU) vs. 1.54 +/- 0.77 HU in placebo, P = 0.04], suggesting an increase in muscle adiposity. Together, these results demonstrate that neutralization of TNF-alpha in obese humans results in differential effects on critical adipokines and body composition indexes. These findings may help to explain the lack of effect on insulin sensitivity and extend our knowledge of the biological effects of TNF-alpha neutralization in obesity.

Topics: Adipocytes, White; Adiponectin; Adiposity; Adult; Cytokines; Double-Blind Method; Etanercept; Female; Humans; Immunoglobulin G; Leptin; Male; Metabolic Syndrome; Middle Aged; Muscle, Skeletal; Placebos; Receptors, Tumor Necrosis Factor; Resistin; Tumor Necrosis Factor-alpha

To observe the efficacy of diet control and aerobic exercises on the patients with metabolic syndrome(MS).. Sixty sedentary patients with MS were randomly divided into a diet control group, an aerobic exercise group, and a diet control combined with aerobic exercise group, each group with 20 persons. Patients in the simple diet control group ate a low-salt, low-cholesterol, low-calorie and high-cellulose diet; patients in the simple aerobic exercises group performed aerobic exercise 30 minutes every time, 3-5 times per week for 12 weeks; while patients in the combination therapy group performed aerobic exercises and diet control. Fasting serum insulin and free fatty acid (FFA) were measured by radio immunity and enzyme-colorimetric method. Serum leptin concentration was measured by enzyme linked immunosorbent assay (ELISA). Homeostasis model assessment (HOMA) insulin resistance index was calculated using the homeostasis model assessment equation. Twenty healthy subjects were selected as the control group.. Serum concentration of FFA, blood pressure, and leptin and insulin resistance index (IRI)of patients with MS significantly increased compared with those of the controls. After 12 weeks, IRI and body mass index (BMI)significantly decreased but blood fat and leptin did not change significantly in the diet control group. IRI and BMI significantly decreased, and triglyceride, FFA and leptin also significantly decreased in the combination therapy group.. Simple diet control and aerobic exercises are beneficial for patients with MS. It could significantly improve the effect of diet control combined with aerobic exercises on patients with metabolic syndrome.

Topics: Adult; Aged; Body Mass Index; Diet; Exercise; Exercise Therapy; Fatty Acids, Nonesterified; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Triglycerides

Forty-four patients with the metabolic syndrome were placed on a reduced-calorie and reduced-fat regimen to lose weight throughout a 56-week period. The patients were treated in a crossover fashion with placebo and the angiotensin-converting enzyme inhibitor quinapril for 24 weeks each. The study measured endothelial-dependent flow-mediated dilation plus serum obesity markers of adiponectin and leptin. Metabolic parameters improved after 56 weeks. Serum adiponectin level increased by 18% (P<.05 vs baseline) and serum leptin level decreased by 16% with placebo (P<.05 vs baseline). These findings were potentiated further in the quinapril group. In comparison with baseline, flow-mediated dilation was increased by 13% in the placebo group (P=.055 vs baseline) and by 43% in the quinapril group (P<.001 vs baseline and placebo). These findings suggest that weight loss therapy improves endothelial function and markers of obesity. These results are potentiated with quinapril and are independent of changes in metabolic parameters.

Topics: Adiponectin; Adult; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Double-Blind Method; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Prognosis; Quinapril; Tetrahydroisoquinolines; Vasodilation; Weight Loss

Patients with chronic kidney disease (CKD) present a high prevalence of insulin resistance (IR). Some studies suggest that angiotensin II may influence some cellular pathways that contribute to the pathogenesis of IR and stimulate the release of proinflammatory cytokines. Fifty-two patients who had stages 3 and 4 CKD and no diabetes were administered an angiotensin receptor blocker (ARB), olmesartan (40 mg), for 16 wk. Before and after ARB treatment, metabolic and inflammatory parameters and adipokines were measured. IR was calculated by Homeostasis Model Assessment (HOMA) index. Baseline data were compared with data that were obtained from 25 healthy control individuals of similar age and normal renal function. Compared with control subjects, patients with CKD presented significantly higher BP and waist circumference, higher triglycerides and lower HDL levels, higher insulin levels, and higher mean HOMA index (6.0 +/- 2.7 versus 2.9 +/- 2.2 muU/ml x mmol/L; P < 0.001). In addition, patients with CKD had increased levels of high-sensitivity C-reactive protein, TNF-alpha, and IL-6. In patients with CKD, leptin was positively correlated to abdominal obesity, insulin levels, and IL-6, and adiponectin was inversely correlated to abdominal obesity and insulin levels. Olmesartan treatment resulted in a significant decrease of BP, urinary protein excretion, plasma glucose (99 +/- 16 versus 92 +/- 14 mg/dl; P < 0.05), insulin (23.1 +/- 8.8 versus 19.9 +/- 9; P < 0.05), HOMA index (6.0 +/- 2.7 versus 4.7 +/- 2.8; P < 0.05), and glycated hemoglobin (5.33 +/- 0.58 versus 4.85 +/- 0.81%; P < 0.01). At the same time, there was a significant reduction of high-sensitivity C-reactive protein levels, from 4.45 mg/L (2.45 to 9.00) to 3.55 mg/L (1.80 to 5.40; P < 0.05) and fibrinogen (412 +/- 100 versus 370 +/- 105 mg/dl; P < 0.05). There were no significant differences in adipokine levels after olmesartan treatment. These data demonstrate that patients with CKD have a high prevalence of IR, metabolic syndrome, and chronic inflammation and that the administration of the ARB olmesartan improves IR and inflammation markers in these patients. Plasma adipokine levels that are related to several metabolic risk factors in patients with CKD were not modified by ARB therapy.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; C-Reactive Protein; Chronic Disease; Female; Humans; Imidazoles; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Kidney Diseases; Leptin; Male; Metabolic Syndrome; Middle Aged; Olmesartan Medoxomil; Tetrazoles; Waist-Hip Ratio

To specify changes in clinicolaboratory parameters in reduction of obesity in patients with diabetes mellitus type 2 (DM-2).. Antropometry, densitometry of fat tissue (FT) were made and parameters of fat and carbohydrate metabolism (lipidogram, glycated hemoglobin, immunoreactive insulin), FT secretory activity (leptin, adiponectin, TNF-alpha) were studied in 75 obese DM-2 patients. After the above primary examination all the patients were randomized into 2 groups: group 1 (n = 55) received xenical (120 mg 3 times a day) and kept moderate hypocaloric diet; group 2 (n = 20) received only the above diet therapy. Active treatment lasted 24 weeks.. In addition to symptoms of metabolic syndrome (MS) the patients were found to have secretory disturbances of FT activity: elevation of leptin and TNF-alpha levels, subnormal adiponectin. These alterations directly correlated with body mass, FT mass gain, increase in waist circumference. Hyperleptinemia, hyperinsulinemia and hypoadiponectinemia were considered as markers of insulin resistance (IR) and related conditions. Xenical promoted a significant weight loss resulting in a positive trend in the parameters of adipokines, fat and carbohydrate metabolism, in reduction of IR.. Xenical is beneficial for patients with DM-2 and obesity because it improves metabolic processes.

Topics: Adiponectin; Adipose Tissue; Anthropometry; Anti-Obesity Agents; Biomarkers; Body Weight; Caloric Restriction; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lactones; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Tumor Necrosis Factor-alpha

This study examined the effects of exercise on metabolic risk variables insulin, leptin, glucose, and triglycerides in overweight/obese postmenopausal women.. Sedentary women (n = 173) who were overweight or obese (BMI > or = 25 kg/m(2) or > or =24 kg/m(2) with > or =33% body fat), 50 to 75 years of age, were randomized to 12 months of exercise (> or =45 minutes of moderate-intensity aerobic activity 5 d/wk) or to a stretching control group. Body composition (DXA) and visceral adiposity (computed tomography) were measured at baseline and 12 months. Insulin, glucose, triglycerides, and leptin were measured at baseline and 3 and 12 months. Insulin resistance was evaluated by the homeostasis model assessment formula. Differences from baseline to follow-up were calculated and compared across groups.. Exercisers had a 4% decrease and controls had a 12% increase in insulin concentrations from baseline to 12 months (p = 0.0002). Over the same 12-month period, leptin concentrations decreased by 7% among exercisers compared with remaining constant among controls (p = 0.03). Homeostasis model assessment scores decreased by 2% among exercisers and increased 14% among controls from baseline to 12 months (p = 0.0005). The exercise effect on insulin was modified by changes in total fat mass (trend, p = 0.03), such that the exercise intervention abolished increases in insulin concentrations associated with gains in total fat mass.. Regular moderate-intensity exercise can be used to improve metabolic risk variables such as insulin and leptin in overweight/obese postmenopausal women. These results are promising for health care providers providing advice to postmenopausal women for lifestyle changes to reduce risk of insulin resistance, coronary heart disease, and diabetes.

Topics: Adipose Tissue; Aged; Blood Glucose; Body Composition; Exercise; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Life Style; Metabolic Syndrome; Middle Aged; Obesity; Patient Compliance; Postmenopause; Risk Factors; Triglycerides

Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factors in obese patients. The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia.. We randomly assigned 1036 overweight or obese patients (body-mass index [the weight in kilograms divided by the square of the height in meters], 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein [HDL] cholesterol of >4.5 among women and >5 among men) to double-blinded therapy with either placebo or rimonabant at a dose of 5 mg or 20 mg daily for 12 months in addition to a hypocaloric diet.. The rates of completion of the study were 62.6 percent, 60.3 percent, and 63.9 percent in the placebo group, the group receiving 5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively. The most frequent adverse events resulting in discontinuation of the drug were depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose of 20 mg was associated with a significant (P<0.001) mean weight loss (repeated-measures method, -6.7+/-0.5 kg, and last-observation-carried-forward analyses, -5.4+/-0.4 kg), reduction in waist circumference (repeated-measures method, -5.8+/-0.5 cm, and last-observation-carried-forward analyses, -4.7+/-0.5 cm), increase in HDL cholesterol (repeated-measures method, +10.0+/-1.6 percent, and last-observation-carried-forward analyses, +8.1+/-1.5 percent), and reduction in triglycerides (repeated-measures method, -13.0+/-3.5 percent, and last-observation-carried-forward analyses, -12.4+/-3.2 percent). Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin levels (repeated-measures method, 57.7 percent, and last-observation-carried-forward analyses, 46.2 percent; P<0.001), for a change that was partly independent of weight loss alone.. Selective CB1-receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.

Topics: Adiponectin; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Cannabinoid Receptor Antagonists; Cholesterol; Double-Blind Method; Dyslipidemias; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Piperidines; Pyrazoles; Rimonabant; Risk Factors; Triglycerides; Weight Loss

To determine the effects of a weight loss program, including dietary modifications, increased physical activity and dietary supplement (L-carnitine or placebo) on anthropometrics, leptin, insulin, the metabolic syndrome (MS) and insulin resistance in overweight /obese premenopausal women.. Participants consumed a hypocaloric diet; 30% protein, 30% fat and 40% carbohydrate in addition to increasing number of steps/day. Carnitine supplementation followed a randomized double blind protocol. Protocol lasted for 10 weeks. Seventy subjects (35 in the control and 35 in the carnitine group) completed the intervention. Anthropometrics, plasma insulin and leptin concentrations and body composition were measured. The number of subjects with the MetSyn and insulin resistance, were assessed at baseline and post-intervention.. Because there were no significant differences between the carnitine and the placebo groups for all measured parameters, participants were grouped together for all analysis. Subjects decreased total energy (-26.6%, p < 0.01) and energy from carbohydrate (-17.3%, p < 0.01) and increased energy from protein by 67% (p < 0.01) and number of steps/day (42.6%, p < 0.01). Body weight (-4.6%, p < 0.001), body mass index (-4.5%, p < 0.01), waist circumference (-6.5%, p < 0.01), total fat mass (-1.7%, p < 0.01), trunk fat mass (-2.0%, p < 0.01), insulin (- 17.9%, p < 0.01) and leptin (-5.9%, p < 0.05) decreased after the intervention. Ten of 19 participants with insulin resistance became insulin sensitive and 7 of 8 participants with the MetSyn no longer had the syndrome after the intervention.. Moderate increases in physical activity and a hypocaloric/high protein diet resulted in multiple beneficial effects on body anthropometrics and insulin sensitivity. Realistic dietary and physical activity goals must be the focus of intervention strategies for overweight and obese individuals.

Topics: Adult; Anthropometry; Body Composition; Carnitine; Diet, Reducing; Dietary Proteins; Dietary Supplements; Double-Blind Method; Exercise; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Obesity; Premenopause; Vitamin B Complex; Weight Loss

Conjugated linoleic acid (CLA) is a group of dietary fatty acids with antiobesity and antidiabetic effects in some animals. The trans10cis12 (t10c12) CLA isomer seems to cause these effects, including improved insulin sensitivity. Whether such isomer-specific effects occur in humans is unknown. The aim of this study was to investigate whether t10c12 CLA or a commercial CLA mixture could improve insulin sensitivity, lipid metabolism, or body composition in obese men with signs of the metabolic syndrome.. In a randomized, double-blind controlled trial, abdominally obese men (n = 60) were treated with 3.4 g/day CLA (isomer mixture), purified t10c12 CLA, or placebo. Euglycemic-hyperinsulinemic clamp, serum hormones, lipids, and anthropometry were assessed before and after 12 weeks of treatment.. Baseline metabolic status was similar between groups. Unexpectedly, t10c12 CLA increased insulin resistance (19%; P < 0.01) and glycemia (4%; P < 0.001) and reduced HDL cholesterol (-4%; P < 0.01) compared with placebo, whereas body fat, sagittal abdominal diameter, and weight decreased versus baseline, but the difference was not significantly different from placebo. The CLA mixture did not change glucose metabolism, body composition, or weight compared with placebo but lowered HDL cholesterol (-2%; P < 0.05).. These results reveal important isomer-specific metabolic actions of CLA in abdominally obese humans. A CLA-induced insulin resistance has previously been described only in lipodystrophic mice. Considering the use of CLA-supplements among obese individuals, it is important to clarify the clinical consequences of these results, but they also provide physiological insights into the role of specific dietary fatty acids as modulators of insulin resistance in humans.

Topics: Adult; Aged; Body Composition; Diabetes Mellitus; Double-Blind Method; Humans; Hyperlipidemias; Insulin Resistance; Isomerism; Leptin; Linoleic Acid; Lipoproteins; Male; Metabolic Syndrome; Middle Aged; Obesity

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

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

Metabolic Syndrome (MetS) is a constellation of 3 or more risk factor (abdominal obesity, high triglycerides, low HDL-c, high blood pressure, and elevated blood glucose) for atherosclerotic cardiovascular disease. Considering these systemic metabolic changes in the biochemical pathways of all biomolecules, Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy is a rapid, low-cost, and reagent-free alternative technique capable of identifying spectral biomarkers that differentiate subjects with MetS from control. In this study, plasma samples from 74 subjects (14 MetS, 60 control) were analyzed on the ATR-FTIR spectrophotometer. The objective was to differentiate subjects with MetS from control with supervised chemometrics modeling (Orthogonal Partial Least Squares-Discriminant Analysis, OPLS-DA). Additionally, the inflammatory status of subjects with MetS and control (supervised by C-reactive protein - CRP, leptin, and cell-free DNA - cfDNA) was verified. The OPLS-DA model achieved 100% sensitivity and specificity in cross-validation. For 1 latent variable (93.4% of variance), RMSECV < 0.002, PRESS CV < 0.0001, and R

Topics: Ataxia Telangiectasia Mutated Proteins; Cell-Free Nucleic Acids; Chemometrics; Humans; Leptin; Metabolic Syndrome; Plasma; Spectroscopy, Fourier Transform Infrared

Background: some studies have evaluated the association of the rs1805134 genetic variant of the LEPR gene with obesity. Aims: the objective was to explore the association of the rs1805134 genetic variant of the LEPR gene with obesity measures and metabolic syndrome in obese Caucasian adults. Methods: we conducted a cross-sectional study in 212 obese subjects with body mass index (BMI) greater than 30 kg/m2. Measurements of adiposity parameters, blood pressure, fasting blood glucose, insulin concentration, insulin resistance (HOMA-IR), lipid profile, C-reactive protein, and prevalence of metabolic syndrome were determined. Results: the distribution of rs1805134 was 128 TT (60.4 %), 77 TC (36.3 %), and 7 CC (3.3 %). C-allele carriers showed higher levels of BMI, body weight, body fat mass, waist circumference, insulin, HOMA-IR, triglycerides, total energy intake, and carbohydrate intake than non-C-allele carriers. A logistic regression analysis reported a high percentage of elevated waist circumference (OR = 2.22, 95 % CI = 1.201-4.97; p = 0.02), hyperglycemia (OR = 1.54, 95 % CI = 1.01-5.44; p = 0.01), and metabolic syndrome percentage (OR = 1.41, 95 % CI = 1.04-5.39; p = 0.03) in C-allele carriers. Conclusions: subjects with the C-allele of the rs1805134 variant of the LEPR gene showed a worse metabolic pattern with a higher percentage of metabolic syndrome, central obesity and hyperglycaemia, probably related to higher energy intake.. Antecedentes: algunos estudios han evaluado la asociación de la variante genética rs1805134 del gen LEPR con la obesidad. Objetivos: el objetivo fue explorar la asociación de la variante genética rs1805134 del gen LEPR con los parámetros de obesidad y síndrome metabólico en adultos caucásicos obesos. Métodos: realizamos un estudio transversal en 212 sujetos obesos con índice de masa corporal (IMC) superior a 30 kg/m2. Se determinaron los parámetros de adiposidad, presión arterial, glucemia en ayunas, concentración de insulina, resistencia a la insulina (HOMA-IR), perfil lipídico, proteína C-reactiva y prevalencia de síndrome metabólico. Resultados: la distribución del rs1805134 fue de 128 TT (60,4 %), 77 TC (36,3 %) y 7 CC (3,3 %). Los portadores del alelo C mostraron niveles más altos de IMC, peso corporal, masa grasa corporal, circunferencia de la cintura, insulina, HOMA-IR, triglicéridos, ingesta total de energía y consumo de carbohidratos que los portadores sin alelo C. El análisis de regresión logística mostró un alto porcentaje de pacientes con elevada circunferencia de la cintura (OR = 2,22, IC 95 % = 1,201-4,97; p = 0,02), hiperglucemia (OR = 1,54, IC 95 % = 1,01-5,44; p = 0,01) y síndrome metabólico (OR = 1,41, IC 95 % = 1,04-5,39; p = 0,03) en los portadores del alelo C. Conclusiones: los sujetos con alelo C de la variante rs1805134 del gen LEPR mostraron un peor patrón metabólico con mayor porcentaje de síndrome metabólico, obesidad central e hiperglucemia, probablemente relacionado con una mayor ingesta energética.

Topics: Adult; Body Mass Index; Cross-Sectional Studies; Eating; Humans; Hyperglycemia; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Polymorphism, Single Nucleotide; Receptors, Leptin

We studied the effect of induced metabolic syndrome (MetS) on the effectiveness of the infarct-limiting effect of remote ischemic postconditioning (RP) in Wistar rats. The involvement of leptin and corticosterone in the formation of arterial hypertension (AH) and in reduction of the effectiveness of RP in MetS was also studied. MetS was induced by high-carbohydrate high-fat diet with replacement of drinking water with 20% fructose solution for 90 days. MetS simulation led to obesity, AH, impaired lipid and carbohydrate metabolism, hyperleptinemia, and moderate stress. All animals were subjected to 45-min coronary occlusion and 120-min reperfusion. In the RP groups, tourniquets were applied on the hind limbs in the area of the hip joint immediately after the end of ischemia (3 cycles consisting of 5-min ischemia and 5-min reperfusion). A direct correlation was found between the severity of AH in rats with MetS and the levels of corticosterone and leptin. In rats with MetS, the effectiveness of RP decreased: a direct correlation between the infarct size and serum content of leptin was revealed in rats with MetS+RP. Corticosterone seems to be one of the factors of AH development in rats with MetS.

Topics: Animals; Corticosterone; Hypertension; Infarction; Ischemia; Ischemic Postconditioning; Leptin; Metabolic Syndrome; Myocardial Reperfusion Injury; Rats; Rats, Wistar

Non-alcoholic fatty liver disease is associated with obesity. A subclinical inflammation state, endothelial dysfunction, and parameters related to metabolic syndrome (MetS), have been documented in children with obesity. We aimed to determine the changes that occur in liver enzymes levels in response to the standard treatment of childhood obesity, also assessing any associations with liver enzyme levels, leptin, and markers of insulin resistance (IR), inflammation, and parameters related to MetS in prepubertal children.. We carried out a longitudinal study in prepubertal children (aged 6-9 years) of both sexes with obesity; a total of 63 participants were recruited. Liver enzymes, C-reactive protein (CRP), interleukin-6, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), soluble intercellular adhesion molecule-1 (sICAM-1), leptin, homeostasis model assessment for IR (HOMA-IR), and parameters related to MetS were measured.. After standard treatment for 9 months, children who lowered their standardised body mass index (SDS-BMI) had significantly lower systolic blood pressure (p = 0.0242), diastolic blood pressure (p = 0.0002), HOMA-IR (p = 0.0061), and levels of alanine aminotransferase (ALT) (p = 0.0048), CRP (p = 0.0001), sICAM-1 (p = 0.0460), and IL-6 (p = 0.0438). There was a significant association between the changes that occur with treatment, in the ALT levels, and changes in leptin (p = 0.0096), inflammation biomarkers [CRP (p = 0.0061), IL-6 (p = 0.0337), NLR (p = 0.0458), PLR (p = 0.0134)], and HOMA-IR (p = 0.0322).. Our results showed that a decrease in ALT levels after the standard treatment for 9 months was associated with favourable changes in IR markers (HOMA-IR) and inflammation (IL-6, CRP, NLR, and PLR).

Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Child; Female; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Liver; Longitudinal Studies; Male; Metabolic Syndrome; Pediatric Obesity

Topics: Adiponectin; Adipose Tissue; Animals; Bees; Corticosterone; Diabetes Mellitus, Type 2; Diet, High-Fat; Dietary Carbohydrates; Honey; Leptin; Male; Metabolic Syndrome; Rats; Rats, Wistar

There is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children's developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother-child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators.. Maternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age.. In mediation models, significant total effects were found for MetS associations with children's development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child's COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models.. The results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children's LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child's cord blood markers (total indirect effects).

Topics: Adiponectin; Body Mass Index; Child Development; Child, Preschool; Cholesterol; Female; Fetal Blood; Humans; Leptin; Lipoproteins, HDL; Metabolic Syndrome; Pregnancy; Triglycerides

Topics: Cartilage, Articular; Cells, Cultured; Chondrocytes; Female; Humans; Leptin; Metabolic Syndrome; Osteoarthritis; Phenotype

Inflammaging refers to the low-grade systemic inflammation that occurs with aging present in chronic non-communicable diseases. MicroRNAs (miRNAs) are potential biomarkers for these diseases in older adults. This study aimed to assess the expression of 21 circulating miRNAs and their associations with inflammatory biomarkers in older adults. This cross-sectional study was performed with 200 individuals participating in ISA-Nutrition. The systemic low-grade inflammation score (SIS) was calculated from the plasma concentration of 10 inflammatory biomarkers. Circulating miRNA expression was assessed using the Fluidigm method. Wilcoxon-Mann-Whitney test was employed to determine differences in SIS among groups distributed according to sex and presence of MetS. Spearman's correlation was used to estimate correlations among SIS, leptin levels, miRNA expression, and variables of interest. Analyses were performed using software R version 4.2.3, with a significance level of 0.05. The final sample consisted of 193 individuals with a mean age of 69.1 (SE = 0.5) years, being 64.7% individuals with metabolic syndrome (MetS). Positive correlations were observed between leptin concentration and metabolic risk factors, and leptin concentration was higher in individuals with MetS compared to those without MetS. The expression of 15 circulating miRNAs was negatively correlated with leptin concentration. GLMs showed negative associations between miRNAs (miR-15a, miR-16, miR-223, miR-363, miR-532), leptin, and/or SIS values; and only miR-21 showed positive association with SIS values. The results suggest the presence of peripheral leptin resistance associated with low-grade inflammation and plasma expression of miRNAs in older adults. These findings suggest the potential role of miRNAs as biomarkers for cardiometabolic risk.

Topics: Aged; Biomarkers; Cross-Sectional Studies; Humans; Inflammation; Leptin; Metabolic Syndrome; MicroRNAs

Topics: Adipose Tissue; Animals; Culture Media, Conditioned; Heart Injuries; Inflammation; Leptin; Metabolic Syndrome; NADP; NADPH Oxidases; Oxidative Stress; Oxidoreductases; Protein Kinase C; Rats; Rats, Wistar; Reactive Oxygen Species; Signal Transduction; Transcription Factor AP-1

Inflammatory adipokines and cytokines play a pivotal role in linking obesity and breast cancer (BC) risk in women. We investigated the longitudinal associations between BMI change and trajectories of inflammatory biomarkers related to BC risk.. A longitudinal study was conducted among 442 Chinese women with 3-year repeated measures from 2019 to 2021. Plasma circulating inflammatory biomarkers related to BC risk, including adiponectin (ADP), resistin (RETN), soluble leptin receptor (sOB-R), insulin-like growth factor-binding protein-3 (IGFBP-3), and C-reactive protein (CRP), were examined annually. Linear mixed-effect models (LMM) were applied to investigate associations of time-varying BMI with trajectories of biomarkers. We additionally examined the modification effect of baseline BMI groups, menopausal status, and metabolic syndrome.. BMI was associated with increased levels of RETN, CRP, sOB-R, and decreased levels of ADP at baseline. An increasing BMI rate was significantly associated with an average 3-year increase in RETN (β = 0.019, 95% CI 0.004 to 0.034) and sOB-R (β = 0.022, 95% CI 0.009 to 0.035), as well as a decrease in ADP (β =  - 0.006, 95% CI  - 0.012 to 0.001). These associations persisted across different baseline BMI groups. An increasing BMI rate was significantly associated with an average 3-year increase in CRP levels among normal weight (β = 0.045, 95% CI 0.001 to 0.088) and overweight (β = 0.060, 95% CI 0.014 to 0.107) women. As BMI increased over time, a more remarkable decrease in ADP was observed among women with metabolic syndrome (β =  - 0.016, 95% CI - 0.029 to - 0.004) than those without metabolic syndrome at baseline.. A higher increase rate of BMI was associated with poorer trajectories of inflammatory biomarkers related to BC risk. Recommendations for BMI reduction may benefit BC prevention in women, particularly for those with metabolic syndrome.

Topics: Adiponectin; Biomarkers; Body Mass Index; Breast Neoplasms; C-Reactive Protein; Female; Humans; Leptin; Longitudinal Studies; Metabolic Syndrome

In this study, metabolic syndrome-affected rats were studied to examine how intermittent and continuous swimming training influenced adipokines and pro-inflammatory cytokines.. Forty-eight male Wistar rats were randomized in this experimental study into four groups (n=8), including normal control (NC), metabolic syndrome (MS), continuous swimming training with metabolic syndrome (CT-MS: load 0-3% body mass, 5 d/wk, for 8 weeks), and intermittent swimming training with metabolic syndrome (IT-MS: load 5-16% body mass, 5 d/wk, for 8 weeks). The serum levels of metrnl, adipolin, irisin, leptin, TNF-α, and IL-6 were measured using the ELISA test.. The IT-MS and NC groups exhibited significantly lower leptin concentrations than the CT-MS group (p=0.001). The irisin, meteorin, and adipolin serum levels increased significantly in CT-MS and IT relative to the NC and CT-MS groups (p=0.001), with the changes being more pronounced in the IT group (p=0.05). TNF-α and IL-6 were inclined in the CT-MS group compared with the other three groups (p=0.001), while IL-6 was increased in the IT group (p=0.024).. Intermittent swimming is more effective than continuous swimming training in improving adipokines in rats with metabolic syndrome.

Topics: Adipokines; Animals; Cytokines; Fibronectins; Interleukin-6; Leptin; Male; Metabolic Syndrome; Rats; Rats, Wistar; Swimming; Tumor Necrosis Factor-alpha

Leptin and interleukin-1 beta (IL-1β) are two extensively studied biomarkers associated with metabolic syndrome (MetS) and osteoarthritis (OA). Previous studies have mostly focused on either MetS or OA alone, with no available data on Vietnamese patients. This study aimed to investigate the levels of leptin and IL-1β in this patient population and explore their association with clinical parameters of MetS and OA. The study included 164 patients with primary knee OA, who were classified into two categories based on the presence of MetS, and 78 healthy controls. The plasma leptin and IL-1β levels were quantified by ELISA and correlated with clinical parameters. Leptin levels were higher in patients with OA (11.50±10.04 ng/mL) than in healthy controls (0.54±0.37 ng/mL) and increased in patients with MetS compared to those without MetS. IL-1β levels were also significantly higher in OA patients (14.63±15.87 pg/mL) than in controls (7.79±5.11 pg/mL), but were not significantly different between the MetS and non-MetS groups. Leptin levels were positively correlated with body mass index, waist-to-hip ratio, visual analogue scale scores, HbA1c and insulin levels, and HOMA-IR index, whereas IL-1β levels were only correlated with insulin levels and HOMA-IR index. ROC curve analysis revealed that leptin and IL-1β levels could distinguish individuals with and without OA (AUC=0.96; 0.88, respectively), and individuals with and without MetS (AUC=0.82; 0.71, respectively). Our findings suggested that both leptin and IL-1β levels were associated with both MetS and OA and may play a critical role in the pathogenesis of MetS-related OA.

Topics: Cross-Sectional Studies; Humans; Insulins; Interleukin-1beta; Leptin; Metabolic Syndrome; Osteoarthritis, Knee; Southeast Asian People

Obesity can be categorized as metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). However, individuals with MHO are characterized by the absence of metabolic syndrome (MS) and appear to have lower inflammation levels compared to MUO. This study aimed to investigate the association of obesity phenotypes with leptin (LEP) and adiponectin (ADP). According to the inclusion and exclusion criteria, we selected 178 subjects from the previous cross-sectional survey. Based on the body mass index (BMI) and diagnostic criteria of MS, we divided the individuals into three groups, including healthy control group (HC group), metabolically healthy obesity group (MHO group) and metabolically unhealthy obesity group (MUO group). The concentrations of LEP and ADP in serum were measured, and the association of these two cytokines with different obesity phenotypes were subsequently analyzed. Compared to both the HC and MHO groups, the MUO group showed significantly higher BMI, waist circumference (WC), waist-hip ratio (WHR), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (Homa-IR) and blood pressure (P < 0.05). In contrast, serum high-density lipoprotein cholesterol (HDL-C) was notably lower in the MUO group (P < 0.05). ADP was found to have a positive correlation with systolic blood pressure (SBP) and a negative correlation with FPG in the MHO group. In the MUO group, LEP demonstrated a positive correlation with fasting insulin (FINS) and Homa-IR, while ADP showed a positive correlation with TC and SBP. Linear regression analysis further indicated that SBP (β = 0.234, P = 0.043), TG (β = - 0.292, P = 0.001) and LDL-C (β = 0.626, P = 0.000) were independently correlated with ADP, and BMI (β = 0.398, P = 0.002) was independently correlated with LEP in obese individuals. In conclusion, ADP and LEP were closely related with glucose and lipid metabolism in obese individuals, these two cytokines might play critical roles in obesity-associated metabolic disorders.

Topics: Adiponectin; Body Mass Index; Cholesterol, LDL; Cross-Sectional Studies; Cytokines; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Obesity, Metabolically Benign; Phenotype; Triglycerides

Metabolic syndrome (MS) is a growing social, economic, and health problem. MS coexists with nearly half of all patients with affective disorders. This study aimed to evaluate the neurobiological parameters (clinical, anthropometric, biochemical, adipokines levels, and ultrasound of carotid arteries) and their relationship with the development of MS in patients with bipolar disorder. The study group consisted of 70 patients (50 women and 20 men) hospitalized due to episodes of depression in the course of bipolar disorders. The Hamilton Depression Rating Scale was used to assess the severity of the depression symptoms in an acute state of illness and after six weeks of treatment. The serum concentration of adipokines was determined using an ELISA method. The main finding of this study is that the following adipokines correlated with MS in the bipolar depression women group: visfatin, S100B, and leptin had a positive correlation, whereas adiponectin, leptin-receptor, and adiponectin/leptin ratio showed a negative correlation. Moreover, the adiponectin/leptin ratio showed moderate to strong negative correlation with insulin level, BMI, waist circumference, triglyceride level, treatment with metformin, and a positive moderate correlation with HDL. The adiponectin/leptin ratio may be an effective tool to assess MS in depressed female bipolar patients.

Topics: Adipokines; Adiponectin; Bipolar Disorder; Female; Humans; Leptin; Male; Metabolic Syndrome

Topics: Adipokines; Adiponectin; Bipolar Disorder; Body Mass Index; Cholesterol, HDL; Female; Humans; Leptin; Lithium; Male; Metabolic Syndrome; Obesity; Valproic Acid

The main manifestations of metabolic syndrome (MS) are disorders of carbohydrate and lipid metabolism and their hormonal regulation. The combined nature of metabolic disorders can significantly affect the course and prognosis of CHF in elderly people with metabolic syndrome. To determine the features of the combined effect of metabolic laboratory parameters and biological active factors of adipose tissue in patients with CHF and metabolic syndrome on the course of the disease. A comparison was made between a group of patients with CHF complicated by MS(n=37) and a group of patients with CHF without MS (n=37). The parameters of lipid metabolism (cholesterol CH and lipoproteins LP), the lipid transport system (ApoA1 and ApoB), leptin, adiponectin and resistin and their mutual relations were studied. The ratio of ApoB/ApoAI levels was indicative, which was 0.80±0.32 in patients with CHF without MS, and 1.12±0.46 in patients with CHF with MS (p <0.05). A significant correlation was found between the ratio of ApoB/ApoA1 levels and abdominal obesity (r=0.42, p<0.05), functional class of CHF (r=0.463, p<0.05), LDL-C level (r=0.518, p<0.05), and triglycerides (r=0.476, p<0.05). Also, significant results were obtained for the leptin/adiponectin ratio. For this ratio, 4 ranks were derived depending on the value of the leptin (ng/ml)/adiponectin (mcg/ml) ratio: less than 1 - rank 0 was assigned, with values of the ratio in the range 1 - 3 - rank 1, in the range 3.1 - 6 - rank 2, and above the value 6 - rank 3. Of the 22 patients who had improved CHF at the end of hospitalization, all at the beginning of hospitalization had a rank 0 or 1 ApoB/ApoA1 ratio. Thus, ranking the values of the ratio of ApoB/ApoA1 levels, and especially leptin/adiponectin, can suggest the probability of successful treatment of CHF or the probability of deterioration of the patient's condition, up to a fatal outcome.

Topics: Adiponectin; Adipose Tissue; Aged; Apolipoproteins B; Humans; Laboratories; Leptin; Metabolic Syndrome

Babies born small for gestational age (SGA) are at risk of obesity and metabolic syndrome (MetS). Spexin (SPX) is a novel peptide implicated in food intake and obesity. Spexin levels are lower in obese subjects. This study investigated the potential association of SPX and some obesity related peptides such as leptin and active ghrelin with size at birth and MetS components in prepubertal children born term and either SGA or appropriate for GA (AGA). Secondary aim was to identify whether any of the investigated peptides were associated with MetS components.. We conducted a cross-sectional study of 37 consecutive (median age: 5.6 y) SGA- and 50 (median age: 5.9 y) AGA-born children. Clinical evaluations were performed using standard methods. Several biochemical variables (SPX, total leptin, and active ghrelin levels) were analyzed. Age-dependent cut-off values were used to define MetS components, including excess adiposity, hypertension, insulin resistance, and dyslipidemia. The associations between the assessed clinical and laboratory variables and MetS components were investigated.. Children born SGA had higher frequencies of MetS components than AGA-born peers (p < 0.01). None of the investigated peptides were different between children born SGA and AGA after correcting for body mass index (p > 0.05 for all). Serum SPX levels were lower in children with at least one metS component than those without MetS components (p = 0.018).. Size at birth had no association with serum SPX. Serum SPX levels are decreased in prepubertal children with MetS components.

Topics: Birth Weight; Child, Preschool; Cross-Sectional Studies; Female; Ghrelin; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin; Leptin; Metabolic Syndrome; Obesity; Peptide Hormones

Owing to advances in treatment modalities and supportive care, overall survival rates have reached up to 90% among children with acute lymphoblastic leukemia (ALL). However, due to the underlying illness and therapy, they are at a greater risk of developing lifestyle diseases. Hence, special attention is paid to early detection of the components of metabolic syndrome (MetS). This study aimed at investigating the association of plasma levels of nine diabetes markers with being overweight and components of MetS in ALL survivors. The study included 56 subjects with mean age of 12.36 ± 5.15 years. The commercially available Bio-Plex Pro Human Diabetes 10-Plex Panel kit was used to evaluate levels of diabetes biomarkers. ALL survivors presented statistically higher concentrations of GIP (p = 0.026), glucagon (p = 0.001), leptin (p = 0.022), and PAI-1 (p = 0.047), whereas the concentration of ghrelin was lower (p < 0.001) compared to the control group. Moreover, subjects within normal BMI range showed higher GIP (p = 0.005) and lower ghrelin concentration (p < 0.001) compared to healthy peers. At least one risk factor of MetS was present in 58.9% of participants, who showed significantly higher levels of C-peptide (p = 0.028), leptin (p = 0.003), and PAI-1 (p = 0.034) than survivors who did not meet any MetS criteria. In conclusion, ALL survivors are at greater risk of disturbances in carbohydrate metabolism. Understanding the pathogenesis and applicability of diabetes markers is crucial for developing strategies to prevent metabolic syndrome in ALL survivors.

Topics: Adolescent; Biomarkers; Child; Ghrelin; Glucose; Humans; Leptin; Metabolic Syndrome; Plasminogen Activator Inhibitor 1; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survivors

Recently, we proposed two pathophysiologic subtypes of type 2 diabetes mellitus (T2DM), one related and one unrelated to metabolic syndrome. To begin to understand the pathophysiology of the subtype unrelated to metabolic syndrome, we now measured selected hormones and signaling molecules in affected individuals. In this cross-sectional analysis, we examined 138 women out of the monocenter, post gestational diabetes study PPSDiab. Of these women, 73 had prediabetes or screening-diagnosed T2DM, 40 related to metabolic syndrome and 33 unrelated. The remaining 65 women were normoglycemic controls. Our analysis included medical history, anthropometrics, oral glucose tolerance testing, laboratory chemistry, and cardiopulmonary exercise testing. In addition, plasma proinsulin/insulin ratio, growth hormone (hGH) nadir during oral glucose tolerance testing, Insulin-like Growth Factor I (IGF-I), Leptin, Resistin, Adiponectin, Fetuin-a, FGF21, and myostatin were measured. Compared to controls, women with prediabetes or screening-diagnosed T2DM unrelated to metabolic syndrome depicted higher plasma Leptin [10.47(6.6-14.57) vs. 5.52(3.15-10.02); p<0.0001] and IGF-I [193.01(171.00-213.30) vs. 167.97(138.77-200.64); p=0.0008], as well as a lower hGH nadir [0.07(0.05-0.15) vs. 0.14(0.08-0.22; p<0.0001]. These differences were independent of body adiposity. Women with prediabetes or T2DM related to metabolic syndrome, in comparison to controls, displayed elevated Leptin, Fetuin-a, and FGF21, as well as reduced Adiponectin and hGH nadir. Based on our study, altered Leptin and hGH/IGF-I signaling could potentially contribute to the pathophysiology of prediabetes and T2DM unrelated to metabolic syndrome. Further mechanistic investigations of these signaling pathways in the context of lean T2DM are necessary to test causal relationships.

Topics: Adiponectin; alpha-2-HS-Glycoprotein; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Insulin-Like Growth Factor I; Leptin; Metabolic Syndrome; Prediabetic State; Pregnancy

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

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

Lichen planus (LP) is a chronic inflammatory dermatosis, involving the skin, appendages, and mucous membranes. There is a growing body of evidence about higher risk of metabolic syndrome and dyslipidemia in some dermatoses including LP.. To evaluate lipid profile, leptin, and CRP status among Iranian LP patients, compared to healthy controls, and peruse the relationship between abnormal values of these parameters with the disease duration and physical characteristics of patients.. 40 LP patients and 40 age- and sex-matched healthy controls were enrolled in the study. Data on weight, height, lipid profile, leptin, and CRP values were recorded and compared.. The mean values for leptin, CRP, and lipid profile parameters (except for HDL) were higher in patients, compared to controls. Total cholesterol level was negatively associated with disease duration in patients (. Screening of LP patients in regard to their lipid profile might be more reasonable in men or those who have other cardiovascular risk factors to prevent morbidity and mortality in result of developing cardiovascular events.

Topics: Cross-Sectional Studies; Female; Humans; Incidence; Iran; Leptin; Lichen Planus; Lipids; Male; Metabolic Syndrome; Prospective Studies

Metabolic syndrome (MetS) is a risk factor for prostate cancer (PCa) progression. Thus, this life-threatening disease demands a proactive treatment strategy. Andrographis paniculata (AP) is a promising candidate with various medicinal properties. However, the bioactivity of AP is influenced by its processing conditions especially the extraction solvent.. In the present study, bioassay-guided screening technique was employed to identify the best AP extract in the management of MetS, PCa, and MetS-PCa co-disease in vitro.. Five AP extracts by different solvent systems; APE1 (aqueous), APE2 (absolute methanol), APE3 (absolute ethanol), APE4 (40% methanol), and APE5 (60% ethanol) were screened through their phytochemical profile, in-vitro anti-cancer, anti-obese, and anti-hyperglycemic properties. The best extract was further tested for its potential in MetS-induced PCa progression.. In conclusion, AP extracts rich with andrographolide has the potential to be used as an alternative to ameliorate PCa progression induced by factors highly expressed in MetS.

Topics: Andrographis; Andrographis paniculata; Biological Assay; Diterpenes; Ethanol; Humans; Leptin; Male; Metabolic Syndrome; Methanol; Plant Extracts; Prostatic Neoplasms; Solvents

Antipsychotic-induced metabolic syndrome (APs-induced Mets) is the most common adverse drug reaction, which affects more than 60% of the psychiatric patients. Although the etiology of APs-induced Mets has been extensively investigated, there is a lack of integrated analysis of the genetic and epigenetic factors. In this study, we performed genome-wide, whole-exome sequencing (WES) and epigenome-wide association studies in schizophrenia (SCZ) patients with or without APs-induced Mets to find the underlying mechanisms, followed by in vitro and in vivo functional validations. By population-based omics analysis, we revealed that rare functional variants across in the leptin and peroxisome proliferator-activated receptors (PPARs) gene sets were imbalanced with rare functional variants across the APs-induced Mets and Non-Mets cohort. Besides, we discovered that APs-induced Mets are hypermethylated in ABCG1 (chr21:43642166-43642366, adjusted P < 0.05) than Non-Mets, and hypermethylation of this area was associated with higher TC (total cholesterol) and TG (triglycerides) levels in HepG2 cells. Candidate genes from omics studies were furtherly screened in C. elegans and 17 gene have been verified to associated with olanzapine (OLA) induced fat deposit. Among them, several genes were expressed differentially in Mets cohort and APs-induced in vitro/in vivo models compared to controls, demonstrating the validity of omics study. Overexpression one of the most significant gene, PTPN11, exhibited compromised glucose responses and insulin resistance. Pharmacologic inhibition of PTPN11 protected HepG2 cell from APs-induced insulin resistance. These findings provide important insights into our understanding of the mechanism of the APs-induced Mets.

Topics: Animals; Antipsychotic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 1; Caenorhabditis elegans; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Multiomics; Peroxisome Proliferator-Activated Receptors

Previous studies have been reported that vitamin D deficiency increased the risk of metabolic syndrome (MetS). Nonetheless, the exact mechanisms underlying this association is unclear. Besides, inflammation and deregulation of adipokines secretion have been recognized as pivotal factors that contribute to the pathogenesis of these conditions. Therefore, we assessed whether serum vitamin D status is associated with serum levels of adipokines and inflammatory markers in these patients.. This case-control study was carried out among 65 patients with MetS who had vitamin D insufficiency (cases) and 130 MetS patients who had vitamin D sufficiency (controls). Cases and controls were recruited from among those referred to health centers in Zabol County, Iran. Vitamin D insufficiency was regarded as a serum 25-hydroxyvitamin D [25(OH)D] concentration below 30 ng/ml. Serum concentrations of leptin, adiponectin, visfatin, and resistin and also adiponectin/leptin ratio along with serum levels of interleukin 6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-α), were evaluated.. Serum levels of leptin, resistin, and TNF-α were significantly higher, whereas, serum adiponectin and adiponectin/leptin ratio were significantly lower in cases than the controls. There was no significant difference in serum visfatin, IL-6, and IL-10 between the groups. Serum levels of 25(OH)D were inversely correlated with leptin, resistin, and TNF-α in both unadjusted models and after adjustment for potential confounders.. Our findings indicated that vitamin D insufficiency in MetS patients is associated with increased inflammation and serum adipokine abnormalities which may be associated with developing metabolic complications in these patients.

Topics: Adipokines; Adiponectin; Case-Control Studies; Humans; Inflammation; Interleukin-10; Interleukin-6; Leptin; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Resistin; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency; Vitamins

Abdominal obesity coupled with polygenic hereditary defects is considered the initial event in the development of metabolic syndrome (MS). The purpose of this study was to analyse the frequency with which polymorphic loci of adiponectin (

Topics: Adiponectin; Chloroform; Glycated Hemoglobin; Humans; Leptin; Metabolic Syndrome; Phenols; Polymorphism, Single Nucleotide; Receptors, Bombesin; Receptors, Colony-Stimulating Factor; Receptors, Formyl Peptide; Receptors, Leptin; Ryanodine Receptor Calcium Release Channel

Metabolic syndrome (MetS) is a phenotype caused by the interaction of host intrinsic factors such as genetics and gut microbiome, and extrinsic factors such as diet and lifestyle. To demonstrate the interplay of intestinal microbiota with obesity, MetS markers, and some dietary ingredients among samples of Egyptian women. This study was a cross-sectional one that included 115 Egyptian women; 82 were obese (59 without MetS and 23 with MetS) and 33 were normal weight. All participants were subjected to anthropometric assessment, 24 h dietary recall, laboratory evaluation of liver enzymes (AST and ALT), leptin, short chain fatty acids (SCFA), C-reactive protein, fasting blood glucose, insulin, and lipid profile, in addition to fecal microbiota analysis for Lactobacillus, Bifidobacteria, Firmicutes, and Bacteroid. Data showed that the obese women with MetS had the highest significant values of the anthropometric and the biochemical parameters. Obese MetS women consumed a diet high in calories, protein, fat, and carbohydrate, and low in fiber and micronutrients. The Bacteroidetes and Firmicutes were the abundant bacteria among the different gut microbiota, with low Firmicutes/Bacteroidetes ratio, and insignificant differences between the obese with and without MetS and normal weight women were reported. Firmicutes/Bacteroidetes ratio significantly correlated positively with total cholesterol and LDL-C and negatively with SCFA among obese women with MetS. Findings of this study revealed that dietary factors, dysbiosis, and the metabolic product short chain fatty acids have been implicated in causing metabolic defects.

Topics: Bacteroidetes; Blood Glucose; C-Reactive Protein; Cholesterol, LDL; Cross-Sectional Studies; Eating; Egypt; Fatty Acids, Volatile; Female; Firmicutes; Gastrointestinal Microbiome; Humans; Insulins; Leptin; Metabolic Syndrome; Micronutrients; Obesity

Secretion of insulin is compromised in type 2 diabetes (T2DM) individuals and inadequate to accommodate for insulin resistance (IR) in peripheral tissue. Hyperleptinemia reflects leptin resistance, which is a key factor in the production of IR in T2DM patients, making leptin a potential biomarker for evaluating IR levels. The objective of the study was to assess the association of serum leptin and insulin levels among T2DM patients. This case-control research was carried out on T2DM patients. A total of 73 patients diagnosed with T2DM (the case group) and 40 healthy participants (control; group 3) were enrolled according to the American Diabetes Association (ADA) criteria. In the case group, T2DM patients were enrolled with metabolic syndrome (group 1, n = 38) or without metabolic syndrome (group 2, n = 35) according to the WHO criteria. Metabolic profiles of T2DM patients with or without metabolic syndrome were evaluated, and compare these two groups with healthy controls. The subjects of all groups were age- and gender-matched. Body mass index (BMI, P < .01), fasting (P = .0133) and postprandial (P < .01) blood sugar levels, % glycated hemoglobin (HbA1c, P < .01), and lipid profile (P < .01) were found significantly different and higher in group 1 as compared to groups 2 and 3. Serum leptin and insulin levels were found higher and significant in patients with metabolic syndrome (P < .01 for both). The values of serum leptin levels were 10.01 ± 2.7 ng/mL, 6.9 ± 2.4 ng/mL, and 4.11 ± 1.8 ng/mL, and those of serum insulin 120 ± 40.7 µIU/mL, 20.43 ± 5.2 µIU/mL, and 11.4 ± 2.5 µIU/mL in groups 1, 2, and 3, respectively. There was a positive linear correlation between BMI, blood sugar, HbA1c, serum cholesterol (TC), and triglycerides (TG) with serum insulin and leptin levels in the case group. An extremely significant correlation (R = 0.74, P < .001) was found in BMI and serum leptin level in the case group. Serum leptin and insulin levels have a positive association, with serum leptin being a significant predictor of IR syndrome (Evidence Level: 5; Technical Efficacy: Stage 3).

Topics: Blood Glucose; Body Mass Index; Case-Control Studies; Cholesterol; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Triglycerides

Adult-onset asthma (AOA) is usually more severe compared to childhood onset asthma (CoA). Given the increasing evidence that AoA is associated with obesity, we investigated the relationship of other related metabolic comorbid conditions with AoA compared to CoA.. This cross-sectional study compared the metabolic syndrome and lipid derived inflammatory markers in patients with AoA, CoA and age- and sex-matched control subjects without asthma. Participants were asthma patients visiting the outpatient clinic of two teaching hospitals in Rotterdam, The Netherlands. All participants underwent lung function tests, blood tests and physical activity tracking. AoA was defined as asthma age of onset after the age of 18 years. Metabolic syndrome was defined according to the international joint interim statement criteria.. AoA was associated with the metabolic syndrome and its related pro-inflammatory endocrine and cytokine status. This may suggest adipose tissue derived inflammatory markers play a role in the pathophysiology of AoA.

Topics: Adiponectin; Adolescent; Adult; Age of Onset; Asthma; Biomarkers; Body Mass Index; Child; Cross-Sectional Studies; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Respiratory Function Tests

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

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

A fraction of children with obesity have increased serum cortisol levels. In this study, we describe the clinical characteristics of obese children and adolescents with elevated morning serum cortisol levels and the relationship between the cortisol levels and components of the metabolic syndrome.. Retrospective medical record review study of children aged 4 to 18 years with overweight or obesity seen for obesity management in the Pediatric Obesity Clinic of the UZ Brussel between 2013 and 2015.. A total of 234 children (99 boys and 135 girls) with overweight (BMI z-score > 1.3) without underlying endocrine or genetic conditions were included. Mean (SD) age was 10.1 (2.8) years, BMI SD-score 2.5 (0.6), and body fat percentage 37% (7.9). Serum fasting cortisol levels were elevated (>180 μg/L) in 49 children, normal (62-180 μg/L) in 168, and decreased (<62 μg/L) in 12. Serum fasting cortisol was not significantly correlated with gender, age, or degree of adiposity. But correlated significantly with fasting glucose (Rs = 0.193; p < 0.005), triglycerides (Rs = 0. 143; p < 0.05), fibrinogen (Rs = 0.144; p < 0.05) and leptin levels (Rs = 0.145; p < 0.05). After adjustment for serum insulin and leptin, the correlation between serum cortisol and fasting glucose remained significant.. Elevated morning serum cortisol levels were found in 20% of overweight or obese children and adolescents, irrespective of the degree of adiposity, and were associated with higher fasting glucose, irrespective of underlying insulin resistance. The long-term cardiometabolic consequences of hypercortisolemia in childhood obesity needs further study.

Topics: Adolescent; Belgium; Blood Glucose; Child; Child, Preschool; Fasting; Female; Humans; Hydrocortisone; Leptin; Male; Metabolic Syndrome; Overweight; Pediatric Obesity; Retrospective Studies

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

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

The aim: To compare lipid metabolism and leptin levels among the children with and without hypertension to identify associated risk factors for the course of metabolic syndrome in children.. Materials and methods: This observational, cross-sectional study recruited children from the Rheumocardiology Department of Children's Clinical Hospital No 6 in Kyiv, with metabolic syndrome, identification of waist-to-height ratio, leptin level, homeostasis model assessment of insulin resistance and lipid profile. The main group included 41 children with metabolic syndrome and hypertension and the control group included 40 children with metabolic syndrome without hypertension. Statistical data analysis was performed using the MedStat 2.6.2. package.. Results: A total of 81 children aged 10 to 17 with metabolic syndrome were examined. The group of children with hypertension had significantly lower high-density lipoprotein cholesterol (0.85±0.04) than children without hypertension (0.94±0.03), with p < 0.05. Leptin resistance was detected in 65.2% of children with hypertension and 35.3% of children with normal blood pressure (p < 0.01).. Conclusions: Children with metabolic syndrome and hypertension had a significantly higher body mass index and waist circumference as opposed to children with normal blood pressure. In the lipid profile high-density lipoprotein cholesterol was significantly lower in hypertensive children. There was no reliable difference in other lipid profile indicators between the two groups, but there was an upward trend of them in group with hypertension. Leptin resistance is also significantly higher in hypertensive children.

Topics: Child; Cross-Sectional Studies; Humans; Hypertension; Leptin; Lipids; Metabolic Syndrome; Ukraine

To investigate metabolic syndrome (MetS), disease activity, and adipokine levels among patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and undifferentiated arthritis (UA) at the time of diagnosis and after 1 year of follow-up.. Patients with inflammatory joint diseases participating in the Northern Savo 2010 population-based longitudinal epidemiological study were evaluated for components of MetS (by National Cholesterol Education Program's Adult Treatment Panel III) and clinical parameters of disease activity. The adipokines adiponectin, adipsin, resistin, and leptin were measured at baseline and after 1 year of treatment with disease-modifying antirheumatic drugs.. Among 176 patients, MetS was detected in 42% of RA, 36% of SpA, and 51% of UA patients. Metabolic syndrome was associated with higher disease activity as measured by patient global assessment in RA and UA patients and increased pain in RA patients. Leptin levels were increased in patients with MetS, showing a linearly increasing trend with the number of components of MetS in SpA and UA, but not in RA. In RA patients, decrease in disease activity correlated with decrease in leptin levels. Resistin did not associate with MetS, but a decrease in resistin correlated with decrease in disease activity in RA and UA. In SpA, increased adiponectin level correlated with relief in disease activity, but not with MetS.. Metabolic syndrome was common in patients with newly diagnosed arthritides and associated with higher disease activity and increased leptin levels. Resistin responded to treatment of arthritis in RA and UA, leptin in RA, and adiponectin in SpA.

Topics: Adipokines; Adiponectin; Arthritis, Rheumatoid; Humans; Leptin; Metabolic Syndrome

This study was conducted as part of a larger study of East Tyrolean health tourism, and investigates the effects of an active seven-day vacation on metabolic parameters and adipokines. Fifty-two healthy vacationers participated in two types of vacation activities (golf vs. Nordic walking or e-biking [nw&eb]). In the former group, 30 subjects played golf for a mean duration of 33.5 h per week; in the NW&EB group, 22 persons performed Nordic walking or e-biking for a mean duration of 14.2 h per week. Metabolic parameters and adipokines, such as leptin, adiponectin, GF-21, irisin, omentin-1, betatrophin, and resistin, were measured one day before and one day after the stay. After one week, only the NW&EB group experienced a significant decrease of 1.0 kg in body weight. Significant changes in HDL-C, FGF-21, irisin, and omentin-1 were seen in the golf group; and in triglycerides, HbA1c, leptin and adiponectin in the NW&EB group. No significant changes in betatrophin or resistin were registered in either group. A seven-day vacation with an activity program for several hours per week causes favorable changes in metabolic parameters and adipokines known to be involved in the pathophysiology of the metabolic syndrome. The changes differed in their magnitude and significance, depending on the type of activity.

Topics: Adipokines; Adiponectin; Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Bicycling; Blood Pressure; Cardiometabolic Risk Factors; Cholesterol, HDL; Cytokines; Female; Fibroblast Growth Factors; Fibronectins; Germany; Glycated Hemoglobin; Golf; GPI-Linked Proteins; Heart Rate; Holidays; Humans; Lectins; Leptin; Male; Metabolic Syndrome; Metabolism; Middle Aged; Peptide Hormones; Resistin; Time Factors; Triglycerides; Walking; Weight Loss

The current study examined the role of sex differences in the development of risk factors associated with obesity and its comorbidities using models that differ in their susceptibility to develop obesity, obesity-resistant S5B/Pl (S5B) and obesity-prone Osborne-Mendel (OM) rats. Male and female rats were fed a low fat or high fat diet (HFD) and markers of metabolic syndrome (MetSyn) and expression of inflammatory cytokines/chemokines in visceral and subcutaneous adipose depots were measured. We hypothesized that male and female OM and S5B rats would exhibit differential responses to the consumption of HFD and that females, regardless of susceptibility to develop obesity, would display decreased obesity-related risk factors. Results suggested that consumption of HFD increased adiposity and fasting glucose levels in male OM and S5B rats, decreased circulating adiponectin levels in male S5B rats, and increased body weight and triglyceride levels in male OM rats. The consumption of HFD increased body weight and adiposity in female OM rats, not female S5B rats. Overall, female rats did not meet criteria for MetSyn, while male rats consuming HFD met criteria for MetSyn. Visceral and subcutaneous adipose tissue inflammation was higher in male rats. In visceral adipose tissue, HFD consumption differentially altered expression of cytokines in male and female S5B and OM rats. These findings suggest that resistance to obesity in males may be overridden by chronic consumption of HFD and lead to increased risk for development of obesity-related comorbidities, while female rats appear to be protected from the adverse effects of HFD consumption.

Topics: Adipose Tissue; Animals; Biomarkers; Body Weight; Diet, High-Fat; Female; Inflammation; Leptin; Male; Metabolic Syndrome; Obesity; Rats; Sex Factors; Weight Gain

The aim: To evaluate anthropometric, hemodynamic parameters, as well as changes in blood and leptin lipid spectrum in children and adults with overweight and obesity.. Materials and methods: We examined 68 overweight children and 90 patients with obesity in combination with stage 2, grade 2 AH who were electively inpatient. The control group consisted of practically healthy individuals - 20 adults and 55 children.. Results: Obesity in childhood isaccompanied by the development of dyslipidemia, hypercholesterolemia, hyperleptinemia and hypertension, and in adulthood may be an additional risk factor for cardiovascular disease, in particular AH. According to the study, total leptin level in overweight children was significantly higher compared to the control group (p<0.01). The concentration of leptin in patients with hypertension in combination with obesity was 3 times higher compared to the control group (p<0.01).. Conclusions: Thus, obesity or overweight, accompanied by hyperleptinemia and an increase in the proatherogenic fractions of the blood lipid spectrum, is an important problem that needs to be addressed in childhood to prevent cardiovascular disease in adulthood.

Topics: Adult; Body Mass Index; Child; Humans; Hypertension; Leptin; Metabolic Syndrome; Overweight; Pediatric Obesity; Risk Factors

Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood.. We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice.. We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA.. D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa.. Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese mice.

Topics: Animals; Cholecalciferol; Diet, High-Fat; Dietary Sucrose; Dietary Supplements; Drug Synergism; Fatty Acids, Omega-3; Glucose Intolerance; Humans; Leptin; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Random Allocation

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is a heterogeneous complex disorder of defined aetiology. Some studies report its association with various endocrine, metabolic and immunological abnormalities. The hunger hormones ghrelin and leptin affect the pathogenesis of PCOS and might lead to the development of Metabolic Syndrome (MS) in obese women.. The study aims at evaluating the role of ghrelin and leptin level in females with polycystic ovary syndrome as a biochemical marker for the diagnosis and monitoring progression.. The study included one hundred PCOS patients and fifty apparently healthy subjects with regular menstrual cycle, visiting gynecology outpatient clinic of Kalar General Hospital, from the beginning of February 2015 to the end of June 2015. Body Mass Index (BMI) along with serum ghrelin, leptin, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) and testosterone levels were measured for both groups. Serum leptin was determined using sandwich ELISA, while serum ghrelin was determined using competitive ELISA. Differences between patient and control groups were assessed by using a t-test. Also, one-way Anova was used to test the relationships among different groups.. A significant decrease in ghrelin level and an increase in leptin levels in women with PCOS were observed compared to the control group. Also, a significant elevation in serum levels of LH, Testosterone, Prolactin, and a decrease in serum FSH in PCOS patients were observed, when compared to the control group. Additionally, serum ghrelin decreased and serum leptin level increased significantly in women with PCOS compared to controls in all age and BMI groups.. A significant decrease in ghrelin and an increase in leptin in PCOS patients were observed than in controls, indicating that they are at high risk for metabolic syndrome development.

Topics: Adolescent; Adult; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Follicle Stimulating Hormone; Ghrelin; Humans; Iraq; Leptin; Luteinizing Hormone; Metabolic Syndrome; Middle Aged; Polycystic Ovary Syndrome; Testosterone; Young Adult

The dietary model of metabolic syndrome has continued to aid our understanding of its pathogenesis and possible management interventions. However, despite progress in research, therapy continues to be challenging for humans; hence, the search for newer treatment and prevention options continues.. The objective of this study was to evaluate the impact of dietary CQ10 supplementation on metabolic, oxidative, and inflammatory markers in a diet-induced mouse model of metabolic syndrome.. Mouse groups were fed a Standard Diet (SD), High-Fat High-Sugar (HFHS) diet, and SD or HFHS diet (with incorporated CQ10) at 60 and 120 mg/kg of feed. At the completion of the study (8 weeks), blood glucose levels, Superoxide Dismutase (SOD) activity, plasma insulin, leptin, adiponectin, TNF-α, IL-10, serum lipid profile, and Lipid Peroxidation (LPO) levels were assessed. The liver was either homogenised for the assessment of antioxidant status or processed for general histology.. Dietary CQ10 mitigated HFHS diet-induced weight gain, decreased glucose, insulin, and leptin levels, and increased adiponectin levels in mice. Coenzyme-Q10 improved the antioxidant status of the liver and blood in HFHS diet-fed mice while also decreasing lipid peroxidation. Lipid profile improved, level of TNF-α decreased, and IL-10 increased following CQ10 diet. A mitigation of HFHS diet-induced alteration in liver morphology was also observed with CQ10.. Dietary CQ10 supplementation mitigates HFHS diet-induced changes in mice, possibly through its anti-oxidant, anti-lipaemic, and anti-inflammatory potential.

Topics: Adiponectin; Animals; Anti-Inflammatory Agents; Antioxidants; Coenzymes; Diet, High-Fat; Dietary Supplements; Insulin; Interleukin-10; Leptin; Lipids; Metabolic Syndrome; Mice; Tumor Necrosis Factor-alpha; Ubiquinone

Topics: Adiponectin; Adolescent; Biomarkers; Body Mass Index; C-Reactive Protein; Humans; Leptin; Metabolic Syndrome

At the same BMI, Asian populations develop cardiometabolic complications earlier than Western populations. We hypothesized that a different secretion of the adipocyte-derived hormones leptin and adiponectin plays a role and investigated the associations of the two hormones with the metabolic syndrome (MetS) in an Indonesian and a Dutch population.. We performed cross-sectional analyses of the Netherlands Epidemiology of Obesity Study (n = 6602) and the SUGAR Scientific Programme Indonesia-Netherlands Study (n = 1461). We examined sex-stratified associations of leptin and adiponectin with MetS, using multivariate logistic regression including adjustment for total body fat. The mean (SD) leptin (mcg/L) were 4.7 (6.0) in Indonesian men, 18.6 (12.0) in Indonesian women, 9.1 (7.7) in Dutch men, and 23.4 (17.4) in Dutch women. The mean (SD) adiponectin (mg/L) were 5.7 (5.4), 7.5 (7.1), 6.6 (3.3), and 11.3 (4.9), respectively. Within the same BMI category, leptin concentrations were similar in the two populations, whereas adiponectin was lower in the Indonesian population. Per SD of leptin, adjusted prevalence odds ratios (ORs, 95%CI) of MetS were 0.9 (0.6-1.2) in Indonesian men, 1.1 (0.9-1.4) in Indonesian women, 2.2 (1.6-2.8) in Dutch men, and 1.2 (1.0-1.5) in Dutch women. Per SD of adiponectin, the ORs were 0.9 (0.7-1.2), 0.8 (0.7-1.0), 0.6 (0.6-0.8), and 0.4 (0.4-0.5), respectively.. Despite lower adiponectin levels, adiponectin was not related to the MetS in the Indonesian population and can not explain their increased cardiometabolic risk at the same BMI.

Topics: Adiponectin; Adiposity; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cardiometabolic Risk Factors; Cross-Sectional Studies; Female; Humans; Indonesia; Leptin; Male; Metabolic Syndrome; Middle Aged; Netherlands; Prevalence; Randomized Controlled Trials as Topic; Risk Assessment; Sex Factors; Young Adult

Limited data exist on the association between maternal diet quality during pregnancy and metabolic traits in offspring during early childhood, which is a sensitive period for risk of obesity-related disorders later in life. We aimed to examine the association of maternal diet quality, as indicated by the Healthy Eating Index-2010 (HEI), in pregnancy with offspring metabolic biomarkers and body composition at age 4-7 years.. We used data from 761 mother-offspring pairs from the Healthy Start study to examine sex-specific associations of HEI >57 vs ≤57 with offspring fasting glucose, leptin, cholesterol, HDL, LDL, percentage fat mass, BMI z score and log-transformed insulin, 1/insulin, HOMA-IR, adiponectin, triacylglycerols, triacylglycerols:HDL, fat mass, and sum of skinfolds. Multivariable linear regression models accounted for maternal race/ethnicity, age, education, smoking habits during pregnancy and physical activity, and child's age.. During pregnancy, mean (SD) HEI score was 55.0 (13.3), and 43.0% had an HEI score >57. Among boys, there was an inverse association of maternal HEI with offspring glucose, insulin, HOMA-IR and adiponectin. For instance, maternal HEI >57 was associated with lower fasting glucose (-0.11; 95% CI -0.20, -0.02 mmol/l), and lower concentrations of: insulin by 15.3% (95% CI -24.6, -5.0), HOMA-IR by 16.3% (95% CI -25.7, -5.6) and adiponectin by 9.3% (95% CI -16.1, -2.0). Among girls, there was an inverse association of maternal HEI with insulin and a positive association with LDL. However, following covariate adjustment, all estimates among girls were attenuated to the null.. Greater compliance with the USA Dietary Guidelines via the HEI may improve the maternal-fetal milieu and decrease susceptibility for poor metabolic health among offspring, particularly boys. Future studies are warranted to confirm these associations and determine the underlying mechanisms.

Topics: Biomarkers; Blood Glucose; Body Composition; Body Mass Index; Child; Child, Preschool; Cholesterol; Diet; Female; Humans; Leptin; Male; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors

Low-grade inflammation is associated with the development of insulin resistance in obese individuals. The present study aims to provide additional evidence strengthening the role of interleukin (IL)-32 in this key process. Using an IL-32 transgenic (IL-32tg) mouse model, we observed that IL-32tg fed a normal diet had greater body weight, due to greater accumulation of white adipose tissue (WAT) along with larger sized adipocytes. This led to metabolic consequences, with significant higher leptin levels and a trend towards hyperinsulinemia, indicating a phenotype resembling the metabolic syndrome. Adipocytes of IL-32tg mice were more prone to induce a pro-inflammatory response locally, which would be expected when predisposed to insulin resistance and type2 diabetes mellitus (T2D). In conclusion, our study provides novel evidence of a direct contribution of IL-32 to pathophysiological perturbations within the adipose tissue, possibly contributing to the metabolic syndrome that precedes frank insulin resistance and T2D. Future research should focus on the role of IL-32 in the obesity epidemic.

Topics: Adipocytes; Adipokines; Adipose Tissue, White; Animals; Body Weight; Cytokines; Hyperinsulinism; Inflammation; Interleukins; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity

Topics: Animals; Blood Glucose; Diet, High-Fat; Drugs, Chinese Herbal; Humans; Insulin; Leptin; Lipids; Magnesium; Metabolic Syndrome; Oxidative Stress; Rats; Salvia miltiorrhiza; Weight Gain; Zinc

Although the role of adiponectin and leptin in the etiology of metabolic syndrome (MetS) has been explored in various populations, limited knowledge is available on the prospective association of adiponectin and leptin with the risk of MetS development. The present study aimed to evaluate the associations of adiponectin, leptin, and the leptin-adiponectin (LA) ratio with the future risk of MetS in middle-aged and older Korean adults. Using a prospective, population-based Ansan-Ansung cohort of the Korean Genome and Epidemiology Study (KoGES), 2691 Korean adults (1317 men and 1374 women) were included in the present study. Serum adiponectin and leptin concentrations were measured using commonly available enzyme-linked immunosorbent assay kits. Multivariable Cox proportional hazard models were used to investigate the relationships of the different adiponectin and leptin concentrations and LA ratio with the incident MetS. During a mean follow-up of 6.75 years, a total of 359 (27.26%) men and 385 (28.02%) women were identified as developing new-onset MetS. After controlling for covariates, higher adiponectin levels were associated with lower incidence of MetS (hazard ratio (HR) for third vs. first tertile: 0.53, 95% confidence interval (CI): 0.40-0.70 for men and HR: 0.54, 95% CI: 0.42-0.71 for women), while higher leptin levels (HR for third vs. first tertile: 2.88, 95% CI: 2.01-4.13 for men and HR: 1.55, 95% CI: 1.13-2.13 for women) and LA ratio (HR for third vs. first tertile: 3.07, 95% CI: 2.13-4.44 for men and HR: 1.94, 95% CI: 1.41-2.66 for women) were associated with an increased incidence of MetS. Among men, in the fully adjusted models an increase by one standard deviation (SD) in adiponectin levels was associated with a 10% decrease in MetS risk (HR per SD: 0.90, 95% CI: 0.85-0.95) while leptin and LA ratio was associated with a 5% (HR per SD: 1.05, 95% CI: 1.01-1.08) and 40% (HR per SD: 1.40, 95% CI: 1.22-1.62) increase in MetS risk, respectively. Among women, a significant association with MetS risk was observed only in adiponectin levels (HR per SD: 0.91, 95% CI: 0.88-0.95). We found that higher adiponectin level was associated with a lower risk of MetS, while higher leptin level and LA ratio were associated with elevated MetS incidence, irrespective of body mass index at baseline in both Korean men and women. Adiponectin and leptin levels and LA ratio could play a role as a useful biomarker in the prediction of future MetS development among midd

Topics: Adiponectin; Aged; Female; Humans; Incidence; Leptin; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Republic of Korea; Risk Factors

The study aimed to investigate association of circulating leptin, adiponectin, chemerin, and omentin-1 with metabolic syndrome (MetS) and cardio-metabolic risk factors in youths. Thirty eight young males were enrolled. Participants underwent anthropometric and blood pressure measures, and fasting blood sampling. Plasma leptin, adiponectin, chemerin, omentin-1 and insulin were measured by ELISA methods. Multiple linear regression models, adjusting for age, MetS traits, C-reactive protein (CRP) and homeostasis model assessment of insulin resistance (HOMA-IR), were applied to determine correlates for each adipokine. Eleven participants meet criteria of MetS. These individuals had higher leptin and chemerin and lower adiponectin plasma concentrations than those without MetS. Plasma leptin and chemerin were positively related, and adiponectin and omentin-1 were inversely related to cardio-metabolic traits. In multivariate models, predictors of leptin were age (β, 0.20, P = 0.01), abdominal obesity (β, 0.24, P = 0.06), raised blood pressure (β, 0.40, P = 0.01), raised triglycerides (β, 0.19, P = 0.01) and CRP (β, 0.31, P = 0.01). Chemerin was associated with abdominal obesity (β, 0.33, P = 0.09) and CRP (β, 0.29, P = 0.04), and adiponectin was associated with raised triglycerides (β, -0.26, P = 0.05), decreased HDL-C (β, -0.28, P = 0.06) and CRP (β, -0.48, P = 0.01). HOMA-IR (β, -0.39, P = 0.09) was the only predictor for omentin. MetS is associated with an altered plasma adipokines profile, with increased leptin and chemerin and decreased adiponectin circulating levels. These findings suggest a beneficial potential of adiponectin and omentin, but a detrimental potential of leptin and chemerin. Further research is needed to lighten the role of adipose tissue-derived adipokines in cardio-metabolic health.

Topics: Adipokines; Adipose Tissue; Adolescent; Adult; C-Reactive Protein; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity, Abdominal; Risk Factors; Triglycerides; Young Adult

Metabolic syndrome (MetS) is the most common condition associated with childhood and adolescent obesity and is a challenging public health issue. Very few studies have described the specificity and sensitivity of serum levels of adropin and apelin-12 as predictors of MetS. The aim of this study was to evaluate the association between serum levels of adropin and apelin-12 and MetS, and their sensitivity as predictors of MetS in obese children.. This study involved 138 children. The study group included obese subjects with MetS, and the two control groups included obese subjects without MetS and normal weight subjects. Anthropometric parameters and clinical data were collected. Plasma levels of apelin-12, adropin, leptin, adiponectin, and TNF-α were also measured.. Obese children with MetS had significantly higher levels of apelin-12 and significantly lower levels of adropin when compared with those in children without MetS. In logistic regressions, we identified that apelin-12 was a risk factor for metabolic syndrome, and adropin was a protecting factor of having MetS after adjusting for age, sex, and puberty. Furthermore, ROC analysis revealed that adropin and apelin-12 are more sensitive predictors of metabolic syndrome than leptin and adiponectin.. Serum adropin and apelin-12 levels can be useful biomarkers for predicting MetS in obese children. Our findings could provide a novel approach for the treatment and prevention of MetS.

Topics: Adiponectin; Adolescent; Body Mass Index; Case-Control Studies; Child; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Pediatric Obesity; Predictive Value of Tests; Risk Factors; ROC Curve

In view of the association of Ramadan intermittent fasting with profound changes in lifestyle both in nondiabetic and diabetic patients, the aim of this study was to investigate the effect of Ramadan fasting on adiponectin, leptin and leptin to adiponectin ratio (LAR), growth hormone (GH), human-sensitive C-reactive protein (hs-CRP), and diabetic and metabolic syndrome factors in patients with Type 2 Diabetes Mellitus (Type 2 DM), their first-degree relatives (FDRs), and healthy controls.. This cohort study involved 98 Yemeni male subjects aged 30-70 years old: 30 Type 2 DM, 37 FDRs of Type 2 diabetic patients, and 31 healthy control subjects. Subjects' body mass index (BMI), waist circumference (WC), and blood pressure (BP) were measured, and venous blood samples were collected twice: the first samples were collected a couple of days prior to Ramadan fasting (baseline) and the second samples after 3 weeks of fasting.. Ramadan fasting did not affect BMI, WC, and BP in Type 2 DM and their FDRs with respect to the baseline levels prior to Ramadan, whereas triglyceride and cholesterol were borderline significantly decreased in Type 2 DM with no effect in FDRs. Fasting blood glucose was not affected in Type 2 DM but was significantly increased in FDRs and control groups, whereas glycated haemoglobin (HbA1c) was slightly decreased in Type 2 DM, FDRs, and healthy controls. C-peptide, insulin, and insulin resistance (HOMA-IR) were significantly increased in Type 2 DM and FDRs, with no effect in the control group, whereas. Ramadan intermittent fasting decreased adiponectin and increased leptin, LAR, insulin, and insulin resistance in both Type 2 DM and FDRs as well as decreased GH in both FDRs and healthy controls and increased hs-CRP in healthy controls. Moreover, Ramadan intermittent fasting neither worsens a patient's glycemic parameters nor improves it, with the exception of a slight improvement in HbA1c in Type 2 DM, FDRs, and healthy controls.

Topics: Adipokines; Adiponectin; Adult; Aged; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; C-Reactive Protein; Cohort Studies; Diabetes Mellitus, Type 2; Fasting; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Triglycerides; Waist Circumference

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

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

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

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

Topics: Adiponectin; Case-Control Studies; Glutathione; Humans; Leptin; Malondialdehyde; Metabolic Syndrome; Oxidative Stress; Sleep Apnea, Obstructive; Superoxide Dismutase

To assess the prevalence of metabolic syndrome (MS) and its parameters in a cohort of overweight and obese Tunisian schoolchildren and to investigate the involvement of leptin, and insulin in MS development via obesity.. A total of 306 schoolchildren between 10- 12 years: obese (n=35), overweight (n=99) and normal weight (n=172) were included in the study. Height, weight, waist circumference were measured and body mass index (BMI) was calculated. A blood sample was collected from each subject to measure glycemia, triglycerides, HDL cholesterol, leptin and insulin. MS diagnosis was based on criteria of  the International Diabetes Federation.. Prevalence of MS was 14.3% in obese children compared to 1% in overweight and 0% in controls (p0.001). Abdominal obesity and hypertension  were the most frequent parameters (88.6% and 25.7% respectively) in obese children. Leptin levels were significantly higher in children with MS (p0.001). In obese children, leptin was positively correlated to waist circumference (r=0.55; p=0.001) and insulin (r=0.52; p=0.002). After adjustment for BMI, leptin remained correlated with insulin (r=0.47; p0.001).. MS is relatively common among Tunisian overweight and obese children. Obesity is an important risk factor for MS development. Early management of childhood obesity is necessary to avoid metabolic complications.

Topics: Case-Control Studies; Child; Cross-Sectional Studies; Female; Humans; Leptin; Male; Metabolic Syndrome; Overweight; Pediatric Obesity; Prevalence; Retrospective Studies; Tunisia

Insulin resistance is an important clinical feature of metabolic syndrome, which includes obesity and type 2 diabetes. Increased adipose energy storage in obesity promote insulin resistance and other metabolic adverse effects. To identify a new link between adipocyte and insulin resistance, we performed targeted metabolite profiling of differentiated adipocytes and studied the association between adipogenic metabolites and insulin resistance. We found a correlation between 2-aminoadipic acid (2-AAA) and adipogenic differentiation. Also, circulatory 2-AAA was positively associated with obesity-related factors (fat mass, fat percent, waist circumference, BMI, BMI z-score, triglycerides, insulin, and HOMA-IR) at baseline and after 2 years in the children cohort study. Of these factors, increased BMI z-score and HOMA-IR were the primary independent factors associated with higher 2-AAA levels, and the baseline 2-AAA level was an indicator of the BMI z-score after 2 years. To validate the relationship between 2-AAA and obesity-related factors, we analyzed changes in 2-AAA levels following obesity intervention programs in two independent studies. In both studies, changes in 2-AAA levels during the intervention period were positively correlated with changes in the BMI z-score and HOMA-IR after adjusting for confounders. Moreover, the 2-AAA levels were increased in cell and mouse models of obesity-related insulin resistance. Excess 2-AAA levels led to impaired insulin signaling in insulin-sensitive cells (liver, skeletal muscle and adipose cells) and caused abnormal gluconeogenesis. Our results demonstrate that 2-AAA is associated with adipogenesis and insulin resistance. In this regard, 2-AAA could be a potential biomarker of obesity and obesity-related metabolic disorders.

Topics: 2-Aminoadipic Acid; Adipocytes; Adipogenesis; Adipose Tissue; Adiposity; Adolescent; Animals; Biomarkers; Blood Glucose; Body Mass Index; Cell Differentiation; Child; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Pediatric Obesity; Republic of Korea; Triglycerides; Waist Circumference

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic effects in small clinic trials in reproductive-age women with PCOS. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin-angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS, and blood pressure (BP) in postmenopausal PCOS. Four-week-old female Sprague Dawley rats were treated with DHT or placebo for 17 months. Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass, and homeostasis model assessment of insulin resistance index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, Lira did not modify BP but increased heart rate in PCOS. The angiotensin-converting-enzyme inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira coadministration with enalapril further reduced BP only in control rats. In summary, Lira has beneficial effects for several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP-lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS.

Topics: Animals; Blood Pressure; Body Composition; Body Weight; Disease Models, Animal; Drug Evaluation, Preclinical; Eating; Female; Glucagon-Like Peptide-1 Receptor; Heart Rate; Hyperandrogenism; Insulin Resistance; Leptin; Lipids; Liraglutide; Metabolic Syndrome; Polycystic Ovary Syndrome; Postmenopause; Random Allocation; Rats, Sprague-Dawley; Renin-Angiotensin System

The present study was designed to evaluate the relationship between bone traits [bone mineral density (BMD) and trabecular bone score (TBS)] and the accumulation of fat in adipose tissues [abdominal subcutaneous (SAT), visceral (VAT), marrow (MAT) and intrahepatic lipids (IHL)], as well as insulin resistance, in subjects with Cushing's disease (CD). The study included control (C = 27), paired (P = 16) and Cushing's disease (CD = 10) groups, which underwent biochemical assessment, dual X-ray absorptiometry, TBS, and magnetic resonance imaging to determine fat deposits. The CD group showed higher serum levels of glucose and insulin, as well as HOMA-IR values, but lower circulatory levels of osteocalcin, in comparison to C and P. The CD group exhibited lower L1-L4 BMD than P (P = 1.059 ± 0.141 vs CD = 0.935 ± 0.093 g/cm2, p < 0.05) (Fig 1A). The lumbar spine BMD from the C group was similar to the other groups. TBS was lower in CD than in P and C (C = 1.512±0.077 vs P = 1.405±0.150 vs CD = 1.135±0.136; p<0.05); there was also significant difference between C and P (p<0.05). MAT, VAT, and IHL were higher in CD than in C and P (p<0.05). Considering all subjects, there was a positive association between TBS with both lumbar spine BMD (R2 = 0.45; p<0.0001) and osteocalcin (R2 = 0.44; p = 0.05). TBS was negatively associated with MAT (R2 = 0.49; p = 0.01), VAT (R2 = 0.55; p<0.05), and HOMA-IR (R2 = 0.44; p<0.01). MAT was positively related with VAT (R2 = 0.44; p<0.01) and IHL (R2 = 0.41; p<0.05). In CD, insulin resistance and adipose tissue dysfunction, including high MAT, are active players in bone deterioration, as confirmed by lower lumbar spine BMD and lower TBS. Thus, our findings point to an additional component of the already well-known complex mechanisms of osteoporosis associated with hypercortisolism.

Topics: Adiponectin; Adipose Tissue; Adult; Body Weight; Bone and Bones; Bone Density; Bone Marrow; Cancellous Bone; Humans; Insulin Resistance; Leptin; Linear Models; Lipids; Metabolic Syndrome; Pituitary ACTH Hypersecretion

Authors discuss the musculoskeletal aspects of obesity by applying a novel approach. Biochemical changes associated with obesity and especially metabolic syndrome, may have a great impact on the function of bones, joints and muscles. Therefore we need a new view and new strategies in rheumatic diseases. Obesity-associated metabolic changes should be considered during the progress of as well as the selection of treatment in inflammatory rheumatic diseases. Individualised treatment is necessary due to associated comorbidities as well. Orv Hetil. 2019; 160(44): 1727-1734.. Absztrakt: A szerzők az elhízás mozgásszervi vonatkozásait új megközelítésben, elsősorban annak metabolikus hatásait kiemelve ismertetik. Az elhízással és különösen a metabolikus szindrómával járó biokémiai változások megváltoztatják a csont, az ízületi struktúrák és az izomzat működését. Ezek alapján szemléletváltozás szükséges bizonyos kórképekben az eddig kialakult nézetekben. A gyulladásos reumatológiai betegségek lefolyásának súlyosságában és az alkalmazott kezelések megválasztásában is figyelembe kell venni az elhízással járó anyagcsere-változásokat. A társuló komorbiditások miatt a személyre szabott kezelés fontossága kiemelt jelentőségű. Orv Hetil. 2019; 160(44): 1727–1734.

Topics: Adipokines; Arthritis; Humans; Joint Diseases; Leptin; Metabolic Syndrome; Musculoskeletal Diseases; Obesity; Osteoarthritis; Rheumatic Diseases

Topics: Adipose Tissue; C-Reactive Protein; Female; Humans; Inflammation; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Pericardium; Risk Factors; Sex Characteristics

This paper aimed to investigate the regulating role of adipokine expression level in body fat distribution of patients with type 2 diabetes mellitus (T2MD) as well as its correlation with metabolic syndrome (MS).. One hundred forty patients with T2MD admitted in the Endocrinology Department of the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 2017 to July 2017 were selected; their body height and weight were measured to calculate Body Mass Index (BMI); patients with a BMI ≤23.9 kg/m2 were included into control group (N.=49), and those with a BMI ≥24 kg/m2 into observation group (N.=91). Based on whether the patients were complicated with MS, they were divided into non-metabolic syndrome (N-MS) group (N.=79) and MS group (N.=61); the levels of serum dipeptidyl peptidase-4 (DPP-4), adiponectin (ADPN) and leptin as well as the contents of body fat and lean tissue of the two groups of patients were measured.. The serum DPP-4 level in observation group was remarkably elevated compared with that in control group (P<0.05), but there were no significant differences in the leptin and ADPN levels between the two groups (P>0.05). The serum DPP-4 and leptin levels were positively correlated with the total body fat mass (FAT) of the patients in observation group (r=0.461, P=0.004; r=0.433, P=0.007); DPP-4 level had a positive correlation with trunk fat mass (TRUNK F) (r=0.545, P=0.001) and limb fat mass (LIMB F) (r=0.412, P=0.005); the leptin level was positively correlated with LIMB F (r=0.513, P=0.001); the leptin and ADPN levels were negatively correlated with the content of lean tissue (r=-0.476, P=0.001; r=-0.344, P=0.021). Compared with those in N-MS group, the levels of serum DPP-4 and leptin were increased significantly, while the ADPN level was decreased notably (P<0.05) in MS group.. The adipokines DPP-4 and leptin in the serum can influence the body fat distribution of patients with T2MD; there is an important association of DPP-4, leptin and ADPN levels with MS, which may be used as therapeutic targets for multiple metabolism disorders of T2MD.

Topics: Absorptiometry, Photon; Adipokines; Adiponectin; Adult; Body Fat Distribution; Body Mass Index; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged

To determine the efficacy of Corchorus olitorius (C. olitorius) leaf extract in the prevention of metabolic syndrome induced in rats by high-fat diet (HFD) and compare it with that of orlistat.. Phytochemical analysis was performed. Effect of orlistat and C. olitorius extract on lipase activity and acute food intake were investigated. Body weight, biochemical parameters and histopathological examination were demonstrated.. Corchorus olitorius extract inhibited the pancreatic lipase activity, but orlistat was more potent. Cumulative food intake has not changed by the tested agents. In obese rats, C. olitorius or orlistat significantly decreased weight gain and visceral white adipose tissue. They exhibited a significant reduction in serum glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol, free fatty acids, IL-1β, tumour necrosis factor-α (TNF-α), insulin and leptin levels of obese rat groups while high density lipoprotein cholesterol and adiponectin levels were significantly increased by them. Histopathological examination of the liver revealed that C. olitorius was more effective than orlistat in the alleviating of steatosis and adipocyte hypertrophy shown in obese control rats.. Corchorus olitorius is effective as orlistat in preventing obesity, hyperlipidaemia, steatosis and insulin resistance. These actions may be mediated by inhibiting of lipase activity, TNF-α, IL-1β and leptin resistance along with increasing of adiponectin.

Topics: Adiponectin; Animals; Anti-Obesity Agents; Corchorus; Cytokines; Diet, High-Fat; Hyperlipidemias; Insulin; Insulin Resistance; Leptin; Lipase; Male; Metabolic Syndrome; Obesity; Orlistat; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Weight Gain

Equine Metabolic Syndrome (EMS) is characterized by abnormalities in insulin regulation, increased adiposity and laminitis, and has several similarities to human metabolic syndrome. A large amount of environmental variability in the EMS phenotype is not explained by commonly measured factors (diet, exercise, and season), suggesting that other environmental factors play a role in EMS development. Endocrine disrupting chemicals (EDCs) are associated with metabolic syndrome and other endocrine abnormalities in humans. This led us to hypothesize that EDCs are detectable in horse plasma and play a role in the pathophysiology of EMS. EDCs acting through the aryl hydrocarbon and estrogen receptors, were measured in plasma of 301 horses from 32 farms. The median (range) TEQ (2,3,7,8-TCDD equivalent) and EEQ (17β-estradiol equivalent) were 19.29 pg/g (0.59-536.36) and 10.50 pg/ml (4.35-15000.00), respectively. TEQ was negatively associated with plasma fat extracted and batch analyzed. EEQ was positively associated with pregnancy and batch analyzed, and negatively associated with being male and superfund score ≤100 miles of the farm. Of particular interest, serum glucose and insulin, glucose and insulin post oral sugar challenge, and leptin concentrations were associated with EEQ, and serum triglyceride concentration was associated with TEQ. Overall, we demonstrated that EDCs are present in the plasma of horses and may explain some of the environmental variability in measured EMS phenotypes. This is the first example of EDCs being associated with clinical disease phenotype components in domestic animals.

Topics: Animals; Blood Glucose; Endocrine Disruptors; Female; Horse Diseases; Horses; Insulin; Leptin; Male; Metabolic Syndrome; Phenotype; Pregnancy

Background Obesity is a chronic inflammatory disorder in which leptin, adiponectin and C-reactive protein (CRP) play an important role. This study aimed to investigate the relationship between markers of adiposity such as leptin, adiponectin and high sensitivity C-reactive protein (hs-CRP) in obese children, and to determine whether these adipokines are significant markers in defining metabolic syndrome (MetS) in pediatric population. Methods A cross-sectional study was conducted over a period of 1 year, between July 2013 and June 2014, on 122 cases of obesity in children diagnosed at the Louis Ţurcanu Emergency Hospital for Children Timişoara, in the departments of Diabetes and Nutritional Diseases, Endocrinology and Cardiology. The patients were divided into two groups, according to the presence of MetS. Results MetS was present in 27% of obese children. The groups were homogenous with respect to age, sex and body mass index (BMI). Adiponectin, leptin and hs-CRP were significantly modified in the group with MetS (p=0.04, p=0.04, p=0.01, respectively). Conclusions hs-CRP, leptin and adiponectin can be used as predictors of cardiovascular risk in pediatric population.

Topics: Adiponectin; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; Child; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Leptin; Male; Metabolic Syndrome; Obesity; Prognosis; Risk Factors

Metabolic Syndrome (MetS) affects 35% of American adults > 40 yr and portends an increased risk for both atherosclerotic cardiovascular disease (ASCVD) and diabetes. The role of mast cells in the proinflammatory state of MetS is not well elucidated. We propose that mast cells in subcutaneous adipose tissue (SAT) of MetS patients without diabetes or clinical ASCVD contribute to insulin resistance and inflammation. Matched controls ( n = 15) and MetS ( n = 19) subjects were recruited from Sacramento, CA, and selected based on Adult Treatment Panel III criteria. SAT biopsy was performed on all subjects and processed for immunohistochemistry. The SAT sections were stained using Astra Blue stain and tryptase stain for mast cells. Fasting blood was obtained for chemistries and biomarkers. Abundance of mast cells (Astra Blue stain) in SAT of MetS subjects compared with controls was increased 2.5-fold ( P < 0.0001). Mast cells correlated positively and significantly with waist circumference, glucose, triglycerides, homeostatic model of assessment-insulin resistance (HOMA-IR), AT insulin resistance, leptin, interleukin (IL)-1β, IL-6, chemerin, p38 MAPK activity, and nuclear factor κB activity in circulating monocytes. Mast cells also correlated significantly with markers of fibrosis and angiogenesis. Tryptase staining of mast cells in AT revealed a significant increase ( P = 0.008) with similar correlations. We make the novel observation that there are increased mast cells in SAT of MetS, and these mast cells correlate with insulin resistance (hepatic and adipose tissue), inflammation, and AT fibrosis. Hence, these immune cells appear to occupy a pivotal role in the pathogenesis of MetS.

Topics: Adipose Tissue; Adult; Aged; Blood Glucose; Case-Control Studies; Chemokines; Female; Fibrosis; Humans; Inflammation; Insulin Resistance; Interleukin-1beta; Interleukin-6; Leptin; Male; Mast Cells; Metabolic Syndrome; Middle Aged; Monocytes; Neovascularization, Pathologic; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Subcutaneous Fat; Triglycerides; Waist Circumference; Young Adult

Polycystic ovarian syndrome (PCOS) is of frequent occurrence in Saudi females and is often associated with obesity, insulin resistance, hypogonadotropic hypogonadism, and infertility. Since these features are also associated with leptin receptor (LEP-R) deficiency, several studies have attempted to link LEP-R gene polymorphisms to PCOS.. The purpose of this study is to assess the possible association of LEP-R gene polymorphism (rs1137101) with the main obesity-linked metabolic parameters in Saudi female patients affected by PCOS. A cohort of 122 Saudi female subjects, attending the outpatient's clinics at Makkah, Saudi Arabia and diagnosed with PCOS was investigated. Metabolic parameters in serum samples, including lipidogram, glucose, leptin, ghrelin and insulin and obesity markers (BMI, W/H ratio, HOMA) were assayed and compared with values from 130 healthy female volunteers (controls). The genotyping of rs1137101 polymorphism in the leptin receptor gene by amplification (PCR) followed by DNA sequencing, was conducted in both groups (PCOS and controls).. Waist/hip ratio (W/H ratio), leptin serum levels and triglycerides appeared to be associated with PCOS but, aside from W/H ratio (AA s GG p = 0.009), this association also occurred for controls. No significant association in the leptin gene polymorphic locus rs1137101 with PCOS was seen in the results of the present study. In the control group, BMI, W/H ratio, leptin, Insulin, and HOMA-IR were significantly higher in the GG genotype compared to AA.. Despite previous suggestion about a relationship between rs1137101, serum leptin levels, and PCOS, our studies do not show any statistical association and further investigations; possibly by also evaluating obese patients should be needed to elucidate this issue better.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Genotype; Humans; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Receptors, Leptin; Saudi Arabia

Topics: Animals; Benzhydryl Compounds; Grape Seed Extract; Leptin; Male; Metabolic Syndrome; Phenols; Rats; Rats, Wistar; Resveratrol; Vitamin E

The prevalence of obesity, metabolic syndrome and type 2 diabetes mellitus is increased among patients with severe mental disorders, and particularly use of second generation antipsychotic drugs is associated with metabolic side effects. Antipsychotics have been found to alter levels of adipokines which regulate insulin sensitivity, but their role in antipsychotic-associated insulin resistance is not established, and it is unclear whether adipokines affect insulin resistance independently of body mass index (BMI).. We included 1050 patients with severe mental disorders and 112 healthy controls aged 18-65 years from the Oslo area, Norway. Clinical variables, BMI and use of medication were assessed, fasting blood samples were obtained for calculation of the leptin/adiponectin ratio (L/A ratio) and estimate of insulin resistance using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Case-control analyses were followed by mediation analyses to evaluate the possible direct effect of antipsychotics on HOMA-IR and indirect effect mediated via the L/A ratio. This was performed both with and without adjustment for BMI, in the total sample and in an antipsychotic monotherapy subsample (N = 387).. BMI, L/A ratio and HOMA-IR were significantly higher in patients than controls (p < 0.001-p = 0.01). There was a significant direct effect from use of antipsychotics in general on HOMA-IR both without (b = 0.03, p = 0.007) and with adjustment for BMI (b = 0.03, p = 0.013), as well as a significant mediating effect via L/A ratio both without (b = 0.03, p < 0.001) and with adjustment for BMI (b = 0.01, p = 0.041). Use of olanzapine (b = 0.03, p < 0.001) or aripiprazole (b = 0.04, p < 0.001) in monotherapy showed significant effects on HOMA-IR mediated via L/A ratio.. The study suggests that use of antipsychotics may alter adipokine levels, and that increased L/A ratio may play a role in the development of insulin resistance associated with use of antipsychotics also independently of BMI.

Topics: Adipokines; Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Mental Disorders; Metabolic Syndrome; Middle Aged; Norway; Obesity

To investigate the association between visceral adipose tissue loss and insulin resistance and hyperleptinemia in adolescents with obesity submitted to interdisciplinary weight-loss therapy.. A total of 172 post-pubertal adolescents (body mass index greater than the 95th percentile of the Centers for Disease Control and Prevention reference growth charts) were recruited for the study. The adolescents were assigned to long-term weight-loss therapy. Body composition, visceral and subcutaneous fat, glucose metabolism, lipid profile, hepatic enzymes and leptin concentration were measured. After the therapy, the adolescents were allocated to three different groups according to the tertile of visceral fat reduction.. Positive effects on body composition were observed in all analysed groups independent of visceral fat reduction. It was found that visceral fat was an independent predictor of insulin resistance in the investigated population. Obese adolescents who lost a higher proportion of visceral adipose tissue (>1.8 cm) demonstrated improved metabolic and inflammatory parameters twice as much than those who presented smaller losses. Positive correlations between visceral fat reduction and glucose metabolism, lipid profile, hepatic enzymes and homeostasis model assessment of insulin resistance index were demonstrated.. The magnitude of the reduction in visceral fat was an independent predictor of insulin resistance, hyperleptinemia and metabolic disorders related to obese adolescents.

Topics: Adiposity; Adolescent; Age Factors; Biomarkers; Blood Glucose; Female; Health Status; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipids; Male; Metabolic Syndrome; Pediatric Obesity; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Loss; Young Adult

non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the western world. Although NAFLD prevalence is higher in patients with a BMI > 25 kg /m2, it is unclear if there are differences between overweight and obese patients. The associated biochemical, dietary and genetic parameters were compared between overweight and obese patients with NAFLD.. patients with biopsy-proven NAFLD (n = 203) were enrolled in a cross-sectional study. The MEDAS questionnaire was used to assess adherence to the Mediterranean diet. Biochemical, anthropometrical parameters and the I148M variant (rs738409) of the PNPLA3 gene and rs180069 of the TNF-α gene were evaluated.. overweight patients had higher serum adiponectin levels (22.5 ± 21.9 vs 11.2 ± 18.1 ng/ml; p < 0.05) and lower resistin (3.3 ± 1.7 vs 8.1 ± 8 ng/ml; p < 0.001) and leptin concentrations (22.9 ± 21.9 vs 55.8 ± 45 ng/ml; p < 0.001) than obese patients. Non-alcoholic steatohepatitis (NASH) was more frequent in the obese group (59.3% vs 41.3%; p = 0.02). The multivariate analysis showed adherence to the Mediterranean diet to be an independent protective factor for NASH and liver fibrosis in overweight patients (OR 0.7, 95% CI 0.5-0.8).. NASH was more prevalent in obese patients than in overweight subjects. HOMA-IR and adherence to the Mediterranean diet provided protection against fibrosis in overweight patients. Adherence to the Mediterranean diet was the only independent factor associated with NASH in these patients.

Topics: Adiponectin; Adult; Analysis of Variance; Biopsy, Needle; Body Mass Index; Cross-Sectional Studies; Diet, Mediterranean; Female; Humans; Insulin Resistance; Leptin; Lipase; Liver; Male; Membrane Proteins; Metabolic Syndrome; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Overweight; Polymorphism, Single Nucleotide; Prevalence; Resistin; Surveys and Questionnaires; Tumor Necrosis Factor-alpha

Phytoestrogens, such as daidzein and genistein, may be used to treat various hormone-dependent disorders. Daidzein can be metabolized by intestinal microbes to S-equol. However, not all individuals possess bacteria producing this metabolite, resulting in categorization of equol vs nonequol producers. Past human and rodent studies have suggested that supplementation of this compound might yield beneficial metabolic and behavioral effects. We hypothesized that administration of S-equol to diet-induced obese male and female mice would mitigate potential diet-induced metabolic and comorbid neurobehavioral disorders. To test this possibility, we placed 5-week-old C57 mice on a high-fat diet (HFD) to mimic the diet currently consumed by many Western adults. Animals were randomly assigned to S-equol supplementation (10 mg/kg body weight) or vehicle control group. After 4 weeks on HFD with or without S-equol supplementation, metabolic and behavioral phenotyping was performed. Although the initial hypothesis proposed that S-equol treatment would improve metabolic and neurobehavioral outcomes, this supplementation instead exacerbated aspects of HFD-induced metabolic disease, as indicated by suppressed physical activity in treated individuals, reduced energy expenditure in treated males, and serum chemistry changes (hyperglycemia in treated individuals; hyperinsulinemia and hypoleptinemia in treated males). Conversely, S-equol individuals exhibited less anxiety-like and depressive-like behaviors, as evidenced by increased exploratory time in the elevated plus maze by treated males and increased time spent mobile in the tail suspension test for treated individuals. In summary, S-equol may be beneficial in mitigating depression and anxiety disorders in individuals, but for indeterminate reasons, supplementation may worsen facets of metabolic disorders in obese individuals.

Topics: Animals; Anxiety; Anxiety Disorders; Behavior, Animal; Blood Glucose; Depression; Depressive Disorder; Dietary Supplements; Equol; Female; Hindlimb Suspension; Insulin; Isoflavones; Leptin; Male; Maze Learning; Metabolic Diseases; Metabolic Syndrome; Mice, Inbred C57BL; Phytoestrogens; Sex Factors

Growing evidence suggests an independent relationship between obstructive sleep apnea syndrome (OSAS) and metabolic syndrome (MS). Patients with OSAS always show clustering of metabolic components. However, the understanding of interplay between OSAS and metabolic components is still lacking.. Participants were consecutively enrolled from our sleep center during the period 2009-2013. Anthropometric variables, metabolic indicators, and sleep parameters were collected from all participants. The factor structure for MS in OSAS and non-OSAS was examined by confirmatory factor analysis.. The OSAS and non-OSAS demonstrated clustering of metabolic components. MS in patients with OSAS was strongly associated with insulin resistance (standardized factor loading = 0.93, p < 0.001), obesity (loading = 0.92, p < 0.001), and the lipid profile (loading = 0.72, p < 0.001). Furthermore, insulin resistance was correlated with obesity and lipid profile (r = 0.86, p < 0.001; r = 0.68, p < 0.001, respectively). Obesity and lipid profile were also highly correlated in OSAS (r = 0.66, p < 0.001). In non-OSAS, MS was strongly associated with insulin resistance, obesity, and lipid profile (loading = 0.95, p < 0.001; loading = 0.74, p < 0.001; loading = 0.68, p < 0.001, respectively). Insulin resistance was most strongly associated with fasting insulin (loading = 0.65, p < 0.001). Lipid profile was most strongly associated with TG (loading = 0.88, p < 0.001). Obesity was most strongly associated with BMI (loading = 0.80, p < 0.001).. OSAS is more prone to show clustering of metabolic components compared with non-OSAS. In particular, insulin resistance, obesity, and the lipid profile were independently and strongly correlated with MS in OSAS.

Topics: Adult; Body Mass Index; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Polysomnography; Risk Factors; Sleep Apnea, Obstructive

Obesity is a chronic condition whose incidence is growing due to lack of exercise and frequent nutrition disorders. Childhood obesity has reached epidemic proportions worldwide. One of the best treatment methods is physical training. However, conflicting results have been reported regarding its clinical effectiveness. These contrasting findings may be due to the type and intensity of the adopted physical training program. Therefore, the purpose of the current study was to investigate the effect of an 8-week individualized physical training program on endothelial function, blood biomarkers and adipokine levels in obese children with and without metabolic syndrome (MS). One-hundred-and-twenty-two obese adolescents (71 obese without MS and 51 obese with MS) aged 14 ± 2 years were included in this study. The 8-week individualized training program decreased glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol and leptin in obese subjects with and without MS. However, adiponectin and endothelial-dependent vasodilatation increased in the follow-up study in both groups. Taken together, the findings suggest that individualized training program is an effective means for the treatment of obesity and MS in pediatric populations.

Topics: Adipokines; Adolescent; Biomarkers; Body Mass Index; Child; Cholesterol, LDL; Exercise; Female; Follow-Up Studies; Humans; Leptin; Male; Metabolic Syndrome; Pediatric Obesity; Triglycerides

The adipocyte expansion is a critical process with implications in the pathogenesis of obesity associated metabolic syndrome. Impaired adipogenesis leads to dysfunctional, hypertrophic adipocytes, local inflammation and peripheric insulin resistance.. We assessed the relationship between the adipogenic differentiation capacity of the subcutaneous adipose derived stem cells (ASCs), evaluated by total lipid accumulation, and the metabolic and hormonal profile in a group of obese female patients proposed for bariatric surgery (N = 20) versus normal weight female controls (N = 7).. The lipid accumulation (measured as optical density at 492 nm) of ASCs during their differentiation to adipocytes was significantly lower in ASCs isolated from obese patients as compared to ASCs isolated from normal weight patients (0.49 ± 0.1 vs. 0.71 ± 0.1, p < 0.001). Significant negative correlations between lipid accumulation in adipogenic differentiated ASCs and plasma concentrations of triglycerides (p < 0.01), insulin (p < 0.001), HOMA-IR (p < 0.01), adiponectin (p < 0.05) and leptin/adiponectin ratio (p < 0.05) were found in obese group.. In severely obese female patients, the abnormal adipogenesis is related to insulin resistance and leptin/adiponectin ratio. The abnormal lipid accumulation in the mature adipocyte derived from obese ASCs could possible predict the further development of type 2 diabetes mellitus in severely obese patients and influence the selection of patients for bariatric surgery.

Topics: Adiponectin; Adult; Bariatric Surgery; Cell Differentiation; Cells, Cultured; Female; Fluorescent Antibody Technique; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Obesity; Subcutaneous Fat

Metabolic Syndrome (MetS) is a common global disorder that predisposes to both Type 2 diabetes mellitus (T2DM) and cardiovascular disease (ASCVD). Adipose tissue (AT) contributes significantly to increased inflammation and insulin resistance (IR) in MetS which appear to be the crucial underpinnings of MetS. Compared to macrophages and lymphocytes in human subcutaneous AT (SAT), there is sparse data on the role of other immune cells, especially eosinophils (EOS). In this study, we investigated the abundance of EOS in the SAT of 19 patients with MetS without diabetes, ASCVD, smoking or any inflammatory condition, and matched controls.. SAT EOS were quantified by immunohistochemistry.. Both circulating and SAT EOS were significantly increased 2-fold in MetS and correlated with each other. Circulating EOS correlated significantly with triglycerides (TG), high-sensitivity CRP, leptin, and IL-6. SAT EOS correlated significantly with plasma glucose, TG, FFA, adipose-IR, leptin, IL-6, endotoxin, chemerin and inversely with adiponectin. They also correlated with SAT markers of fibrosis: collagen and Sirius red staining of SAT.. We make the novel and seminal observation that eosinophils are increased in SAT of MetS patients, and are associated with the pro-inflammatory state. Hence, in humans, they appear to contribute to the dysregulation of SAT biology in MetS.

Topics: Adipose Tissue; Adult; Biomarkers; C-Reactive Protein; Eosinophils; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Subcutaneous Fat; Triglycerides

This study aimed to evaluate the association between serum vitamin D levels and nonalcoholic fatty liver disease (NAFLD) parameters, such as metabolic syndrome (MS), inflammatory cytokines (tumor necrosis factor, high sensitive C-reactive protein) and adipokines (adiponectin, leptin).. From August 2013 to August 2016, a community-based study was performed in the north-eastern region of Taiwan. All subjects received a demographic survey, blood testing and abdominal ultrasonography (US). The vitamin D level was evaluated by quartile divide or used the classification of deficiency (< 20 ng/ml), insufficiency (20-30 ng/ml) and sufficiency (> 30 ng/ml).. Subjects were divided into NAFLD group and normal control (subjects number = 564 in each group) following abdominal US study and matching age and gender. The mean age was 57.1 years in NAFLD group and 57.5 in control group. Subjects in NAFLD group had a lower mean vitamin D than those in the control group (28.5 ± 9.5 ng/ml vs. 29.9 ± 10.2 ng/ml, P = 0.018). Subjects with serum vitamin D deficiency or insufficiency had higher odds for MS than those with sufficient vitamin D levels [deficiency vs. sufficiency, adjusted odds ratio (aOR) =1.860 (95% CI = 1.234-2.804), P = 0.003; insufficiency vs. sufficiency, aOR = 1.669 (95% CI = 1.237-2.251), P = 0.001]. Similarly, subjects in the lowest quartile of vitamin D had higher odds for MS than those in the highest quartile of vitamin D (aOR = 2.792, 95% CI = 1.719-4.538, P < 0.001). Vitamin D level was positively correlated with age and male, but negatively correlated with serum leptin level.. Subjects with low vitamin D level had higher odds for MS, but higher levels of leptin, compared to those with high vitamin D levels.

Topics: C-Reactive Protein; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Non-alcoholic Fatty Liver Disease; Taiwan; Tumor Necrosis Factor-alpha; Vitamin D Deficiency

Maternal metabolic syndrome during gestation and lactation leads to several Se-status-related metabolic changes in offspring. MS leads to hepatomegaly, liver oxidation, resistance to insulin challenges and selenoptroteins expression upregulation, producing an energy imbalance in hepatocytes. As Se is necessary for correct heart function, Se deposits are depleted and selenoproteins expression downregulated in heart; this depletion being related to cardiovascular damage. Recently, selenoproteins have been directly implicated in the central endocrine regulation of appetite and energy homeostasis.. To obtain information about how Se is involved in regulating endocrine peripheral energy balance during MS process, two experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65% and Se: 0.1 ppm). At the end of lactation (21d old), the pups' appetite profile, tissular Se deposits and peptides from gastrointestinal tract (including pancreas), leptin, skeletal growth markers and cytokines in serum were measured.. MS-exposed pups present changes in Se homeostasis, appetite profile and endocrine energy balance signals related to impaired insulin secretion and high leptin serum values. This profoundly affects the pups' growth profile since muscle and bones are in catabolic process and brown adipose tissue (BAT) mass decreases.. These results indicate that the pups are suffering a process similar to diabetes type 1 which appeared when dams received low Se dietary supply and they point to Se as an important marker and key treatment for these disorders during gestation and lactation that affect future adult health.

Topics: Animals; Biomarkers; Endocrine System Diseases; Energy Metabolism; Female; Fetal Development; Homeostasis; Insulin Resistance; Leptin; Male; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Selenium

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

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

Obesity and metabolic syndrome (MeS) are more frequently observed in bipolar patients than the general population. This may result from the differences of adipocytokines and ghrelin levels in bipolar disorder.. We evaluated the leptin, adiponectin, resistin and ghrelin levels in bipolar patients (n = 30) in manic episode and in a control group (n = 30). After treatment, the same patients were evaluated again during the euthymic episode. We also measured the insulin, glucose, insulin resistance (HOMA), trygliceride (TG), total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) in relation to the (MeS).. When controlling for age, BMI and glucose, leptin levels were higher in the bipolar disorder manic episode group (BD-ME) and bipolar euthymic episode group (BD-EE) than the control group; resistin levels were higher in the BD-ME compared to the control group and it had a positive correlation with Young Mania Rating Scale (YMRS). After treatment, ghrelin levels were higher in the BD-EE compared to the BD-ME group. There was no difference among the groups with respect to adiponectin.. The present results point that high leptin, resistin and ghrelin levels may be involved in the early pathophysiological process which can lead to later obesity and MeS in patients with bipolar disorder.

Topics: Adiponectin; Adult; Bipolar Disorder; Blood Glucose; Female; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Resistin; Young Adult

Metabolic syndrome is a major risk factor for the development of cardiovascular diseases and diabetes, among other conditions. Studies have shown that aging and metabolic syndrome share several metabolic alterations, and that aged individuals, in particular females, are at an increased risk of developing metabolic disorders. Although several studies have investigated the effects of hypercaloric diets in the development of obesity and metabolic syndrome in young animals, few studies have investigated these parameters in aged animals, especially in females. Therefore, the aim of this study was to investigate the effects of a hypercaloric diet in metabolic parameters of young and aged female rats, including its effects on lipid and glycemic profile and on liver lipid content. When compared to young animals, the aged rats presented increased serum levels of triglycerides and decreased serum levels of HDL cholesterol and glycemia, as well as increased hepatic levels of triglycerides and total cholesterol. The hypercaloric diet increased food intake, body weight gain and adiposity index, leading both young and aged animals to a dyslipidemia, represented by increased serum levels of triglycerides. The hypercaloric diet increased the glycemia and the HOMA index only in the young animals. On the other hand, the diet increased the frequency of hepatocellular microvacuolar degeneration only in the aged animals. In summary, it was observed that the females from different ages respond differently to hypercaloric diet intake: while the aged animals were more resistant to the changes in the glycemic profile, they were more susceptible to the hepatic damage caused by this diet.

Topics: Adiposity; Aging; Animals; Blood Glucose; Body Weight; Dyslipidemias; Energy Intake; Female; Hyperglycemia; Leptin; Lipid Metabolism; Liver; Metabolic Syndrome; Rats; Rats, Wistar; Triglycerides

Multiple studies have found a direct relationship between leptin concentrations and disease activity in rheumatoid arthritis.. We studied 77 patients with the diagnosis of rheumatoid arthritis; the leptin determination was through an enzyme immunoassay. Disease activity was assessed by the DAS-28 CRP. A multivariate logistic regression model was used to determine the association between significant variables and leptin concentrations.. 40.3% of the patients were in remission, 41.6% were mildly active, 11.7% were moderately active and 6.5% were severely active. The results show an independent association between higher concentrations of leptin and disease activity (OR 1.7; 95% CI 1.4-3.2; p .03), the number of swollen joints (OR 4.6; 95% CI 1.7-8.3; p .000), the number of painful joints (OR 3.4; 95% CI 1.6-4.6; p .000), and the presence of metabolic syndrome (OR 1.3; 95% IC 1.2-1,9; p .045).. The data suggest that serum leptin is elevated in patients with active RA.

Topics: Adult; Anthropometry; Arthritis, Rheumatoid; C-Reactive Protein; Female; Humans; Immunoenzyme Techniques; Interleukin-6; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Severity of Illness Index

The patients with schizophrenia are at increased risk for problems regarding metabolic parameters due to their lifestyle and antipsychotic treatment.. In this study, we aimed to evaluate the levels of adiponectin, leptin, irisin in patients with schizophrenia who were nondiabetic, nonobese and under antipsychotic treatment.. 5 ml sample of venous blood was collected from each participant. Blood cells were separated from the serum. The serum samples were stored in a -80°C freezer. Biochemical analyses were performed on these samples. Adiponectin, leptin and irisin levels were measured by Enzyme Linked Immunosorbent Assay method.. The study included 88 subjects. Of them, 44 were patients with schizophrenia and 44 were healthy controls. There were no statistically significant results when the c-reactive protein, adiponectin, leptin and irisin levels were compared between the schizophrenia and the control group (p>0.05).. In our study, adiponectin, leptin and irisin levels in patients with schizophrenia did not present a statistically significant difference from healthy controls. Therefore, there is a need for studies including more participants to investigate the level of irisin in patients with schizophrenia.

Topics: Adiponectin; Adult; Antipsychotic Agents; Biomarkers; C-Reactive Protein; Diagnostic and Statistical Manual of Mental Disorders; Enzyme-Linked Immunosorbent Assay; Female; Fibronectins; Hospitals, Teaching; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Reproducibility of Results; Risk Factors; Schizophrenia; Turkey

Leptin levels are reported to be increased with excessive body fat and is a potential determinant of obesity and its complications. Our Objective is to evaluate the relationship between leptin levels and BMI, waist circumference and metabolic syndrome components in normal and obese females classified according to their BMI.. A total of 136 female subjects aged between 20 and 60 years were recruited for the current study. Anthropometric measures included body mass index and waist circumference. The blood samples were used for estimation of plasma fasting blood glucose and serum was used for estimation of triglycerides, total cholesterol, low and high density lipoproteins, and total leptin.. Correlation between glucose and lipids profile with waist circumference among the whole study group (obese and non-obese) is reflecting that a strong positive correlation between BMI and blood glucose, serum TGs, cholesterol and LDL, a negative correlation was reported between BMI and serum HDL. Mean of leptin concentrations in two groups were found to be 5.77 ng/ml (±1.00) in non-obese and 28.89 ng/ml (±4.91) in the obese with metabolic syndrome. Leptin had a positive correlations with triglycerides (r = 0.84, p < 0.001), total cholesterol (r = 0.77, p < 0.001), LDL (r = 0.83, p < 0.001), waist circumference (r = 0.86, p < 0.001) and BMI (r = 0.72, p < 0.001) in the test group. a negative correlation was reported between BMI and serum HDL (r = -0.48, p < 0.001).. Leptin levels were high in Saudi women with high BMI and waist circumference. There was a significant correlation between leptin levels and Obesity.

Topics: Adult; Biomarkers; Body Constitution; Female; Follow-Up Studies; Humans; Leptin; Metabolic Syndrome; Middle Aged; Obesity; Prognosis; Retrospective Studies; Waist Circumference; Young Adult

In this study, gamma-aminobutyric acid (GABA) enriched rice bran (ERB) was supplemented to obese rats to investigate the attenuation of metabolic syndromes induced by high-fat diet. ERB-containing diet stimulated butyrate and propionate production by promoting Anaerostipes, Anaerostipes sp., and associated synthesizing enzymes. This altered short-chain fatty acid (SCFA) distribution further enhanced circulatory levels of leptin and glucagon-like peptide-1, controlling food intake by downregulating orexigenic factors. Together with the enhanced fatty acid β-oxidation highlighted by Prkaa2, Ppara, and Scd1 expression via AMPK signaling pathway and nonalcoholic fatty liver disease pathway, energy expenditure was positively modulated. Serum lipid compositions showed ERB supplement exhibited a more efficient effect on lowering serum sphingolipids, which was closely associated with the status of insulin resistance. Consistently, genes of Ppp2r3b and Prkcg, involved in the function of ceramides in blocking insulin action, were also downregulated following ERB intervention. Enriched GABA and phenolic acids were supposed to be responsible for the health-beneficial effects.

Topics: Adipose Tissue; Animals; Ceramides; Diet; Diet, High-Fat; DNA; Energy Metabolism; Fatty Acids, Volatile; Food, Fortified; gamma-Aminobutyric Acid; Gastrointestinal Microbiome; Glucagon-Like Peptide 1; Insulin Resistance; Leptin; Liver; Male; Metabolic Syndrome; Obesity; Oryza; Rats; Rats, Sprague-Dawley; Seeds; Sphingolipids

The purpose of this study was to compare adipokines levels in plasma and synovial fluid (SF) between knee osteoarthritis (OA) patients with and without metabolic syndrome (MetS), and to evaluate the associations between adipokines levels and clinical severity of knee osteoarthritis.. Eighty female patients with knee osteoarthritis were enrolled in the study. These patients were divided into two groups: patients with and without MetS. Clinical severity was evaluated according to visual analogue scale (VAS) pain scores and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores. Adipokines and soluble leptin receptor levels in plasma and SF were determined by a sandwich enzyme-linked immunosorbent assay.. Forty-three (54%) osteoarthritis patients with MetS and 37 (46%) osteoarthritis patients without MetS were enrolled as MetS-OA group and nMetS-OA group, respectively. VAS pain and WOMAC scores were higher in MetS-OA group compared with those in nMets-OA group (p < 0.01). The leptin and free leptin levels in plasma and SF were significantly higher in MetS-OA group than those in nMetS-OA group, while the adiponectin levels were lower (All p < 0.01). Significant differences existed even after adjustment for body mass index (BMI) (p < 0.05). There were no significant associations between adipokines levels and the clinical severity of OA in MetS-OA group and nMetS-OA group respectively (p > 0.05).. Leptin was higher and adiponectin was lower in knee osteoarthritis patients with MetS compared to those without MetS, independent of BMI. The higher SF and plasma levels of leptin in MetS-OA patients may need further studies to delineate their pathophysiological relationships.

Topics: Adiponectin; Aged; Body Mass Index; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Metabolic Syndrome; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Severity of Illness Index; Synovial Fluid

The genome-wide association study has founded hypertension-related single nucleotide polymorphism (SNP) rs11191548 near CYP17A1 encoding a key enzyme involved in steroid metabolism, but the molecular mechanisms are not understood and the associations of the SNP with hypertension-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNP and two hypertension-related traits, lipids and leptin.. We genotyped the SNP in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study.. The SNP rs11191548 was significantly associated with high-density lipoprotein cholesterol (HDL) (P = 0.014 and 0.028, respectively) and leptin (P = 0.011 and 0.026, respectively) under an additive model after adjustment for age, gender, and systolic blood pressure (SBP) or diastolic blood pressure (DBP). There was a statistically significant association of rs11191548 with high leptin after adjustment for age, gender, and SBP or DBP. The P-values remain significant after correction for multiple testing.. We demonstrate for the first time that the SNP rs11191548 near CYP17A1 is associated with HDL and leptin in Chinese children. These novel findings provide important evidence that HDL and leptin maybe possibly mediate the process of CYP17A1 involved in hypertension.

Topics: Adolescent; Asian People; Blood Pressure; Child; China; Cholesterol, HDL; Cross-Sectional Studies; Female; Genotyping Techniques; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Polymorphism, Single Nucleotide; Steroid 17-alpha-Hydroxylase

Visceral fat deposition is associated with impairment of glucose and lipid metabolism while leptin levels are frequently related to subcutaneous fat area. At present, there is considerable controversy regarding the role of visceral adipose tissue accumulation in the development of metabolic syndrome (MS). Here we show the effects of omentectomy on the liver and MS in a diet induced obesity rat model. Our results reveal that undergoing omentectomy previously the establishment of the diet-induced-obesity reduced significantly body weight gain and avoid the development of MS, including non-alcoholic fatty liver disease. Intriguingly, the significantly lower body weight gain was due to decreased food intake. Omentum drives obesity progression through leptin resistance mediated by C-reactive protein, Interleucin (IL)-6 and high lipolysis activity. Omentum removal reversed immediately the increased plasma levels of CRP and IL-6 and gradually food intake, weight gain, and features of MS in diet-induced-obesity. Omentectomy caused no changes in normal-weigh-rats. This report displays causal mechanism by which omentum promotes obesity and propose omentectomy as a promising procedure in MS prevention.

Topics: Adipogenesis; Animals; Appetite; Body Weight; C-Reactive Protein; Disease Models, Animal; Interleukin-6; Leptin; Metabolic Syndrome; Obesity; Omentum; Rats; Surgical Procedures, Operative; Treatment Outcome

Leptin and adiponectin play an important role in the regulation of body weight and energy homeostasis. The purpose of the present study was to ascertain the relationship between leptin to adiponectin ratio (L:A) and metabolic risk factors in postmenopausal women.This is a cross sectional case-control study. A total of 523 postmenopausal women were recruited for the study 270 postmenopausal women with metabolic syndrome and 253 apparently healthy control postmenopausal women without metabolic syndrome. Biochemical and Anthropometrical parameters were measured. Leptin and adiponectin levels were determined by sandwich enzyme-linked immunosorbent assay, insulin resistance was determined by homeostasis model assessment for insulin resistance (HOMA-IR). Results of this study indicate that leptin (15.92 ± 10.50 vs.9.43 ± 4.39 pg/ml, p < 0.001), L:A ratio (1.08 ± 1.06 vs.0.42 ± 0.38 pg/ml, p < 0.001), HOMA-IR, the lipid profile, and other metabolic risk factors (waist circumference (WC), waist-to-hip ratio(WHR), body mass index((BMI)), fasting plasma glucose (FPG) level and fasting plasma insulin(FPI)) were significantly higher but HDL, HDL/LDL and adiponectin level (20.55 ± 10.76 vs.30.08 ± 13.08 pg/ml, p < 0.001)were significantly lower in postmenopausal women with metabolic syndrome than in women without the syndrome (p < 0.001). Further, in postmenopausal women with metabolic syndrome, L: A ratio was significantly positive (p < 0.05 or p < 0.001) correlated with WC, BMI, WHR, TG, FPG, TC/HDL, LDL/HDL, FPI and HOMA-IR (p < 0.01), and negatively correlated with HDL and HDL/LDL (p < 0.001). Conclusively L: A ratio was found to be significantly associated with central obesity and other metabolic risk factors so that high L:A ratio may act as a diagnostic marker for metabolic syndrome in postmenopausal women.

Topics: Adiponectin; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Middle Aged; Postmenopause; Risk Factors

Leptin is an adipokine which regulates appetite and energy balance through a mechanism partially mediated by neurotensin (NT) in central nervous system. Besides acting as a neurotransmitter, NT is expressed in human intestine where it promotes fat absorption and its circulating levels associate with obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease. Whether a relation exists between circulating leptin and NT levels has not been investigated yet. The aim of this study was to test the hypothesis of an association between plasma leptin and NT concentration in adults with or without T2DM.. We recruited a population of 72 subjects (M/F: 39/33; age: 49.5 ± 10.6 years; BMI: 26.5 ± 4.7 kg/m. Circulating leptin is associated with higher proNT levels independent of diabetes, obesity and metabolic syndrome components; besides its effects on central leptin signaling, NT may influence energy balance by modulating circulating leptin concentration likely through a mechanism involving gut fat absorption.

Topics: Adult; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Neurotensin; Obesity

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

Single nucleotide polymorphisms in serotonin 2C receptor (HTR2C), leptin (LEP), and leptin receptor (LEPR) genes are reportedly associated with the presence of metabolic syndrome (MS). We investigated whether HTR2C:rs518147 (-697G/C), rs12836771 (A/G), LEP: rs7799039 (-2548G/A) and LEPR:rs1137101 (668A/G) are related to MS in psychotic disorder patients treated with atypical antipsychotics.. A cross-sectional study including 200 patients was conducted; genetic polymorphisms in HTR2C (rs518147 and rs12836771), LEP (rs7799039) and LEPR (rs1137101) were genotyped. The presence of MS was evaluated according to the 2005 International Diabetes Federation (IDF) Asia criteria. The associations of genetic factors with the presence of MS are analysed.. Two SNPs in the HTR2C gene but not LEP and LEPR were associated with the presence of MS after adjustment for the combination of atypical antipsychotics. With respect to the effect of gender after treatment with risperidone and clozapine was statistically significant. Moreover, genotype combinations had no effect on MS.. Therefore, HTR2C genetic variants may be involved in the susceptibility to MS in patients treated with atypical antipsychotics. Additionally, there was a gender effect in the presence of MS. No effect of LEP or LEPR polymorphisms or the combination of HTR2C-LEP and HTR2C-LEPR was observed for the presence of MS.

Topics: Adult; Antipsychotic Agents; Cross-Sectional Studies; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT2C; Receptors, Leptin; Treatment Outcome

Dietary guidelines for obesity typically focus on three food groups (carbohydrates, fat, and protein) and caloric restriction. Intake of noncaloric nutrients, such as salt, are rarely discussed. However, recently high salt intake has been reported to predict the development of obesity and insulin resistance. The mechanism for this effect is unknown. Here we show that high intake of salt activates the aldose reductase-fructokinase pathway in the liver and hypothalamus, leading to endogenous fructose production with the development of leptin resistance and hyperphagia that cause obesity, insulin resistance, and fatty liver. A high-salt diet was also found to predict the development of diabetes and nonalcoholic fatty liver disease in a healthy population. These studies provide insights into the pathogenesis of obesity and diabetes and raise the potential for reduction in salt intake as an additional interventional approach for reducing the risk for developing obesity and metabolic syndrome.

Topics: Adult; Aged; Aged, 80 and over; Animals; Diabetes Mellitus; Fructokinases; Fructose; Humans; Leptin; Metabolic Syndrome; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Sodium Chloride, Dietary; Sucrose; Transcription Factors

We investigated the associations of cardiometabolic risk factors with academic achievement and whether motor performance, cardiorespiratory fitness, physical activity, or sedentary behaviour mediated these associations. Altogether 175 children 6-8 years-of-age participated in the study. We assessed body fat percentage (BF%), waist circumference, insulin, glucose, triglycerides, HDL cholesterol, and systolic and diastolic blood pressure, leptin, alanine aminotransferase, and gamma-glutamyltransferase (GGT). Reading fluency, reading comprehension, and arithmetic skills were assessed using standardized tests. Speed/agility, balance, and manual dexterity test results were used to calculate motor performance score and physical activity was assessed by combined heart rate and movement sensor and cardiorespiratory fitness by maximal cycle ergometer test. In boys, BF% was inversely associated with reading fluency (β = -0.262, P = 0.007) and reading comprehension (β = -0.216, P = 0.025). Motor performance mediated these associations. Leptin was inversely related to reading fluency (β = -0.272, P = 0.006) and reading comprehension (β = -0.287, P = 0.003). The inverse association of leptin with reading fluency was mediated by motor performance. In girls, GGT was inversely associated with reading fluency independent of confounders (β = -0.325, P = 0.007). The inverse association of BF% with academic achievement among boys was largely explained by motor performance. Leptin in boys and GGT in girls were inversely associated with academic achievement independent of confounding factors.

Topics: Academic Success; Adiposity; Alanine Transaminase; Cardiorespiratory Fitness; Child; Exercise; Female; gamma-Glutamyltransferase; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Motor Skills; Risk Factors; Sedentary Behavior

Large yellow tea is a traditional beverage in China with a unique toasty flavor. A preliminary study using 3T3-L1 cells indicated that large yellow tea possessed more potent lipid-lowering efficacy than green, black, dark, and white teas. In the present study we further investigated its influence on metabolic syndrome in a high-fat diet (HFD) mouse model with an emphasis on dose response. Thirty-two C57BL/6 male mice were randomly divided into 4 groups: low-fat diet (LFD), HFD, HFD + 2.5% large yellow tea hot-water extract (YT, equivalent to 10 cups of tea daily for humans), HFD + 0.5% YT. Our data indicated that YT treatment for 12 weeks significantly reduced body weight, liver weight, and adipose tissue weight of the mice; lowered serum insulin and leptin; and raised serum adiponectin with dose effect. H&E staining showed that the HFD group exhibited significant enlargement of adipose cell sizes and the corresponding decrease of adipose cell numbers, which were dose-dependently attenuated in both YT groups. IHC results revealed that YT decreased macrophage recruitment in the liver, epididymal adipose tissue, and subcutaneous adipose tissue and depressed serum inflammatory cytokines including TNF-α, MCP-1, IFN-γ, IL-6, and IL-1β, in a dose-dependent manner. In addition, YT decreased serum glucose, TC, TG, LDL-C, and HDL-C, as well as ameliorated glucose intolerance and insulin resistance independent of dose. Overall, YT would be a unique tea with dose-independent antihyperglycemic and robust lipid-lowering efficacies.

Topics: 3T3-L1 Cells; Adipose Tissue; Animals; Camellia sinensis; China; Diet, High-Fat; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Liver; Macrophages; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Tea; Tumor Necrosis Factor-alpha

Many studies have reported the causes of obese metabolic syndrome (MS); however, the causes of nonobese MS (NMS) remain unknown. In this study, we demonstrated that inflamed dysfunctional adipose tissue plays a crucial role in cholesterol-induced NMS. Control (C), high cholesterol (HC) and HC with 10% fructose in drinking water (HCF) diets were fed to Sprague-Dawley rats for 12 weeks. After 12 weeks, the body weights of the C- and HC-fed rats were comparable, but the weights of the HCF-fed rats were relatively low. Cholesterol caused metabolic problems such as high blood pressure, hypercholesterolemia and hypoinsulinemia. The HCF-fed rats exhibited whole-body insulin resistance with low circulating high-density lipoprotein levels. Increases in the tumor necrosis factor α level in the plasma, the number of CD68+ macrophages and the free nuclear factor-κB level in gonadal white adipose tissue (gWAT) resulted in local inflammation, which appeared as inflamed dysfunctional gWAT. Reduced superoxide dismutases (SODs) deteriorate natural antioxidant defense systems and induce reactive oxygen species in gWAT. Dysregulation of plasma levels of catecholamine, adipokines (leptin and adiponectin), hormone-sensitive lipase and perilipin in cholesterol-induced inflamed adipose tissue contributed to increased lipolysis and increased circulating nonesterified fatty acids. Cholesterol activated inflammation, lipolysis and cell death in 3T3-L1 adipocytes. Moreover, Chol-3T3-CM reduced the population of M2-type Raw264.7 macrophages, indicating that the macrophage polarization is mediated by cholesterol. Together, our findings indicate that inflamed dysfunctional adipocytes are critical in NMS, supporting the development of anti-inflammatory agents as potential therapeutic drugs for treating NMS.

Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Adipose Tissue, White; Animals; Cell Death; Cholesterol; Energy Metabolism; Epinephrine; Fatty Acids; Feeding Behavior; Fructose; Inflammation; Insulin; Insulin Resistance; Leptin; Lipolysis; Macrophages; Male; Metabolic Syndrome; Mice; Norepinephrine; Obesity; Phosphorylation; Rats, Sprague-Dawley; RAW 264.7 Cells

Leptin and adiponectin are adipokines which have opposing roles in the development of insulin resistance and metabolic syndrome (MetS). Leptin/adiponectin ratio (L/A ratio) has been proposed as a good biomarker for MetS in general population. This study aimed to compare the strength of association between MetS and leptin, adiponectin and L/A ratio, as well as to assess their performance to diagnose MetS in patients with schizophrenia.. Patients diagnosed with DSM-IV schizophrenia and under clozapine or olanzapine monotherapy for at least six months were recruited. We used the modified ATP III criteria for Asians to evaluate subjects for a diagnosis of MetS.. We recruited 262 study subjects with schizophrenia, and classified them into those with MetS (n = 87) and those without MetS (n = 175). Leptin level was positively correlated with BMI, waist circumference, and insulin level. Adiponectin level was negatively correlated with most metabolic parameters, except glucose level. L/A ratio was positively correlated with most metabolic parameters, except levels of glucose and HDL-C. Significant gender differences existed in leptin levels, adiponectin levels, and L/A ratio. Without and with adjustment of age and gender, binary logistic regression analysis showed that leptin level, adiponectin level, and L/A ratio were significantly associated with MetS. The area under curve (AUC) of L/A ratio and leptin level for MetS was 0.744 (95% CI = 0.685-0.802) and 0.666 (95% CI = 0.601-0.731). The AUC of adiponectin level for the absence of MetS was 0.717 (95% CI = 0.655-0.780). The discriminative strength of L/A ratio for MetS was better in men than in women.. The present study results suggest that L/A ratio may be a preferential marker of metabolic syndrome in patients with schizophrenia compared to leptin or adiponectin alone.

Topics: Adipokines; Adiponectin; Adult; Biomarkers; Body Mass Index; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Schizophrenia; Sex Factors; Waist Circumference

Topics: Adiponectin; Animals; Fatty Liver; Glucose Tolerance Test; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Mice; Mice, Inbred ICR; Phosphorylation; PPAR gamma; Proto-Oncogene Proteins c-akt; Trialkyltin Compounds

ErbB4, a member of the EGF receptor family, plays a variety of roles in physiological and pathological states. Genetic studies have indicated a link between ErbB4 and type 2 diabetes and obesity, but its role in metabolic syndrome (MetS) has not been reported. In the current study we found that mice with ErbB4 deletion developed MetS after 24 wk on a medium-fat diet (MFD), as indicated by development of obesity, dyslipidemia, hepatic steatosis, hyperglycemia, hyperinsulinemia, and insulin resistance, compared with wild-type mice. ErbB4 deletion mice also exhibited increased amounts of subcutaneous and visceral fat, with increased serum leptin levels, compared with wild-type mice, whereas levels of adiponectin were not significantly different. Histologically, severe inflammation, indicated by F4/80 immunostaining and M1 macrophage polarization, was detected in inguinal and epididymal white adipose tissue in ErbB4 deletion mice. ErbB4 expression decreased during 3T3-L1 preadipocyte differentiation. Administration of neuroregulin 4, a specific ligand for ErbB4, to 3T3-L1 adipocytes had no effect on adipogenesis and lipolysis but significantly inhibited lipogenesis, promoted browning, induced GLUT4 redistribution to the cell membrane, and increased glucose uptake. Neuroregulin 4 also significantly increased glucose uptake in adipocytes isolated from wild-type mice, while these effects were significantly decreased in adipocytes isolated from ErbB4 deletion mice. In conclusion, our results indicate that ErbB4 may play an important role in glucose homeostasis and lipogenesis. ErbB4 deficiency-related obesity and adipose tissue inflammation may contribute to the development of MetS.

Topics: 3T3-L1 Cells; Adipogenesis; Adiponectin; Adipose Tissue, White; Animals; Dietary Fats; Dyslipidemias; Fatty Liver; Gene Deletion; Genetic Predisposition to Disease; Glucose Transporter Type 4; Hyperglycemia; Hyperinsulinism; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipogenesis; Macrophages; Male; Metabolic Syndrome; Mice; Neuregulins; Obesity; Receptor, ErbB-4; Subcutaneous Fat

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

Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienol has been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.

Topics: Adiponectin; Animals; Bixaceae; Bone Resorption; Cancellous Bone; Carotenoids; Diet, High-Fat; Dietary Carbohydrates; Hyperglycemia; Hypertension; Inflammation; Leptin; Male; Metabolic Syndrome; Osteoblasts; Plant Extracts; Rats, Wistar; Tocotrienols; X-Ray Microtomography

Numerous investigations prove a higher incidence of carcinogenesis in metabolic syndrome (MetS). They indicate the important role of obesity, elevated inflammatory biomarkers, hyperinsulinemia, hyperglycemia, and dyslipidemia as well. Elevated plasma insulin and free insulin-like growth factor-1 (IGF-1) levels stimulate cell proliferation. The present publication considers the role of neuroendocrine and immune disequilibrium in MetS as a reason for transition to carcinogenesis. It emphasizes the role of hormonal disbalance, i.e. hyperleptinemia, hyperinsulinemia, hypercortisolemia, hypercatecholaminemia, hyperestrogenemia and hyperandrogenemia in MetS. It is presumed that these important components modify cellular microenvironment towards carcinogenesis. The interactions between neurotrophins, leptin, and mast cells and the alterations in the hypothalamo-hypophyseal-adrenal axis in MetS are discussed. It is assumed that they are the consequence of inflammatory distress followed by hormonal and immune disbalance at a central level as well as of enlarged adipose tissue and changed adipocyte microenvironment leading, finally, to carcinogenesis.

Topics: Adiponectin; Adipose Tissue; Carcinogenesis; Catecholamines; Cell Proliferation; Estrogens; Homeostasis; Humans; Hydrocortisone; Immune System; Insulin; Insulin-Like Growth Factor I; Leptin; Mast Cells; Metabolic Syndrome; Models, Theoretical; Mutation; Neoplasms; Nerve Growth Factors; Neurosecretory Systems; Obesity

Available studies on metabolic syndrome (MS) after hematopoietic stem cell transplantation (HSCT) are retrospective with heterogeneous inclusion criteria, and little is known about the early post-transplant phase. In our prospective study, clinical and laboratory data were collected in 100 HSCT recipients, 48 allogeneic and 52 autologous, at baseline, at + 30, + 100 and + 360 days. At baseline, MS was observed in 24 patients, significantly associated with insulin resistance and leptin on multivariate analysis. At + 30, the diagnosis of MS was confirmed in 43 patients, significantly related to insulin resistance and allogeneic transplants. If the whole series was considered, patients with MS had significantly higher mortality from any cause. The baseline presence of any MS feature was a predictor of + 30 MS. Isolated occurrences of MS features were related to hyperleptinemia and hyperinsulinemia, except in the case of low HDL cholesterol, linked to adiponectin and resistin. Our data confirm that patients undergoing HSCT have a high prevalence of MS, with hyperleptinemia playing a major role. The early peak of new MS cases is primarily attributable to insulin resistance, notably but not exclusively immunosuppression-induced; the subsequent long-term increase in MS cases may be an effect of persistent adipokine imbalance.

Topics: Adult; Aged; Allografts; Autografts; Female; Hematopoietic Stem Cell Transplantation; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Prevalence; Prospective Studies

Topics: Adipose Tissue, Brown; Alzheimer Disease; Animals; Blood Glucose; Diet, High-Fat; Disease Models, Animal; Eating; Homeostasis; Humans; Hyperphagia; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Mice; Mice, Transgenic; Obesity

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

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

To study if the leptin to adiponectin (L:A) ratio, can be a potential biomarker for postprandial triglyceride clearance, insulin resistance (IR) or leptin resistance (LR) in apparently healthy obese, and obese individuals with established metabolic disease.. Fifty adult subjects with obesity (BMI ≥30); of which 36 metabolic healthy obese (MHO), and 14 metabolic dysregulated obese (MDO), with clinical and/or biochemical signs of metabolic disease were included. Seventeen healthy, normal weight subjects represented the control group. Postprandial triglyceride (TG) levels were measured in an 8 h oral fat tolerance test (OFTT). IR by HOMA-IR, L:A ratio and indirect LR were measured. In the MHO group, 71.4%, 69.4% and 86.1%, had delayed TG clearance, IR and LR, respectively; whereas in the MDO group this was detected in 85.7%, 71.4% and 91.7%, respectively. A combination of all three metabolic risk factors was found in 39.8% of the MHO and in 42.9% of the MDO patients. Receiver operating characteristics (ROC) analysis revealed that a cut-off value for the L:A ratio of >1.65 for the control group (PPV 1.0, NPV 0.91) and >3.65 for the obese subjects (PPV 0.86, NPV 0.48) predicted the delayed TG clearance with a good specificity and sensitivity. Detecting a combined risk with at least 2/3 metabolic risk factors, the ROC yielded the most suitable L:A ratio cut-off at >1.88.. L:A ratio was able to detect early metabolic disturbances in obese individuals, and may be a potential useful clinical surrogate biomarker of metabolic disorders.

Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Body Mass Index; Dyslipidemias; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity, Metabolically Benign; Postprandial Period; Predictive Value of Tests; Time Factors; Triglycerides; Young Adult

Metabolic syndrome (MetS) is widespread among hypertensive patients. Clinical features and potential biomarkers of MetS in the presence of hypertension and resistant hypertension (RHTN) represent a great area of interest for investigation.. The purpose of this study was to evaluate the prevalence of MetS and the clinical features associated with it in resistant and mild to moderate hypertensives.. This cross-sectional study included 236 patients, (i) 129 mild to moderate hypertensive patients and (ii) 107 patients with RHTN. We measured blood pressure (BP) and adipokines levels, and performed bioelectrical impedance analysis. Microalbuminuria (MA), cardiac hypertrophy and arterial stiffness were also assessed. The significance level of alpha = 0.05 was adopted.. We found a MetS prevalence of 73% in resistant and 60% in mild-to-moderate hypertensive patients. In a multiple regression analysis, MA (odds ratio = 8.51; p = 0.01), leptin/adiponectin ratio (LAR) (odds ratio = 4.13; p = 0.01) and RHTN (odds ratio = 3.75; p = 0.03) were independently associated with the presence of MetS apart from potential confounders.. Our findings suggest that both resistant and controlled hypertensive subjects have a high prevalence of MetS. In addition, MetS-related metabolic derangements may cause early renal and hormonal changes. Finally, LAR may be useful as a reliable biomarker for identifying those hypertensive subjects who are at risk for developing MetS.

Topics: Adiponectin; Aged; Antihypertensive Agents; Blood Pressure; Brazil; Cross-Sectional Studies; Echocardiography; Electric Impedance; Female; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Prevalence; Pulse Wave Analysis; Regression Analysis; Risk Factors; Severity of Illness Index; Statistics, Nonparametric

Activating receptor ligand for nuclear factor (RANKL) has been identified as a ligand attached to the cell membrane of osteoblasts and odontoclasts.. To determine a possible association of sRANKL in saliva and serum with the parameters of metabolic syndrome (MS) in paediatric population aged 8-12 years.. This was a clinical, analytical and comparative study. Students between 6 and 12 years with good oral hygiene were included. Anthropometry, clinical analysis, dentobacterial plaque registration were registered as well as sRANKL in total saliva and serum through the ELISA technique.. A total of 43 children were enrolled, with a mean age of 9.7 (±0.8 years). Contrasting the groups by the presence or absence of the waist circumference above the normal limit, the difference in serum sRANKL concentration was statistically significant (P ≤ 0.05). A negative statistical significance was found in the correlation between serum sRANKL and HDLc (r. A good oral hygiene seems to avoid the effects of MS on the oral cavity.

Topics: Anthropometry; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Child; Cholesterol, HDL; Female; Humans; Leptin; Male; Metabolic Syndrome; Mexico; Obesity; Oral Health; Oral Hygiene; RANK Ligand; Saliva; Triglycerides

We investigated whether serum leptin can be a predictor for incident cases of MetS in a population-based study.. This is a prospective cohort study of 1590 adults aged between 40 and 70 years, who did not have MetS in 2005-2008 (at baseline) and 2008-2011 (follow-up). The baseline serum leptin concentrations were measured by radioimmunoassay.. During an average of 2.8 years of follow-up, 113 men (17.1%) and 148 women (15.9%) developed MetS. In multivariable adjusted models, the odds ratio of incident MetS when comparing the lowest to the highest quartiles of leptin levels was 3.17 in men and 2.79 in women; nevertheless, the significance disappeared after adjusting for the body mass index (BMI). In subsidiary analyses by BMI, logistic regression analysis showed that subjects with the highest tertile of serum leptin level were 3.04 and 2.12 times more likely to have MetS than those with the lowest tertile in lean subjects (OR 3.04; 95% CI 1.44-6.41; p = .004 in men vs. OR 2.12; 95% CI 1.06-4.25; p = .036 in women, respectively).. Obesity is an effect regulator, which can predict an association between increased serum leptin level and the incidence of MetS in lean subjects.

Topics: Adult; Aged; Cohort Studies; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Prospective Studies; Radioimmunoassay

Asian Indians have been shown to have a high prevalence of metabolic syndrome (MetS), related to insulin resistance and possibly genetic factors. The aim of this study was to determine the genetic patterns associated with MetS in Asian Indians living in Durban, South Africa.. Nine hundred and ninety nine participants from the Phoenix Lifestyle Project underwent clinical, biochemical and genetic assessment. MetS was diagnosed according to the harmonized definition. The apolipoprotein A5 Q139X, lipoprotein lipase (LPL) Hinf I, human paraoxonase 1 (PON1) 192Arg/Gln, cholesteryl ester transfer protein (CETP) Taq1B, adiponectin 45T>G and leptin (LEP) 25CAG were genotyped by real-time polymerase chain reaction in participants with and without MetS. Univariate-unadjusted and multivariate-adjusted relations were conducted for all analyses.. The prevalence of MetS was high (49.0%). More females had MetS than males (51.0 vs 42.8%). There was no significant difference in the distribution of genotypes between participants with MetS and those without. Males with the MetS who had the adiponectin TG genotype and human paraoxonase 1 AA genotype were more likely to have reduced high-density lipoprotein cholesterol (HDL-C) (P=0.001) and higher systolic blood pressure (P=0.018), respectively.. About half of the Asian Indians living in Phoenix had MetS. No association between the polymorphisms studied and the risk for MetS was observed. The adiponectin TG genotype may be associated with reduced HDL-C and the human paraoxonase 1 AA genotype with hypertension in males. This suggested that lifestyle factors were the major determinant for MetS in this ethnic group and the genetic risk might be related to its component risk factors than to MetS as an entity.

Topics: Adiponectin; Aged; Apolipoprotein A-V; Aryldialkylphosphatase; Asian People; Cholesterol Ester Transfer Proteins; Cholesterol, HDL; Female; Genetic Association Studies; Humans; Hypertension; Leptin; Lipid Metabolism; Lipoprotein Lipase; Male; Metabolic Syndrome; Middle Aged; Polymorphism, Genetic; Sex Characteristics; South Africa

To determine the role of nonspecific inflammation in the formation of IR and metabolic syndrome in patients with chronic hepatitis C.. The study included 205 patients with CHC aged 18 to 69 years. Patients with CHC are randomized into two groups depending on the presence of IR: group 1 - patients with a HOMA index ≥2.77, which corresponded to IR (n=110); group 2 (n=95). The levels of serum iron, C-reactive protein (CRP), serum ferritin and adipose tissue hormones [leptin, resistin, adiponectin and tumor necrosis factor-α (TNF-α)] were additionally investigated.. At all stages of development of IR, nonspecific inflammation was detected (according to ferritin, CRP and serum iron), increasing with increasing HOMA index [Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)] (Matthews D., 1985), metabolic syndrome and its components. In the analysis of indicators in patients with chronic hepatitis C with a body mass index <25 kg/m2, conjugacy of IR with low-intensity inflammation, high viral load and hypersecretion of TNF-α was detected.. Given the high predictor role of CRP indicators in predicting IR, it should be used as a surrogate screening marker of IR in patients with chronic hepatitis C and should be actively treated for violations.

Topics: Adiponectin; Adolescent; Adult; Aged; Hepatitis C, Chronic; Humans; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Random Allocation; Young Adult

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

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

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

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

Adipokines may play a role in the pathogenesis of the metabolic syndrome (MetS) in children. We aimed to evaluate the association of leptin, adiponectin, and its ratio (L/A ratio) with the metabolic syndrome (MetS) in a subsample of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) cohort.. Leptin, adiponectin and MetS parameters were measured in a subsample of 1253 children (3-9.9 years) participating to the IDEFICS study, grouped as: Non-OW (underweight/normal weight) and OW/Ob (overweight/obese). MetS was defined using the sex- and age-specific cut-offs based on the distribution of MetS components in the IDEFICS cohort. The prevalence of the MetS among OW/Ob was 24.8% and 27.1% in boys and girls respectively, whereas ≤2% among Non-OW. OW/Ob had significantly higher leptin and L/A ratio as compared to Non-OW. Significantly higher leptin was found in OW/Ob with MetS as compared with OW/Ob without MetS. Significantly lower adiponectin was observed only in OW/Ob girls as compared to Non-OW. A 1SD increase in leptin and L/A ratio z-scores or a 1SD decrease in adiponectin z-score were significantly associated with higher risk of MetS. After adjustment for BMI or body fat mass (BFM) the association remained significant only for leptin.. We showed that in European children, higher leptin concentration is associated with MetS, even after adjusting for BMI or BFM, confirming an early role of leptin in MetS, while the association of adiponectin with MetS seems be mediated by body fat in this age range.

Topics: Adiponectin; Adiposity; Age Factors; Biomarkers; Body Mass Index; Child; Child, Preschool; Cross-Sectional Studies; Europe; Female; Humans; Leptin; Male; Metabolic Syndrome; Pediatric Obesity; Prevalence

The plasma leptin-adiponectin ratio (L:A) has been suggested as a one of the potentially independent predictor of metabolic risk and Insulin resistance in women with polycystic ovarian syndrome (PCOS).. This is a case-control study, total 439 female subjects, comprises in to two group 223 cases (PCOS) and 216 control (non-PCOS women) according to their clinical characteristics. Further both case and control group were sub-grouped in PCOS and non-PCOS with metabolic syndrome (wMetS) and without metabolic syndrome (woMetS) as per National Cholesterol Education Program Treatment Panel (NCEPATP) guidelines. Anthropometrical measurements and biochemical analysis were done. Leptin and adiponectin level were estimated by enzyme-linked immunosorbent assay.. Results indicated that SAD, WHR, BMI, BP, lipid profile, FPG, fasting plasma insulin, IR (HOMA-IR), leptin and L:A ratio were significantly higher (p=<0.001) in PCOS women compare to non PCOS. Furthermore anthropometrical values and level of FPG, TC, TG, Insulin, IR (HOMA-IR) and L:A ratio were significantly high (p=<0.001) in PCOS wMetS compare woMetS, however HDL (p=<0.001) and adiponectin level (p=<0.001) were significantly low. The same trend was also found in comparison between with and without MetS among non-PCOS women. The correlation between L:A Ratio with different metabolic risk markers, L:A ratio was positively significant with SAD (r=0.97, p <0.001), FPG (r=0.96, p<0.001), TC (r=0.44, p<0.001), insulin (r=0.98, p<0.001), IR (r=0.97, p<0.001), Adiponectin (r=0.21, p<0.01) and negatively significant with HDL(r=-0.42, p<0.001) in PCOS wMetS whereas L:A ratio was also positively correlated with SAD, BMI, TG in PCOS woMetS.. Study concluded L:A ratio may be one of the potential biomarker for metabolic syndrome and insulin resistance which is independent for presence of PCOS disease.

Topics: Adiponectin; Adult; Biomarkers; Case-Control Studies; Female; Follow-Up Studies; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Polycystic Ovary Syndrome; Prognosis

In addition to testosterone (T), the emerging role of sex hormone-binding globulin (SHBG) in pathogenesis of metabolic syndrome (MetS) has been noted recently. However, reports of associations with serum adipocytokine levels are still limited. Therefore, we conducted this study to evaluate whether serum T and SHBG levels are independent predictors for the risk of MetS that are associated with adiponectin and leptin levels in 614 Taiwanese men over 40 years old collected from a free health screening. Subjects in the lowest quartile of TT and SHBG levels are exposed to a 1.58 and 3.22 times risk of developing MetS, as compared to those in the highest quartile of TT and SHBG levels. However, SHBG retains its significance independent of TT as a MetS risk predictor, but not vice versa. In addition, SHBG was significantly correlated with both adiponectin and leptin levels even after adjusting for TT levels. In conclusion, SHBG served as a major predictor for the risk of MetS and was correlated with serum adiponectin and leptin levels that are independent of T. Further studies are needed to elucidate the true role of SHBG in the pathogenesis of MetS and possible mechanisms associated with serum adiponectin and leptin levels.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Comorbidity; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Receptors, Cell Surface; Testosterone

Atypical antipsychotics particularly olanzapine are associated with obesity and serious metabolic disturbances. As green tea (Camellia sinensis) is generally associated with beneficial effects on obesity and other metabolic disturbances, this study was undertaken to evaluate the effect of green tea aqueous extract (GTAE) on olanzapine induced weight gain and metabolic abnormalities in rats. Male Wistar rats were divided into eight groups: control, olanzapine (5mg/kg/day, IP.), GTAE (25, 50 and 100mg/kg/day, IP.) plus olanzapine and GTAE (25, 50 and 100mg/kg/day, IP.). Treatments were continued for 11 days. Body weight gain, average food and water intake were measured during the experiment. Plasma lipid, glucose and leptin levels, mean systolic blood pressure and total locomotion were evaluated at the end of experiment. Olanzapine induced significant weight gain at the end of treatment (10.38% of body weight) when compared to control (3.13% of body weight) in male Wistar rats. Average food and water intake were increased by olanzapine treatment. 11days olanzapine administration led to hyperleptinemia, hyperglycemia and dyslipidemia. Olanzapine also increased mean systolic blood pressure and decreased total locomotion. GTAE decreased significantly body weight gain and average food and water intake, improved the changes in lipid profile as well as fasting blood glucose, and finally decreased hyperleptinemia and hypertension induced by olanzapine. Results of this study demonstrated that GTAE could exert protective effects against olanzapine induced obesity partially due to its lowering effect on leptin. GTAE improved other metabolic abnormalities including dyslipidemia, hyperglycemia and hypertension induced by olanzapine in rats.

Topics: Animals; Benzodiazepines; Blood Glucose; Blood Pressure; Body Weight; Drinking; Feeding Behavior; Leptin; Lipids; Male; Metabolic Syndrome; Motor Activity; Olanzapine; Polyphenols; Protective Agents; Rats, Wistar; Systole; Tea; Triglycerides

Schizophrenia appears to be linked to higher incidence of metabolic syndrome even in the absence of antipsychotic treatment. Atypical antipsychotics substantially differ in their propensity to induce metabolic alterations. Aripiprazole is considered to represent an antipsychotic drug with low risk of metabolic syndrome development. The aim of this study was to evaluate metabolic phenotype of neurodevelopmental polyI:C rat model and assess metabolic effects of chronic aripiprazole treatment with regard to complex neuroendocrine regulations of energy homeostasis. Polyinosinic:polycytidylic acid (polyI:C) was administered subcutaneously at a dose of 8 mg/kg in 10 ml on gestational day 15 to female Wistar rats. For this study 20 polyI:C and 20 control adult male offspring were used, randomly divided into 2 groups per 10 animals for chronic aripiprazole treatment and vehicle. Aripiprazole (5 mg/kg, dissolved tablets, ABILIFY

Topics: Administration, Oral; Animals; Antipsychotic Agents; Aripiprazole; Body Weight; Cytokines; Disease Models, Animal; Ghrelin; Glucagon-Like Peptide 1; Leptin; Male; Metabolic Syndrome; Poly I-C; Random Allocation; Rats, Wistar; Schizophrenia

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

Sleep fragmentation (SF) is highly prevalent and has emerged as an important contributing factor to obesity and metabolic syndrome. We hypothesized that SF-induced increases in protein tyrosine phosphatase-1B (PTP-1B) expression and activity underlie increased food intake, inflammation, and leptin and insulin resistance.. Wild-type (WT) and ObR-PTP-1b-/- mice (Tg) were exposed to SF and control sleep (SC), and food intake was monitored. WT mice received a PTP-1B inhibitor (RO-7d; Tx) or vehicle (Veh). Upon completion of exposures, systemic insulin and leptin sensitivity tests were performed as well as assessment of visceral white adipose tissue (vWAT) insulin receptor sensitivity and macrophages (ATM) polarity.. SF increased food intake in either untreated or Veh-treated WT mice. Leptin-induced hypothalamic STAT3 phosphorylation was decreased, PTP-1B activity was increased, and reduced insulin sensitivity emerged both systemic and in vWAT, with the latter displaying proinflammatory ATM polarity changes. All of the SF-induced effects were abrogated following PTP-1B inhibitor treatment and in Tg mice.. SF induces increased food intake, reduced leptin signaling in hypothalamus, systemic insulin resistance, and reduced vWAT insulin sensitivity and inflammation that are mediated by increased PTP-1B activity. Thus, PTP-1B may represent a viable therapeutic target in the context of SF-induced weight gain and metabolic dysfunction.

Topics: Adipose Tissue, White; Animals; Eating; Hypothalamus; Inflammation; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Macrophages; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Receptor, Insulin; Signal Transduction; Sleep Deprivation; STAT3 Transcription Factor; Tyrosine; Weight Gain

Adipokines are elaborated by adipose tissue and are associated with glycemic, lipid, and vascular traits. We hypothesized that in a cross-sectional analysis circulating adipokines are altered among subsets of obesity stratified by presence versus absence of metabolic syndrome (MetS) and prospectively predict the incidence of MetS.. Participants in the community-based Framingham Third Generation Cohort who attended examination cycle 1 were included in the study (2002-2005; N=3777, mean age, 40 years; 59% women). Circulating adiponectin, leptin, leptin receptor, fetuin-A, fatty acid-binding protein 4, and retinol binding protein 4 were assayed and related to incident MetS in follow-up (mean 6 years). The adipokines were compared among individuals with excess body weight (body mass index ≥25 kg/m. In our community-based sample of young to middle-aged adults, metabolically healthy obese individuals demonstrated an adverse adipokine profile. Higher circulating levels of retinol-binding protein 4 and fetuin-A marked future cardiometabolic risk.

Topics: Adipokines; Adiponectin; Adult; alpha-2-HS-Glycoprotein; Biomarkers; Chi-Square Distribution; Cross-Sectional Studies; Fatty Acid-Binding Proteins; Female; Humans; Incidence; Leptin; Logistic Models; Longitudinal Studies; Male; Massachusetts; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Obesity; Odds Ratio; Prospective Studies; Receptors, Leptin; Retinol-Binding Proteins, Plasma; Risk Factors

Observational studies have shown a beneficial effect of obesity on bone health; however, most of those studies were not based on bone biopsies. Metabolic syndrome (MetS) could have an effect on bone remodeling. However, there are no data on the effects of MetS in the presence of renal osteodystrophy.. The aim of this study was to investigate associations between MetS and renal osteodystrophy using the bone histomorphometric turnover-mineralization-volume (TMV) classification.. This observational cross-sectional study included 55 hemodialysis patients (28 women/27 men) who were evaluated for MetS and bone histomorphometry. Biochemical parameters included calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, free serum leptin, fibroblast growth factor 23 (FGF23), intact osteocalcin, sclerostin (Scl), glucose, insulin, and thyroid hormones. Robust models of multivariate linear regressions were used for the statistical analyses.. Females had higher iPTH levels (1,143 vs. 358, p = 0.02). Patients with normal bone volume (BV/TV) had a higher prevalence of MetS (73.6% vs. 41.7%, p = 0.02) and higher serum phosphorus, C-terminal FGF23 and insulin levels. The multivariate regression analysis showed that low-density lipoprotein cholesterol (LDL) was positively correlated with bone formation rate (BFR/BS) and negatively associated with mineralization lag time. Bone volume was negatively associated with age but positively associated with MetS. Body mass index (BMI) was not correlated with any of the bone histomorphometric parameters.. Our results suggest that MetS is not a risk factor for low bone volume in hemodialysis patients. Furthermore, BMI alone was not related to bone volume in this population.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Bone Density; Bone Morphogenetic Proteins; Chronic Kidney Disease-Mineral and Bone Disorder; Cross-Sectional Studies; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Genetic Markers; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Osteocalcin

Hypothyroidism results in disturbances of metabolism influencing many regulatory systems and active molecules as adipocytokines. Objective of the study was to investigate leptin and adiponectin in patients with visceral obesity and hypothyroidism in relation to metabolic status, insulin resistance and systemic inflammation. A total of 118 patients (59 hypothyroid and 59 euthyroid) were enrolled divided into four age-matched groups according to body wеight (BMI) and thyroid function. Laboratory panel includes TSH, FT4, FT3 (CMIA), adiponectin and leptin (ELISA), IL- 6 (ECLIA), CRP, insulin, glucose, apolipoprotein B and lipoprotein (a) - Lp(a). Hypothyroid patients revealed significant positive correlations of TSH, adiponectin and Lp(a). Their medians of 10.4 mU/l, 12.5 µg/ml and 116.3 mg/l respectively were significantly higher than in euthyroid patients- 1.5 mU/l, 6.26 µg/ml and 32.0 mU/l (p < 0.0001). Leptin in both obese groups was significantly higher than in patients with normal weight. Leptin in hypothyroid patients was lower but not significant to euthyroid ones (9.7 ng/ml vs 13.4 ng/ml respectively, p = 0.16), correlated negatively to TSH and positively to CRP, IL-6, ApoB, Lp(a) and BMI. HOMA-IR and serum insulin at 120 min in OGTT were significantly higher in hypothyroid than in euthyroid patients independent of BMI (p < 0.001). Adiponectin, insulin resistance and chronic inflammation indices in hypothyroid patients correlated positively to TSH, BMI and atherogenic lipoproteins subclasses ApoB/Lp(a). Increased adiponectin in thyroid deficiency could be due to secondary resistance of adiponectin receptors or appeared as a compensatory pathogenetic factor in hypothyroidism.

Topics: Adiponectin; Adult; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypothyroidism; Inflammation; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity, Abdominal; Thyroid Gland

The aim of the present work was to study whether the leptin-adiponectin axis may have a pathophysiological role in the increased systemic inflammation and oxidative stress observed in patients with the metabolic syndrome (MS). Leptin, adiponectin, and markers of inflammation and oxidative stress were measured in a sample of 140 Caucasian subjects (74 males/66 females), aged 28-82 years, 60 with and 80 without the MS. Total concentrations of adiponectin as well as its multimeric forms HMW, MMW and LMW were significantly lower in individuals with the MS. The ratio adiponectin/leptin, a marker of dysfunctional adipose tissue, was dramatically decreased in the MS group. Systemic oxidative stress, as evidenced by levels of thiobarbituric acid reactive substances (TBARS), as well as markers of inflammation such as serum amyloid A (SAA), C-reactive protein (CRP) and osteopontin were significantly increased in subjects with the MS. Total adiponectin concentrations were negatively correlated with levels of TBARS and CRP levels. Furthermore, the ratio adiponectin/leptin was negatively correlated with SAA concentrations as well as with CRP levels. We concluded that a dysfunctional adipose tissue as suggested by a low adiponectin/leptin ratio may contribute to the increased oxidative stress and inflammation, hallmarks of the MS.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Chemical Analysis; Female; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress

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

An increased risk for metabolic syndrome (MS) has been described for people with psychotic and mood disorders. The aim of this study was to determine the influence of valproic acid (VPA) treatment on adiponectin, leptin levels and oxidative stress in bipolar disorder (BD).. Forty patients with BD receiving VPA monotherapy and 20 healthy control subjects were included in this study. BD patients were divided into two groups with and without MS as group 1 and group 2, respectively. Twenty BD patients diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders (DSM IV) were assessed for MS according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria. Adiponectin, leptin, protein carbonyls, sulfhydryl (-SH) and malondialdehyde (MDA) levels were measured in 40 BD patients and 20 control subjects.. Serum adiponectin levels were significantly lower in group 1 patients than in group 2 and control subjects ( p<.001). Serum leptin levels were significantly higher in group 1 patients than in group 2 and control subjects ( p<.001). Serum -SH levels were significantly lower in group 2 patients than in group 1 ( p<.001) and control subjects ( p<.05). Serum carbonyl levels were significantly higher in group 1 and group 2 patients than in control subjects ( p<.001). Serum MDA levels were significantly higher in group 1 patients than in group 2 and control subjects ( p<.001).. These results provide further evidence that VPA treatment for patients with BD contributed to the metabolic disturbances, such as the decreased serum adiponectin and -SH levels, as well as the increased serum leptin, MDA and carbonyl levels.

Topics: Adiponectin; Adult; Bipolar Disorder; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Risk Factors; Valproic Acid

We investigated the combined effect of cardiorespiratory fitness and the clustered score of inflammatory biomarkers (InflaScore) on the cardiometabolic risk score in adolescents.. This is a cross-sectional analysis with 529 adolescents (267 girls) aged 12-18 years. The shuttle run test was used to assess cardiorespiratory fitness. Continuous scores of clustered inflammatory biomarkers (high sensitivity C-reactive protein, complement factors C3 and C4, fibrinogen and leptin); cardiometabolic risk score (systolic blood pressure, triglycerides, ratio total cholesterol/HDL, HOMA-IR and waist circumference) were computed.. Adolescents with a higher inflammatory profile had the highest cardiometabolic risk score; adolescents with high InflaScore and low fitness had the highest odds of having a high cardiometabolic risk (OR 16.5; 95% CI 7.8-34.5), followed by adolescents with a higher InflaScore but fit (OR 7.5; 95% CI 3.7-8.4), and then by adolescents with a low InflaScore and unfit (OR 3.7; 95% CI 1.6-8.4) when compared to those with low InflaScore and fit, after adjustments for age, sex, pubertal stage, adherence to a Mediterranean dietary pattern and socioeconomic status.. The findings of our study suggest that the combination of high inflammatory state and low cardiorespiratory fitness is synergistically associated with a significantly higher cardiometabolic risk score and thus supports the relevance of early targeted interventions to promote physical activity and preservation as part of primordial prevention.

Topics: Adolescent; Biomarkers; Blood Pressure; C-Reactive Protein; Cardiorespiratory Fitness; Cholesterol; Complement C3; Complement C4; Exercise; Female; Fibrinogen; Humans; Leptin; Male; Metabolic Syndrome; Triglycerides; Waist Circumference

Metabolic syndrome (MetS) is characterized by a cluster of key features, which include abdominal obesity, insulin resistance, hypertension, and dyslipidemia. The aim of this study was to assess the impact of elevated glucocorticoid levels on the development of MetS in middle-aged female rhesus monkeys (Macaca Mulatta) after ovariectomy. Six female ovariectomized rhesus monkeys (9-13years) were randomly assigned to either a control group (normal diet, n=3) or a group in which MetS was facilitated (n=3). The MetS group fed with HFD (15% fat) and received oral prednisone acetate treatment (50mg/day). After 24months, the GCs treatment was withdrawn with continuation of high-fat feeding for a further 12months. After 24months, the MetS group displayed a significant increase in body weight and abdominal circumference. Additionally, the MetS animals displayed abnormal serum lipids, insulin resistance and impaired glucose tolerance. Histology of liver biopsies indicated marked accumulation of lipid droplets in hepatocytes of MetS animals. Withdrawal of GCs treatment led to recovery from above-mentioned metabolic disorders. Whereas GCs treatment increased leptin expression, it lowered expression of adiponectin and other factors in adipose tissue. Expression of Hydroxy-steroid dehydrogenase-1 and glucose transporter type-4 in the livers of MetS animals were reduced. We conclude that in the context of high fat diet, high levels of exogenous GCs contribute to the development of MetS in non-human primates.

Topics: Adipose Tissue; Animals; Body Weight; Diet, High-Fat; Disease Models, Animal; Glucocorticoids; Humans; Insulin; Leptin; Liver; Macaca mulatta; Metabolic Syndrome; Ovariectomy

Leptin and adiponectin have opposite effects on subclinical inflammation and insulin resistance, both involved in the development of metabolic syndrome (MS). We aimed to investigate whether leptin/adiponectin ratio (L/A), as a marker of these two adipokines imbalance, may improve diagnosis of MS in children and adolescents, and determined its cut-off value in the diagnosis of MS.. A total of 3,428 subjects aged 6-18 years were selected from Beijing Child and Adolescent Metabolic Syndrome study. Adipokine leptin and adiponectin were measured using enzyme-linked immunosorbent assay. Odds ratio of MS per 1 z-score of adipokine was examined using logistic regression. Diagnosis accuracy was assessed using c-statistics (AUC) and net reclassification index.. The levels of leptin and L/A increased with number of positive MS components, while the levels of adiponectin declined in both boys and girls (all P <0.001). AUCs for diagnosis of MS in girls were 0.793, 0.773, and 0.689 using L/A, leptin and adiponectin, respectively; and AUCs in boys were 0.822, 0.798, and 0.697 for L/A, leptin and adiponectin, respectively. Notably, L/A outperformed individual leptin or adiponectin in discriminating a diagnosis of MS (all P < 0.02 in AUC comparisons). In addition, the optimal cut-offs of L/A by ROC curve differed by genders and pubertal stages, which were 1.63, 1.28, 1.95 and 1.53 ng/ug for total, pre-, mid- and postpubertal boys, respectively and 2.19, 0.87,1.48 and 2.27 ng/ug for total, pre-, mid- and postpubertal girls, respectively, yielding high sensitivity and moderate specificity for a screening test.. In this pediatric population, leptin-adiponectin imbalance, as reflected by an increase in L/A level, was found to be a better diagnostic biomarker for MS than leptin or adiponectin alone. Future longitudinal studies are needed to further validate the gender-specific cutoff values.

Topics: Adiponectin; Adolescent; Asian People; Beijing; Biomarkers; Child; Child, Preschool; Confidence Intervals; Female; Humans; Leptin; Male; Metabolic Syndrome; Odds Ratio; Puberty

Metabolic syndrome (MS) increases cardiovascular risk and is associated with cardiac dysfunction and arrhythmias, although the precise mechanisms are still under study. Chronic inflammation in MS has emerged as a possible cause of adverse cardiac events. Male Wistar rats fed with 30% sucrose in drinking water and standard chow for 25-27 weeks were compared to a control group. The MS group showed increased weight, visceral fat, blood pressure, and serum triglycerides. The most important increases in serum cytokines included IL-1

Topics: Adrenergic beta-Agonists; Animals; Arrhythmias, Cardiac; Cells, Cultured; Cytokines; Disease Models, Animal; Echocardiography; Heart; Interleukin-1beta; Isoproterenol; Leptin; Male; Metabolic Syndrome; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Rats; Rats, Wistar; Serum; Tomography, X-Ray Computed; Tumor Necrosis Factor-alpha; Ventricular Fibrillation; Whole Body Imaging

Metabolic syndrome (MetS) is a collection of clinical conditions, including central obesity, hypertension, glucose intolerance and dyslipidemia. The long-term inflammatory and metabolic dysfunction associated with MetS may contribute to osteoarthritic processes leading up to total joint arthroplasty (TJA). The purpose of this study was to investigate levels of metabolic biomarkers and the prevalence of MetS in patients undergoing TJA.. Under IRB approval, citrated plasma samples were collected from 41 patients undergoing total hip and knee arthroplasty (THA/TKA) preoperatively and day 1 postoperatively. Control group consisted of 25 healthy human plasma samples (female and male, 18-35 years old) purchased from George King Biomedical Inc. (Overland Park, KS, USA). Samples were profiled for c-peptide, ferritin, IL-6, insulin, resistin, TNF-α, IL-1a, leptin, and PAI-1 using metabolic biochips purchased from RANDOX Co. (Antrim, Northern Ireland). NCEP/ATP III guidelines were used to evaluate which patients met MetS criteria.. Levels of IL-6, resistin, TNF-a, IL-1a, leptin, and PAI-1 were significantly elevated in patients undergoing TJA compared to normal. C-peptide and insulin were both decreased in TJA compared to normal. No significance was found when comparing TJA to normal for ferritin. TNFα was significantly lower in TJA+MetS compared to TJA-MetS, while other biomarkers showed no difference in TJA±MetS populations. Insulin & c-peptide both showed a significant decrease in TJA-MetS compared to normal, but levels in TJA+MetS patients were not significantly different from controls. Resistin showed significant increases in TJA+MetS vs. normal, but not in TJA-MetS vs. normal.. Overall, the differing metabolic profile seen in patients undergoing TJA suggest ongoing metabolic dysfunction. Insulin and c-peptide patterns among the different test groups hint toward a complex and dysfunctional metabolic process involved, with leptin and underlying insulin resistance playing a role. Increased resistin in TJA+MetS, but not in TJA-MetS, compared to normal, suggests that while elevated resistin levels may be associated with the osteoarthritic process, levels are further attenuated by MetS, which is highly prevalent in this population. Increased TNFα in TJA-MetS compared to TJA+MetS may be an artifact of differing sample populations or a true complication of the complex pathophysiology and medical regimen seen in patients with both OA and MetS. The lack of difference seen in the remaining biomarkers suggest that having MetS as a comorbidity does not contribute to the elevated levels seen in patients undergoing TJA.

Topics: Adolescent; Adult; Aged; Arthroplasty, Replacement; Biomarkers; C-Peptide; Case-Control Studies; Female; Ferritins; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Tumor Necrosis Factor-alpha; United States; Young Adult

The effect of rapid weight loss program on adipocytokines is not yet clear. Therefore the aim of the present study was the effect of rapid weight loss (4%) on leptin, adiponectin, and insulin resistance in elite free style wrestlers.. For this purpose, fifteen young freestyle wrestlers (weight 67.6±0.8, BMI 22.5±0.21 kg/m², body fat percent 6.12±0.18, waist to hip circumference ratio 0.82±0.08) in two weight categories (60 and 66 kg) were randomly selected. Caloric intake (mean 7 days measured by Food analyzer software) measured at 1 week before weight loss program by standard methods. Wrestlers performed a week rapid weight loss (average of 4% of body weight loss) protocol by caloric and water restriction by 60% (600-700 kcal per day), under the supervision of their coach. Anthropometric characteristics, leptin, adiponectin and insulin resistance were measured before and 12 and 36 hours after rapid weight loss program.. Rapid weight loss program with 4% of weight loss had a significantly reduced impact on anthropometric factors; leptin level, insulin resistance, and increased beta cell function, while the changes of adiponectin were not significant after rapid weight loss.. Findings of this study shows that rapid weight loss program significantly decreased leptin, L/A ratio and HOMA-IR, without significant changes on adiponectin levels. These changes may have harmful physiological effects on wrestlers' bodies but they can be useful to regulate of fatty acid, glucose metabolism, and insulin resistance.

Topics: Adiponectin; Anthropometry; Body Mass Index; Body Weight; Humans; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Weight Loss; Weight Reduction Programs; Wrestling; Young Adult

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

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

Metabolic syndrome (MetS), a cluster of cardiometabolic risk factors, is a challenging public health issue. The aim of current study was to test the hypothesis that concentrations of plasma adropin and leptin differ between patients with MetS and comparable age- and sex-matched control groups. This case-control study involved 153 subjects (51 per group). The study group included obese subjects with MetS and the two control groups included weight-matched subjects without MetS ("healthy": obese) and normal weight subjects without MetS. Body composition parameters were measured using bioelectrical impedance analysis. Plasma levels of adropin, leptin, and their ratio were measured. Leptin was significantly different between obese patients with/without MetS groups and normal weight subjects. Patients with MetS had higher levels of leptin (14 ± 12.4) compared with those without MetS (11.2 ± 9.3 vs. 7 ± 7.1 obese and normal weight without MetS, respectively; p = .002). Compared with healthy obese and normal weight subjects, MetS subjects had lower levels of plasma adropin ( p < .001) and a lower plasma adropin to leptin ratio ( p < .001), which remained significant when adjusted for body fat mass by analysis of covariance ( p < .001). This study demonstrates low levels of adropin are correlated with MetS and hence identify it as a potentially protective agent against MetS development. Variation in adropin levels may partly explain the "healthy obese" phenomenon.

Topics: Adiponectin; Adult; Anthropometry; Biomarkers; Blood Proteins; Body Mass Index; Case-Control Studies; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Peptides; Risk Factors

Type 2 diabetes mellitus (T2DM) is a consequence of complex interactions among multiple genetic variants and environmental risk factors. This complex disorder is also characterized by changes in various adipokines. In this study, our objective was to estimate the levels of adiponectin, leptin, and resistin (ALR) in T2DM patients, besides studying the effect of various drugs on their levels. Study participants included 400 diabetic and 300 normal patients from the Department of Endocrinology and Department of Biochemistry, Govt Medical College Srinagar. Subjects were categorized under various groups, i.e., Group 1 (metformin treated) and Group 2 (glimepiride treated), and cases were also categorized as obese with T2DM (Group A), obese without T2DM (Group B), and T2DM only (Group C). The serum ALR levels were estimated by ELISA (Alere), and biochemical parameters were also evaluated before and after treatment. Adiponectin levels were found to be significantly lower in T2DM cases as compared to controls (12 ± 5.5 versus 22.5 ± 7.9 μg/ml), while leptin and resistin levels were found to be significantly higher than controls (14.3 ± 7.4 versus 7.36 ± 3.73 ng/ml) (13.4 ± 1.56 versus 7.236 ± 2.129 pg/ml). Taking the effect of drugs into consideration, the effect on adiponectin and resistin levels was found to be highly significant in Group 2 before and after treatment (11 ± 5 versus 19.2 ± 4.5 μg/ml) (13.6 ± 2.5 versus 7.3 ± 2.9 pg/ml), while more effect was observed in leptin among Group 1 (metformin)-treated cases (27 ± 15 ng/ml versus 15 ± 15 ng/ml). Further the adiponectin levels were found to be significantly lower in Group B, while leptin and resistin levels were found to be significantly higher among obese cases when compared to T2DM cases only. Glimepiride also shows more effect on FBG, HbA1c% levels, while metformin shows more effect on Lipid profile levels. From the study, it can be concluded that ALR levels are affected by use of antidiabetic drugs among which glimepiride shows more effect on adiponectin and resistin levels, while leptin gets affected more by metformin. It can also be proposed that ALR levels are not affected by diabetes only, suggesting that their alterations in T2DM may be due to obesity as we observed more ALR changes in obese cases when compared to T2DM cases, and so there might be an important link between adiposity and insulin resistance.

Topics: Adiponectin; Adult; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Leptin; Male; Metabolic Syndrome; Metformin; Middle Aged; Resistin; Sulfonylurea Compounds

Metabolic syndrome (MetS) is more common in HIV-infected adults and children than in the general population. Adipocytokines and inflammatory markers may contribute to the pathophysiology of this condition and could be useful indices for monitoring MetS. The objective of this study was to provide information on the prevalence of MetS and investigate the role of adipocytokines and other biomarkers in this syndrome in HIV-infected pediatric patients.. A cross-sectional study was conducted between October 2013 and March 2014 in the outpatient clinics of 2 tertiary pediatric referral hospitals. Fifty-four HIV-infected children and adolescents were included. MetS was defined according to the International Diabetes Federation and modified National Cholesterol Education Program Adult Treatment Panel III criteria. Measurements included anthropometry, waist circumference, blood pressure, fasting lipids, glucose and insulin, adiponectin, leptin, interleukin-6, vitamin D and C-reactive protein and clinical lipodystrophy assessment.. Among the total, 3.7% of patients met the International Diabetes Federation criteria for MetS and 7.4% met the National Cholesterol Education Program Adult Treatment Panel III criteria. C-reactive protein and leptin levels were significantly higher and adiponectin level significantly lower in patients with MetS, regardless of the criteria used. Insulin resistance was observed in 40.7% of patients; abnormal quantitative insulin sensitivity check index values were found in 88.9%. Eighteen patients (33.3%) had vitamin D deficiency.. The prevalence of MetS was similar to that observed in larger cohorts of HIV-infected patients in our setting. Adipocytokine dysregulation seems to be related to MetS in HIV-infected children. A high percentage of patients showed insulin resistance, which should be strictly monitored.

Topics: Adiponectin; Adolescent; Biomarkers; Child; Cross-Sectional Studies; Female; HIV-Associated Lipodystrophy Syndrome; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Risk Factors; Spain; Vitamin D Deficiency

Combatting overweight or obesity can lead to large fluctuations in an individual's body weight, often referred to as weight cycling or 'yo-yo' dieting. Current evidence regarding the potentially damaging effects of these changes is conflicting.. Here, we assess the metabolic effects of weight cycling in a murine model, comprising three dietary switches to normal or high-fat diets at 6 week intervals; male C57BL/6 mice were fed either a control (C) or high-fat (F) diet for 6 weeks (n=140/group). C and F groups were then either maintained on their initial diet (CC and FF, respectively) or switched to a high-fat (CF) or control (FC) diet (n=35/group). For the final 6 week interval, CC and CF groups were returned to the control diet (CCC and CFC groups), while FC and FF groups were placed on a high-fat diet (FCF and FFF) (n=28/group).. For the majority of metabolic outcomes changes aligned with dietary switches; however, assessment of neuropeptides and receptors involved in appetite regulation and reward signalling pathways reveal variable patterns of expression. Furthermore, we demonstrate that multiple cycling events leads to a significant increase in internal fat deposition, even when compared with animals maintained on a high-fat diet (internal fat: FCF: 7.4±0.2 g vs FFF: 5.6±0.2 g; P<0.01).. Increased internal adipose tissue is strongly linked to the development of metabolic syndrome associated conditions such as type 2 diabetes, cardiovascular disease and hypertension. Although further work will be required to elucidate the mechanisms underlying the neuronal control of energy homoeostasis, these studies provide a causative link between weight cycling and adverse health.

Topics: Adipose Tissue; Animals; Diet, Fat-Restricted; Diet, High-Fat; Disease Models, Animal; Energy Intake; Energy Metabolism; Gastric Inhibitory Polypeptide; Insulin; Interleukin-6; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Weight Gain; Weight Loss

This study aimed to investigate effects of curcumin on high fructose diet (HFD)-induced metabolic syndrome (MetS) in rats and the possible mechanisms involved. MetS was induced in male albino rats (n = 20), over 8 weeks, by 65% HFD. For 8-week experiment period, rats were assigned to 2 equal groups: curcumin-treated rats received curcumin (200 mg/kg, p.o, once daily) along with HFD, and untreated rats were fed with HFD only. We evaluated body mass (BM), systolic blood pressure (SBP), homeostasis model assessment of insulin resistance (HOMA-IR), and serum levels of glucose, insulin, leptin, total cholesterol (TC), triglycerides (TGs), uric acid, malondialdehyde (MDA; lipid peroxidation product), and tumor necrosis factor-α (TNF-α; inflammatory cytokine), and serum catalase (endogenous antioxidant) activity and immunohistochemical expression of nuclear factor κB (NF-κB; inflammation-related transcription factor) in hepatocytes. HFD produced increases in BM, SBP, HOMA-IR, and serum levels of glucose, insulin, leptin, TC, TGs, uric acid, MDA, and TNF-α, a decrease in catalase activity, and strong positive expression of NF-κB in hepatocytes. Curcumin, in presence of HFD, produced significant improvements in all glucose and fat metabolism parameters, and in oxidative stress and inflammation biomarkers. Curcumin may potentially be useful in the treatment of MetS through its ability to modulate oxidation stress status and inflammation cascades.

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Catalase; Cholesterol; Curcumin; Fructose; Hepatocytes; Insulin; Leptin; Liver; Male; Malondialdehyde; Metabolic Syndrome; NF-kappa B; Oxidative Stress; Rats; Tumor Necrosis Factor-alpha; Uric Acid

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

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

Insulin and IGF1 signaling are important for adipose tissue development and function; however, their role in mature adipocytes is unclear. Mice with a tamoxifen-inducible knockout of insulin and/or IGF1 receptors (IR/IGF1R) demonstrate a rapid loss of white and brown fat due to increased lipolysis and adipocyte apoptosis. This results in insulin resistance, glucose intolerance, hepatosteatosis, islet hyperplasia with hyperinsulinemia, and cold intolerance. This phenotype, however, resolves over 10-30 days due to a proliferation of preadipocytes and rapid regeneration of both brown and white adipocytes as identified by mTmG lineage tracing. This cycle can be repeated with a second round of receptor inactivation. Leptin administration prior to tamoxifen treatment blocks development of the metabolic syndrome without affecting adipocyte loss or regeneration. Thus, IR is critical in adipocyte maintenance, and this loss of adipose tissue stimulates regeneration of brown/white fat and reversal of metabolic syndrome associated with fat loss.

Topics: Adipocytes; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Cell Differentiation; Cell Proliferation; Fatty Liver; Gene Deletion; Glucose Intolerance; Hyperglycemia; Insulin; Insulin Resistance; Insulin-Secreting Cells; Leptin; Lipodystrophy; Metabolic Syndrome; Mice; Organ Specificity; Receptor, IGF Type 1; Receptor, Insulin; Regeneration; Tamoxifen

Preterm, very-low-birth-weight (PT-VLBW) neonates are at-risk for metabolic syndrome later in life. At 1-3 y, they exhibit excessive weight-for-length z-scores (Wt-L. This was a cross-sectional cohort study of PT-VLBW infants at 1, 2, and 3 y of age (40/cohort). We measured SBP, abdominal circumference (AC) and anthropometrics; calculated age/gender-specific z-scores for Wt, L, Wt-L and subscapular skin fold (SS. Serum leptin was unaffected by chronologic age and gender, but was positively correlated with weight, Wt-L. Although serum leptin was unrelated to advancing age, gender, and SBP in PT-VLBW infants, levels correlated with measures of adiposity at 1 and 3 y, females > males, suggesting leptin resistance may occur in early infancy.

Topics: Adiponectin; Adiposity; Age Factors; Biomarkers; Blood Pressure; Child Development; Child, Preschool; Cross-Sectional Studies; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Leptin; Male; Metabolic Syndrome; Resistin; Risk Factors; Sex Factors; Skinfold Thickness; Waist Circumference; Weight Gain

The ratio of serum leptin to adiponectin (L/A ratio) could be used as a marker for insulin resistance. However, few prospective studies have investigated the impact of L/A ratio on improvement of metabolic components in high-risk individuals with metabolic syndrome. We examined the association between L/A ratio and the regression of metabolic syndrome in a population-based longitudinal study.. A total of 1017 subjects (431 men and 586 women) with metabolic syndrome at baseline (2005-2008) were examined and followed (2008-2011). Baseline serum levels of leptin and adiponectin were analyzed by radioimmunoassay. Area under the receiver operating characteristics curve (AUROC) analyses were used to assess the predictive ability of L/A ratio for the regression of metabolic syndrome.. During an average of 2.8 years of follow-up, metabolic syndrome disappeared in 142 men (32.9%) and 196 women (33.4%). After multivariable adjustment, the odds ratios (95% confidence interval) for regression of metabolic syndrome in comparisons of the lowest to the highest tertiles of L/A ratio were 1.84 (1.02-3.31) in men and 2.32 (1.37-3.91) in women. In AUROC analyses, L/A ratio had a greater predictive power than serum adiponectin for the regression of metabolic syndrome in both men (p=0.024) and women (p=0.019).. Low L/A ratio is a predictor for the regression of metabolic syndrome. The L/A ratio could be a useful clinical marker for management of high-risk individuals with metabolic syndrome.

Topics: Adiponectin; Adult; Biomarkers; Female; Humans; Insulin Resistance; Leptin; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Odds Ratio; Population Surveillance; Prospective Studies

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

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

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

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

This study analyzed the frequency of cardiometabolic risk markers and metabolic syndrome occurrence in overweight and obese children and adolescents.. The participants included 161 overweight (n=65) and obese (n=96) individuals aged between 5 and 19 years. Clinical markers were assessed (body mass index, body fat percentage, waist circumference, acanthosis, systolic and diastolic blood pressures, laboratory parameters [glucose, insulin, cholesterol (total and fractions) and triglyceride levels and homeostasis model assessment of insulin resistance (HOMA-IR) index] and leptin and adiponectin levels). The frequency of changes, odds ratios and correlations among markers were determined. Metabolic syndrome was assessed according to International Diabetes Federation criteria.. A high frequency of acanthosis (51.6%); increased waist circumference (45.4%), systolic blood pressure / diastolic blood pressure (8.1% / 9.3%), glucose (10%), insulin (36.9%) and HOMA-IR (44.3%) values; and reduced high-density lipoprotein levels (47.2%) were observed. Leptin levels were increased in 95% of obese and in 66% of overweight subjects. Adiponectin was decreased in 29.5% of obese and in 34% of overweight subjects. An odd ratio analysis revealed a greater probability of increased waist circumference (9.0), systolic blood pressure (4.1), triglyceride (2.3) and insulin (2.9) levels and HOMA-IR (3.0) in the obese group than in the overweight group. The clinical and laboratory parameters and leptin levels exhibited significant correlations, whereas adiponectin was negatively correlated with systolic blood pressure. The occurrence rate of metabolic syndrome was 13.6%.. The high frequency of changes in clinical, laboratory and adipokine markers indicates the need for early interventions aimed at preventing cardiometabolic complications in adulthood.

Topics: Adiponectin; Adolescent; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Child; Child, Preschool; Cholesterol; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Obesity; Overweight; Predictive Value of Tests; Prospective Studies; Triglycerides; Waist Circumference; Young Adult

Modified Lingguizhugan Decoction (MLD) came from famous Chinese medicine Linggui Zhugan Decoction. The MLD is used for the treatment of metabolic syndrome in the clinical setting. Our study focuses on the comprehensive treatment of MLD incorporated with dietary restriction and exercise in a rat model of the metabolic syndrome (MS).. Rats were divided into five groups: control group (Cont), high-fat diet group (HFD), high-fat diet incorporated with dietary restriction group (HFD-DR), exercise incorporated with dietary restriction group (HFD-DR-Ex) and MLD incorporated with dietary restriction and exercise group (HFD-DR-Ex-MLD). Treatments were conducted for 1 week after feeding high-fat diet for 12 weeks. The effects of treatments on high fat diet-induced obesity, hyperglycemia, hyperlipidemia, hypertension, hepatic injury and insulin resistance in rats of MS were examined. In addition, the tumor necrosis factor-α (TNF-α), leptin and protein kinase B (PKB) in rats serum and liver were also examined by enzyme-linked immunosorbent assay (ELISA).. After a week's intervention by dietary restriction, dietary restriction incorporated with exercise or MLD, compared with HFD rats, the relative weight of liver and fat, levels of triglyceride, total cholesterol, low-density lipoprotein, free fatty acid, aspartate aminotransferase, glutamic-pyruvic transaminase and alkaline phosphatase, insulin, were significantly decreased (p < 0.05 or 0.01). This treatment also inhibited abnormal increases of TNF-α, leptin and PKB in serum and liver.. MLD incorporated with dietary restriction and exercise treatment exhibit effects in alleviating high-fat diet-induced obesity, hyperglycemia, hyperlipidemia, hypertension, hepatic injury and insulin resistance, which are possibly due to the down-regulation of TNF-α, leptin and PKB.

Topics: Adipose Tissue; Animals; Blood Pressure; Caloric Restriction; Drugs, Chinese Herbal; Hyperglycemia; Hyperlipidemias; Hypertension; Insulin; Leptin; Lipids; Liver; Magnoliopsida; Male; Metabolic Syndrome; Obesity; Physical Conditioning, Animal; Phytotherapy; Poria; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

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

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

In search of inflammatory molecular markers helpful in detection of increased risk and prognosis of severity of syntropic occupational bronchial asthma and metabolic syndrome, the authors conducted a study covering 140 examinees with confirmed occupational bronchial asthma. According to IDF criteria (2005), the patients were assigned into a group with combined occupational bronchial asthma and metabolic syndrome, and a group of occupational bronchial asthma without metabolic syndrome. All the examinees underwent studies of inflammation markers - biochemical (C-reactive protein, leptine) and molecular-genetic ( polymorphism of Gln223Arg gene of leptine receptor (LEPR), polymorphism of C174G gene of interleukin-6 (IL-6), polymorphism of G308A gene of (TNF-a) tumor necrosis factor alpha). Evidences are that the patients with combined bronchial asthma and metabolic syndrome demonstrate higher activity of inflammatory processes (higher level of C-reactive protein, leptine) - that manifests in clinically more severe course of bronchopulmonary disease. Moleculary-genetic markers revealed are associated with higher activity of inflammation and therefore with increased risk of occupational bronchial asthma associated with metabolic syndrome and diabetess mellitus 2 type (polymorphisms of LEPR gene, IL-6 gene).

Topics: Air Pollutants, Occupational; Asthma, Occupational; Biomarkers; C-Reactive Protein; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Russia

Consumption of sugar-sweetened beverages promotes the development of metabolic syndrome (MetS) and type 2 diabetes mellitus in humans. One factor related to the appearance of MetS components is the dysfunction of the adrenal gland. In fact, the experimental generation of hyperglycemia has been associated with morphological and microvascular changes in the adrenal glands of rats. We hypothesized that high sucrose consumption from infancy promotes histological disruption of the adrenal glands associated with the appearance of metabolic syndrome indicators. Male Wistar rats were separated at weaning (21 days old) into two groups: free access to tap water (control group, C) or 30 % sucrose diluted in water (sugar-fed group). After 12 weeks, high sucrose consumption promoted an increase in visceral fat accumulation, adipose cell number, and insulin resistance. Also, a rise in the concentration of triglycerides, very low-density lipoprotein, insulin and leptin was observed. In control rats, a histomorphometric asymmetry between the right and left adrenal glands was found. In the sugar-fed group, sucrose consumption produced a major change in adrenal gland asymmetry. No changes in corticosterone serum level were observed in either group. Our results suggest that a high sucrose liquid-diet from early life alters the morphology of adrenocortical zones, leading to MetS indicators.

Topics: Adrenal Glands; Age Factors; Animals; Dietary Sucrose; Hyperglycemia; Insulin; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Microvessels; Rats; Rats, Wistar; Triglycerides

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

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

To determine whether patients with Duchenne/Becker muscular dystrophy (DMD/BMD) have components of metabolic syndrome (MetSy) and to evaluate whether leptin is associated with components of MetSy.. This study included 78 patients (nine, <6 years of age; 54, 6 to <16 years of age; and 15 patients, ≥16 years of age). Obesity and body fat mass were determined by waist circumference and dual-energy X-ray absorptiometry, respectively. A 12-h fasting blood sample was collected in the morning. Patients were categorized into four groups according to the number of criteria for MetSy: group 0: none; group 1: one; group 2: two and group 3: three or more criteria.. All age groups showed components of MetSy. The concentration of these components was significantly higher in patients ≥16 years old. The prevalence of hypertriglyceridemia was from ~37% to 46% in all age groups. The prevalence of MetSy was 7.1% for patients from 6 to <16 years of age and 24% for patients ≥16 years of age. Serum leptin levels increased significantly (P < 0.05) with age; the highest (13.43 ± 9.4 ng/ml) value was observed in patients >16 years of age. Total leptin was correlated with the number of patients with MetSy (r = 0.383; P = 0.001).. Components of MetSy are significant in patients with DMD/BMD. A high prevalence of hypertriglyceridemia was observed. Younger patients with DMD/BMD have risk factors for MetSy. Although leptin increased according to different degrees of MetSy, this relation disappeared when the body fat was corrected by leptin; therefore, the association could be caused by a common risk factor-fat.

Topics: Adolescent; Adult; Child; Female; Humans; Leptin; Male; Metabolic Syndrome; Muscular Dystrophy, Duchenne; Prevalence

Metabolic syndrome (MetS) has been described in autoimmune diseases. However, there are scarce data about MetS and adipocytokine profile in primary Sjögren's syndrome (pSS). Seventy-one female pSS patients (American-European Consensus Group Criteria, 2002) aged 18-65 years and 71 age-, race-matched control women were enrolled in this case-control study. Clinical data were collected by a standardized protocol. Blood levels of glucose, cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, interleukin-1beta (IL-1beta)/IL-6, B-cell activating factor (BAFF), insulin, and leptin/adiponectin/visfatin/resistin were determined. Patients and controls were comparable regarding body mass index (BMI), smoking, sedentariness, and menopause (p > 0.05). MetS (39.4 vs. 16.9 %, p = 0.005), hypertension (p = 0.004), and dyslipidemia (p = 0.002) were more frequent in patients than controls. IL-1beta, IL-6, BAFF, resistin, and adiponectin levels were higher in patients than controls (p < 0.05). pSS patients with MetS (n = 28) had higher BMI, waist circumference, cholesterol, LDL-C, triglycerides, insulin, leptin and HOMA-IR values, and greater hypertension and diabetes rates than pSS patients without MetS (n = 43) (p < 0.05). Current and/or previous prednisone use (75.0 vs. 62.8 %, p = 0.313), current (3.0 ± 4.5 vs. 1.6 ± 3.2 mg/day, p = 0.299), and cumulative prednisone doses (p = 0.495) were similar in both groups. Otherwise, IL-1beta level was higher in MetS patients than in non-MetS patients (p = 0.012), and this finding was confirmed (p = 0.048) by multivariate analysis with adjustments for age, ethnicity, prednisone use, current and cumulative prednisone doses, and duration of use. We identified high MetS frequency and abnormal adipocytokine profile in pSS. The association of MetS with elevated IL-1beta level suggests that inflammation plays an important role in its pathogenesis.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Aged; Blood Glucose; Case-Control Studies; Cholesterol; Female; Humans; Insulin; Insulin Resistance; Interleukin-1beta; Interleukin-6; Leptin; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Sjogren's Syndrome; Triglycerides; Young Adult

To assess sex hormones, leptin and insulin-resistance in men with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and to study associations between androgens and histologic score of prostate tissue in PCa.. Two hundred ten men older than 45 years selected from 2906 participants of a population screening for PCa were studied: 70 with PCa, 70 with BPH and 70 controls (CG), matched by body mass index and age. Insulin, IGF-1, PSA, leptin, total, free (fT) and bioavailable testosterone (bT) and estradiol were measured. Each group was subdivided into two subgroups considering the presence of metabolic syndrome (MS); androgens and leptin levels were analyzed in the subgroups.. Prostate cancer and BPH patients presented higher total, fT and bT levels than CG. IGF-1, insulin and HOMA index were higher in BPH than in the other two groups. PCa presented higher leptin [median (range) 6.5 (1.3-28.0) versus 4.8 (1.1-12.3) ng/ml; p < 0.01] and estradiol [median (range) 37.0 (20-90) versus 29.0 (20-118) pg/ml; p = 0.025] levels than CG. After dividing men considering the presence of MS, leptin was higher and total testosterone was lower in MS patients in all the groups.. It was observed a coexistence of an altered hormone profile with increased sex hormones and leptin in PCa patients, in accordance with the new perspective of PCa pathogenesis.

Topics: Aged; Case-Control Studies; Estradiol; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Male; Metabolic Syndrome; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone

Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance.. WAT inflammation was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS) of the breast. Two independent groups were examined in cross-sectional (cohort 1) and retrospective (cohort 2) studies. Cohort 1 included 100 women undergoing mastectomy for breast cancer risk reduction (n = 10) or treatment (n = 90). Metabolic syndrome-associated circulating factors were compared by CLS-B status. The association between CLS of the breast and the metabolic syndrome was validated in cohort 2, which included 127 women who developed metastatic breast cancer. Distant recurrence-free survival (dRFS) was compared by CLS-B status.. In cohorts 1 and 2, breast WAT inflammation was detected in 52 of 100 (52%) and 52 of 127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and IL6 and lower high-density lipoprotein cholesterol and adiponectin (P < 0.05) in cohort 1. In cohort 2, breast WAT inflammation was associated with hyperlipidemia, hypertension, and diabetes (P < 0.05). Compared with patients without breast WAT inflammation, the adjusted HR for dRFS was 1.83 (95% CI, 1.07-3.13) for patients with inflammation.. WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis. Clin Cancer Res; 22(9); 2283-9. ©2015 AACR.

Topics: Adipocytes; Adipose Tissue, White; Adult; Aged; Breast; Breast Neoplasms; C-Reactive Protein; Cross-Sectional Studies; Female; Glucose; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Macrophages; Metabolic Syndrome; Middle Aged; Obesity; Retrospective Studies; Triglycerides

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

Confined space, limited exercise equipment, rotating shift work and reduced sleep may affect cardiometabolic health in submariners. To test this hypothesis, 53 male U.S. Submariners (20-39 years) were studied before and after a 3-month routine submarine patrol. Measures included anthropometrics, dietary and physical activity, biomarkers of cardiometabolic health, energy and appetite regulation, and inflammation. Before deployment, 62% of submariners had a body fat % (BF%) ≥ 25% (obesity), and of this group, 30% met the criteria for metabolic syndrome. In obese volunteers, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), leptin, the leptin/adiponectin ratio, and pro-inflammatory chemokines growth-related oncogene and macrophage-derived chemokine were significantly higher compared to non-obese submariners. Following the patrol, a significant mean reduction in body mass (5%) and fat-mass (11%) occurred in the obese group as a result of reduced energy intake (~2000 kJ) during the patrol; and, independent of group, modest improvements in serum lipids and a mean reduction in interferon γ-induced protein 10 and monocyte chemotactic protein 1 were observed. Since 43% of the submariners remained obese, and 18% continued to meet the criteria for metabolic syndrome following the patrol, the magnitude of weight loss was insufficient to completely abolish metabolic dysfunction. Submergence up to 3-months, however, does not appear to be the cause of obesity, which is similar to that of the general population.

Topics: Adiponectin; Adipose Tissue; Adult; Blood Glucose; Body Mass Index; Chemokines; Energy Intake; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Military Personnel; Obesity; Sedentary Behavior; Ships; Sleep; Weight Loss; Work; Young Adult

Crescent literature data demonstrated a role of adipokines in immune responses, particularly leptin is involved in wide spectrum of pro-inflammatory functions. Several evidences suggested that leptin is able to inhibit T regulatory cells proliferation and function in vitro models. In the present study, we investigate the relationship between leptin and circulating T regulatory cells (Tregs) in patients affected by systemic lupus erythematosus (SLE).. 13 SLE patients and 11 healthy controls were enrolled. Metabolic syndrome and cardiovascular parameters were evaluated. Serum leptin levels were detected by commercial ELISA kit and circulating regulatory T cells were determined by FACS analysis as CD4+CD25highFOP3+ lymphocytes.. Metabolic syndrome, defined by ATPIII criteria, was more prevalent in SLE compared to controls (38.4% vs. 0%, p = 0.04), as well as arterial hypertension (38.4% vs. 0%, p = 0.04). We did not find significant differences in mean leptin levels among SLE and controls (13.13 ± 1.51 ng/ml vs. 9.48 ± 8.67 ng/ml, p = 0.6). Mean Tregs percentage of total CD4 were 1.27 ± 0.9 in SLE vs. 2.8 ± 1.2 in healthy controls (p = 0.001). We found a negative correlation between leptin levels and Tregs percentage of total CD4 in SLE patients (r = 0.4, p = 0.01).. Our results suggest a role of leptin in the regulation of circulating T regulatory cells amount in human SLE.

Topics: Adipokines; Adult; Biomarkers; CD4-Positive T-Lymphocytes; Cell Proliferation; Cohort Studies; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Metabolic Syndrome; Middle Aged; T-Lymphocytes, Regulatory

Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol.

Topics: Adrenal Glands; Animals; Blood Glucose; Body Weight; Cholesterol; Diet, Protein-Restricted; Eating; Female; Insulin; Insulin Resistance; Leptin; Male; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Pancreas; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar

The aim of this work was to determine the effect of a fructose rich diet (FRD) consumed by the pregnant mother on the endocrine-metabolic and in vivo and in vitro adipose tissue (AT) functions of the male offspring in adulthood. At 60 days of age, rats born to FRD-fed mothers (F) showed impaired glucose tolerance after glucose overload and high circulating levels of leptin (LEP). Despite the diminished mass of retroperitoneal AT, this tissue was characterized by enhanced LEP gene expression, and hypertrophic adipocytes secreting in vitro larger amounts of LEP. Analyses of stromal vascular fraction composition by flow cytometry revealed a reduced number of adipocyte precursor cells. Additionally, 60 day-old control (C) and F male rats were subjected to control diet (CC and FC animals) or FRD (CF and FF rats) for three weeks. FF animals were heavier and consumed more calories. Their metabolic-endocrine parameters were aggravated; they developed severe hyperglycemia, hypertriglyceridemia, hyperleptinemia and augmented AT mass with hypertrophic adipocytes. Our study highlights that manipulation of maternal diet induced an offspring phenotype mainly imprinted with a severely unhealthy adipogenic process with undesirable endocrine-metabolic consequences, putting them at high risk for developing a diabetic state.

Topics: Adipose Tissue; Adiposity; Age Factors; Animal Nutritional Physiological Phenomena; Animals; Biomarkers; Blood Glucose; Dietary Carbohydrates; Energy Intake; Female; Fructose; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Sex Factors; Weight Gain

Accumulating evidences suggests that obesity and metabolic syndrome (MetS) contribute towards lower urinary tract symptoms (LUTS) through alterations in the phenotype of bladder and prostate gland. Clinical studies indicate a link between MetS and LUTS. Nevertheless, there is lack of suitable animal model(s) which could illustrate an association linking obesity to LUTS. We examined the lower urinary tract function in an obesity-initiated MetS mouse model.. Male C57BL/6N wild-type and obese B6.V-Lepob/J maintained on regular diet for 28 weeks were subjected to the assessment of body weight (BW), body length (BL), waist circumference (WC), body mass index (BMI), blood glucose (BG), plasma insulin (INS), plasma leptin (LEP), total cholesterol (CHO), free fatty acid (FFA), and measurement of urinary functions. Whole animal peritoneal and subcutaneous adipose tissue measurements as well as prostate and bladder volumes were analyzed by MRI followed by histological evaluation. These parameters were used to draw correlations between MetS and LUTS.. Obesity parameters such as BW, WC, and BMI were significantly higher in B6.V-Lepob/J mice compared to C57BL/6N mice (P < 0.01). Higher levels of total CHO and FFA were noted in B6.V-Lepob/J mice than C57BL/6N mice (P < 0.05). These results were concurrent with frequency, lower average urine volume and other urinary voiding dysfunctions in B6.V-Lepob/J mice. MRI assessments demonstrate marked increase in body fat and prostate volume in these mice. Compared to C57BL/6N mice, histological analysis of the prostate from B6.V-Lepob/J mice showed increased proliferation, gland crowding, and infiltration of immune cells in the stroma; whereas the bladder urothelium was slightly thicker and appears more proliferative in these mice. The regression and correlation analysis indicate that peritoneal fat (R = 0.853; P < 0.02), CHO (R = 0.729; P < 0.001), BG (R = 0.712; P < 0.001) and prostate volume (R = 0.706; P < 0.023) strongly correlate with LUTS whereas BMI, WC, INS, and FFA moderately correlate with the prevalence of bladder dysfunction.. Our results suggest that LUTS may be attributable in part to obesity and MetS. Validation of an in vivo model may lead to understand the underlying pathophysiological mechanisms of obesity-related LUTS in humans. Prostate 76:964-976, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Adipose Tissue; Animals; Biometry; Body Composition; Cholesterol; Disease Models, Animal; Leptin; Lower Urinary Tract Symptoms; Magnetic Resonance Imaging; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Peritoneum; Prostate; Urinary Bladder; Urination Disorders

Chronic inflammation is known to be associated with visceral obesity and insulin resistance and is characterized by altered levels of production of adipokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, leptin, and adiponectin. Metabolic syndrome (MetS) is a major and escalating public health and clinical challenge worldwide, and patients with MetS have an increased risk of developing cardiovascular disease and type 2 diabetes mellitus. Electroacupuncture (EA) was tested as a means of decreasing inflammation in genetically obese Zucker fatty rats, which serve as a model of MetS. Repeated application of EA at the Zhongwan/Guanyuan acupoints decreased serum TNF-α, but produced no significant alterations in serum leptin, adiponectin, or IL-10. EA had no significant effect on the levels of these four adipokines in white adipose tissue. These findings are consistent with the supposition that EA inhibits proliferation and/or infiltration of macrophages into the adipose tissue of obese rats and stimulates the release of IL-10 from the decreased numbers of macrophages present in adipose tissue. Compared with the control animals, no significant change in body weight occurred. The blood glucose (BG) level over a 30-minute interval in Week 2 was relatively the same as that in Week 1, suggesting that EA treatment does not increase the likelihood of developing hyperglycemia.

Topics: Animals; Disease Models, Animal; Electroacupuncture; Humans; Interleukin-10; Interleukin-6; Leptin; Male; Metabolic Syndrome; Obesity; Rats; Rats, Zucker; Tumor Necrosis Factors

Equine metabolic syndrome (EMS) can be diagnosed by hormonal measurements; however, it would be important to find simpler measurements that allow easy identification of affected or at risk individuals. In horses, the dorsal neck region is one of the most frequent anatomical sites for fat deposition and neck obesity has been linked to EMS. The aim of this study was to evaluate the association of hormonal markers of obesity (leptin) and insulin resistance (insulin) with morphometric and ultrasonographic neck measurements in Andalusian horses. Plasma leptin and insulin concentrations were measured by RIA in 127 Andalusian horses. Neck circumferences (NC) were measured at 3 equidistant locations at 25%, 50%, and 75% of neck length (NC-25%, NC-50%, and NC-75%). At the same 3 locations, subcutaneous fat thickness (SFT-25%, SFT-50%, and SFT-75%) was measured ultrasonographically. In the population under study, a tendency to adiposity was confirmed by the elevated plasma leptin levels (7.47 ± 5.03 ng/mL). However, plasma insulin concentrations (4.05 ± 3.74 μIU/mL) were within normal range in most horses. Our results indicate that NC showed significant sexual dimorphism and did not correlate well with hormonal measurements. Ultrasonographic assessment of fat thickness at the base of the neck (SFT-75%) was significantly correlated with both plasma leptin and insulin and did not show differences between males and females. Thus, in the search for a single objective parameter which can be used in large populations, SFT-75% is a potential candidate and may be a meaningful parameter to predict EMS.

Topics: Adiposity; Animals; Female; Horse Diseases; Horses; Insulin; Leptin; Male; Metabolic Syndrome; Neck; Obesity; Spain; Ultrasonography

Low birth weight is associated with increased rates of obesity, insulin resistance and type 2 diabetes, but the precise mechanisms for this association remain unclear. We aimed to assess the relationships between birth weight and markers of glucose homeostasis or obesity in adults.. Cross-sectional population-based study on 1458 women and 1088 men aged 35-75 years living in Lausanne, Switzerland. Birth weight was self-reported and categorized into ≤ 2.5, 2.6-3.5, 3.6-4.0 and >4.0 kg. Body composition was assessed by bioimpedance. Leptin and adiponectin levels were measured by ELISA.. Women with low birth weight (≤ 2.5 kg) had higher levels of fasting plasma glucose, insulin, HOMA, diabetes and metabolic syndrome; a non significant similar trend was seen in men. In both genders, height increased with birth weight, whereas a U-shaped association was found between birth weight and body mass index, waist circumference and body fat percentage. After adjusting for age, smoking status, physical activity and fat mass, an inverse association was found between leptin and birth weight categories: adjusted mean ± standard error 17.3 ± 0.7, 16.2 ± 0.3, 15.6 ± 0.5 and 14.0 ± 0.8 ng/dL for birth weight categories ≤ 2.5, 2.6-3.5, 3.6-4.0 and >4.0 kg, respectively, in women (p < 0.05) and 9.8 ± 0.8, 9.1 ± 03, 7.8 ± 0.4 and 7.7 ± 0.5 ng/dL in men (p < 0.05). An inverse association was also found between reported birth weight and leptin to fat mass ratio: mean ± standard error 0.77 ± 0.04, 0.73 ± 0.02, 0.69 ± 0.03 and 0.62 ± 0.04 in women (p < 0.05); 0.46 ± 0.05, 0.45 ± 0.02, 0.39 ± 0.02 and 0.38 ± 0.03 in men (p < 0.05). No differences in adiponectin levels were found between birth weight groups.. Middle-aged adults born with a low weight present a higher prevalence of diabetes and obesity and also higher leptin levels and leptin to fat mass ratio than adults born with a normal weight. The higher leptin levels and leptin to fat mass ratio among adults born with a low weight might be related to nutritional factors during childhood or to the development of leptin resistance and/or higher leptin production by body fat unit. Subjects born with a low weight should be counselled regarding the risks of developing diabetes and/or cardiovascular disease.

Topics: Adult; Aged; Body Composition; Cross-Sectional Studies; Diabetes Mellitus; Exercise; Female; Humans; Infant, Low Birth Weight; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Switzerland

The associations between Helicobacter pylori infection, serum vitamin D level, and metabolic syndrome (MS) are controversial. The present community-based study aimed to investigate the effect of H pylori infection and serum vitamin D deficiency on MS development.Individuals from the northeastern region of Taiwan were enrolled in a community-based study from March, 2014 to August, 2015. All participants completed a demographic survey and underwent the urea breath test (UBT) to detect H pylori infection as well as blood tests to determine levels of vitamin D, adiponectin, leptin, and high-sensitivity C-reactive protein. The ATP III criteria for MS were used in this study.A total of 792 men and 1321 women were enrolled. The mean age was 56.4 ± 13.0 years. After adjusting for age and sex, the estimated odds of MS development for a UBT-positive subject were 1.503 (95% confidence interval [CI]: 1.206-1.872, P < 0.001) when compared to a UBT-negative subject. For participants with vitamin D deficiency (<20 ng/mL), the odds of MS development were 1.423 (95% CI: 1.029-1.967, P = 0.033) when compared to those with sufficient vitamin D level (>30 ng/mL). For participants with both H pylori infection and vitamin D deficiency, the odds of MS development were 2.140 (95% CI: 1.348-3.398, P = 0.001) when compared to subjects without H pylori infection and with sufficient vitamin D levels.H pylori infection and vitamin D deficiency could be predictors of MS. For individuals with both H pylori infection and vitamin D deficiency, the odds of MS development were 2.140 when compared to individuals without H pylori infection and with sufficient vitamin D levels.

Topics: Adiponectin; Adult; Aged; Breath Tests; C-Reactive Protein; Female; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Taiwan; Urea; Vitamin D; Vitamin D Deficiency

Adults with metabolic syndrome from different race/ethnicities are often predisposed to developing type 2 diabetes (T2D); however, growing evidence suggests that healthy diets and lifestyle choices can significantly slow or prevent progression to T2D. This poorly understood relationship to healthy dietary patterns and prevention of T2D motivated us to conduct a retrospective analysis to determine the potential impact of a minor dietary lifestyle change (daily mushroom consumption) on known T2D risk factors in racially diverse adults with confirmed features of the metabolic syndrome. Retrospectively, we studied 37 subjects who had participated in a dietary intervention focused on vitamin D bioavailability from white button mushrooms (WBM). All 37 had previously completed a 16-week study where they consumed 100 g of WBM daily and were then followed-up for one month during which no mushrooms were consumed. We analyzed differences in serum risk factors from baseline to 16-week, and from baseline to one-month follow-up. Measurement of serum diabetic risk factors included inflammatory and oxidative stress markers and the antioxidant component naturally rich in mushrooms, ergothioneine. Significant beneficial health effects were observed at 16-week with the doubling of ergothioneine from baseline, increases in the antioxidant marker ORAC (oxygen radical absorption capacity) and anti-inflammatory hormone, adiponectin and significant decreases in serum oxidative stress inducing factors, carboxymethyllysine (CML) and methylglyoxal (MG), but no change in the lipid oxidative stress marker 8-isoprostane, leptin or measures of insulin resistance or glucose metabolism. We conclude that WBM contain a variety of compounds with potential anti-inflammatory and antioxidant health benefits that can occur with frequent consumption over time in adults predisposed to T2D. Well-controlled studies are needed to confirm these findings and identify the specific mushroom components beneficial to health.

Topics: Adiponectin; Adult; Agaricus; Antioxidants; beta-Glucans; Biomarkers; Body Mass Index; Chitin; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diet; Dinoprost; Ergothioneine; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin Resistance; Leptin; Linear Models; Lysine; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Oxidative Stress; Polyphenols; Pyruvaldehyde; Retrospective Studies; Risk Factors; Triglycerides; Vitamin D

Incretins stimulated by oral meals are claimed to be protective for the pancreatic beta cells, to increase insulin secretion, to inhibit glucagon release, slow gastric emptying (glucagon-like peptide-1) and suppress appetite. Recently it has however been suggested that glucagon-like peptide-1 (GLP-1) is putative early biomarker of metabolic consequences of the obesity associated proinflammatory state. The study was aimed to compare the release of incretins and some of early markers of inflammation at the fasting and postprandial period induced by functional oral glucose as well as lipid load in healthy controls and patients with metabolic syndrome (MS) to see if functional tests may be helpful in searching for the inflammatory status of patients. Fifty patients with MS and 20 healthy volunteers (C) participated in this study. The 3-hour oral glucose (OGTT) and the 8-hour oral lipid (OLTT) tolerance tests were performed. At fasting leptin and adiponectin, as well as every 30 minutes of OGTT and every 2 hours of OLTT blood concentration of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, insulin, triglycerides, free fatty acids, glutathione peroxidase, interleukin-6, sE-selectin, monocyte chemoattractant protein-1 (MCP1) and visfatin were measured. At fasting and during both OGTT and OLTT the level of incretins did not differ between the MS and the C group. Both glucose and lipids reach food activated incretins secretion. Glucose was the main GLP-1 release activator, while the lipid load activated evidently GIP secretion. A significantly larger AUC-GIP after the lipid-rich meal over the carbohydrate meal was observed, while statistically bigger value of AUC-GLP-1 was noticed in OGTT than in OLTT (P < 0.001) within each of the investigated groups. In patients with the highest fasting plasma GIP concentration (3(rd) tertile), IL-6, MCP-1, sE-selectin and visfatin blood levels were increased and correlated with glutathione peroxydase, leptin/adiponectin ratio, higher visfatin and interleukin-6 levels. The fat containing meals stimulate the long-lasting release of incretins, mainly GIP, parallel to the increase of the markers of low grade inflammation associating obesity in metabolic syndrome. The possibility of use of the postprandial (OLTT) GIP release measurement for the low grade inflammation progress in MS patients is suggested.

Topics: Adiponectin; Adult; Aged; Blood Glucose; Cytokines; E-Selectin; Fasting; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Interleukin-6; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Postprandial Period

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

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

Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offspring through epigenetic changes in the adiponectin and leptin genes. Additionally, we investigated whether a normal diet during subsequent generations abolished the epigenetic changes associated with paternal HFD exposure before conception. We observed the effects of paternal HFD exposure before conception over multiple generations on offspring metabolic traits, including weight and fat gain, glucose intolerance, hypertriglyceridemia, abnormal adipocytokine levels, hypertension, and adiponectin and leptin gene expression and epigenetic changes. Normal diet consumption by male offspring during the subsequent generation following paternal HFD exposure diminished whereas consumption for two generations completely abolished the effect of paternal HFD exposure on metabolic traits and adipocytokine promoter epigenetic changes in the offspring. The effects of paternal HFD exposure on offspring were relatively weaker than those following HFD exposure in utero. However, paternal HFD exposure had an additive metabolic effect for two generations, suggesting that both paternal and maternal nutrition might affect offspring metabolism through epigenetic modifications of adipocytokine genes for multiple generations.

Topics: Adipokines; Adiponectin; Animals; Chromatin Immunoprecipitation; Diet, High-Fat; Epigenesis, Genetic; Female; Gene Expression; Glucose Intolerance; Hypertension; Hypertriglyceridemia; Leptin; Male; Metabolic Syndrome; Mice; Obesity; Paternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; RNA, Messenger; Weight Gain

Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype.. The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model.. Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice.. Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P = .04), whereas there was no difference in systolic blood pressure between treated and placebo-treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 ± 3984.4 vs placebo: 29687.14 ± 8258.7; P = .003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol-treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 ± 976.4 pg/dL vs placebo: 24181.9 ± 3128.2 pg/dL, P = .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D-chiroinositol-treated dams compared with the placebo group (myoinositol/D-chiroinositol: 10.9 ± 0.5 g vs 12.6 ± 0.6 g, P = .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol-treated and nontreated pregnant dams with metabolic-like syndrome and obesity.. Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic-like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams.

Topics: Animals; Biomarkers; Blood Glucose; Dietary Supplements; Disease Models, Animal; Female; Gastric Inhibitory Polypeptide; Gestational Age; Ghrelin; Glucose Tolerance Test; Inositol; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase Type III; Obesity; Pregnancy; Pregnancy Complications; Weight Gain

There is an ever increasing body of evidence that demonstrates that paternal over-nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether paternal under-nutrition can also program impaired health in offspring and if any detrimental health outcomes in offspring could be prevented by micronutrient supplementation (vitamins and antioxidants). We discovered that restricting the food intake of male rodents reduced their body weight, fertility, increased sperm oxidative DNA lesions and reduced global sperm methylation. Under-nourished males then sired offspring with reduced postnatal weight and growth but somewhat paradoxically increased adiposity and dyslipidaemia, despite being fed standard chow. Paternal vitamin/antioxidant food fortification during under-nutrition not only normalised founder oxidative sperm DNA lesions but also prevented early growth restriction, fat accumulation and dyslipidaemia in offspring. This demonstrates that paternal under-nutrition reduces postnatal growth but increases the risk of obesity and metabolic disease in the next generation and that micronutrient supplementation during this period of under-nutrition is capable of restoring offspring metabolic health.

Topics: Adiposity; Animals; Antioxidants; Body Composition; Embryonic Development; Female; Food, Fortified; Founder Effect; Infertility, Male; Insulin; Leptin; Lipids; Male; Malnutrition; Metabolic Syndrome; Mice, Inbred C57BL; Paternal Inheritance; Reactive Oxygen Species; Sperm Count; Sperm Motility

Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level in the high-fat diet-induced MetS rat. In MetS rats, PRAT-derived leptin expression increased concomitant with dysfunction of adipogenesis, and the activities of the angiotensin II-angiotensin II type 1 receptor and the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas receptor axes were imbalanced in PRAT. PRAT-derived leptin from MetS rats promoted proliferation of rat glomerular endothelial cells (GERs) by activating the p38 MAPK (mitogen-activated protein kinase) pathway, thereby contributing to the development of nephropathy. Long-term telmisartan treatment improved metabolic parameters and renal function, decreased the amount of PRAT, promoted adipogenesis, increased the expression of angiotensin-converting enzyme 2, restored balanced activities of the angiotensin II-AT1R and angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axes, and exerted an indirect renoprotective effect on MetS rats by decreasing PRAT-derived leptin release. Our results demonstrate a novel link between nephropathy and PRAT in MetS and show that telmisartan confers an underlying protective effect on visceral adipose tissue and the kidney, suggesting that it has potential as a therapeutic agent for the treatment of MetS-associated nephropathy.

Topics: Adipogenesis; Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Benzoates; Disease Models, Animal; Intra-Abdominal Fat; Kidney Diseases; Leptin; Male; Metabolic Syndrome; Protective Agents; Rats; Rats, Wistar; Telmisartan

Since Selenium (Se) forms part of glutathione peroxidase (GPx), which appears to have a dual role in Metabolic Syndrome (MS), this study evaluates the implication of Se in the transmission of this pathology to the progeny.. Se body distribution, glucose, triglycerides, cholesterol, insulin and metabolic hormones [glucagon, leptin, gastric inhibitory polypeptide (GIP), and triiodothyronine (T3)], growth factors, receptor activator of nuclear factor kappa-B ligand (RANK-L) and osteopontin, as well as oxidative hepatic balance in the offspring of dams exposed to a fructose-rich diet (65%) with normal Se content (0.01 ppm) during gestation and lactation, were measured according to sex.. Fructose pups had lower body weight; however, male pups had a lower body mass index and growth indicators in serum. Fructose pups, especially females, had lower levels of serum insulin and HOMA-IR. With regard to Se homeostasis, fructose pups presented a depletion of Se in heart and muscle, and repletion in kidneys, pancreas and thyroid, although only female pups showed a repletion of Se in the liver. Fructose pups presented lower superoxide dismutase activity and only female fructose pups had higher GPx activity, which provoked hepatic oxidation.. Se balance and Se tissue deposits in MS pups during lactation are altered by gender. This difference is focused on hepatic Se deposits that affect GPx activity, which could be related to a disruption in the insulin-signaling cascade in females. Furthermore, although female fructose pups had greater metabolic disorders, only the males' growth and development were affected. Particularly relevant is the depletion of Se found in the heart of fructose pups, as this element is essential for correct heart function.

Topics: Animals; Animals, Newborn; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; Cholesterol; Female; Fetal Development; Fructose; Gastric Inhibitory Polypeptide; Glucagon; Glutathione Peroxidase; Homeostasis; Insulin; Leptin; Liver; Male; Metabolic Syndrome; Osteopontin; Oxidative Stress; RANK Ligand; Rats; Rats, Wistar; Selenium; Sex Factors; Triglycerides; Triiodothyronine

The benefits of aerobic exercise training on insulin sensitivity in subjects with metabolic syndrome (MetS) are, at least in part, associated with changes in cytokines. Recent studies identified novel cytokines (e.g., fractalkine, omentin, and osteopontin) that are strongly involved in glucose homeostasis and therefore potentially contribute in the exercise-induced changes in insulin sensitivity. Therefore, we aim to examine changes in skeletal muscle RNA expression and plasma levels of novel cytokines after exercise training and correlate these changes to the exercise-induced changes in insulin sensitivity.. Women with metabolic syndrome (MetS, n = 11) and healthy women (n = 10) participated in a 6-month aerobic exercise training intervention (three times a week, 45 min per session at 65%-85% of individual heart rate reserve). Before and after training, we examined insulin sensitivity (M value during hyperinsulinemic euglycemic clamp) and circulating blood levels of cytokines (venous blood sample; leptin, adiponectin, omentin, fraktalkin, and osteopontin). The skeletal muscle RNA expression of these cytokines (muscle biopsy) was examined in two subgroups (MetS, n = 6; healthy women, n = 6).. At baseline, plasma levels of omentin (85.8 ± 26.2 ng·mL) and adiponectin (5.0 ± 1.7 μg·mL) levels were significantly higher in controls compared with MetS (51.1 ± 27.1; 3.6 ± 1.1 respectively), and leptin levels were lower in controls (18.7 ± 11.5 vs 53.0 ± 23.5 ng·mL). M value was significantly higher in controls (8.1 ± 1.9 mg·kg·min) than in MetS (4.0 ± 1.7). Exercise training significantly improved M values in both groups (P < 0.01). Exercise training did not alter plasma and skeletal muscle RNA expression levels of cytokines, but no correlation was observed between changes in cytokine level/RNA expression and M values (P > 0.05).. Although exercise training successfully improves insulin sensitivity in MetS and healthy women, we found no change in plasma and mRNA expression levels of novel cytokines.

Topics: Adiponectin; Chemokine CX3CL1; Cytokines; Exercise; Female; Gene Expression; GPI-Linked Proteins; Humans; Insulin Resistance; Lectins; Leptin; Metabolic Syndrome; Middle Aged; Muscle, Skeletal; Osteopontin; RNA

It has been suggested that food components such as ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and (poly)phenols counteract diet-induced metabolic alterations by common or complementary mechanisms. To examine the effects of a combination of ω-3 PUFAs and (poly)phenols on such alterations, adult Wistar-Kyoto rats were fed an obesogenic high-fat high-sucrose diet supplemented, or not, for 24 weeks with: eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) 1 : 1 (16.6 g kg(-1) feed); proanthocyanidin-rich grape seed extract (GSE, 0.8 g kg(-1) feed); or EPA/DHA 1 : 1 + GSE. Body weight, feed intake, and plasma glucose were evaluated every 6 weeks, while adipose tissue weight, insulin, glucagon, ghrelin, leptin, adiponectin, cholesterol, and triglycerides were evaluated at the end of the experiment. ω-3 PUFAs reduced plasma leptin and cholesterol levels, but did not modify diet-induced perigonadal fat or plasma insulin levels; while GSE increased plasma triglyceride levels. The combined action of ω-3 PUFAs and the proanthocyanidins reduced plasma insulin and leptin, as well as partially prevented perigonadal fat accumulation. While separate supplementation with ω-3 PUFAs or grape proanthocyanidins may not counteract all the key metabolic changes induced by a high-energy-dense diet, the combination of both supplements reverts altered insulin, leptin and triglyceride levels to normal.

Topics: Adiponectin; Adiposity; Animals; Blood Glucose; Body Weight; Cholesterol; Diet; Dietary Supplements; Disease Models, Animal; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; Ghrelin; Glucagon; Insulin; Leptin; Metabolic Syndrome; Proanthocyanidins; Rats; Rats, Inbred WKY; Triglycerides; Vitis

To investigate the relationship of leptin receptor gene rs1137100 and rs1137101 single nucleotide polymorphrism (SNP) with metabolic syndrome (MS) in older Han adults from major cities in China.. A total of 2082 older Han adults were selected from 18 major cities including 15 provinces/municipalities of China National Nutrition and Health Survey in 2002. According to the MS definition proposed by Joint Interim Statement (JIS), the subjects were divided into MS and control groups. Plasma leptin and insulin levels were measured. The genotypes of rs1137100 and rs1137101 were detected by Taqman method. Association of genotypes of leptin receptor gene SNPs with MS was investigated.. The MS group showed higher body mass index (BMI), waist circumference, fasting serum glucose, systolic blood pressure (SBP) and diastolic blood pressure (DBP), triglycerides (TG), serum total cholesterol (TC), insulin, homeostasis model of assessment for insulin resistence index (HOMA-IR) and leptin levels than those of control individuals, while the high density lipoprotein cholesterol (HDL-c) was significantly lower than the control group. The, GG, AA, GA genotypes distribution and the A allele frequency of rs1137100 and rs1137101 were similar between the two groups. The DBP and SBP level were obviously higher in AA genotype. The HDL-c concentration Was significantly lower in AA and GA + AA genotype. The AA and GA genotypes carriers in rs1137100 had similar risk for MS when comparing with the GG genotypes, and the OR values were 1.23 (95% CI 0.90-1.67) and 2.23 (95% CI 0.83-6.44), respectively. The AA and GA genotypes carriers in rs1137101 had similar risk for MS when comparing with the GG genotypes, and the OR values were 1.23 (95% CI 0.90-1.67) and 2.23 (95% CI 0.83-6.44), respectively.. Leptin receptor genes rs1137100 and rs1137101 are not associated with pathogenesis of MS in older Han adults, but it may relate with hypertension or lipid abnormality.

Topics: Blood Glucose; Blood Pressure; Body Mass Index; Case-Control Studies; China; Cholesterol, HDL; Cities; Gene Frequency; Genotype; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Polymorphism, Single Nucleotide; Receptors, Leptin; Triglycerides; Waist Circumference

We previously reported that offspring heterozygous mice partially lacking endothelial nitric oxide synthase (eNOS) gene, and born to hypertensive eNOS-/- Knockout mother, are hypertensive. We hypothesized that those offspring when placed on high-fat diet (HFD) will undergo altered metabolic programming increasing their risk for developing metabolic syndrome.. eNOS-/-KO and wild-type mice (eNOS+/+WT) were cross-bred to produce heterozygous offspring: maternal heterozygous (Mat, eNOS-/+), born from hypertensive eNOS-/-KO mothers; and paternal heterozygous (Pat, eNOS-/+), born from normotensive WT mothers. Mat, eNOS-/+ and Pat, eNOS-/+ female were allocated to HFD or control diet (CD) until 8 weeks of age. Then a metabolic profile was obtained: weight, glucose/insulin tolerance test (GTT, ITT), systolic blood pressure (SBP), serum fasting levels of insulin, adiponectin, leptin, and a lipid panel.. Weight was not different between all offspring within each diet. GTT curve was higher in Mat, eNOS-/+ vs. Pat, eNOS-/+ offspring on both diet (P < 0.001). In ITT, glucose level at 15 minutes was higher in Mat, eNOS-/+ on HFD. Insulin level was increased in Mat, eNOS-/+ vs. Pat, eNOS-/+ on either diet. SBP was elevated in Mat, eNOS-/+ vs. Pat, eNOS-/+ on CD and was further raised in Mat, eNOS-/+ offspring on HFD (P < 0.001). No other differences were seen except for lower high-density lipoprotein levels in Mat, eNOS-/+ fed HFD (P < 0.003).. Mat, eNOS-/+ offspring exposed in utero to maternal hypertension and fed HFD postnatally have increased susceptibility for metabolic abnormalities. Thus, maternal HTN is a risk factor for altered fetal metabolic programming.

Topics: Adiponectin; Animals; Biomarkers; Blood Glucose; Blood Pressure; Diet, High-Fat; Disease Models, Animal; Female; Genetic Predisposition to Disease; Heterozygote; Hypertension; Insulin; Leptin; Lipids; Metabolic Syndrome; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase Type III; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Time Factors; Weight Gain

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

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

The study aimed to compare the effect of obesity with and without metabolic syndrome on asthma severity, quality of life, sleep quality, sleep disordered breathing and inflammatory markers as compared to non-obese asthma patients.. 60 asthma patients recruited for the study were divided equally into non-obese (NOA), obese without metabolic syndrome (OANMS) and obese with metabolic syndrome (OAMS) groups. Study cohorts were assessed for severity of asthma, quality of life and quality of sleep using questionnaires and inflammatory markers (FENO, hs-CRP, IL-5, IL-6 and leptin). Institutional ethical committee approved the study.. The results suggests OAMS patients may be a subtype of asthmatics having significantly severe asthma (p < 0.05), poor quality of life (p < 0.05), high risk of OSA (p< 0.05), decreased lung volumes (FRC) (p< 0.05), higher levels of inflammatory markers (leptin and IL-6) (p < 0.05), and high incidence of sleep disordered breathing (p < 0.05) in comparison to NOA and OANMS patients.. The present study has shown that obese asthmatics especially with metabolic syndrome represent a subtype of asthmatic population. Hence, the treatment of metabolic syndrome may be necessary in addition to asthma to achieve optimal control.

Topics: Adolescent; Adult; Asthma; Biomarkers; C-Reactive Protein; Cohort Studies; Cytokines; Female; Humans; Immunoglobulin E; India; Leptin; Male; Metabolic Syndrome; Middle Aged; Nitric Oxide; Obesity; Quality of Life; Severity of Illness Index; Sleep Apnea Syndromes; Surveys and Questionnaires; Young Adult

Genetic predisposition is implicated in the etiology of metabolic syndrome. This study aimed to investigate the1397645907association of vaspin rs2236242 and leptin rs7799039 polymorphisms with their serum levels and with the risk of developing metabolic syndrome in Egyptian women.. This case control study included 100 Egyptian women with metabolic syndrome and 100 without metabolic syndrome. The genotypes of vaspin rs2236242 and leptin rs7799039 were detected by a methodology based on PCR-RFLP. Serum vaspin and leptin levels were determined by ELISA.. The metabolic syndrome group was associated with higher serum vaspin and leptin levels when compared to the nonmetabolic syndrome group. The AA genotype of leptin rs7799039 was associated with metabolic syndrome and with higher serum leptin levels, while the different genotypes of vaspin rs2236242 were not associated with metabolic syndrome or different serum vaspin levels.. The AA genotype of leptin rs7799039 was associated with metabolic syndrome and higher serum leptin levels. Serum leptin and vaspin can be used as diagnostic markers of metabolic syndrome.

Topics: Case-Control Studies; Egypt; Female; Genotype; Humans; Leptin; Metabolic Syndrome; Polymorphism, Genetic; Serpins

The presented article studies the role of selected inflammatory and anti-inflammatory serum markers of psoriatic patients in the pathogenesis of metabolic syndrome (MS) and psoriasis. The study is based on the comparison between the group of psoriatic patients (74) and the control group (65). We found significantly higher BMI (

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adiponectin; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Body Mass Index; C-Reactive Protein; Case-Control Studies; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Psoriasis; Resistin; Waist Circumference; Young Adult

Obesity is associated with a mild chronic inflammatory response, which has been suggested to be pivotal in the development of cardiometabolic alterations of obesity. However, little is known about the involvement of acute inflammation.. To evaluate whether circulating neutrophils, markers of acute inflammation, are associated (quantitatively and qualitatively) with adolescent obesity and whether leptin modulates these associations.. We assessed 528 adolescents (16.8 yr old, 47% females), without chronic/acute illness. We measured anthropometry and dual energy X-ray absorptiometry and calculated fat mass percentage (FM%). Fasting serum glucose, high-density lipoprotein (HDL)-cholesterol, and triglycerides were used with blood pressure and waist circumference to compute a metabolic z-score. Leukocyte and neutrophil counts were obtained, together with levels of serum leptin. In a subsample of 23 males, flow cytometry was used to assess degranulation (CD66b expression) of neutrophils.. Female sex and obesity were positively related to mean neutrophil counts (p < 0.05). When accounting for sex and weight status, leptin was associated with neutrophil counts (p < 0.05), partially explaining the association between obesity and neutrophil counts. Neutrophil counts were related to metabolic risk z-scores, controlling for fat mass. Participants with elevated FM% showed more neutrophil degranulation than controls (p < 0.05).. Participants with increased adiposity had higher circulating neutrophil counts, suggesting acute inflammation. Furthermore, the neutrophils showed more degranulation, indicating inflammation. Obesity-induced alteration of the adipose secretory pattern (i.e., changes in leptin levels) could be involved in acute inflammation.

Topics: Adipose Tissue; Adiposity; Adolescent; Body Mass Index; C-Reactive Protein; Chile; Cohort Studies; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Leptin; Male; Metabolic Syndrome; Neutrophils; Panniculitis; Pediatric Obesity; Risk Factors; Severity of Illness Index; Up-Regulation

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including insulin resistance, dyslipidemia, high blood pressure, and abdominal adiposity. Obese patients develop leptin resistance, and an increased waist circumference (WC) due to deposition of abdominal fat. The aim of this study was to evaluate the association between circulating leptin levels and MetS among sample adult Mexican workers.. A total of 204 workers aged 20-56 were evaluated. Anthropometric index, blood pressure, fasting plasma glucose, and lipid profile were measured by spectrophotometric methods. Fasting insulin and leptin were measured by inmunoenzimatic methods. Furthermore, homeostasis model assessment for insulin resistance (HOMA-IR) was calculated.. The prevalence of MetS according to the ATP-III criteria was 33.8% and leptin concentrations were 2.5 times higher in women than men. Subjects with MetS had higher levels of leptin (26.7 ± 13.7) compared with those without MetS (20.1 ± 13.9; P <0.001). Leptin increased significantly while BMI increased as well (normal 14.0 ± 8.9, overweight 22.7 ± 11.7 and obese 31.4 ± 14.6) in addition to other variables such as WC, HDL-C, insulin levels, and HOMA index. Each component of MetS was stratified by sex and submitted by linear regression with a 95% of accuracy. The 50% and 53% of the BMI is explained by the concentration of leptin in men and women, respectively (P < 0.001).. This study found that leptin was associated with the MetS, especially in obesity and insulin resistance, indicating a high risk for university workers to develop hypertension, DM2, and cardiovascular disease.

Topics: Adult; Age Factors; Anthropometry; Blood Glucose; Blood Pressure; Fasting; Female; Humans; Immunoassay; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Mexico; Middle Aged; Obesity; Retrospective Studies; Risk Factors; Sex Factors; Spectrum Analysis; Waist Circumference; Young Adult

Many epidemiological studies find an inverse correlation between carotenoids intake or carotenoids plasma concentrations and body mass index (BMI), insulin resistance or metabolic syndrome in the general population. However, it is not clear whether these relationships occur in obese population.. We conducted a cross-sectional study in 108 obese non-diabetic patients.. There was an inverse correlation between plasma levels of pro-vitamin A carotenoids (α-carotene, β-carotene and β-cryptoxanthin) and both BMI and insulin resistance (estimated by the HOMA-IR). No correlation between plasma concentrations of lycopene or lutein/zeaxanthin and BMI or insulin resistance was found. The inverse association between the three pro-vitamin A carotenoids and HOMA-IR disappeared after adjustment for BMI and waist circumference. Interestingly, we identified a positive association between concentrations of β-carotene and adiponectin in plasma that was independent of sex, age, smoking status, BMI and waist circumference. To our knowledge, such association has never been described in obese patients.. These results suggest the existence of a favourable effect of β-carotene on insulin sensitivity in obese individuals that could involve a positive regulation of adiponectin, either directly or via its pro-vitamin A activity. The demonstration of the potential benefits of β-carotene towards insulin sensitivity would open the way to dietary strategies to prevent metabolic syndrome.

Topics: Adiponectin; Adolescent; Adult; Aged; beta Carotene; Body Mass Index; Carotenoids; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Diabetes Mellitus; Diet; Female; Humans; Insulin Resistance; Interleukin-1; Leptin; Linear Models; Lutein; Lycopene; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Obesity; Plasminogen Activator Inhibitor 1; Triglycerides; Tumor Necrosis Factor-alpha; Young Adult; Zeaxanthins

To test several circadian rhythm variables in a female population to identify the best tool to assess chronodisruption in obesity and metabolic syndrome (MetS) to define a score to be used for chronodisruption characterization in clinical practice.. Anthropometric measurements and markers of circadian rhythms, such as sleep and feeding diary, Horne-Ostberg questionnaire, melatonin and cortisol measurements, and wrist temperature measurements, were determined. MetS variables were also analyzed. Study was conducted in 70 women. Data were subjected to factor analysis. Receiver operating characteristic curves were used as predictors of chronodisruption risk, and a score was calculated to classify the subjects of risk.. Factor analysis showed that the first-factor grouped variables were related to the skin temperature measurement. Second factor consisted of variables related to salivary cortisol levels and obesity-related measurements. Third factor included variables related to sleep-wake cycle. Fourth factor referred to peripheral temperature variables and included the classification of subjects according to the Horne-Ostberg questionnaire. To obtain a final punctuation we performed the weighted mean of the first four factors. The final range was from 27 to 57, mean value of 42. Punctuation was defined as the "chronodisruption score." Women displaying higher chronodisruption scores had higher MetS risk.. The study demonstrates that wrist temperature recordings, together with two questions of sleep onset and offset, and one morning salivary cortisol determination could be enough to characterize the chronobiology of obesity and MetS, a new chronodisruption score was developed.

Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Chronobiology Phenomena; Circadian Rhythm; Factor Analysis, Statistical; Female; Humans; Hydrocortisone; Leptin; Melatonin; Metabolic Syndrome; Middle Aged; Obesity; Sleep; Surveys and Questionnaires; Triglycerides

Gaucher disease type I (GD type I) is characterized by clinical heterogeneity and is associated with metabolic abnormalities such as increased basal metabolic rate.. To evaluate ghrelin, leptin and adiponectin levels in patients with GD type I on enzyme replacement therapy (ERT).. A cross-sectional study of patients with GD type I (n = 15), matched for sex, age and BMI with healthy controls. The levels of glucose, insulin, ghrelin, leptin and adiponectin were assessed in both groups. Insulin resistance was defined by the index HOMA-IR.. Eight patients had adequate weight, seven were overweight (4 preobese, 3 obese class I). Eight patients presented metabolic syndrome, five of whom with insulin resistance. The median levels of ghrelin, leptin and adiponectin of the patients did not differ from those of the controls. Ghrelin and adiponectin levels were correlated with each other; inversely correlated with BMI, waist circumference and triglyceride levels; and directly correlated with HDL-cholesterol. Leptin levels were inversely correlated with LDL-cholesterol and directly correlated with BMI, waist circumference, enzyme dosage, triglycerides, insulin, and HOMA-IR.. Metabolic syndrome and overweight appear to be common in patients with GD type I on ERT. As leptin was strongly associated with insulin and HOMA index, it could become a biomarker to assess early evidence of insulin resistance in patients with GD. Further studies are needed to investigate the associations found.

Topics: Adiponectin; Adult; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Enzyme Replacement Therapy; Female; Gaucher Disease; Ghrelin; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Nutrition Assessment; Nutritional Status; Overweight; Triglycerides; Young Adult

Metabolic syndrome (MetS) is considered as a proinflammatory and prothrombotic state with atherogenic risk factors including dyslipidemia, obesity and glucose intolerance. Oxidative stress is a unifying basis of several disorders including diabetes mellitus (DM) and MetS. We therefore designed this cross-sectional study to investigate the potential interaction among iron metabolism, inflammation and endothelial plexus in MetS and DM patients.. A total of 62 patients [median age 54 (23-76) years; male/female 16/46] and 18 healthy controls [median age 38 (30-64) years; male/female 6/12] were included in the study. Patient population was classified as MetS (n = 30) and DM (n = 32).. Leukocyte count (p = 0.002) and osteopontin (OPN) levels (p = 0.008) were significantly higher, while C-reactive protein (CRP) (p = 0.056) and IL-6 (p = 0.059) represented a relative increase in the patient group. Leptin, endothelin 1 (ET1), hepcidin, nitric oxide synthase (NOS), erythrocyte sedimentation rate (ESR), iron, transferrin saturation (TS) and ferritin levels were not significantly different between the patient and control groups. Endothelin 1 was found to be higher in the DM group compared to MetS group (p = 0.15, p = 0.049). Leukocyte count, leptin, hepcidin, OPN, NOS, IL-6, ESR, CRP, iron, TS and ferritin levels were not different between DM and MetS groups. A positive correlation was demonstrated between leptin and OPN (p = 0.001, r = 0.360), ferritin and hepcidin (p < 0.01, r = 0.633), IL-6 and CRP (p = 0.023, r = 0.319), leptin and NOS (p = 0.005, r = 0.309) and OPN and NOS (p < 0.001, r = 0.803). There was a negative correlation between hepcidin and NOS (p = 0.009, r = -0.289). When the study cohort was divided into two particular groups based on median ferritin and hepcidin levels, hepcidin (p = 0.002), ALT (p = 0.001) and LDL (p = 0.049) levels were higher in the high-ferritin group. Nitric oxide synthase levels (p = 0.033) were lower, whereas ferritin levels (p = 0.004) were higher in the high-hepcidin group.. Mechanisms involved in the vicious circle of MetS including inflammation, endothelial vasculature and iron metabolism remain to be elucidated. The role of iron metabolism in this complex interaction should be confirmed with further studies.

Topics: Adult; Aged; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus; Endothelium, Vascular; Female; Ferritins; Glucose Intolerance; Hepcidins; Humans; Inflammation; Interleukin-6; Iron; Leptin; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Young Adult

Excessive sleep fragmentation (SF) is common in pregnant women. Adult-onset metabolic disorders may begin during early development and exhibit substantial sex dimorphism. We hypothesized that metabolic dysfunction induced by gestational SF in male mice would not be apparent in female littermates.. Body weight and food consumption were measured weekly in male and female offspring after late gestational SF or control sleep (SC). At 20 weeks, plasma leptin, adiponectin, lipid profiles, and insulin and glucose tolerance tests were assessed. Leptin and adiponectin, M1, and M2 macrophage messenger RNA expression and polarity were examined. Adiponectin gene promoter methylation levels in several tissues were assessed.. Food intake, body weight, visceral fat mass, and insulin resistance were higher, and adiponectin levels lower in male but not female offspring exposed to gestational SF. However, dyslipidemia was apparent in both male and female offspring exposed to SF, albeit of lesser magnitude. In visceral fat, leptin messenger RNA expression was selectively increased and adiponectin expression was decreased in male offspring exposed to gestational SF, but adiponectin was increased in exposed female offspring. Differences in adipokine expression also emerged in liver, subcutaneous fat, and muscle. Increased M1 macrophage markers were present in male offspring exposed to SF (SFOM) while increased M2 markers emerged in SF in female offspring (SFOF). Similarly, significant differences emerged in the methylation patterns of adiponectin promoter in SFOM and SFOF.. Gestational sleep fragmentation increases the susceptibility to obesity and metabolic syndrome in male but not in female offspring, most likely via epigenetic changes. Thus, sleep perturbations impose long-term detrimental effects to the fetus manifesting as sex dimorphic metabolic dysfunction in adulthood.

Topics: Adiponectin; Animals; Body Weight; Disease Susceptibility; DNA Methylation; Eating; Epigenesis, Genetic; Female; Glucose Tolerance Test; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipids; Liver; Macrophages; Male; Metabolic Syndrome; Mice; Muscles; Obesity; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Promoter Regions, Genetic; Sex Characteristics; Sleep; Sleep Deprivation; Subcutaneous Fat

Higher levels of leptin and homocysteine (Hcy) have been evaluated as risk factors of chronic kidney disease in patients and general population. The aim of this study was to examine gender differences in the associations of leptin and Hcy levels and renal function a representative healthy young population in Taiwan.. The participants aged ≥18 years who underwent health examinations were included and categorized into three groups by gender-specific tertiles of leptin and Hcy levels. Estimated glomerular filtration rates (eGFR) were estimated according to the modified equation of Modification of Diet in Renal Disease (MDRD).. A higher mean Hcy level was found in male subjects than females. Mean values of metabolic syndrome risk factors significantly elevated with increasing leptin levels in both genders. Both male and female subjects with higher plasma Hcy levels were more likely to have a lower eGFR. Plasma Hcy levels were significantly negatively correlated with eGFR in linear regression models adjusted for age and smoking. The associations persisted even after mean arterial pressure and fasting plasma glucose were included for adjustments both genders. Plasma Hcy level was negatively associated eGFR and the association was more profound for females.. Leptin levels did not reveal strong or consistent evidence to support a significant association with eGFR. Hcy had a more decisive effect on renal function impairment than leptin and may be considered a more sensitive biomarker for Taiwanese adults.

Topics: Adult; Asian People; Body Mass Index; Creatinine; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Homocysteine; Humans; Leptin; Linear Models; Male; Metabolic Syndrome; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Sex Factors; Smoking; Taiwan

Chronic sleep restriction in human beings results in metabolic abnormalities, including changes in the control of glucose homeostasis, increased body mass and risk of cardiovascular disease. In rats, 96h of REM sleep deprivation increases caloric intake, but retards body weight gain. Moreover, this procedure increases the expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which may be involved with the molecular mechanism proposed to mediate insulin resistance. The goal of the present study was to assess the effects of a chronic protocol of sleep restriction on parameters of energy balance (food intake and body weight), leptin plasma levels and its hypothalamic receptors and mediators of the immune system in the retroperitoneal adipose tissue (RPAT). Thirty-four Wistar rats were distributed in control (CTL) and sleep restriction groups; the latter was kept onto individual narrow platforms immersed in water for 18h/day (from 16:00h to 10:00h), for 21days (SR21). Food intake was assessed daily, after each sleep restriction period and body weight was measured daily, after the animals were taken from the sleep deprivation chambers. At the end of the 21day of sleep restriction, rats were decapitated and RPAT was obtained for morphological and immune functional assays and expression of insulin receptor substrate 1 (IRS-1) was assessed in skeletal muscle. Another subset of animals was used to evaluate blood glucose clearance. The results replicated previous findings on energy balance, e.g., increased food intake and reduced body weight gain. There was a significant reduction of RPAT mass (p<0.001), of leptin plasma levels and hypothalamic leptin receptors. Conversely, increased levels of TNF-α and IL-6 and expression of phosphorylated NFκ-β in the RPAT of SR21 compared to CTL rats (p<0.01, for all parameters). SR21 rats also displayed reduced glucose clearance and IRS-1 expression than CTL rats (p<0.01). The present results indicated that 21days of sleep restriction by the platform method induced metabolic syndrome-related alterations that may be mediated by inflammation of the RPAT.

Topics: Adipose Tissue; Animals; Body Weight; Cytokines; Eating; Hypothalamus; Inflammation; Insulin Receptor Substrate Proteins; Leptin; Male; Metabolic Syndrome; Muscle, Skeletal; Phosphorylation; Rats; Rats, Wistar; Receptors, Leptin; Sleep Deprivation

Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection.. In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin.. In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 mice was reduced from 55% to 20% by an 8-week pre-feeding of an HFD to induce obesity and metabolic syndrome. The addition of metformin reduced mortality to 3%.. It is an interesting observation that both the high fat diet and the metformin, which are known to differentially attenuate host metabolism, effectively modified mortality in T. cruzi-infected mice. In humans, the metabolic syndrome, as presently construed, produces immune activation and metabolic alterations that promote complications of obesity and diseases of later life, such as myocardial infarction, stroke, diabetes, Alzheimer's disease and cancer. Using an evolutionary approach, we hypothesized that for millions of years, the channeling of host resources into immune defences starting early in life ameliorated the effects of infectious diseases, especially chronic infections, such as tuberculosis and Chagas disease. In economically developed countries in recent times, with control of the common devastating infections, epidemic obesity and lengthening of lifespan, the dwindling benefits of the immune activation in the first half of life have been overshadowed by the explosion of the syndrome's negative effects in later life.

Topics: Adipose Tissue, White; Adiposity; Animals; Cell Line; Chagas Disease; Cytokines; Energy Metabolism; Foreskin; Heart Ventricles; Humans; Hypoglycemic Agents; Leptin; Male; Metabolic Syndrome; Metformin; Mice, Inbred Strains; Models, Immunological; Obesity; Random Allocation; Survival Analysis; Trypanosoma cruzi

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

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

Undercarboxylated osteocalcin (ucOC) has been proved as a regulator of glucose and fat mass in an animal model. This study examined the association between osteocalcin and metabolic syndrome (MetS) in postmenopausal women.. We selected 135 postmenopausal women and determined anthropometric values [waist-hip ratio (WHR), visceral fat area (VFA), body fat mass (BFM), and skeletal muscle mass (SMM)], the lipid profile, fasting plasma glucose (FPG), insulin, high-sensitivity C-reactive protein (hs-CRP), homeostasis model assessment of insulin resistance (HOMA-IR), serum leptin and adiponectin level, and serum tOC and ucOC level.. There were 52 postmenopausal women in the MetS group. After adjusting for age and years since menopause, ucOC was negatively correlated with WHR, VFA, BFM, triglyceride, fasting insulin, HOMA-IR, and serum leptin and was positively correlated with serum adiponectin. The odds ratio for MetS was significantly lower in the highest quartile than the lowest quartile after adjusting for age, years since menopause, and BMI. In multiple regression analysis, serum leptin and HOMA-IR were the most important predictors of the independent variables that affect serum ucOC.. ucOC showed an inverse correlation with markers of insulin resistance, central obesity, and the presence of MetS in postmenopausal women and appears to protect against MetS. Further large-scale clinical and experimental studies are needed to clarify the potential of ucOC as a predictor of MetS in postmenopausal women.

Topics: Adiponectin; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Fasting; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Middle Aged; Osteocalcin; Postmenopause; Prospective Studies; Triglycerides; Waist-Hip Ratio

Visfatin, also known as nicotinamide phosphoribosyltransferase, is an adipokine that has been implicated in obesity, insulin resistance (IR) and diabetes mellitus. Since obesity profoundly affects serum lipids, insulin, and glucose metabolism, the aim of this study was to evaluate the relationships between visfatin and metabolic parameters in childhood obesity.. A total of 73 Iranian children and adolescents (31 controls; 42 obese), between the ages of 7 and 16 years, were selected and clinically evaluated. Serum visfatin, leptin, insulin and adiponectin were measured using ELISA, and insulin resistance was calculated by the Homeostasis Model of Assessment of Insulin Resistance (HOMA-IR). Fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), LDL-C and HDL-C were also measured. Metabolic syndrome (MetS) was determined according to IDF criteria.. Obese subjects presented significantly higher levels of insulin, LDL-C, HOMA-IR, and leptin and lower levels of adiponectin. Serum Visfatin was higher in obese children than in the control children, and it was significantly higher in obese children with MetS or IR, compared with obese children without MetS or IR. Visfatin levels showed positive correlations with FPG, insulin, and HOMA-IR, in obese subjects and a negative correlation with adiponectin, but no correlation with leptin. Adiponectin levels were correlated with HDL-C and Insulin levels in obese subjects. Leptin levels were correlated with Body mass index (BMI) but not with metabolic parameters.. Visfatin is increased in obese children and adolescents, and has a more prominent association with IR and MetS parameters, compared with leptin and adiponectin.

Topics: Adiponectin; Adolescent; Body Mass Index; Case-Control Studies; Child; Cytokines; Female; Humans; Insulin Resistance; Iran; Leptin; Male; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Obesity

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

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

Recent studies demonstrate that epigenetic changes under malnutrition in utero might play important roles in transgenerational links with metabolic diseases. We have previously shown that exposure to a high-fat diet (HFD) in utero may cause a metabolic syndrome-like phenomenon through epigenetic modifications of Adiponectin and Leptin genes. Because an association of obesity between mother and offspring endured in multiple generations, we examined whether HFD exposure in utero might affect the metabolic status of female offspring through multigenerational epigenetic changes of Adiponectin and Leptin genes and whether a normal diet in utero for multiple generations might abolish such epigenetic changes after exposure to a HFD in utero using ICR mice. We observed that the effect of maternal HFD on offspring over multiple generations in metabolic syndrome-like phenomenon such as weight and fat mass gain, glucose intolerance, hypertriglyceridemia, abnormal adiponectin and leptin levels, and hypertension, were accumulated with expression and epigenetic changes in Adiponectin and Leptin genes. A normal diet in utero in the subsequent generations after HFD exposure in utero diminished, and a normal diet in utero for 3 generations completely abolished, the effect of HFD in utero on weight and fat mass gain, insulin resistance, serum triglyceride, adiponectin, and leptin levels, with epigenetic changes of Adiponectin and Leptin genes. Exposure to a HFD in utero might affect glucose and lipid metabolism of female offspring through epigenetic modifications to Adiponectin and Leptin genes for multiple generations. Obesogenic and diabetogenic traits were abolished after a maternal normal diet for 3 generations.

Topics: Adiponectin; Animals; Blood Glucose; Body Weight; Diet, High-Fat; Epigenesis, Genetic; Female; Gene Expression; Glucose Intolerance; Glucose Tolerance Test; Hypertriglyceridemia; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Mice; Mice, Inbred ICR; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Real-Time Polymerase Chain Reaction; RNA, Messenger; Triglycerides

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

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

Metabolic syndrome and T2D produce significant health and economic issues. Many available animal models have monogenic leptin pathway mutations that are absent in the human population. Development of the ZDSD rat model was undertaken to produce a model that expresses polygenic obesity and diabetes with an intact leptin pathway. A lean ZDF rat with the propensity for beta-cell failure was crossed with a polygenetically obese Crl:CD (SD) rat. Offspring were selectively inbred for obesity and diabetes for >30 generations. In the current study, ZDSD rats were followed for 6 months; routine clinical metabolic endpoints were included throughout the study. In the prediabetic metabolic syndrome phase, ZDSD rats exhibited obesity with increased body fat, hyperglycemia, insulin resistance, dyslipidemia, glucose intolerance, and elevated HbA1c. As disease progressed to overt diabetes, ZDSD rats demonstrated elevated glucose levels, abnormal oral glucose tolerance, increases in HbA1c levels, reductions in body weight, increased insulin resistance with decreasing insulin levels, and dyslipidemia. The ZDSD rat develops prediabetic metabolic syndrome and T2D in a manner that mirrors the development of metabolic syndrome and T2D in humans. ZDSD rats will provide a novel, translational animal model for the study of human metabolic diseases and for the development of new therapies.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose Intolerance; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Rats; Signal Transduction

We investigated the effect of glatiramer acetate (GA) on the modulation of immune cell subpopulations and serum levels of multiple immune/metabolic markers in patients with relapsing-remitting multiple sclerosis (RRMS) to understand whether the treatment with GA could induce a specific change in the immunometabolic asset of patients with RRMS.. We performed an extensive peripheral blood immunophenotyping and measured serum levels of several parameters involved in the pathogenesis of RRMS and also relevant in the pathogenesis of metabolic syndrome and obesity such as leptin, soluble leptin-receptor (sLep-R), myeloperoxidase (MPO), soluble CD40 ligand (sCD40-L), soluble tumor necrosis factor-receptor (sTNF-R), monocyte chemoattractant protein 1 (MCP-1), soluble Inter-Cellular Adhesion Molecule-1 (sICAM-1) and osteoprotegerin (OPG), in 20 naïve-to-treatment RRMS patients and 20 healthy controls. We repeated these analyses over time at 6 and 12 months after starting GA treatment.. Our analysis showed that naïve-to-treatment RRMS patients had a lower number of CD16(+)CD56(+) NK cells, CD19(+) B cells, CD4(+) T cells co-expressing the MHC class II activation marker HLA-DR (CD4(+)DR(+)) and naïve CD4(+)CD45RA(+) T cells in basal conditions. GA treatment induced a specific and significant decrease of circulating CD19(+) B cells. Naïve-to-treatment RRMS patients also showed a significantly higher number of CD4(+) T cells with a memory phenotype (CD4(+)CD45RO(+)) whose peripheral frequency was not affected by GA treatment. These changes over time associated with a higher serum concentration of leptin and lower levels of MPO. GA treatment also reduced significantly the circulating levels of sCD40-L and sTNF-R overtime.. Our data suggest that the clinical outcome of GA treatment is associated with changes in immune cell subpopulations and modulation of specific immunometabolic markers. These data add substantial evidence of the immune modulating effect of GA during RRMS and could be of relevance in understanding the pathogenesis of disease and its follow-up.

Topics: Adult; Biomarkers; CD4-Positive T-Lymphocytes; Female; Glatiramer Acetate; Humans; Leptin; Longitudinal Studies; Lymphocyte Count; Male; Metabolic Syndrome; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Obesity; Peptides

Experimental models of intermittent hypoxia (IH) have been developed during the last decade to investigate the consequences of obstructive sleep apnea. IH is usually associated with detrimental metabolic and vascular outcomes. However, paradoxical protective effects have also been described depending of IH patterns and durations applied in studies. We evaluated the impact of short-term IH on vascular and metabolic function in a diet-induced model of metabolic syndrome (MS).. Mice were fed either a standard diet or a high fat diet (HFD) for 8 weeks. During the final 14 days of each diet, animals were exposed to either IH (1 min cycle, FiO2 5% for 30s, FiO2 21% for 30s; 8 h/day) or intermittent air (FiO2 21%). Ex-vivo vascular reactivity in response to acetylcholine was assessed in aorta rings by myography. Glucose, insulin and leptin levels were assessed, as well as serum lipid profile, hepatic mitochondrial activity and tissue nitric oxide (NO) release.. Mice fed with HFD developed moderate markers of dysmetabolism mimicking MS, including increased epididymal fat, dyslipidemia, hepatic steatosis and endothelial dysfunction. HFD decreased mitochondrial complex I, II and IV activities and increased lactate dehydrogenase (LDH) activity in liver. IH applied to HFD mice induced a major increase in insulin and leptin levels and prevented endothelial dysfunction by restoring NO production. IH also restored mitochondrial complex I and IV activities, moderated the increase in LDH activity and liver triglyceride accumulation in HFD mice.. In a mouse model of MS, short-term IH increases insulin and leptin levels, restores endothelial function and mitochondrial activity and limits liver lipid accumulation.

Topics: Animals; Diet, High-Fat; Disease Models, Animal; Endothelium, Vascular; Glycolysis; Hypoxia; Insulin; Leptin; Lipid Metabolism; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mitochondria, Liver; Nitric Oxide; Sleep Apnea, Obstructive

The aim of this study was to determine the levels of leptin (Lep) and adiponectin (AdipoQ) in patients with gout and its relationship with joint inflammatory data and/or with metabolic syndrome (MetS) variables, during 1 year follow-up.Forty-one patients (40 males) with gout diagnosis, attending for the first time to a rheumatology department, were included. Evaluations were performed baseline, at 6 and 12 months. Variables included the following: demographic, clinical and laboratory data related to gout and associated diseases. Lep and AdipoQ determinations by the ELISA method were performed in frozen serum from each visit. The pharmacological and no-pharmacological treatment for gout and associated diseases was individualized for each patient according to published guidelines. Statistical analysis included Mann-Whitney U test, Fisher test, x, ANOVA, Cochran Q, Pearson and Spearman correlation tests, as well as linear regression.In the baseline evaluation, 29.2% had MetS (hypertriglyceridemia 66%, hypertension 44% and obesity 37%); patients with MetS had higher C reactive protein (CRP) levels [34.1 ± 28.6 vs. 12.2 ± 11.2 mg/dL, P = 0.033]. Although not significant, also had higher Lep and lower AdipoQ levels (3.2 ± 3.0 vs. 1.9 ± 1.2 ng/mL, P = 0.142 and 40.5 ± 26.8 vs. 38.0 ± 24.9 ng/mL, P = 0.877, respectively). During follow-up, our patients had significant improvement in serum uric acid (sUA) levels and variables evaluating pain and joint swelling (P ≤ 0.05). Metabolic abnormalities tended to persist or even worsen during the monitoring period: significant increase in total cholesterol (P = 0.004), tendency to higher triglycerides (P = 0.883) and slight improvement in glycaemia (P = 0.052). Lep values increased significantly during follow-up (P = 0.001) while AdipoQ levels diminished slightly (P = 0.317). Neither Lep nor AdipoQ values showed important correlation (r > 0.5) with metabolic variables or joint swelling.This study suggests that in patients with gout, concentrations of Lep and AdipoQ are more in line with the metabolic state than with clinical disease activity.

Topics: Adiponectin; Adult; Female; Follow-Up Studies; Gout; Humans; Joints; Leptin; Male; Metabolic Syndrome; Middle Aged; Prospective Studies

To investigate adipokines levels in obese children with acanthosis nigricans (AN) and to explore the relationship between AN and metabolic syndrome (MS).. A cross-sectional study was performed on 109 obese children and 47 age- and gender-matched normal controls. The obese children were divided into two groups with AN and without AN. Serum levels of adiponectin, leptin, TNF-α and retinol-binding protein 4 (RBP4) were measured using ELISA. Multiple logistic regression analysis was performed to estimate the association of clinical parameters with MS.. Waist-hip ratio, systolic blood pressure, triglyceride, fasting insulin and insulin resistance index (HOMA-IR) were significantly higher in obese children with AN than in those without AN and normal controls (P<0.05). The obese children with AN and without AN had lower adiponectin levels than normal controls (P<0.05), on the contrary, the obese children with AN had higher leptin levels than those without AN and normal controls (P<0.05). Multiple logistic regression analysis revealed that AN (OR=3.469, 95%CI: 1.518-7.929) and BMI (OR=7.108, 95%CI: 2.359-21.416) were independent risk factors for MS.. As a visible marker of insulin resistance, AN is associated with abnormal adipokines secretion. Reducing the incidence of AN and losing weight may prevent obesity associated MS.

Topics: Acanthosis Nigricans; Adiponectin; Adolescent; Child; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Logistic Models; Male; Metabolic Syndrome; Obesity

To clarify metabolic syndrome induced stone formation mechanisms we investigated the metabolic and immunohistochemical characteristics associated with renal crystal deposition using a model of mice with metabolic syndrome administered a high fat diet and ethylene glycol.. Ob/Ob mice with Leptin gene deficiencies and metabolic syndrome related characteristics were compared with wild heterozygous lean mice. Four study groups were fed standard food and water (control group), a high fat diet and normal water (high fat diet group), 1% ethylene glycol and standard food (ethylene glycol group) or a high fat diet and 1% ethylene glycol (high fat diet plus ethylene glycol group). Blood, urine and kidney samples were taken after 14 days.. Ob/Ob mice in the high fat diet plus ethylene glycol group showed diffuse renal crystal depositions. Lean and Ob/Ob mice in the high fat diet plus ethylene glycol group showed significant excretion of urinary calcium oxalate crystals. Ob/Ob mice had significant hypercalciuria, hyperphosphaturia and hyperlipidemia, massive lipid fragments in tubular lumina and fat droplets in renal tubular cells. Ob/Ob mice in the high fat diet plus ethylene glycol group had markedly increased expression of osteopontin, monocyte chemoattractant protein-1, interleukin-6 and tumor necrosis factor-α. In Ob/Ob mice the number of proinflammatory macrophages was considerably elevated.. We induced renal crystal deposition in mice with metabolic syndrome using a high fat diet and ethylene glycol. Increases in luminal mineral and lipid density, and proinflammatory adipocytokines and macrophages facilitated renal crystal formation in mice with metabolic syndrome.

Topics: Adipokines; Animals; Calcium Oxalate; Cell Count; Diet, High-Fat; Disease Models, Animal; Ethylene Glycol; Inflammation Mediators; Kidney Calculi; Leptin; Macrophages; Male; Metabolic Syndrome; Mice; Mice, Obese

The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged > or =18 years from the Libertador district in Merida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients' self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

Topics: Adult; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Prevalence; Risk Factors; Sex Factors; Thyrotropin; Thyroxine; Venezuela

To describe the relationship between metalloproteinase (MMP) 2, MMP-9, and leptin in drivers of public service vehicles with metabolic syndrome in the city of Armenia (Quindio, Colombia).. Leptin was measured using Millipore ELISA kits. MMP-2 and MMP-9 were measured with ELISA kits from R&D Systems.. Fifty-seven male drivers with metabolic syndrome with a mean age of 45.35years, BMI of 29.81, and an abdominal circumference of 105.75cm were identified. Blood pressure values were 126.5/82.5mmHg. Leptin, MMP-2, and MMP-9 levels were 24.6ng/mL, 28,1ng/mL, and 7.5ng/mL respectively. The relationship between leptin and waist circumference was statistically significant (P<.001). The explained variation (R(2)) in waist circumference, is explained in a 80.12% for the study variables, has a statistically significant association with BMI (P<.001), MMP-2 (P=.01), age (P=.01), SBP (P<.001) and DBP (P<.001). The R(2) of leptin, is explained in a 69.56% for the study variables, has a statistically significant association with BMI (P<.001), MMP-2 (P=.05) and triglycerides (P=.02). The R(2) of MMP-2, explained in 41.82% of the study variables and has a statistically significant association with waist circumference (P=.01), glucose (P=.01) and age (P=.03).. Statistically significant associations were found between waist circumference and MMP-2; leptin and MMP-2, and MMP-2 and waist circumference and blood glucose.

Topics: Adult; Age Factors; Armenia; Automobile Driving; Blood Glucose; Body Mass Index; Cross-Sectional Studies; Humans; Leptin; Life Style; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Metabolic Syndrome; Middle Aged; Motor Vehicles; Occupations; Oxidative Stress; Risk Factors; Waist Circumference

The pathobiological impact of individual components of the metabolic syndrome (MS) on cardiac structural and functional parameters in women with isolated MS is not known. The objectives of this study were (1) to compare biochemical (prothrombotic, lipogenic, and inflammatory) and imaging (carotid intima-media thickening and basic cardiac structural measurements) markers in women with and without MS and (2) to examine if any of these markers associated or predicted cardiac structural differences between the 2 groups. This cross-sectional pilot study included 88 women with MS and 35 women without it. MS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Patients with diagnosis of diabetes were excluded. Compared with healthy subjects, women with MS had higher levels of intercellular adhesion molecule, myeloperoxidase, C-reactive protein, plasminogen activator inhibitor-1, leptin, apolipoprotein-B, and lower levels of apolipoprotein-A1 (p <0.001 for all). They also had higher mean ventricular septum, posterior wall thickness, left ventricular (LV) mass, carotid intima-media thickness (p <0.001 for all), and left atrial diameter (p = 0.015). In multivariable regression models, waist circumference and systolic blood pressure (BP) were significant predictors of: ventricular septum (p = 0.005 and p = 0.001, respectively), posterior wall thickness (p = 0.008 and p = 0.040, respectively), and LV mass (p <0.001 and p = 0.013, respectively). Significant predictors for carotid intima-media thickness were systolic BP, glucose, and leptin (p <0.0001, p = 0.034, and p = 0.002, respectively). In conclusion, there are significant clinical, biochemical, and cardiovascular structural differences in women with isolated MS compared with those without. Waist circumference and systolic BP had the strongest association with cardiac structural differences in this group of women.

Topics: Acrylamides; Adolescent; Adult; Aged; Apolipoproteins A; Apolipoproteins B; beta-Alanine; Blood Pressure; C-Reactive Protein; Carotid Intima-Media Thickness; Cross-Sectional Studies; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Peroxidase; Pilot Projects; Plasminogen Activator Inhibitor 1; Waist Circumference; Young Adult

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

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

Growing evidence indicates that the metabolic syndrome (MS) is rooted in adverse exposures during fetal life. The aim of this study was to assess the possible associations between biomarkers of inflammation during third trimester of pregnancy and markers of MS in adult offspring.. High-sensitive C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleuki-6 (IL-6) were measured in serum samples obtained in gestational week 30. Offspring were clinically examined at age 20 years. Analyses based on 439 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, prepregnancy body mass index (BMI), education, and offspring's sex. Offspring MS markers included waist circumference, BMI, blood pressure, HOMA insulin resistance, and plasma levels of fasting glucose, triglycerides, cholesterol fractions, insulin, and leptin.. The median level was 2.8 (interquartile range = 3.3) µg/ml for CRP, for TNF-α: 5.7 (3.2) pg/ml, for IL-1β: 0.5 (0.4) pg/ml, and for IL-6: 1.1 (0.7) pg/ml. Concentrations were not significantly associated with MS markers in the offspring. The results remained essentially unchanged after correction for potential confounding.. Markers for subclinical inflammation in third trimester in healthy women were not associated with components of MS in their adult offspring.

Topics: Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Cholesterol; Female; Follow-Up Studies; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-1beta; Interleukin-6; Leptin; Linear Models; Longitudinal Studies; Male; Metabolic Syndrome; Multivariate Analysis; Pregnancy; Pregnancy Trimester, Third; Triglycerides; Tumor Necrosis Factor-alpha; Waist Circumference; Young Adult

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

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

Leptin's in vivo effect on the rodent skeleton depends on the model used and the mode of administration. Superactive mouse leptin antagonist (SMLA) was produced and then pegylated (PEG) to prolong and enhance its in vivo activity. We blocked leptin signaling by injecting this antagonist peripherally into normal mice at various time points and studied their metabolic and skeletal phenotypes. Subcutaneous PEG-SMLA injections into 4-wk-old female C57BL/6J mice increased weight gain and food consumption significantly after only 1 mo, and the effect lasted for the 3 mo of the experiment, proving its central inhibiting activity. Mice showed a significant increase in serum glucose, cholesterol, triglycerides, insulin, and HOMA-IR throughout the experiment. Quantification of gene expression in "metabolic" tissues also indicated the development of insulin resistance. Bone analyses revealed a significant increase in trabecular and cortical parameters measured in both the lumbar vertebrae and tibiae in PEG-SMLA-treated mice in the 1st and 3rd months as well as a significant increase in tibia biomechanical parameters. Interestingly, 30 days of treatment with the antagonist in older mice (aged 3 and 6 mo) affected body weight and eating behavior, just as they had in the 1-mo-old mice, but had no effect on bone parameters, suggesting that leptin's effect on bones, either directly or through its obesogenic effect, is dependent upon stage of skeletal development. This potent and reversible antagonist enabled us to study leptin's in vivo role in whole body and bone metabolism and holds potential for future therapeutic use in diseases involving leptin signaling.

Topics: Animals; Biomechanical Phenomena; Blood Glucose; Body Weight; Bone and Bones; Cholesterol; Diabetes Mellitus, Type 2; Disease Models, Animal; Eating; Female; Gene Expression; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Metabolism; Mice; Mice, Inbred C57BL; Triglycerides

Vitamin D deficiency and metabolic syndrome are 2 very common health problems in the Spanish population. It has been suggested that patients with metabolic syndrome may be vitamin D deficient more often than subjects without it and that low vitamin D levels may predispose to metabolic syndrome development. However, the results of prospective and intervention studies have been different and such relationship remains unclear. We assessed the relationship between 25-hydroxyvitamin D levels and the prevalence and incidence of metabolic syndrome.. We undertook a population-based cohort study in Spain. At baseline (1996-1998), 1,226 subjects were evaluated. Follow-up visits were performed in 2002-2004 and 2005-2007.At baseline and follow-up, participants underwent an interview and a standardized clinical examination with an oral glucose tolerance test in those subjects without known diabetes. At the second visit, 25-hydroxyvitamin D levels and intact parathyroid hormone levels were measured.. The prevalence of metabolic syndrome at the second and third visit was 29.4 and 42.5%, respectively. Mean levels of 25-hydroxyvitamin D were lower in subjects with metabolic syndrome: 21.7 (6.21) vs 23.35 (6.29) ng/ml, P<.001.The prevalence of vitamin D deficiency (25-hydroxyvitamin D<20 ng/ml) at the second evaluation was 34.7%, with significant differences between subjects with and without metabolic syndrome(34.6 vs 26.5%, P<.01). Men with vitamin D deficiency had more frequently hypertension and metabolic syndrome than men with normal levels. Women with vitamin D deficiency had more frequently hyperglycemia, hypertension, increased waist circumference and hypertriglyceridemia. In a prospective study, 25-hydroxyvitamin D values<20 ng/ml were not significantly associated with an increased risk of developing metabolic syndrome in the next 5 years (odds ratio 0,99, 95% confidence interval 0.57-1.7, P=.97) after adjusting by sex and age.. Vitamin D deficiency is associated with an increased prevalence but not with an increased incidence of metabolic syndrome.

Topics: Adiponectin; Adult; Body Mass Index; Comorbidity; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Hypertension; Hypertriglyceridemia; Interleukin-6; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Prevalence; Prospective Studies; Resistin; Risk Factors; Sex Factors; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency; Waist Circumference

The present study determines the fat depot-specific expression of leptin and TNF-α and its association with biochemical parameters in postmenopausal women. A total of 108 postmenopausal women were recruited prospectively; 54 were with metabolic syndrome (cases) and 54 were without metabolic syndrome (controls). Leptin and TNF-α mRNA expression in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were done by Real Time-RT PCR. In cases, the mean (±SD) serum estrogen was significantly lower (41.33±24.90 vs. 23.95±14.45, p<0.001) while leptin (12.85±4.51 vs. 10.34±3.89, p=0.002) and TNF-α (13.81±7.13 vs. 8.00±4.38, p<0.001) were significantly higher as compared to controls. Further, the mean relative VAT mRNA expression of both leptin (0.33±0.29 vs. 0.05±0.09, p<0.001) and TNF-α (0.32±0.31 vs. 0.13±0.09, p<0.001) and expression of SAT leptin (4.91±4.01 vs. 0.50±0.92, p<0.001) also lowered significantly in cases as compared to controls. Further, the relative VAT expression of both leptin (r=-0.32, p<0.001) and TNF-α (r=-0.23, p<0.01) showed significant and negative correlation with glucose; expression of SAT leptin showed significant and positive correlation with HDL (r=0.20, p<0.05) and serum estrogen (r=0.30, p<0.01) while negative correlation with glucose (r=-0.26, p<0.01) and serum TNF-α (r=-0.29, p<0.01); and expression of SAT TNF-α showed significant and positive correlation with insulin (r=0.21, p<0.05) and HOMA (r=0.20, p<0.05). In conclusion, the VAT and SAT leptin mRNA expressions may have a modulatory role in metabolic syndrome.

Topics: Aged; Blood Glucose; Estrogens; Female; Gene Expression; Humans; India; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Metabolic Syndrome; Middle Aged; Postmenopause; RNA, Messenger; Subcutaneous Fat; Tumor Necrosis Factor-alpha

Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors.. In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponectin, leptin, and resistin among metabolically benign normal weight, at-risk normal weight, metabolically benign obese, and at-risk obese women using components of the ATP III definition of the metabolic syndrome (metabolically benign: ≤1 of the four components; at-risk phenotype: ≥2 components or diabetes).. Overall, 382/699 normal-weight women (54.6%) and 328/1,194 overweight/obese women (27.5%) were metabolically benign. Among normal-weight women, at-risk women had higher leptin and lower adiponectin levels compared to metabolically benign women; multivariate-adjusted odds ratios were significant for having leptin (OR: 2.51; 95% CI: 1.28-5.01) and resistin (1.46; 1.03-2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81-3.84). Compared to metabolically benign overweight/obese women, at-risk obese women had higher odds of having leptin in the top tertile (1.62; 1.24-2.12) and adiponectin in the bottom tertile (2.78; 2.04-3.77).. Overall, metabolically benign overweight/obese women had an intermediate adipokine profile (between at-risk obese and metabolically benign normal-weight women), whereas at-risk normal-weight women had a less favorable profile compared to metabolically benign normal-weight women. As adiponectin was the only adipokine independent of BMI, it may be most likely to have a role in the etiological pathway of these phenotypes.

Topics: Adiponectin; Aged; Case-Control Studies; Female; Health Behavior; Humans; Leptin; Logistic Models; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Obesity; Overweight; Postmenopause; Resistin; Risk Factors

AT₁ receptor antagonists decrease body weight gain in models of murine obesity. However, fewer data are available concerning the anti-obesity effects of these antagonists, given as a treatment after obesity had been established.. In spontaneously hypertensive rats, obesity was established by cafeteria diet (CD) feeding for 19 weeks. Rats were then were treated with telmisartan (8 mg·kg⁻¹·d⁻¹) or amlodipine (10 mg·kg⁻¹·d⁻¹; serving as blood pressure control) or telmisartan + amlodipine (2 + 10 mg·kg⁻¹·d⁻¹; to control for dose-dependency) for 17 weeks. Rats receiving only chow (C(chow)) or CD-fed rats treated with vehicle (C(CD)) served as controls.. The CD feeding induced obesity, hyperphagia, hyperlipidaemia, and leptin and insulin resistance. Telmisartan reduced the CD-induced increase in body weight and abdominal fat mass. Whereas energy intake was higher rather than lower, the respiratory ratio was lower. After telmisartan, leptin-induced energy intake was reduced and respiratory ratio was increased compared with C(CD) rats. Telmisartan also decreased plasma levels of triglycerides, free fatty acids and low-density lipoprotein. Amlodipine alone or the combination telmisartan + amlodipine did not affect body weight and eating behaviour. Telmisartan, but not amlodipine and telmisartan + amlodipine, improved glucose utilization. The decrease in BP reduction was almost the same in all treatment groups.. Telmisartan exerted anti-obesity effects and restored leptin sensitivity, given as a treatment to rats with obesity. Such effects required high doses of telmisartan and were independent of the decrease in blood pressure.

Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Animals; Anti-Obesity Agents; Antihypertensive Agents; Behavior, Animal; Benzimidazoles; Benzoates; Diet, High-Fat; Dietary Sucrose; Drug Therapy, Combination; Energy Intake; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Random Allocation; Rats; Rats, Inbred SHR; Telmisartan; Weight Gain

Epigenetic alterations have been suggested to be associated with obesity and related metabolic disorders. Here we examined the correlation between obesity and insulin resistance with the methylation frequency of the leptin (LEP) and adiponectin (ADIPOQ) promoters in obese adolescents with the aim to identify epigenetic markers that might be used as tools to predict and follow up the physiological alterations associated with the development of the metabolic syndrome.. One hundred and six adolescents were recruited and classified according to body mass index and homeostasis model of assessment-insulin resistance index. The circulating concentrations of leptin, adiponectin and of several metabolic markers of obesity and insulin resistance were determined by standard methods. The methylation frequency of the LEP and ADIPOQ promoters was determined by methylation-specific PCR (MS-PCR) in DNA obtained from peripheral blood samples.. Obese adolescents without insulin resistance showed higher and lower circulating levels of, respectively, leptin and adiponectin along with increased plasmatic concentrations of insulin and triglycerides. They also exhibited the same methylation frequency than lean subjects of the CpG sites located at -51 and -31 nt relative to the transcription start site of the LEP gene. However, the methylation frequency of these nucleotides dropped markedly in obese adolescents with insulin resistance. We found the same inverse relationship between the combined presence of obesity and insulin resistance and the methylation frequency of the CpG site located at -283 nt relative to the start site of the ADIPOQ promoter.. These observations sustain the hypothesis that epigenetic modifications might underpin the development of obesity and related metabolic disorders. They also validate the use of blood leukocytes and MS-PCR as a reliable and affordable methodology for the identification of epigenetic modifications that could be used as molecular markers to predict and follow up the physiological changes associated with obesity and insulin resistance.

Topics: Adiponectin; Adolescent; Biomarkers; Blood Glucose; Body Mass Index; Child; DNA Methylation; Enzyme-Linked Immunosorbent Assay; Female; Genes, Regulator; Homeostasis; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Mexico; Obesity; Polymerase Chain Reaction

Obesity is associated with vascular diseases that are often attributed to vascular oxidative stress. We tested the hypothesis that vascular oxidative stress could induce obesity. We previously developed mice that overexpress p22phox in vascular smooth muscle, tg(sm/p22phox), which have increased vascular ROS production. At baseline, tg(sm/p22phox) mice have a modest increase in body weight. With high-fat feeding, tg(sm/p22phox) mice developed exaggerated obesity and increased fat mass. Body weight increased from 32.16 ± 2.34 g to 43.03 ± 1.44 g in tg(sm/p22phox) mice (vs. 30.81 ± 0.71 g to 37.89 ± 1.16 g in the WT mice). This was associated with development of glucose intolerance, reduced HDL cholesterol, and increased levels of leptin and MCP-1. Tg(sm/p22phox) mice displayed impaired spontaneous activity and increased mitochondrial ROS production and mitochondrial dysfunction in skeletal muscle. In mice with vascular smooth muscle-targeted deletion of p22phox (p22phox(loxp/loxp)/tg(smmhc/cre) mice), high-fat feeding did not induce weight gain or leptin resistance. These mice also had reduced T-cell infiltration of perivascular fat. In conclusion, these data indicate that vascular oxidative stress induces obesity and metabolic syndrome, accompanied by and likely due to exercise intolerance, vascular inflammation, and augmented adipogenesis. These data indicate that vascular ROS may play a causal role in the development of obesity and metabolic syndrome.

Topics: Adipogenesis; Animals; Cytochrome b Group; Diet, High-Fat; Drug Resistance; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Smooth, Vascular; NADPH Oxidases; Obesity; Oxidative Stress; Reactive Oxygen Species; Vascular Diseases

To date, only a few studies on child obesity concerned Trace Elements (TE). TE is involved in the pathogenesis of obesity and obesity related diseases. We tried to assess trace elements status [zinc (Zn), copper (Cu), selenium (Se), iron (Fe), and chromium (Cr)] in obese Egyptian children and their relationships with serum leptin and metabolic risk factors of obesity.. This was a case-control study performed with 80 obese children (BMI ≥ 95thcentile for age and gender) and 80 healthy non-obese children with comparable age and gender as the control group. For all subjects, serum Zn, Cu, Se, Fe, ferritin and Cr as well as biochemical parameters including lipid profile, serum glucose and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed. Levels of serum leptin were measured by (enzyme-linked immunosorbent assay [ELISA] method), and serum insulin was measured by an electrochemiluminesce immunoassay.. Compared to the control group, serum Zn, Se, and Fe levels were significantly lower (all P < 0.01) and serum Cu level was significantly higher (P < 0.01) in the obese children. Meanwhile, no significant differences were observed in serum ferritin or Cr levels (P > 0.05). A significant negative correlation was found between serum leptin and zinc levels in the obese children (r = -0.746; P < 0.01). Further, serum Zn showed significant negative correlations with total cholesterol TC levels (P < 0.05) and were positively correlated with high density lipoprotein- cholesterol HDL-C levels (P < 0.01) in the obese children. In addition, serum Se levels showed significant positive correlations with HOMA-IR values in the obese children (P < 0.01).. The obese children may be at a greater risk of developing imbalance (mainly deficiency) of trace elements which may be playing an important role in the pathogenesis of obesity and related metabolic risk factors.

Topics: Biomarkers; Body Composition; Child; Child, Preschool; Egypt; Enzyme-Linked Immunosorbent Assay; Female; Humans; Incidence; Insulin; Leptin; Male; Mass Spectrometry; Metabolic Syndrome; Pediatric Obesity; Prognosis; Retrospective Studies; Risk Factors; Trace Elements

The pathogenesis of diabetic retinopathy (DR) in metabolic syndrome (MetS) and type 2 diabetes (T2D) is not well studied, partly because an appropriate model has not been developed. Recently, we introduced a novel model of spontaneous T2D and MetS that replicates the relevant features of the human disease. In the current study, we investigated the retinal vascular changes in these animals. Experimental DR in streptozotocin (STZ)-injected rodents is described as an inflammatory disease, in which intercellular adhesion molecule 1 (ICAM-1) plays a key role. In comparison, advanced diabetes (HbA1c>10%) in the Nile grass rat (NGR) was associated with lower ICAM-1 protein expression when compared with that in normal or moderately diabetic animals. Vascular cell adhesion molecule 1 (VCAM-1) expression, however, was unaffected by the disease state. As opposed to the STZ-induced model of DR, in diabetic NGRs, most leukocytes accumulated in the retinal arteries. Consistent with the ICAM-1 reduction, leukocyte accumulation was significantly reduced in advanced disease. Similarly, leukocyte adhesions were significantly lower, with elevated plasma triglycerides (>200 mg/dl), and cholesterol (>240 mg/dl). However, these adhesions were significantly higher in animals with higher plasma insulin (>5 μIU/ml) and leptin (>20 ng/ml), suggesting a role for these hormones in diabetic retinal leukostasis. Diabetic NGRs showed substantial retinal endothelial injury, primarily in the microvessels, including vascular tortuosity, obliterated acellular capillaries, and pericyte ghosts. The NGR provides a convenient and realistic model for investigation of retinal changes in MetS/T2D with convincing advantages over the commonly used STZ-induced T1D.

Topics: Adiponectin; Animals; Blood-Retinal Barrier; Cell Adhesion; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Models, Animal; Female; Glycated Hemoglobin; Inflammation; Insulin; Intercellular Adhesion Molecule-1; Leptin; Leukocytes; Lipids; Male; Metabolic Syndrome; Rats; Retina; Retinal Vessels; Streptozocin; Triglycerides; Vascular Cell Adhesion Molecule-1

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

There is much data supporting a role for adipokines in both obesity and metabolic syndrome. Insulin resistance and low-grade inflammation are crucial in the genesis of both disorders. Although data suggest that the ratio of leptin/adiponectin correlates with insulin resistance and predicts cardiovascular disease (CVD), there is scanty data on the relationship between the retinol-binding protein-4 (RBP4)/adiponectin ratio with insulin resistance and inflammation. We tested the relationship of both these ratios with measures of insulin resistance and inflammation.. In 72 individuals, including controls and patients with metabolic syndrome, we calculated the homeostasis model assessment of insulin resistance (HOMA-IR) and assayed high-sensitivity C-reactive protein (hsCRP) and the adipokines, adiponectin, leptin, and RBP4.. Whereas both the leptin/adiponectin and RBP4/adiponectin ratios did not correlate with HOMA-IR, both correlated significantly with the prototypic biomarker of inflammation, hsCRP. Also in patients with metabolic syndrome following adjustment for adiposity, only the RBP4/adiponectin ratio was significantly increased.. Hence it appears that whereas both the leptin/adiponectin and RBP4/adiponectin ratios correlate with inflammation, only the RBP4/adiponectin ratio was significantly increased in metabolic syndrome and would be more useful to predict CVD, especially in metabolic syndrome.

Topics: Adiponectin; Adult; Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Retinol-Binding Proteins, Plasma

There is compelling evidence that obstructive sleep apnoea (OSA) can affect metabolic syndrome (MetS) and cardiovascular risk, but the intermediate mechanisms through which it occurs have not been well defined. We explored the impact of OSA in morbidly obese patients with MetS on adipokines, pro-inflammatory markers, endothelial dysfunction, and atherosclerosis markers.. We included 52 morbidly obese patients in an observational study matched for age, gender and central obesity in 3 groups (OSA-MetS, Non-OSA-MetS, and Non OSA-non-MetS). Anthropometrical, blood pressure, and fasting blood measurements were obtained the morning after an overnight polysomnography. VEGF, soluble CD40 ligand (sCD40L), TNF-α, IL-6, leptin, adiponectin, and chemerin were determined in serum by ELISA. OSA was defined as apnea/ hypopnea index ≥ 15 and MetS by NCEP-ATP III.. Cases and control subjects did not differ in age, BMI, waist circumference, and gender (43 ± 10 years, 46 ± 5 kg/m(2), 128 ± 10 cm, 71% females). The cases had severe OSA with 47 (32-66) events/h, time spent < 90% SpO2 7% (5%-31%). All groups presented similar serum cytokines, adipokines, VEGF, and sCD40L levels.. In a morbidly obese population with established MetS, the presence of OSA did not determine any differences in the studied mediators when matched by central obesity. Morbidly obese NonOSA-NonMetS had a similar inflammatory, adipokine VEGF, and sCD40L profile as those with established MetS, with or without OSA. Obesity itself could overwhelm the effect of sleep apnea and MetS in the studied biomarkers.. Salord N; Gasa M; Mayos M; Fortuna-Gutierrez AM; Montserrat JM; Sánchez-de-la-Torre M; Barceló A; Barbé F; Vilarrasa N; Monasterio C. Impact of OSA on biological markers in morbid obesity and metabolic syndrome.

Topics: Adiponectin; Adult; Biomarkers; Case-Control Studies; CD40 Ligand; Chemokines; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Metabolic Syndrome; Obesity, Morbid; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Obesity in many species is associated with reduced fertility and increased risk of metabolic disorders and cardiovascular dysfunction in offspring. Equine metabolic syndrome (EMS) is associated with obesity and characterized by insulin resistance, decreased adiponectin, and elevated insulin, leptin, and pro-inflammatory cytokines. These alterations can potentially disrupt follicular development and impair fertility. We hypothesized that mares with EMS have an altered follicular environment when compared to their normal counterparts, affecting gene regulation for follicle and oocyte maturation. Samples were collected from light-horse mares (11 to 27 yr) in a clinical assisted reproductive program. Mares were screened based on phenotype. Insulin sensitivity was determined by using two proxies, the reciprocal of the square root of insulin (RISQI) and the modified insulin-to-glucose ratio (MIRG). Insulin resistant mares (RISQI < 0.32 and MIRG > 5.50) were allocated to the EMS group (n = 8), and the remaining mares were considered normal controls (CON, n = 12). Follicular fluid (FF) and granulosa cells (GC) from preovulatory follicles were aspirated 24 ± 2 h after administration of a GnRH analog (SucroMate, 0.9 to 1.4 mg, i.m.) and hCG (Chorion, 1500 to 2000 IU, i.v.). After an overnight fast, blood was collected on the morning of follicle aspiration to evaluate serum concentrations of insulin, leptin, adiponectin, and inflammatory cytokines. Expression of 32 genes related to metabolism, follicle maturation, and oocyte maturation were assessed in GC. Concentrations of insulin, leptin, adiponectin, and cytokines were highly correlated between serum and FF (P < 0.001). Insulin was lower (P < 0.001) in serum and FF of CON compared to EMS, but leptin and IL1β tended (P = 0.07 and P = 0.10, respectively) to be lower in FF of CON than EMS. Tumor necrosis factor-α in serum and FF was lower (P < 0.07 and P < 0.05, respectively) in CON than EMS. Conversely, adiponectin was higher (P < 0.05) in serum and FF in CON versus EMS. In GC from CON when compared to EMS, gene expression for epiregulin was elevated (P < 0.05) and tissue inhibitor of matrix metalloproteinase-2 tended to be lower (P = 0.09). Our findings demonstrate that the intrafollicular environment in the mare is influenced by metabolic disease, consistent with findings in other species. Influences on follicular development, oocyte maturation, and subsequent offspring by perturbations due to metabolic disease n

Topics: Adiponectin; Animals; Cytokines; Female; Gene Expression Regulation; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Ovarian Follicle

Recent reports indicated that nutrition in early infancy might influence later child health outcomes such as obesity and metabolic syndrome. Therefore, we examined the effects of maternal high fat diet (HFD) during lactation on the onset of a metabolic syndrome in their offspring. All offspring were cross-fostered by dams on the same or opposite diet to yield 4 groups: offspring from HFD-fed dams suckled by HFD-fed dams (OHH) and by control diet (CD)-fed dams (OHC) and CD-fed dams suckled by HFD-fed dams (OCH) and by CD-fed dams (OCC) mice. We examined several metabolic syndrome-related factors including body weight, blood pressure, glucose tolerance and adipocytokines. Mean body weights of OHH and OCH mice were significantly higher than those of OHC and OCC mice, respectively, with elevated systolic blood pressure. Moreover, OHH and OCH mice revealed significantly worse glucose tolerance compared with the OHC and OCC mice, respectively. Triglyceride and leptin levels were significantly increased and adiponectin levels were significantly reduced by the maternal HFD during lactation, with similar changes in leptin and adiponectin mRNA expression but without histone modifications in adipose tissues. In addition, maternal obesity induced by HFD during lactation increased and prolonged the leptin surge in the offspring and the gender differences of leptin surge were observed. Our data suggested that maternal HFD during lactation might have an additive effect on the onset of the metabolic syndrome in the offspring, irrespective of the nutritional status in utero through the modified leptin surge.

Topics: Adiponectin; Adipose Tissue; Animals; Animals, Newborn; Blood Glucose; Dietary Fats; Female; Gene Expression Regulation; Lactation; Leptin; Male; Maternal Exposure; Metabolic Syndrome; Mice; Mice, Inbred ICR; Obesity; Sex Characteristics

The prevalence of metabolic syndrome (MS) accompanied with cardiometabolic complications has progressively increased in Thailand. The roles of insulin resistance, leptin, adiponectin, and free testosterone as prognostic indicators of MS among Thai population were evaluated. Men and women aged 34 to 89 years (n = 308) having 0-5 criteria of MS according to NCEP III with Asian-specific cut-points for waist circumference were enrolled in this cross-sectional study. Blood glucose, lipids, insulin, leptin, adiponectin, and free testosterone were measured. Each component of MS, especially the enlarged waist, adversely affected insulin sensitivity. MS subjects were at higher risk for developing insulin resistance, decreasing of plasma adiponectin, and increasing of leptin and the leptin/ adiponectin ratio in comparison to non-MS individuals. The hormonal changes that have been shown to be associated with increased cardiometabolic risk were amplifiedas more MS criteria have been met. Odds ratios of increased leptin/adiponectin ratio among MS group were highest in comparison to others. Free testosterone levels declined with age and did not discriminate men with MS.. The results indicate the benefit of hormonal assessment, particularly the leptin/adiponectin ratio in identifying MS individuals with high cardiometabolic disease risk.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Cross-Sectional Studies; Female; Humans; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Testosterone; Thailand; Urban Population

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

Metabolic syndrome (MetS) correlates with systemic inflammation. A relation of MetS to periodontitis has been reported. This study aims to evaluate whether periodontitis is associated with untreated MetS, plasma adiponectin, and leptin among Thai people.. One hundred twenty-five participants (aged 35 to 76 years) were recruited. Demographic and biologic data, bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) of all teeth were examined. Plasma adiponectin and leptin levels were measured.. Forty-four participants (35.2%) were healthy, and 81 (64.8%) had MetS. All periodontal conditions (BOP, PD, and CAL) were significantly worse in patients with MetS than healthy participants. After adjustment for confounders, MetS was strongly associated with severe periodontitis (odds ratio [OR] = 3.60, 95% confidence interval [CI]: 1.34 to 9.65). MetS with four to five components had a higher association with periodontitis than did MetS with three components (OR = 5.49, 95% CI: 1.75 to 17.19), whereas each separate component had no association with periodontitis, except for high diastolic blood pressure. Periodontitis was also associated with age (OR = 1.08, 95% CI: 1.01 to 1.14) and education (OR = 3.76, 95% CI: 1.05 to 13.40). The risk of MetS was predicted by body mass index and plasma adiponectin (OR = 1.90, 95% CI: 1.24 to 2.92 and OR = 0.93, 95% CI: 0.88 to 0.98, respectively).. There may be a relationship between untreated MetS and periodontitis in Thai people. Periodontal diagnosis should be regularly conducted in patients with MetS.

Topics: Adiponectin; Adult; Age Factors; Aged; Blood Pressure; Body Mass Index; Diabetes Complications; Educational Status; Female; Humans; Hyperglycemia; Hypertension; Hypertriglyceridemia; Hypoalphalipoproteinemias; Leptin; Male; Metabolic Syndrome; Middle Aged; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Thailand; Waist Circumference

Metabolic syndrome (MetS) is a serious public health problem and one of the important risk factors contributing to cardiovascular disease in developed countries. Adipose tissue is considered a secretory organ that releases a variety of molecules referred to adipocytokines such as leptin, so polymorphism of these protein genes may play an important role in development of MetS. Therefore, the aim of this study was to determine the genetic varieties of Lep-2548G/A between MetS and healthy subjects.. In this case-control study, the relationship between LEP G-2548A polymorphism and MetS was evaluated in Iranian participants, 200 patients (142 women and 58 men) and 200 controls (122 women and 78 men) who were randomly selected from Hamadan city. Blood samples were collected; moreover, routine biochemical analysis, DNA extraction, and serum leptin measurements were done. LEP G-2548A genotypes were identified by a PCR-RFLP technique.. Our findings showed significant differences between biochemical factors and leptin concentration between two groups. Females show more serum leptin concentration than males. There was no significant difference in polymorphism of Lep-2548G/A between MetS and healthy subjects. Although we cannot find any correlation between leptin concentration and BMI, some relation exists with LDL-C, HDL-C and TG (p < 0.05).. In summary, it is concluded that leptin probably has a key role in metabolic syndrome development and further research in this area is needed.

Topics: Adult; Female; Genotype; Humans; Iran; Leptin; Male; Metabolic Syndrome; Middle Aged; Polymorphism, Genetic; Promoter Regions, Genetic

Early adiposity rebound (AR <5 years) has been consistently associated with increased obesity risk, but its relationship with metabolic markers is less clear; in addition, the biologic mechanisms involved in these associations have not been established.. The objective of this study was to assess the association between timing of AR and metabolic status at age 7 years, evaluating the potential role of adiposity, adipose functionality and skeletal maturation in this association.. We estimated the age of AR from the body mass index (BMI) trajectories from 0 to 7 years in 910 children from the Growth and Obesity Chilean Cohort Study (GOCS). At 7 years, we measured waist circumference (WC) and blood glucose, insulin, triglycerides and high-density lipoprotein-cholesterol levels and constructed a metabolic risk score. We also measured percent fat mass (adiposity), plasma concentrations of leptin and adiponectin (adipose functionality) and bone age using wrist ultrasound (skeletal maturation).. We found that 44% of the children had an AR <5 years. Earlier AR was associated with larger WC (β: 5.10 (95% confidence interval (CI): 4.29-5.91)), higher glucose (β: 1.02 (1.00-1.03)), insulin resistance (β Homeostatic Model Assessment: 1.06 (1.03-1.09)), triglycerides (β: 10.37 (4.01-6.73)) and adverse metabolic score (β: 0.30 (0.02-0.37)). Associations decreased significantly if adiposity was added to the models (i.e. β WC: 0.85 (0.33-1.38)) and, to a lesser extent, when adipokines (i.e. β WC: 0.73 (0.14-1.32)) and skeletal maturation (i.e. β WC: 0.65 (0.10-1.20)) were added.. In GOCS children, AR at a younger age predicts higher metabolic risk at 7 years; these associations are mostly explained by increased adiposity, but adipose dysfunction and accelerated skeletal maturation also have a role.

Topics: Adiponectin; Adiposity; Age Factors; Age of Onset; Biomarkers; Blood Glucose; Body Composition; Body Mass Index; Child; Child Development; Chile; Cholesterol, HDL; Cohort Studies; Female; Humans; Leptin; Lipoproteins, HDL; Male; Metabolic Syndrome; Pediatric Obesity; Risk Factors; Triglycerides; Waist Circumference; Weight Gain

To verify the relationship between leptin and cardiometabolic risk factors in obese children and adolescents.. A cross-sectional study evaluated 200 children and adolescents treated in Campina Grande, Brazil, from April 2009 to March 2010. Leptin, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides were determined. The t-test was used to compare leptin means of two groups and analysis of variance to compare means of three groups. Multiple comparisons of pairs of group means were performed with Tukey's test. In all tests, a significance level of 0.05 was adopted.. The leptin sample mean was 22.7 ± 10.0 μg/L (95% confidence interval: 21.3 μg/L to 24.1 μg/L). Leptin was significantly higher in the following groups: female, teenager, increased waist circumference, high systolic blood pressure, elevated triglycerides hyperinsulinemia, insulin resistance and metabolic syndrome. Most cardiometabolic risk factors had higher means in the last quartile of leptin, except total-cholesterol, LDL-C and triglycerides levels. HDL-C was reduced in the last quartile of leptin. Simple linear regression analysis showed a significant negative correlation between leptin and HDL-C and a positive correlation between leptin and triglycerides, insulin, HOMA-IR, body mass index, waist circumference, and systolic and diastolic blood pressure. Multiple linear regression models showed an independent association between leptin and HDL-C, triglycerides, insulin, HOMA-IR, body mass index, waist circumference, systolic and diastolic blood pressure, after age and gender control.. Leptin may be a useful marker of metabolic syndrome and insulin resistance in obese adolescents.

Topics: Adolescent; Biomarkers; Blood Glucose; Brazil; Child; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Pediatric Obesity; Risk Factors

The effect of a mixture of probiotic strains (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, Bifidobacterium animalis VKB) on the development of experimental obesity in rats induced by neonatal administration of monosodium glutamate has been studied. It was shown that in rats of 4 months age, the injection of monosodium glutamate (4 mg/g) at 2, 4, 6, 8, 10 days after birth elicited abdominal obesity and metabolic syndrome. An intermittent administration of a probiotic mixture to rats treated with monosodium prevented the development of obesity. In the group of rats treated with probiotics, anthropometric parameters (weight and body length, Lee index, body mass index) did not differ from the level of intact rats. Visceral fat mass was decreased by probiotics by 38.5% (P < 0.05) compared to rats treated with water. Probiotics improved lipid metabolism: reduced the level of VLDL by 32.2% (P < 0,05), the level of LDL by 30.6% (P < 0.05), increased HDL by 25.7% (P <0,05) compared to obese control rats. Probiotic strains restored the secretion of adipocytes hormones (leptin and adiponectin) to the normal level of intact animals. The results show the effectiveness of probiotics for the prevention of obesity.

Topics: Abdominal Fat; Adipocytes; Adiponectin; Alanine Transaminase; Animals; Animals, Newborn; Aspartate Aminotransferases; Bifidobacterium; Body Mass Index; Body Size; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Lacticaseibacillus casei; Leptin; Lipid Metabolism; Male; Metabolic Syndrome; Obesity; Probiotics; Rats; Sodium Glutamate

To measure serum levels of adipsin, leptin, resistin, adiponectin, visfatin, ghrelin and insulin in postmenopausal women screened for the metabolic syndrome (METS).. Serum of 100 postmenopausal women was analyzed using multiplex technology for the mentioned analytes. In addition, values for the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Comparisons were performed in accordance to the presence or not of the METS and each of its components. Criteria of the American Heart Association were used to define the METS.. Age and time since menopause onset were similar in women with the METS (n=57) as compared to those without the syndrome (n=43). METS women displayed significantly higher levels of adipsin, leptin, resistin, insulin and HOMA-IR values and lower adiponectin levels. These differences were mainly observed among women with abdominal obesity, independent of fulfilling METS criteria or not. In this same sense, lower adiponectin levels significantly related to low HDL-C and high triglyceride levels; and higher insulin and HOMA-IR values related to high triglyceride and glucose levels, respectively.. In this sample, postmenopausal women with the METS displayed higher insulin and adipokine levels. These were mainly related to abdominal obesity and metabolic and lipid abnormalities. More research is warranted in this regard.

Topics: Adipokines; Adiponectin; Adult; Aged; Blood Glucose; Cholesterol, HDL; Cohort Studies; Complement Factor D; Cytokines; Female; Ghrelin; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity, Abdominal; Postmenopause; Resistin; Triglycerides

Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity.

Topics: Adiposity; Analysis of Variance; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Drug Resistance; Female; Fetal Development; Inheritance Patterns; Leptin; Lipids; Liver Diseases; Male; Malnutrition; Metabolic Syndrome; Obesity; Overnutrition; Swine; Time Factors; Weaning

The metabolic syndrome is a worldwide problem mainly caused by obesity. FTO was found to be a obesity-risk gene in humans and FTO deficiency in mice led to reduction in adipose tissue. Thus, FTO is an important factor for the development of obesity. Leptin-deficient mice are a well characterized model for analysing the metabolic syndrome. To determine the relevance of FTO for the development of the metabolic syndrome we analysed different parameters in combined homozygous deficient mice (Lep(ob/ob);Fto(-/-)). Lep(ob/ob);Fto(-/-) mice showed an improvement in analysed hallmarks of the metabolic syndrome in comparison to leptin-deficient mice wild type or heterozygous for Fto. Lep(ob/ob);Fto(-/-) mice did not develop hyperglycaemia and showed an improved glucose tolerance. Furthermore, extension of beta-cell mass was prevented in Lep(ob/ob);Fto(-/-)mice and accumulation of ectopic fat in the liver was reduced. In conclusion this study demonstrates that FTO deficiency has a protective effect not only on the development of obesity but also on the metabolic syndrome. Thus, FTO plays an important role in the development of metabolic disorders and is an interesting target for therapeutic agents.

Topics: Adipose Tissue; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Animals; Body Weight; Disease Models, Animal; Fatty Liver; Female; Genetic Predisposition to Disease; Hepatocytes; Hyperglycemia; Islets of Langerhans; Leptin; Lipid Metabolism; Male; Metabolic Syndrome; Mice; Mice, Knockout; Mixed Function Oxygenases; Oxo-Acid-Lyases

Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, β-hexachlorocyclohexane, and p,p'-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003-2005, we enrolled 499 boys aged 8-9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10-13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass index (BMI) (weight (kg)/height (m)(2))) effects of prepubertal OCP tertiles and quintiles with biomarkers. In multivariable models, higher p,p'-dichlorodiphenyldichloroethylene (quintile 5 vs. quintile 1) was associated with lower leptin, with relative mean decreases of 61.8% (95% confidence interval: 48.4%, 71.7%) in models unadjusted for BMI and 22.2% (95% confidence interval: 7.1%, 34.9%) in models adjusted for BMI; the direct effect of p,p'-dichlorodiphenyldichloroethylene on leptin accounted for 27% of the total effect. IR prevalence was 6.6% at ages 12-13 years. Higher hexachlorobenzene (tertile 3 vs. tertile 1) was associated with higher odds of IR in models adjusted for BMI (odds ratio = 4.37, 95% confidence interval: 1.44, 13.28). These results suggest that childhood OCPs may be associated with IR and lower leptin.

Topics: Adolescent; Biomarkers; Blood Glucose; Child; Cholesterol; Humans; Hydrocarbons, Chlorinated; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Pesticides; Prospective Studies; Regression Analysis; Triglycerides

The aim of this study was to evaluate the usefulness of follicle-stimulating hormone (FSH) determination in the postmenopausal women with metabolic syndrome (MetS) in a comparative analysis with biomarkers such as C-reactive protein (CRP), adiponectin, leptin and leptin-to-adiponectin ratio (L/A).. 135 postmenopausal women with MetS and 153 without MetS were subjected to examinations.. The increase in the probability of MetS, when the value of the marker concentration decreased or increased by 1 standard deviation, was two times higher for FSH-based models than for models including CRP and leptin, and was similar to models including adiponectin and L/A. The areas under the ROC curves were 0.78 for FSH, 0.68 for CRP, 0.72 for leptin, 0.76 for adiponectin and 0.80 for L/A.. Our results suggest that the FSH concentration assesses the probability of MetS similarly to L/A or adiponectin and better than CRP or leptin in postmenopausal women.

Topics: Adiponectin; Biomarkers; C-Reactive Protein; Female; Follicle Stimulating Hormone; Humans; Leptin; Metabolic Syndrome; Middle Aged; Postmenopause

The metabolic syndrome or overeating syndrome is a phylogenetically conditioned sequence of symptoms with common pathogenesis. The etiological factor of metabolic syndrome is higher consumption of food which is optimal on all other parameters. The enterocytes and adipocytes of omentum constitute in phylogenesis sense a unified cenosis regulated paracrinally and realizing by turns biological reactions of exo- and endotrophy. The visceral adiposity, higher level of unesterified fatty acids, formation of fatty acids pool in the form of micelle in blood, their embedding into endothelium membrane and increase of size of enterocytes are causes of increasing of hydro-dynamic pressure. The associates of albumin with more than physiologically needed amount of fatty acids are accepted by toll-similar receptors as "alien" and reaction of inflammation is initiated. In cells, overloaded with lipids "endoplasmatic stress" is developed, synthesis (folding) of proteins is disordered and their destruction similar to apoptosis is activated In a phylogenesis sense, the visceral fat is fatty acids 'depot to implement biological functions of homeostasis, trophology, endoecology and adaptation and which is regulated at the level of paracrin cenosis an is anatomically limited. The subcutaneous depot is a consequence of implementation of function of locomotion and has no limits in size. The visceral fatty cells have no receptors to philogenically late insulin. The specialized adipocytes with receptors to insulin and glucose transporter type 4 are the cells of subcutaneous depot of fatty acids. They are regulated philogenetically with late humoral mode at the level of organism. The leptin is an initiator of humoral hypothalamic regulation in vivo of size of visceral and insensible to insulin fatty acids qualitatively programmed in ontgogeny. Leptin prevents "endoplasmatic stress" and apoptosis of cells and regulates amount of consumed food Leptin initiates switching storage of fatty acids from visceral pool of fatty acids to subcutaneous pool of adipocytes. Adiponectin represents phylogenetically late humoral initiator of regulation of optimal number of cells from level of hypothalamus in vivo. Adiponectin is biologically assigned to regulate number (proliferation) insulin-depended adipocytes in subcutaneous fatty tissue.

Topics: Adiponectin; Animals; Humans; Hyperphagia; Leptin; Lipid Metabolism; Metabolic Syndrome; Obesity

Glycyrrhizic acid (GA) ameliorates many components of the metabolic syndrome, but its potential therapeutic use is marred by edema caused by inhibition of renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). We assessed whether 100 mg/kg per day GA administered orally could promote metabolic benefits without causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a high-sucrose diet supplemented with GA. Rats were then culled and renal 11β-HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin levels were determined. Histological analyses were performed to assess changes in adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal tissue morphology. This dosing paradigm of GA attenuated the increases in serum leptin levels and visceral, but not subcutaneous adipocyte size caused by the high-sucrose diet. Although GA decreased renal 11β-HSD2 activity, it did not affect serum electrolyte or angiotensin II levels, indicating no onset of edema. Furthermore, there were no apparent morphological changes in the liver or kidney, indicating no toxicity. In conclusion, it is possible to reap metabolic benefits of GA without edema using the current dosage and treatment time.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 2; Administration, Oral; Angiotensin II; Animals; Dietary Sucrose; Edema; Glycyrrhizic Acid; Kidney; Leptin; Liver; Male; Metabolic Syndrome; Potassium; Rats; Rats, Sprague-Dawley; Sodium

The aim of the study was to estimate potential associations of vitamin D concentration with metabolic and hormonal indices in women with polycystic ovary syndrome (PCOS) presenting abdominal and gynoidal type of obesity.. Twenty-six women with PCOS (19-49 years old, BMI: 26.8-53.8 kg/m2), presenting predominantly abdominal and gynoidal type of obesity were recruited. Anthropometric measures, body composition using dual-energy absorptiometry, fasting serum 25-hydroxyvitamin D, leptin, glucose, insulin, homeostatic model of assessment (HOMA), lipids, androgens and sex hormone-binding globulin (SHGB) were estimated.. Vitamin D insufficiency was found in 2, and deficiency or deep deficiency in 12 patients. Levels of vitamin D were lower in obese than non-obese women, and in patients with abdominal as compared to gynoidal obesity (9.60±3.7 vs. 16.02±3.3 ng/mL, p<0.04). In obese women, vitamin D correlated negatively with all, except for gynoidal fat, measures of obesity fasting glucose levels, and HOMA. No correlations with androgens were found. In women with abdominal obesity vitamin D correlated with luteinizing hormone/follicle-stimulating hormone ratio (LH/FSH) and SHBG.. We demonstrated that women with PCOS are often vitamin D deficient. Its concentration was lower in patients with predominantly abdominal obesity as compared to subjects with gynoidal fat excess. In overweight/obese subjects with PCOS, vitamin D correlated with fasting glucose and HOMA. The correlation with LH/FSH suggests that vitamin D status may contribute to hormonal dysregulation. Further studies are needed to elucidate a potentially different impact of abdominal and subcutaneous fat on vitamin D metabolism.

Topics: Adult; Androgens; Blood Glucose; Female; Humans; Leptin; Metabolic Syndrome; Middle Aged; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Vitamin D; Vitamin D Deficiency; Young Adult

To determine the levels of adipokines (leptin, adiponectin, resistin, and visfatin) and the indices of insulin sensitivity/ resistance, and to examine the relationship among them in patients with metabolic syndrome (MetS).. The study groups included 45 subjects with MetS (31 women/14 men), and 45 sex- and age-matched non-MetS healthy volunteers (31 women/14 men). The levels of adipokines were determined by enzyme-linked immunosorbent assay.. The levels of leptin and visfatin were significantly higher in the MetS than in the non-MetS subjects (P < 0.01). There was no difference in adiponectin levels in subjects with and without MetS (P = 0.052). Similarly, resistin did not show any statistically significant difference. A statistically significant positive correlation ofleptin with insulin levels was observed, while negative correlations of visfatin levels with age, and resistin levels with the ratio of adiponectin to leptin, were found in the MetS (P <0.05). The combination of adipokines, insulin resistance-sensitivity parameters, and MetS criteria parameters gave more significant differences than a single parameter.. Since the parameters mentioned above might affect, interact with, and/or interfere with each other, the combinations of these parameters might give more reliable results to evaluate the insulin resistance/sensitivity in MetS patients.

Topics: Adipokines; Adiponectin; Adult; Homeostasis; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase

Adipose tissue secretes a variety of adipokines involved in the regulation of energy metabolism and insulin resistance. Metabolic syndrome corresponds to a clinical condition in which white adipose tissue is characterized by an increased production and secretion of inflammatory molecules which may have local effects on adipose tissue physiology but also systemic effects on other organs. The aim of this study was to assess the expression of leptin, NGF and adiponectin in women with metabolic syndrome compared to healthy controls. Plasma leptin, NGF and adiponectin levels were measured by the ELISA method. Leptin and NGF immunohistochemical expression was analyzed in subcutaneous adipose tissue. The results indicated that in women with metabolic syndrome waist circumference, body mass index, HOMA index, glucose, total cholesterol and triglyceride levels were significantly increased in parallel with overxpressed plasma levels of leptin and NGF and decreased adiponectin. The immunohistochemical expression of leptin and NGF was very strong. In conclusion, this is the first study demonstrating a complex of immunochemical and immunohistochemical expression of the key adipokines including leptin, NGF and adiponectin in women with metabolic syndrome. Locally-produced pro-inflammatory adipokines probably contribute to the ethiopathogenic mechanisms ofmetabolic syndrome.

Topics: Adiponectin; Adult; Case-Control Studies; Female; Gene Expression Regulation; Humans; Leptin; Metabolic Syndrome; Middle Aged; Nerve Growth Factor

What is already known about this subject African Americans are disproportionately affected by obesity and other metabolic risk factors in comparison to White Americans. Increasing prevalence of obesity has been associated with concomitant increases in childhood hypertension, dyslipidaemia and type 2 diabetes. Oxidative stress is associated with obesity in both adults and children. What this study adds Oxidative stress is positively associated with total body fat and truncal fat, but not with body mass index (BMI) or BMI z-score in healthy youth. Oxidative stress is associated with diastolic blood pressure in African American but not in White American healthy youth.. Oxidative stress is elevated in obese youth, but less is known regarding racial disparities in the relationship of oxidative stress with metabolic risk factors.. To determine the relationship between oxidative stress and metabolic risk factors, adiposity, leptin, adiponectin and cardiovascular fitness (VO2PEAK ) in healthy African American and White American youth.. A marker of oxidative stress (F2 -isoprostane), validated markers of metabolic risk factors, fitness and body composition were measured in African American (n = 82) and White American (n = 76) youth (8-17 years old) recruited over a range of BMI percentiles (4th to 99th).. F2 -isoprostane concentration was positively correlated with percentage body fat (r = 0.198) and percentage truncal fat (r = 0.173), but was not different between African American and White American males and females (P = 0.208). African American youth had significantly higher mean systolic and diastolic blood pressure (P = 0.023 and P = 0.011, respectively), body weight, BMI percentile and Tanner stage. After adjusting for gender, age, BMI and Tanner stage, African American youth varied from White Americans in the association of F2 -isoprostane with diastolic blood pressure (P = 0.047), but not with systolic blood pressure, triglycerides, VO2PEAK or homeostatic model assessment for insulin resistance (all P > 0.05).. Oxidative stress, as measured by urinary F2 -isoprostane concentrations, was positively associated with percent body fat and truncal fat in youth. Oxidative stress levels were similar among African American and White American youth. Among markers of the metabolic syndrome, a significant difference between African American and White American youth was demonstrated only in the association of oxidative stress with diastolic blood pressure.

Topics: Adiponectin; Adiposity; Adolescent; Black or African American; Blood Glucose; Blood Pressure; Child; F2-Isoprostanes; Female; Humans; Leptin; Male; Metabolic Syndrome; Molecular Sequence Data; Oxidative Stress; Risk Factors; Triglycerides; United States; White People

This study aimed to determine the association between circulating leptin levels and total depressive symptoms as well as depressive symptom dimensions (cognitive and somatic) after controlling for important confounding factors.. The study sample was comprised of 135 participants with the metabolic syndrome. Depressive symptoms were measured using the Beck Depression Inventory-II. Leptin was measured using a leptin-specific enzyme immunoassay. Inflammation was assessed using C-reactive protein and interleukin-6 levels.. Leptin was significantly associated with somatic depressive symptoms (β = 0.33, P = 0.018), but not total depressive symptoms (β = 0.27, P = 0.067) or cognitive depressive symptoms (β = 0.21, P = 0.182), after controlling for age, gender, body mass index, and insulin resistance. Further adjustment for C-reactive protein and interleukin-6 levels did not alter the relationship (β = 0.32, P = 0.023) between circulating leptin levels and somatic depressive symptoms.. Leptin is independently associated with somatic depressive symptoms in patients with the metabolic syndrome.

Topics: Adult; Body Mass Index; C-Reactive Protein; Depression; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Psychiatric Status Rating Scales; Risk Factors

Individuals with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EA). Obesity contributes to the development of BE and its progression to cancer. We investigated the roles of obesity-induced hyperinsulinemia and dysregulation of adipokines in these processes.. We measured fasting levels of glucose, insulin, leptin, and adiponectin in 392 patients enrolled in the Seattle Barrett's Esophagus Study. We calculated homeostatic model assessment scores (a measure of insulin sensitivity) and identified subjects with metabolic syndrome. We evaluated the association between these measures and the risk of EA using Cox regression models adjusted for known risk factors.. Increasing homeostatic model assessment scores were associated with an increasing risk for EA; the strongest association was observed within the first 3 years after participants entered the study (hazard ratio [HR], 2.45; 95% confidence interval [CI], 1.43-4.1; P trend = .001). Leptin level also was associated significantly with an increased risk of EA within 3 years (HR, 2.51; 95% CI, 1.09-5.81; P trend = .03) and 6 years (HR, 2.07; 95% CI, 1.01-4.26; P trend = .048) of baseline. The level of high-molecular-weight adiponectin had a nonlinear inverse association with risk of EA; the strongest associations were observed in the second tertile (HR, 0.34; 95% CI, 0.14-0.82). Metabolic syndrome was not associated with risk of EA.. Among patients with BE, increased levels of leptin and insulin resistance are associated with increased risk for EA, whereas increased levels of high-molecular-weight adiponectin is associated inversely with EA. These biomarkers might be used to determine cancer risk among patients with BE.

Topics: Adenocarcinoma; Adiponectin; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers; Blood Glucose; Esophageal Neoplasms; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Assessment

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

Topics: Depression; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome

High adiponectin/leptin ratio may be protective from metabolic risks imparted by high triglyceride, low HDL, and insulin resistance.. This cross-sectional study examines plasma adipokine levels in 428 adult men who were subgrouped according to low (<6.5  μ g/mL)and high (≥6.5  μ g/mL)adiponectin levels or a low or high ratio of adiponectin/leptin.. Men with high adiponectin/leptin ratio had lower plasma triglyceride and higher HDL cholesterol than those with low ratio. Similarly, those with high adiponectin/leptin ratio had lower TG/HDL cholesterol ratio and HOMA2-IR than those with low ratio. In contrast, levels of adiponectin or the ratio of adiponectin/leptin did not associate with systolic blood pressure. But the ratio of adiponectin/leptin decreased progressively with the increase in the number of risk factors for metabolic syndrome.. Adipokine levels may reflect adipose tissue triglyceride storage capacity and insulin sensitivity. Leptin is an index of fat mass, and adiponectin is a biomarker of triglyceride metabolism and insulin sensitivity. Men with high adiponectin/leptin ratios have better triglyceride profile and insulin sensitivity than men with a low ratio regardless of waist girth.

Topics: Adiponectin; Adult; Apolipoproteins B; Blood Pressure; Body Mass Index; Cholesterol, HDL; Cross-Sectional Studies; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Risk Factors; Triglycerides; Waist Circumference

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

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

Accumulation of visceral adipose tissue (VAT) is strongly linked to insulin resistance. Variations in the size of any adipose depot are determined by alterations in adipocyte volume and/or number. The individual contribution of each of the latter factors was determined in the major omentum, a fully resectable VAT depot.. Total removal of the major omentum (omentectomy) was performed in conjunction with bariatric surgery in 55 obese patients. Tissue weight as well as mean adipocyte size and number in the omentum were determined. In subgroups, total VAT was estimated by computerized tomography (n = 17) or dual-energy x-ray absorptiometry (n = 34).. The weight of the major omentum (on average 0.6 kg) correlated significantly with total VAT mass estimated by computerized tomography or dual-energy x-ray absorptiometry (r = 0.48-0.7; P < .01). Omental weight in relation to total body fat correlated with several features of the metabolic syndrome and inversely with serum-leptin (P < .001). Mean adipocyte size and total adipocyte number correlated strongly with omental weight (r = 0.6-0.8; P < .0001), irrespective of body mass index and total body fat mass, and accounted almost in total for interindividual variations in omental size. However, stepwise regression analysis demonstrated that adipocyte number was significantly (P < .0001) more important (62%) than adipocyte size (35%).. The size of the major omentum is representative for VAT mass and correlates with a pernicious metabolic profile. Variations in omental weight are primarily determined by adipocyte number and to a lesser degree by adipocyte size, suggesting that increased VAT mass in obesity is predominantly dependent on adipocyte proliferation.

Topics: Adiposity; Adult; Bariatric Surgery; Body Mass Index; Cell Count; Cell Size; Cohort Studies; Female; Humans; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity, Morbid; Omentum; Organ Size; Radiography; Subcutaneous Fat, Abdominal; Young Adult

In addition to adipocytokines, estradiol (E2) and vitamin D have been reported to affect insulin sensitivity, glucose homeostasis and body weight. However, studies about the impact of E2 and vitamin D on metabolic syndrome (MetS) are still limited. The aim of this study is to clarify the roles of circulating E2 and vitamin D on the risk of MetS in middle-aged Taiwanese males. A total of 655 male volunteers, including 243 subjects with MetS (mean age: 56.7±5.8 years) and 412 normal controls (mean age: 55.1±3.6 years), were evaluated. Subjects with MetS had significantly lower circulating E2, 1,25(OH)2D3, and adiponectin, and higher leptin than those without MetS (P<0.001 for all comparisons). E2 and 1,25(OH)2D3 were significantly associated with 4 individual components of MetS; more than adiponectin and leptin that were only associated with 3 individual components. In multivariate regression analysis, E2 (beta = -0.216, P<0.001) and 1,25(OH)2D3 (beta = 0.067, P = 0.045) were still significant predictors of MetS independent of adiponectin and leptin. Further large studies are needed to confirm our preliminary results and elucidate the possible mechanism.

Topics: Adiponectin; Adult; Aged; Cross-Sectional Studies; Estradiol; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Radioimmunoassay; Vitamin D

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

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

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

The use of monosodium glutamate (MSG) as a flavor enhancer spans more than 100 y and there are many studies indicating the safety of general use of MSG. Recently, however, Collison et al. (2010) reported a two-generation study with a low dose of MSG that caused abdominal obesity, insulin resistance and dyslipidemia in mice. Due to public health concerns over metabolic syndrome, their report merits careful analysis. The present study attempted to repeat the Collison et al. findings. Groups of male or female C57BL/6J mice were fed a control diet or one supplemented with high-fructose corn syrup (HFCS) at a level of 20%. Drinking water control was provided or treatment groups were given 0.064% MSG solution (w/v). Diets and MSG administration continued throughout mating and during gestation and lactation periods. To further investigate the effects of ingestion of MSG, the offspring were continued on the same dosing conditions until they reached 32 wk of age. MSG administration in mice fed a normal or a HFCS diet throughout gestation and for 32 wk after birth, did not affect growth, girth size, abdominal fat weight or body composition. This study reports that MSG did not trigger insulin resistance, dyslipidemia or hepatic steatosis, regardless of the diet, not reproducing the results of the above-mentioned study (Collison et al., 2010).

Topics: Abdominal Fat; Adiponectin; Animal Nutritional Physiological Phenomena; Animals; Blood Glucose; Body Composition; Body Weight; Cholesterol; Diet; Dose-Response Relationship, Drug; Dyslipidemias; Fatty Liver; Female; Flavoring Agents; Fructose; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Sodium Glutamate

The increasing prevalence of both asthma and obesity are major health problems. Recent studies established a possible link between obesity and asthma; however, the underlying mechanism is not clear. The aim of the study was to analyze the prevalence of metabolic syndrome in postmenopausal subjects with asthma and search the interactions between adipokines, metabolic syndrome, and asthma. A total of 45 female patients (57.5 ± 13.9 years) with asthma and 30 healthy subjects (59.6 ± 12.8 years) in postmenopausal status were enrolled in this study. For the diagnosis of metabolic syndrome, modified World Health Organization diagnostic criteria were used. Blood levels of glucose, lipid profile, HbA1c, insulin, CRP, leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, IL-8 and plasminogen activator inhibitor-1 (PAI-1) were measured. The mean body mass index was 29.6 ± 5.4 for asthma patients and 28.2 ± 5.3 for the control group. The incidence of metabolic syndrome was found as 26 % for both groups. Insulin resistance as calculated by homeostasis model assessment (HOMA-IR) and fasting insulin levels were significantly higher in asthma patients (p < 0.001 for both parameters). Leptin levels were significantly higher (p = 0.001) and adiponectin levels were lower (p = 0.029) in asthma patients compared to controls. We concluded that although incidence of obesity and metabolic syndrome was not higher in postmenopausal asthma patients than controls, there was an impairment of glucose metabolism and altered adipokine levels in asthma patients.

Topics: Adiponectin; Asthma; Blood Glucose; Body Mass Index; Female; Humans; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Middle Aged; Obesity; Postmenopause

Obesity is a critical risk factor for the development of metabolic syndrome, and many obese animal models are used to investigate the mechanisms responsible for the appearance of symptoms. To establish a new obese mouse model, we screened ∼13,000 ICR mice and discovered a mouse demonstrating spontaneous obesity. We named this mouse "Daruma" after a traditional Japanese ornament. Following the fixation of the genotype, these animals exhibited obese phenotypes according to Mendel's law of inheritance. In the Daruma mouse, the leptin receptor gene sequence carried two base mutations that are good candidates for the variation(s) responsible for the obese phenotype. The Daruma mice developed characteristic visceral fat accumulation at 4 wk of age, and the white adipose and liver tissues exhibited increases in cell size and lipid droplets, respectively. No histological abnormalities were observed in other tissues of the Daruma mice, even after the mice reached 25 wk of age. Moreover, the onset of impaired leptin signaling was early and manifested as hyperleptinemia and hyperinsulinemia. Pair feeding completely inhibited obesity, although these mice rapidly developed hyperphagia and obesity followed by hyperleptinemia when pair feeding ceased and free-access feeding was permitted. Therefore, the Daruma mice exhibited unique characteristics and may be a good model for studying human metabolic syndrome.

Topics: Adipose Tissue; Animals; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Disease Models, Animal; Eating; Ghrelin; Glucose Tolerance Test; Hemodynamics; Hyperphagia; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mutation; Obesity; Real-Time Polymerase Chain Reaction; Receptors, Leptin; Tomography, X-Ray Computed; Triglycerides

We conducted a comparative investigation of the hormonal status (LH, FSH, estradiol, progesterone, testosterone, prolactin, SHBG), energy status (leptin, ghrelin, insulin), and carbohydrate and lipid metabolism in patients with endometrial hyperplasia and neoplasia (168 patients) with or without metabolic syndrome in the background. Patients with metabolic syndrome had a high frequency of elevated estrogen (72%), testosterone (65%), insulin (81%), leptin (68%). There was a marked increase in the basal level of luteinizing hormone, prolactin, index, LH/FSH, but decrease in FSH and progesterone. There were significant changes in carbohydrate and lipid metabolism. The possible mechanisms for the contribution of the investigated factors to the development of the pathological processes in the endometrium are presented.

Topics: Adult; Aged; Dietary Carbohydrates; Endometrial Hyperplasia; Endometrial Neoplasms; Estradiol; Female; Follicle Stimulating Hormone; Ghrelin; Gonadal Steroid Hormones; Humans; Insulin; Leptin; Lipid Metabolism; Luteinizing Hormone; Metabolic Syndrome; Middle Aged; Progesterone; Prolactin; Sex Hormone-Binding Globulin; Testosterone

Metabolic syndrome (MS) related to adult type 2 diabetes mellitus and cardiovascular disease is prevalent among obese children/adolescents. Genetic variants of the leptin-melanocortin system have been associated with components of MS. The aim of our study is to estimate the prevalence of MS (according to Cook's criteria) in a Chilean cross-sectional sample of 259 obese children (47.1% girls, aged 6-12 years), and to assess the association between common genetic variants of leptin-melanocortin pathway genes (LEP, LEPR, POMC, MC3R and MC4R) with components of the MS using logistic regression. We observed an overall MS prevalence of 26.3% (32.2% in girls and 21.1% in boys) in obese Chilean children. No associations were detected between genetic variants of leptin-melanocortin genes and MS components. MS prevalence among our obese children sample is similar to those previously described in Chile, demonstrating the increased risk of diseases in adulthood that obese children carry.

Topics: Child; Cross-Sectional Studies; Female; Humans; Leptin; Male; Melanocortins; Metabolic Syndrome; Mutation; Obesity; Prevalence

Metabolic syndrome (MetS) is a complex and heterogeneous disease characterized by central obesity, impaired glucose metabolism, dyslipidemia, arterial hypertension, insulin resistance and high-sensitivity C-reactive protein. In 2006, a neurotrophic hypothesis of the etiopathogenesis of MetS was launched. This hypothesis considered the neurotrophins a key factor in MetS development. Chronic inflammatory and/or psychoemotional distress provoke a series of neuroimmunoendocrine interactions such as increased tissue and plasma levels of proinflammatory cytokines and neurotrophins, vegetodystonia, disbalance of neurotransmitters, hormones and immunity markers, activation of the hypothalamo-pituitary-adrenal axis, insulin resistance, and atherosclerosis. An early and a late clinical stage in the course of MetS are defined. Meanwhile, evidence of supporting results from the world literature accumulates. This enables the transformation of the definition of the neurotrophic hypothesis into a neurotrophic theory of MetS. The important role of two neurotrophic factors, i.e. the nerve growth factor and brain-derived neurotrophic factor as well as of the proinflammatory cytokines, neurotransmitters, adipokines and, especially, of leptin for the development of MetS, obesity and type 2 diabetes mellitus is illustrated. There are reliable scientific arguments that the metabotrophic deficit due to reduced neurotrophins could be implicated in the pathogenesis of MetS, type 2 diabetes mellitus, and atherosclerosis as well. A special attention is paid to the activity of the hypothalamo-pituitary-adrenal axis after stress. The application of the neurotrophic theory of MetS could contribute to the etiological diagnosis and individualized management of MetS by eliminating the chronic distress, hyponeurotrophinemia and consequent pathology. It helps estimating the risk, defining the prognosis and implementing the effective prevention of this socially significant disease as evidenced by the dramatic recent growth of the world publication output on this interdisciplinary topic.

Topics: Adipokines; Affective Symptoms; Brain-Derived Neurotrophic Factor; Cytokines; Humans; Hypothalamo-Hypophyseal System; Inflammation; Leptin; Metabolic Syndrome; Models, Biological; Nerve Growth Factor; Nerve Growth Factors; Neurotransmitter Agents; Pituitary-Adrenal System

Recent research suggests that cannabinoid receptor CB1 antagonists can affect appetite and body weight gain, although their influence on other parameters related to metabolic syndrome is not well documented. The present study was designed to assess the effects of chronic treatment with the CB1 receptor inverse agonist AM 251 (3 mg/kg for 3 weeks) in obese and lean Zucker rats on parameters related to metabolic syndrome.. Four groups of rats were used: lean Zucker rats, untreated obese Zucker rats, AM 251-treated obese Zucker rats and a pair-fed obese Zucker rat experimental group which received the same amount of food as that consumed by the animals treated with AM251. Food intake, body weight gain, energy expenditure, plasma biochemical parameters, leptin, insulin and hepatic status markers were analysed.. Daily injection of AM 251 in obese Zucker rats produced a marked and sustained decrease in daily food intake and body weight and a considerable increase in energy expenditure in comparison with untreated obese Zucker rats. AM 251 administration to obese rats significantly reduced plasma levels of glucose, leptin, AST, ALT, Gamma GT, total bilirubin and LDL cholesterol whereas HDL cholesterol plasma levels increased. The results also showed a decrease in liver/weight body ratio and total fat content in the liver. The main effects of AM251 (3 mg/kg) found in this study were not observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with AM 251. The results obtained in obese rats can be interpreted as a decrease in leptin and insulin resistance, thereby improving glucose and lipid metabolism, alleviating the steatosis present in the metabolic syndrome and thus favourably modifying plasma levels of hepatic biomarkers.. Our results indicate that the cannabinoid CB1 inverse agonist AM 251 represents a promising therapeutic strategy for the treatment of obesity and metabolic syndrome.

Topics: Animals; Biomarkers; Cannabinoid Receptor Antagonists; Eating; Energy Metabolism; Fatty Liver; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Liver; Male; Metabolic Syndrome; Obesity; Piperidines; Pyrazoles; Rats; Rats, Zucker; Receptor, Cannabinoid, CB1; Weight Gain

The current nutritional habits and lifestyles of modern societies favor energy overloads and a diminished physical activity, which may produce serious clinical disturbances and excessive weight gain. In order to investigate the mechanisms by which the environmental factors interact with molecular mechanisms in obesity, a pathway analysis was performed to identify genes differentially expressed in subcutaneous abdominal adipose tissue (SCAAT) from obese compared to lean male (21-35 year-old) subjects living in similar obesogenic conditions: habitual high fat dietary intake and moderate physical activity. Genes involved in inflammation (ALCAM, CTSB, C1S, YKL-40, MIF, SAA2), extracellular matrix remodeling (MMP9, PALLD), angiogenesis (EGFL6, leptin) and oxidative stress (AKR1C3, UCHL1, HSPB7 and NQO1) were upregulated; whereas apoptosis, signal transcription (CITED 2 and NR3C1), cell control and cell cycle-related genes were downregulated. Interestingly, the expression of some of these genes (C1S, SAA2, ALCAM, CTSB, YKL-40 and tenomodulin) was found to be associated with some relevant metabolic syndrome features. The obese group showed a general upregulation in the expression of inflammatory, oxidative stress, extracellular remodeling and angiogenic genes compared to lean subjects, suggesting that a given genetic background in an obesogenic environment could underlie the resistance to gaining weight and obesity-associated manifestations.

Topics: Adult; Calcium-Binding Proteins; Cell Adhesion Molecules; Humans; Inflammation; Leptin; Male; Matrix Metalloproteinase 9; Membrane Glycoproteins; Metabolic Syndrome; Obesity; Oxidative Stress; Receptors, Glucocorticoid; Subcutaneous Fat; Ubiquitin Thiolesterase; Young Adult

Restrictive type bariatric surgery is an effective therapeutic approach that decreases overall mortality in patients with severe obesity. Several new cytokines, including adipocytokines that control energy metabolism, have been discovered recently, but their role in obesity is not fully recognized. The aim of the study was to evaluate the influence of vertical banded gastroplasty (VBG), one of restrictive type bariatric surgery, on peripheral blood concentrations of some adipocytokines and hormones involved in the control of food intake and energy turnover. The studied group comprised 12 females and 2 males aged from 31 to 59years (46.6±7.4) with simple obesity (BMI: 44.9±7.2) and metabolic syndrome. The patients were examined both before and 3, 6, 12, 24months after bariatric surgery (eight patients were also checked after 36 and six patients after 48months). Measurements of peripheral blood concentration of glucose, insulin, leptin, soluble leptin receptor, obestatin, ghrelin, omentin-1, and retinol binding protein 4 (RBP4) by ELISA method have been performed. After the surgery body weight, BMI and waist circumference significantly decreased. Positive changes considering the components of metabolic syndrome have been noted. Namely glucose, insulin and triglycerides' levels decreased, accompanied by the significantly lower HOMA index. Conversely, HDL cholesterol concentrations increased. Furthermore, peripheral blood concentration of leptin decreased, but the blood levels of soluble leptin receptor and ghrelin gradually increased. The positive correlations between leptin and body weight and BMI were noted as well as between the RBP4 and total cholesterol and LDL cholesterol levels. We did not observe significant differences in levels of obestatin, omentin-1 and RBP4 after surgery. In conclusion, VBG is an effective type of bariatric surgery. Fast decrease of body weight in morbidly obese patients treated by restrictive bariatric surgery leads to significant changes in peripheral blood levels of some adipokines and hormones controlling energy turnover and appetite (leptin and soluble leptin receptor) as well as ghrelin but not omentin-1, obestatin or retinol binding protein (RBP-4).

Topics: Adult; Cytokines; Female; Gastroplasty; Ghrelin; GPI-Linked Proteins; Humans; Lectins; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity, Morbid; Receptors, Leptin; Retinol-Binding Proteins, Plasma; Solubility; Time Factors

To investigate the relationship of adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease (NAFLD).. Group I consisted of 63 obese children with liver steatosis, group II consisted of 12 obese children with elevated serum ALT activity from group I, and group III included 85 obese children without liver steatosis.. Leptin levels were higher in the NAFLD children than in the control group. Serum RBP4 levels in obese children with NAFLD were higher than those in obese children without NAFLD and controls. Adiponectin and resistin levels were negatively correlated and RBP4 levels positively correlated with ALT activity and ultrasonographic grading.. These data suggest that adiponectin, resistin and RBP4 may have a role in the pathogenesis of NAFLD in obese children. Adiponectin, leptin, resistin and RBP4 may be suitable markers for predicting metabolic syndrome and NAFLD.

Topics: Adipokines; Adiponectin; Adolescent; Child; Fatty Liver; Humans; Leptin; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Resistin; Retinol-Binding Proteins, Plasma; ROC Curve

Stress and hypercaloric food are recognized risk factors for obesity, Metabolic Syndrome (MetS) and Type 2 Diabetes (T2D). Given the complexity of these metabolic processes and the unavailability of animal models, there is poor understanding of their underlying mechanisms. We established a model of chronic psychosocial stress in which subordinate mice are vulnerable to weight gain while dominant mice are resilient. Subordinate mice fed a standard diet showed marked hyperphagia, high leptin, low adiponectin, and dyslipidemia. Despite these molecular signatures of MetS and T2D, subordinate mice fed a standard diet were still euglycemic. We hypothesized that stress predisposes subordinate mice to develop T2D when synergizing with other risk factors. High fat diet aggravated dyslipidemia and the MetS thus causing a pre-diabetes-like state in subordinate mice. Contrary to subordinates, dominant mice were fully protected from stress-induced metabolic disorders when fed both a standard- and a high fat-diet. Dominant mice showed a hyperphagic response that was similar to subordinate but, unlike subordinates, showed a significant increase in VO2, VCO2, and respiratory exchange ratio when compared to control mice. Overall, we demonstrated a robust stress- and social status-dependent effect on the development of MetS and T2D and provided insights on the physiological mechanisms. Our results are reminiscent of the effect of the individual socioeconomic status on human health and provide an animal model to study the underlying molecular mechanisms.

Topics: Adiponectin; Animals; Calorimetry, Indirect; Diabetes Mellitus, Type 2; Diet; Diet, High-Fat; Energy Intake; Energy Metabolism; Glucose Tolerance Test; Hyperphagia; Immunohistochemistry; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Mice; Risk Factors; Social Dominance; Social Environment; Stress, Psychological

The metabolic syndrome (MS) is associated with insulin resistance (IR), inappropriate fibrinolysis and high plasma leptin concentrations. The aim of this study was to quantify fibrinolysis and MS-related variables in obese prepubertal children and to evaluate changes in these variables as a result of improved body mass index (BMI), IR and leptin levels following 9 months of treatment.. The homeostasis model assessment for insulin resistance (HOMA-IR), leptin, plasminogen activator inhibitor-1 (PAI-1) and lipid profile were studied at baseline in obese (n = 50) and nonobese children (n = 50), and after 9 months of treatment in obese children.. In the cross-sectional study the mean values for insulin, HOMA-IR, triglycerides, leptin and PAI-1 were significantly higher in obese children than in controls. High-density lipoprotein cholesterol (HDLc) and apolipoprotein A-1 were significantly lower. In the longitudinal study, after 9 months, children with lowered BMI standard deviation score displayed a significant decrease in insulin, HOMA-IR, PAI-1, leptin and triglyceride levels, and an increase in HDLc. Only leptin proved to be an independent predictive factor for changes in PAI-1 (p = 0.010).. Obesity-linked disorders appear in obese children prior to puberty; these disorders can be improved by decreasing BMI. Changes in leptin levels were found to independently predict changes in PAI-1 in obese children and can help to diagnose complications associated with the obesity.

Topics: Apolipoprotein A-I; Body Mass Index; Child; Cholesterol, HDL; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Longitudinal Studies; Male; Metabolic Syndrome; Obesity; Plasminogen Activator Inhibitor 1; Triglycerides

The aim of the present study was to test the possible effects of a novel sturgeon-derived compound  (LD-1227) on inflammatory markers related to metabolic nuclear receptors in patients with metabolic syndrome. The study population consisted of 76 patients with metabolic syndrome and 30 healthy subjects who were maintained to their current treatments and randomly supplemented: A) LD-1227 (n=38) or B) placebo (n=38) as compared to C) healthy controls (n=30). LD-1227 or placebo (water-soluble starch) were given daily at breakfast and dinner for three months. Levels of hs-CRP, IL-6, TNF-α, leptin and adiponectin/ resistin index were assayed at the entry, 1 month and 3 months afterwards. At the end of the study period, as compared to B group, LD-1227-treated patients showed a significant improvement of all parameters tested, irrespective of the presence of diabetes. In particular, levels of adiponectin and adiponectin/ resistin index significantly increased following LD-1227 administration. Although the metabolic syndrome remains a multifaceted condition requiring a complex approach, LD-1227 could be a potential safe therapeutic tool to be integrated into a wider treatment and preventive medicine schedule strategy.

Topics: Biomarkers; Humans; Leptin; Metabolic Syndrome; Receptors, Cytoplasmic and Nuclear; Tumor Necrosis Factor-alpha

Negative factors, such as the "magnificent" five that includes alcoholism, smoking, unhealthy food, lack of movement, and negative emotions, accompany a person almost from birth and trigger powerful internal biochemical reactions leading to disastrous consequences. Those new deleterious reactions force the organism to mobilize all of its internal reserves to neutralize, at least temporarily, the destructive effects of these negative factors. As a result of this continuous struggle for survival, body parts degenerate, starting from connective tissue protein molecules to entire newly formed organs (such as adipose tissue). Today we can state with certainty that the reason for the majority of widespread pathologies causing premature aging and death, such as atherosclerosis and arterial hypertension, is exactly those external negative factors that a person voluntary introduces into their life. However, the margin of safety that Nature enclosed in the human body is really amazing, allowing light-minded and self-destructive people to live up to 60 years and longer. It is quite possible that the lifespan will increase up to 100 years and more if a person stops destroying themself with negative emotions and bad habits, including unhealthy food and overeating. This article examines possible interconnection between unhealthy overeating and the theory of programmed aging and phenoptosis.

Topics: Adipose Tissue; Aging; Animals; Apoptosis; Diet; Humans; Interleukin-6; Leptin; Lipids; Longevity; Metabolic Syndrome; Obesity; Oxidative Stress; Resistin; Tumor Necrosis Factor-alpha

Topics: Body Mass Index; Female; Humans; Leptin; Male; Metabolic Syndrome

Topics: Body Mass Index; Female; Humans; Leptin; Male; Metabolic Syndrome

Extended modified fasting is a frequently practiced tradition in Europe. It is claimed to improve the cardiometabolic state and physical and psychological well-being by an evolutionary co-developed adaptation response. We aimed to investigate the cardiometabolic and psychological effects of a 7-day fast and differences of these responses between patients with or without metabolic syndrome (MetS).. We investigated 30 female subjects (49.0 ± 8.1 years, BMI 30.4 ± 6.7 kg/m(2)) with (n = 12) and without (n = 18) MetS. All subjects participated in a 7-day fast according to Buchinger with a nutritional energy intake of 300 kcal/day and stepwise reintroduction of solid food thereafter. Outcomes were assessed baseline and after fasting and included measures of metabolic and glucoregulatory control, adipokines as well as psychological well-being as assessed by Profile of Mood States (POMS) and Hospital Anxiety and Depression Scale (HADS).. Mean weight decreased from 85.4 ± 18.8 kg to 79.7 ± 18.2 kg accompanied by systolic/diastolic blood pressure (BP) reduction of -16.2 mm Hg (95% CI: -9.1; -23.3 mm Hg) and -6.0 mm Hg (95% CI: -1.8; -10.3 mm Hg), each p < 0.001 and p = 0.005. Fasting led to marked decreases of levels of LDL-cholesterol, leptin, and insulin and increases of levels of adiponectin, leptin receptors, and resistin. Fasting-induced mood enhancement was reflected by decreased anxiety, depression, fatigue, and improved vigor. Patients with MetS showed some greater changes in B P, LDL-cholesterol, triglycerides, adiponectin, leptin, and sleep quality. Fasting was well-tolerated.. Our results point to marked beneficial responses to 7-day modified fasting and a potential role in the prevention of the MetS. Randomized trials with longer observation periods should test the clinical effectiveness of fasting in metabolic diseases.

Topics: Adipokines; Adult; Blood Glucose; Blood Pressure; Cholesterol, LDL; Comorbidity; Energy Metabolism; Fasting; Female; Humans; Insulin; Leptin; Metabolic Syndrome; Middle Aged; Obesity; Prospective Studies; Quality of Life; Receptors, Leptin; Resistin; Surveys and Questionnaires

Adipokines are known to play a fundamental role in the etiology of obesity, that is, in the impaired balance between increased feeding and decreased energy expenditure. While the adipokine-induced changes of insulin resistance in obese diabetic and nondiabetic subjects are well known, the possible role of fat source in modulating insulin sensitivity (IS) remains controversial. The aim of our study was to explore in overweight type 2 diabetic patients (T2DM) with metabolic syndrome IS in different energy storage conditions (basal and dynamic) for relating it to leptin and adiponectin. Sixteen T2DM (5/11 F/M; 59 ± 2 years; 29.5 ± 1.1 kg/m(2)) and 16 control (CNT 5/11; 54 ± 2; 29.1 ± 1.0) underwent an oral glucose tolerance test. Fasting IS was measured by QUICKI, while the dynamic one with OGIS. The insulinogenic index (IGI) described beta cell function. Also, the lipid accumulation product parameter (LAP) was assessed. LAP accounts for visceral abdominal fat and triglycerides, and it is known to be related to IS. Possible interrelationships between LAP and adipokines were explored. In T2DM and CNT, adiponectin (7.4 ± 0.5 vs. 7.8 ± 0.9 μg/mL), leptin (13.3 ± 3.0 vs. 12.4 ± 2.6 ng/mL), and QUICKI (0.33 ± 0.01 vs. 0.33 ± 0.01) were not different (P > 0.40), at variance with OGIS (317 ± 11 vs. 406 ± 13 mL/min/m(2); P = 0.006) and IGI (0.029 ± 0.005 vs. 0.185 ± 0.029 × 10(3) pmolI/mmolG; P = 0.00001). LAP was 85 ± 15 cm × mg/dL in T2DM and 74 ± 10 in CNT (P > 0.1), correlated with OGIS in all subjects (R = -0.42, P = 0.02) and QUICKI (R = -0.56, P = 0.025) in T2DM. Leptin correlated with QUICKI (R = -0.45, P = 0.009), and adiponectin correlated with OGIS (R = 0.43, P = 0.015). In overweight T2DM, insulin sensitivity in basal condition appears to be multifaceted with respect to the dynamic one, because it should be more fat-related. Insulin sensitivity appears to be incompletely described by functions of fasting glucose and insulin values alone and the use of other indices, such as LAP could be suggested.

Topics: Adiponectin; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Insulin-Secreting Cells; Intra-Abdominal Fat; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight

In this study, we evaluated the effect of an analogue of l-carnitine on parameters involved with Metabolic Syndrome in obese Zucker rats. Twenty-four rats were treated for 5 weeks with l-carnitine (300 mg/kg) and its analogue at two concentrations (100 and 250 mg/kg) to assess their impact on glucose, triglycerides and cholesterol in liver and blood samples, as well as the amount of liver glycogen. Liver slices were also analysed. The analogue reduced the levels of glucose, triglycerides and cholesterol in liver and the level of triglycerides in serum. At 100 mg/kg, the analogue proved more effective than l-carnitine in improving the biochemical alterations present in liver. The amount of liver glycogen content was higher in obese animals treated with both l-carnitine and the analogue. No changes on insulin and leptin were observed in animals treated. l-carnitine and its analogue reduced the microvesicular fatty infiltration in liver. This study demonstrated that the analogue tested is more potent and efficient than l-carnitine and improves the pharmacological profile of l-carnitine.

Topics: Animals; Carnitine; Cholesterol; Disease Models, Animal; Dose-Response Relationship, Drug; Glucose; Glycogen; Insulin; Leptin; Liver; Male; Metabolic Syndrome; Obesity; Rats; Rats, Zucker; Triglycerides

To determine the metabolic and immunological effects of the oral administration of DT56a, an enzymatic isolate of soybeans.. DT56a was orally administered to mice in three animal models: leptin deficiency, high-fat diet (HFD) supplementation and immune-mediated hepatitis. Liver damage and immunological status were assessed.. Oral administration of DT56a to leptin-deficient (ob/ob) and HFD mice led to a significant reduction in serum triglyceride (TG) and total cholesterol (TC) levels. DT56a-treated mice in both models exhibited a significant reduction in hepatic levels of TG and marked alleviation of glycemic control as indicated by significant decreases in fasting blood glucose levels and glucose tolerance tests. The levels of liver enzymes were reduced. These metabolic effects were associated with altered distributions of regulatory T (Tregs) and natural killer T (NKT) cells. DT56a suppressed the immune-mediated liver damage induced by concanavalin A indicated by decreased liver enzymes and serum interferon-γ levels and by improved histology and decreased hepatic apoptosis. Oral administration of DT56a also alleviated immune-mediated hepatitis and affected Tregs and NKT cells.. Oral administration of DT56a promotes a hepatoprotective effect associated with an alteration in the distribution of Tregs and NKT cells.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Glucose; Cholesterol; Concanavalin A; Dietary Fats; Fatty Liver; Glucose Tolerance Test; Hepatitis, Autoimmune; Interferon-gamma; Leptin; Liver; Lymphocyte Count; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Natural Killer T-Cells; Plant Extracts; T-Lymphocytes, Regulatory; Triglycerides

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

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

Obesity and diabetes are closely associated with hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the diet-induced obese C57BL/6 mouse was used to test the hypothesis that chronically elevated metabolic parameters associated with the development of obesity such as cholesterol and glucose can aggravate basal HPA axis activity. Because the lipocalin-type prostaglandin D(2) synthase (L-PGDS) knockout (KO) mouse is a model of accelerated insulin resistance, glucose intolerance, and obesity, it was further hypothesized that HPA activity would be greater in this model. Starting at 8 weeks of age, the L-PGDS KO and C57BL/6 mice were maintained on a low-fat or high-fat diet. After 20 or 37 weeks, fasting metabolic parameters and basal HPA axis hormones were measured and compared between genotypes. Correlation analyses were performed to identify associations between obesity-related chronic metabolic changes and changes in the basal activity of the HPA axis. Our results have identified strong positive correlations between total cholesterol, LDL-cholesterol, glucose, and HPA axis hormones that increase with age in the C57BL/6 mice. These data confirm that obesity-related elevations in cholesterol and glucose can heighten basal HPA activity. Additionally, the L-PGDS KO mice show early elevations in HPA activity with no age-related changes relative to the C57BL/6 mice.

Topics: Adrenocorticotropic Hormone; Animals; Corticosterone; Genotype; Hypercholesterolemia; Hyperglycemia; Hypothalamo-Hypophyseal System; Insulin Resistance; Intramolecular Oxidoreductases; Leptin; Lipocalins; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Pituitary-Adrenal System

Psoriasis has been related to metabolic syndrome (MS). Adipocytokines produced by white adipose tissue may be involved in the pathogenesis of psoriasis and its association with MS. Our objectives were to characterize the profile of a number of different inflammatory and atherogenic markers, vitamins, adipokines and cytokines and their potential involvement in MS in patients with moderate-to-severe psoriasis without joint involvement compared to anthropometrically matched controls, and to evaluate correlation with severity of the skin disease and changes after narrow-band UVB (NB-UVB) phototherapy. We designed a prospective cross-sectional study. Baseline waist circumference, body fat composition, lipid, carbohydrate and calcium metabolism profile, inflammation markers, homocysteine and vitamins D, B6, B12 and folic acid, leptin, resistin, omentin, lipocalin-2, adipocyte fatty acid-binding protein, retinol-binding protein-4 (RBP-4), interleukin-6, soluble tumour necrosis factor receptor 1 (sTNFR1) and interleukin-17 of 50 psoriasis patients and 50 gender, age and body mass index-matched controls were recorded, then evaluated after NB-UVB in the patients. The patients had higher baseline serum concentrations of leptin, RBP-4, lipocalin-2 and sTNFR1. Baseline psoriasis area and severity index correlated with serum concentrations of RBP-4 and lipocalin-2 only. Principal components analysis disclosed a component including vitamins B12, B6, folic acid, calcidiol and HDL-cholesterol that was only present in healthy controls and opposed to a cluster of variables which promote MS. This component was absent in the patients. Our results point to lipocalin-2 and RBP-4 as relevant mediators of the trend towards MS in psoriatic patients.

Topics: Acute-Phase Proteins; Adult; Biomarkers; Child; Child, Preschool; Cross-Sectional Studies; Disease Progression; Female; Humans; Infant; Leptin; Lipocalin-2; Lipocalins; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Proto-Oncogene Proteins; Psoriasis; Receptors, Tumor Necrosis Factor, Type I; Retinol-Binding Proteins, Plasma; Severity of Illness Index; Ultraviolet Therapy; Vitamin B 12; Young Adult

To compare the prevalence of metabolic syndrome (MetS) and the levels of related biomarkers in patients with psoriatic arthritis (PsA) and psoriasis without arthritis (PsC).. This study compared patients with PsA and patients with PsC. The presence of MetS was determined. Serum levels of insulin, adiponectin and leptin were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. HOMA-IR, adiponectin and leptin were log-transformed. Continuous variables were compared using the t test and the χ(2) test was used for discrete variables. Multivariate regression models were used to investigate the association of MetS and adiponectin with PsA compared to PsC after adjusting for potential confounding variables.. 203 PsA and 155 PsC patients were analysed. The prevalence of MetS was higher in PsA patients compared to those with PsC. However, this did not reach statistical significance (36.5% vs 27.1%, p=0.056). The levels of adipokines were significantly higher in PsA compared to PsC: adiponectin (8.8±5.2 vs 7.4±4.5 log (µg/ml), p=0.009) and leptin in women (3.1±0.8 vs 2.8±0.8, log (ng/ml), p=0.04). HOMA-IR was also higher in PsA (0.97±0.63 vs 0.68±0.81, p<0.001). No difference was observed in leptin levels in men. In multivariate regression analysis, PsA (p=0.04) and the psoriasis area and severity index score (p=0.02) were associated with MetS. Adiponectin was significantly associated with PsA (p=0.005), the use of anti-tumour necrosis factor α therapy (p=0.03) and active joint count (p=0.001).. MetS and related adipokines correlated with an increased burden of skin and joint inflammation.

Topics: Adipokines; Adult; Antirheumatic Agents; Arthritis, Psoriatic; Biomarkers; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Psoriasis; Risk Factors; Severity of Illness Index

Synthetic biology has significantly advanced the design of genetic devices that can reprogram cellular activities and provide novel treatment strategies for future gene- and cell-based therapies. However, many metabolic disorders are functionally linked while developing distinct diseases that are difficult to treat using a classic one-drug-one-disease intervention scheme. For example, hypertension, hyperglycemia, obesity, and dyslipidemia are interdependent pathologies that are collectively known as the metabolic syndrome, the prime epidemic of the 21st century. We have designed a unique therapeutic strategy in which the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin. Therefore, the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements. Based on this designer signaling cascade, it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc(mIgG)-Leptin, a bifunctional therapeutic peptide hormone that combines the glucagon-like peptide 1 (GLP-1) and leptin via an IgG-Fc linker. In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia. Using a clinically licensed drug to coordinate expression of therapeutic transgenes combines drug- and gene-based therapies for coordinated treatment of functionally related metabolic disorders.

Topics: Animals; Cyclic AMP Response Element-Binding Protein; Dose-Response Relationship, Drug; Drug Design; Gene Expression Regulation; Glucagon-Like Peptide 1; Guanabenz; Leptin; Metabolic Syndrome; Mice; Models, Molecular; Receptors, G-Protein-Coupled; Signal Transduction; Transgenes

To investigate the association between Trp64Arg polymorphism of the beta3-adrenergic receptor (ADRB3) gene and total fat mass, abdominal fat distribution, other metabolic derangements and metabolic syndrome (MS) in Japanese children.. Molecular screening of the ADRB3 gene polymorphism (Trp64Trp, Trp64Arg and Arg64Arg) was carried out in 132 children aged 6-12 years: 73 were obese (45 boys) and 59 were not obese (27 boys). Visceral fat (VF) and subcutaneous fat (SF) area were measured using magnetic resonance imaging, blood pressure, lipid and glucose profiles.. The frequencies of Arg carriers (Trp64Arg or Arg64Arg) were significantly higher in obese children with MS, compared to obese children without MS and nonobese children. In obese children, Arg carriers had significantly higher VF area, systolic and diastolic blood pressure, and low-density lipoprotein cholesterol and triglyceride than Arg noncarriers (Trp64Trp). However, there were no differences in total fat mass and SF area between the two groups. In nonobese children, none of these parameters differed significantly between Arg carriers and noncarriers.. Trp64Arg polymorphism of the ADRB3 gene may affect VF accumulation and be associated with MS, a cluster of conditions involving aggravated lipid metabolism and higher blood pressure, in Japanese children.

Topics: Blood Pressure; Body Mass Index; Child; Comorbidity; Female; Humans; Intra-Abdominal Fat; Leptin; Magnetic Resonance Imaging; Male; Metabolic Syndrome; Obesity, Abdominal; Polymorphism, Genetic; Receptors, Adrenergic, beta-3

Gestational exposures such as dietary changes can alter offspring phenotype through epigenetic modifications and promote increased risk for specific diseases, such as metabolic syndrome. We hypothesized that high-fat diet (HFD) during late gestation would lead increased risk for insulin resistance and hyperlipidemia via associated epigenetic alterations in tissue adipocytokine genes.. Offspring mice of mothers fed a HFD during late gestation (HFDO) were weighed and their food intake measured weekly till age 20 weeks at which time glucose and insulin tolerance tests, plasma lipid and adipocytokine levels were assessed, as well as mRNA expression in visceral fat. Adipocytokine gene methylation levels in visceral fat, liver and muscle were also assayed.. HFDO mice had increased weight accrual and food intake, and exhibited insulin resistance, hyperlipidemia and hyperleptinemia, as well as hypoadiponectinemia. Furthermore, increased methylation of adiponectin and leptin receptor, and decreased methylation of leptin genes with unchanged glucagon-like peptide-1 methylation patterns emerged in HFDO mice.. Taken together, late gestational HFD induces increased risk of metabolic syndrome in the progeny, which is coupled with hypoadiponectinemia as well as with leptin resistance, and concomitant presence of selective tissue-based epigenetic changes among adipocytokine genes.

Topics: Acetylation; Adiponectin; Animals; Animals, Newborn; Body Weight; Diet, High-Fat; Epigenesis, Genetic; Female; Glucose Tolerance Test; Insulin; Insulin Resistance; Leptin; Liver; Male; Metabolic Syndrome; Metabolism, Inborn Errors; Mice; Mice, Inbred C57BL; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects; Time Factors

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

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

Tumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels.. The G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91±6.05) and 272 healthy females without metabolic syndrome (age 30.96±7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion.. Homozygous mutant genotype (AA) (p=<0.001: OR=3.24: 95% CI=2.15-4.89) and mutant allele (A) (p=<0.001: OR=3.04: 95% CI=2.08-4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors.. Our results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia.

Topics: Adult; Anthropometry; Case-Control Studies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; India; Insulin Resistance; Leptin; Metabolic Syndrome; Odds Ratio; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Risk Factors; Tumor Necrosis Factor-alpha

Metabolic syndrome (MetS) describes a clustering of factors including central obesity, hypertension and raised plasma glucose, triglycerides and high-density lipoprotein (HDL) cholesterol. Central obesity is associated with a risk for colorectal cancer, but the impact of MetS on colorectal cancer biology and outcomes is unclear.. A prospective observational study of colorectal cancer patients was carried out in an Irish population. Patients underwent metabolic and anthropometric assessment before treatment, including measurement of serum hormones and adipokines and CT measurement of visceral fat. MetS was defined according to the International Diabetes Federation definition(3) .. One-hundred and thirty consecutive colorectal cancer patients (66 men and 64 women) were recruited. MetS was diagnosed in 38% patients compared with the population norms reported at 21%(21) . Male patients had a significantly greater visceral fat area compared with female patients. MetS was associated with node-positive disease (P = 0.026), percentage nodal involvement (P = 0.033) and extramural vascular invasion (P = 0.049) in male patients but no significant association was observed in female patients. HDL cholesterol was also significantly associated with a more advanced pathological stage (P = 0.014) and node-positive disease (P = 0.028). Leptin was associated with nodal status (P = 0.036), microvascular invasion (P = 0.054), advanced pathological stage (P = 0.046) and more advanced Dukes stage (P = 0.042).. We report a high prevalence of MetS and visceral obesity in a colorectal cancer population. MetS and plasma leptin are associated with a more aggressive tumour phenotype in male patients only.

Topics: Aged; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Carcinoma; Cholesterol, HDL; Cholesterol, LDL; Colorectal Neoplasms; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lymphatic Metastasis; Male; Metabolic Syndrome; Neoplasm Invasiveness; Prospective Studies; Radiography; Sex Factors; Triglycerides; Waist Circumference

The aims of the study were to determine the prevalence of metabolic syndrome (MS) components and examine associations with adipokine concentrations in a healthy pediatric cohort. A cross-sectional study of 1138 children (53% girls; mean age of all participants, 11.2 ± 0.7 years) was performed. Anthropometric and medical information was obtained; and a fasting blood sample was used to measure glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin serum concentrations. Insulin resistance was assessed by the insulin resistance homeostasis model assessment. Body weight status (normal, overweight, and obese) was determined according to the International Obesity Task Force. Estimation of the MS was based on the International Diabetes Federation definition. The prevalence of the MS was 0.7% of children, all of whom were obese. Frequency of abdominal obesity, high fasting glucose, elevated triglycerides, low high-density-lipoprotein cholesterol, and elevated blood pressure was 4.8%, 4.7%, 0, 12.3%, and 33%, respectively. Body mass index (BMI) and z-BMI score increased significantly as the number of cardiometabolic risk factors increased. Regression analysis revealed that adiponectin (β = -0.501, P = .003) and leptin (β = 0.184, P < .0001) independently predicted the number of MS features. This finding was no longer significant after adjustment for BMI. In the present study, we provide the first estimate of the prevalence of the MS among healthy periadolescents in Greece using the International Diabetes Federation criteria. The MS prevalence was low, with elevated blood pressure being the most dominant feature. Finally, associations with adipokines are mediated by BMI.

Topics: Adiponectin; Adolescent; Body Mass Index; Child; Cohort Studies; Cross-Sectional Studies; Diagnostic Techniques, Endocrine; Endocrinology; Female; Humans; Insulin Resistance; International Agencies; Leptin; Male; Mediterranean Region; Metabolic Syndrome; Prevalence; Research Design

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

In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/obese subjects with metabolic syndrome was influenced by the presence of insulin resistance.. Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects' plasmas to allow calculation of % cholesterol efflux.. Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) (P=0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index (P<0.001), directly with arterial insulin concentration (P<0.001) and directly with cholesteryl ester transfer protein (CETP) mass (P=0.044).. Plasmas from overweight subjects with insulin resistance induced greater in vitro cholesterol efflux compared with IS subjects. Efflux inversely correlated with insulin sensitivity suggesting an increase in reverse cholesterol transport in the IR state that may lead to greater transfer of cholesterol to apoB lipoproteins from high-density lipoproteins via CETP as a factor in the association between IR and atherosclerosis.

Topics: ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Australia; Biological Transport; Cholesterol; Cholesterol Ester Transfer Proteins; Coronary Artery Disease; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Macrophages; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors

The cardiometabolic syndrome comprised of multiple correlated traits, but its origin is incompletely understood. Chromogranin A (CHGA) is required for formation of the catecholamine secretory pathway in sympathochromaffin cells. In twin pair studies, we found that CHGA traits aggregated with body mass index (BMI), as well as its biochemical determinant leptin. METHODS Here we used the twin method to probe the role of heredity in generating such risk traits, and then investigated the role of risk-trait-associated CHGA promoter genetic variation in transfected chromaffin cells. Trait heritability (h(2)) and shared genetic determination among traits (pleiotropy, genetic covariance, ρ(G)) were estimated by variance components in twin pairs.. CHGA, BMI, and leptin each displayed substantial h(2), and the traits also aggregated with several features of the metabolic syndrome (e.g., insulin resistance, blood pressure (BP), hypertension, catecholamines, and C-reactive protein (CRP)). Twin studies demonstrated genetic covariance (pleiotropy, ρ(G)) for CHGA, BMI, and leptin with other metabolic traits (insulin resistance, BP, and CRP). We therefore investigated the CHGA locus for mechanisms of codetermination with such metabolic traits. A common functional variant in the human CHGA promoter (G-462A, rs9658634, minor allele frequency ~21%) was associated with leptin and CRP secretion, as well as BMI, especially in women; marker-on-trait effects on BMI were replicated across twin populations on two continents. In CHGA promoter/luciferase reporter plasmids transfected into chromaffin cells, G-462A alleles differed markedly in reporter expression. The G-462A variant disrupted predicted transcriptional control by a PPARγ/RXRα motif and costimulation by PPARγ/RXRα and their cognate ligands, differentially activated the two alleles. During chromatin immunoprecipitation, endogenous PPARγ bound the motif.. Multiple features of the metabolic syndrome are thus under joint (pleiotropic) genetic determination, with CHGA as one such contributory locus: a common polymorphism in the promoter (G-462A) of CHGA predicts such heritable metabolic traits as BMI and leptin. CHGA promoter variant G-462A was not only associated with such metabolic traits but also disrupted a PPARγ/RXRα motif and responded differentially to characteristic trans-activators of that motif. The results suggest novel links between the catecholaminergic system and risk for the metabolic syndrome as well as systemic hypertension.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; C-Reactive Protein; Chromaffin Cells; Chromogranin A; Female; Genetic Pleiotropy; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Polymorphism, Genetic; Promoter Regions, Genetic; Risk; Twins, Dizygotic; Twins, Monozygotic

The morphology of sciatic nerves from leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice, both models for obesity, peripheral diabetic neuropathy, and the metabolic syndrome, has yet to be examined for changes in nerve fibers and in endoneural microvessels. Sciatic nerves from three groups of 4-month-old mice (WT C57BL6, ob/ob, and db/db) were investigated. In ultrathin sections, the thickness of myelin sheaths was significantly reduced in small, medium-sized, and large axons of db/db mice compared with WT mice. In ob/ob mice, only large fibers showed a decrease in myelin sheath thickness. The number of nonmyelinated nerve fibers was lower in ob/ob mice than in the db/db group. A thickened basal lamina of Schwann cells occurred in the ob/ob group only. In contrast, the basement membrane of endoneural microvessels was thickened in both obese groups. For this reason, laminin expression in Western blot analysis was lower in the db/db group than in the ob/ob one. Endoneural microvessels, which had been injected with fluorescein isothiocyanate, depicted signs of vasodilatation in the ob/ob and vasoconstriction in db/db mice. Endoneural vessels displayed two receptors of oxLDL. LOX-1 was strongly expressed in db/db mice, whereas TLR4 was at its maximum in the ob/ob group. We conclude that changes in nerve fibers and in endoneural microvessels are present in sciatic nerve of both mouse models of type 2 diabetes. Upregulation of oxLDL-dependent receptors in endoneural microvessels might be connected to different degrees of oxidative stress in severe diabetic db/db mice and in the mild diabetic ob/ob group.

Topics: Analysis of Variance; Animals; Basement Membrane; Body Weight; CD36 Antigens; Diabetic Neuropathies; Disease Models, Animal; Laminin; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Obese; Microscopy, Electron, Transmission; Microvessels; Myelin Sheath; Obesity; Oxidative Stress; Receptors, Leptin; Scavenger Receptors, Class E; Schwann Cells; Sciatic Nerve; Thiobarbituric Acid Reactive Substances; Toll-Like Receptor 4; von Willebrand Factor

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

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

It is known that Ca therapy may have anti-obesity effects. Since early weaning leads to obesity, hyperleptinaemia and insulin resistance, we studied the effect of dietary Ca supplementation in a rat model. Lactating rats were separated into two groups: early weaning (EW) - dams were wrapped with a bandage to interrupt lactation in the last 3 d of lactation and control (C) - dams whose pups had free access to milk during the entire lactation period (21 d). At 120 d, EW and C offspring were subdivided into four groups: (1) C, received standard diet; (2) CCa, received Ca supplementation (10 g of calcium carbonate/kg of rat chow); (3) EW, received standard diet; (4) EWCa, received Ca supplementation similar to CCa. The rats were killed at 180 d. The significance level was at P < 0·05. Adult EW offspring displayed hyperphagia (28 %), higher body weight (9 %) and adiposity (77 %), hyperleptinaemia (twofold increase), hypertriacylglycerolaemia (64 %), hyperglycaemia (16 %), higher insulin resistance index (38 %) and higher serum 25-hydroxyvitamin D₃ (fourfold increase), but lower adiponectinaemia:adipose tissue ratio (44 %). In addition, they showed Janus tyrosine kinase 2 and phosphorylated signal transducer and activator of transcription 3 underexpression in hypothalamus (36 and 34 %, respectively), suggesting leptin resistance. Supplementation of Ca for 2 months normalised these disorders. The EW group had no change in serum insulin, thyroxine or triiodothyronine, and Ca treatment did not alter these hormones. In conclusion, we reinforced that early weaning leads to late development of some components of the metabolic syndrome and leptin resistance. Dietary Ca supplementation seems to protect against the development of endocrine and metabolic disorders in EW offspring, maybe through vitamin D inhibition.

Topics: Adiposity; Animals; Blood Glucose; Calcitriol; Calcium Carbonate; Calcium, Dietary; Disease Models, Animal; Female; Hyperglycemia; Hyperphagia; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Pregnancy; Rats; Weaning

The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective strategy against insulin resistance and related situations.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cytokines; Diet; Dietary Proteins; Eating; Fish Proteins; Fructose; Glucose Tolerance Test; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Male; Metabolic Syndrome; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Little is known about pancreatic fat accumulation and its possible associations with metabolic syndrome (MetS) and glucose metabolism. The aim of the present study was to quantify pancreatic fat fraction (PFF) in lean and obese adolescents and explore its relation to metabolic parameters.. We recruited 25 lean and 24 obese adolescents. PFF and visceral adipose tissue (VAT) were determined using magnetic resonance imaging. We measured blood pressure, fasting glucose, insulin, liver enzymes, leptin, and lipid levels. Obese subjects underwent an oral glucose tolerance test.. PFF was significantly higher in obese than in lean subjects (4.8±1.2 vs 3.6±0.9; P<0.001) and was associated with VAT, γ-glutamyltransferase, triglycerides, high-density lipoprotein cholesterol, leptin concentrations, and MetS (P<0.05 for all). None of the obese subjects had glucose intolerance, but when adjusted for VAT, the following 3 parameters correlated negatively with PFF: fasting and 30- minute and 120-minute insulin levels. We divided subjects into 3 groups: group I, lean without MetS; group II, obese without MetS; and group III, obese with MetS, and observed that PFF increased gradually among groups (I: 3.56%±0.88%; II: 4.70%±1.06%; III: 5.34%±1.49%; P<0.001).. Obese adolescents accumulate fat in the pancreas. PFF correlates with the presence of MetS. Even in the absence of glucose intolerance, pancreatic fat deposition is associated with impaired insulin response to glucose overload. This suggests that β-cell dysfunction may already be present in nondiabetic obese adolescents, mirroring what has been shown in adults, and that pancreatic fat accumulation may participate in obesity-associated pancreatic endocrine dysfunction.

Topics: Adolescent; Blood Glucose; Case-Control Studies; Child; Cholesterol, HDL; Fasting; Female; gamma-Glutamyltransferase; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Magnetic Resonance Imaging; Male; Metabolic Syndrome; Obesity; Pancreas; Triglycerides

Menopausal status is associated with weight gain, increased central fat mass, abnormal lipid metabolism, insulin resistance and susceptibility to metabolic syndrome (MetS). Leptin is synthesised and secreted by adipocytes. Serum leptin levels are highly correlated with fat mass. We determined the association between MetS and serum leptin levels in 153 postmenopausal women. The difference in serum leptin level between MetS and non-MetS groups showed a statistical significance after adjusting for body mass index (BMI; 19.9 ± 9.5 vs 12.1 ± 5.9 ng/ml, p = 0.013). The indicator of abdominal obesity, waist-to-hip ratio (WHR) and visceral fat area (VFA), had a positive correlation with serum leptin level in non-obese subjects after adjusting for BMI (p = 0.017, p < 0.001, respectively). Of the components of MetS, abdominal obesity and the number of MetS components had a positive correlation with serum leptin level (p < 0.05, p < 0.001, respectively).

Topics: Aged; Cross-Sectional Studies; Female; Humans; Leptin; Metabolic Syndrome; Middle Aged; Obesity; Postmenopause; Retrospective Studies

Skin tags are common cutaneous lesions with an indefinite aetiology.. To assess serum leptin, insulin resistance and metabolic syndrome in different body mass index (BMI) patients with skin tags.. Three equally distributed groups of patients with multiple skin tags: 30 normal BMI, 30 overweight and 30 obese were included. Controls were age-, gender- and BMI-matched healthy subjects. Serum leptin, insulin resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome were assessed in all groups.. Number and extent of skin tags increase with the increase in BMI. Highest leptin levels were found in obese patients, with significant differences when compared to normal BMI and overweight patients. Similar findings existed in controls. Significantly higher leptin levels were found in obese patients compared to obese controls. HOMA-IR was significantly higher in all groups of patients compared to BMI-counterpart controls. Seventy-one per cent of patients fulfilled criteria of metabolic syndrome. Number of skin tags, leptin and HOMA-IR were significantly higher in patients with metabolic syndrome compared to patients without the syndrome. Positive correlations were found between serum leptin and HOMA-IR in obese patients and obese controls. Positive correlations were also found between number of skin tags and waist circumference in all groups of patients.. Serum leptin displays an association with obesity and insulin resistance. Assessment of HOMA-IR in patients with skin tags may serve as a useful approach for diagnosis of insulin resistance. Waist circumference is the only criteria of metabolic syndrome that correlates with number of skin tags.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Skin Neoplasms

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

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

For some years now, reduced testosterone levels have been related to obesity, insulin resistance, type 2 diabetes, heart disease, benign prostatic hypertrophy and even prostate cancer--often considered guilty more by association, than actual cause--with little attention paid to the important role of increased intracellular oestrogen, in the pathogenesis of these chronic diseases. In the final stage of the steroidogenic cascade, testosterone is metabolised to oestradiol by P450 aromatase, in the cytoplasm of adipocytes, breast cells, endothelial cells and prostate cells, to increase intracellular oestradiol concentration at the expense of testosterone. It follows therefore, that any compound that up-regulates aromatase, or any molecule that mimics oestrogen, will not only increase the activation of the mainly proliferative, classic ER-α, oestrogen receptors to induce adipogenesis and growth disorders in oestrogen-sensitive tissues, but also activate the recently identified transmembrane G protein-coupled oestrogen receptors (GPER), and deleteriously alter important intracellular signalling sequences, that promote mitogenic growth and endothelial damage. This paper simplifies how stress, xeno-oestrogens, poor dietary choices and reactive toxins up-regulate aromatase to increase intracellular oestradiol production; how oestradiol in combination with leptin and insulin cause insulin resistance and leptin resistance through aberrant serine phosphorylation; how the increased oestradiol, insulin and leptin stimulate rapid, non-genomic G protein-coupled phosphorylation cascades, to increase fat deposition and create the vasoconstrictive, dyslipidemic features of metabolic syndrome; how aberrant GPER signalling induces benign prostatic hypertrophy; and how increased intracellular oestradiol stimulates mitogenic change and tumour-cell activators, to cause prostate cancer. In essence, the up-regulation of aromatase produces increased intracellular oestradiol, increases ER-α activation and increases GPER activation, in combination with insulin, to cause aberrant downstream transduction signaling, and thus induce metabolic syndrome and mitogenic prostate growth. To understand this fact, that raised intracellular oestradiol levels in men, induce and promote obesity, gynecomastia, metabolic syndrome, type two diabetes, benign prostatic hypertrophy and prostate cancer, rather than low testosterone, represents a shift in medical thinking, a new awareness, that will reduce

Topics: Adiposity; Aromatase; Body Fat Distribution; Diabetes Mellitus, Type 2; Estrogen Receptor alpha; Estrogens; Gynecomastia; Humans; Insulin; Insulin Resistance; Intracellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Obesity; Phosphorylation; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Estrogen; Receptors, G-Protein-Coupled; Signal Transduction; Testosterone; Up-Regulation

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

Animal models of type 2 diabetes exhibit reduced peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) messenger RNA (mRNA) levels, which are associated with decreased oxidative capacity, in skeletal muscles. In contrast, animal models with metabolic syndrome show normal PGC-1α mRNA levels. We hypothesized that a high-fat diet decreases PGC-1α mRNA levels in skeletal muscles of rats with metabolic syndrome, reducing muscle oxidative capacity and accelerating metabolic syndrome or inducing type 2 diabetes. We examined mRNA levels and fiber profiles in the soleus muscles of rats with metabolic syndrome (SHR/NDmcr-cp [cp/cp]; CP) fed a high-fat diet. Five-week-old CP rats were assigned to a sedentary group (CP-N) that was fed a standard diet (15.1 kJ/g, 23.6% protein, 5.3% fat, and 54.4% carbohydrates) or a sedentary group (CP-H) that was fed a high-fat diet (21.6 kJ/g, 23.6% protein, 34.9% fat, and 25.9% carbohydrates) and were housed for 10 weeks. Body weight, energy intake, and systolic blood pressure were higher in the CP-H group than in the CP-N group. Nonfasting glucose, triglyceride, total cholesterol, and leptin levels were higher in the CP-H group than in the CP-N group. There was no difference in insulin levels between the CP-N and CP-H groups. Muscle PGC-1α mRNA levels and succinate dehydrogenase activity were lower in the CP-H group than in the CP-N group. We concluded that a high-fat diet reduces PGC-1α mRNA levels and oxidative capacity in skeletal muscles and accelerates metabolic syndrome.

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Diet, High-Fat; Dietary Fats; Energy Intake; Insulin; Leptin; Male; Metabolic Syndrome; Muscle, Skeletal; Oxidation-Reduction; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PPAR gamma; Rats; Rats, Inbred Strains; RNA-Binding Proteins; RNA, Messenger; Sedentary Behavior; Succinate Dehydrogenase; Transcription Factors; Triglycerides

Renin-angiotensin system blockade improves glucose intolerance and insulin resistance, which contribute to the development of metabolic syndrome. However, the contribution of impaired insulin secretion to the pathogenesis of metabolic syndrome is not well defined. To assess the contributions of angiotensin receptor type 1 (AT₁) activation and high glucose intake on pancreatic function and their effects on insulin signaling in skeletal muscle and adipose tissue, an oral glucose tolerance test (oGTT) was performed in five groups (n = 10/group) of rats: 1) lean strain-control 2) obese Otsuka Long-Evans Tokushima Fatty (OLETF), 3) OLETF + angiotensin receptor blocker (ARB; 10 mg/kg · d olmesartan for 6 wk; OLETF ARB), 4) OLETF + 5% glucose water (HG) for 6 wk (OLETF HG), and 5) OLETF + HG + ARB (OLETF HG/ARB). The glucose response to the oGTT increased 58% in OLETF compared with lean-strain control, whereas glucose supplementation increased it an additional 26%. Blockade of angiotensin receptor reduced the oGTT response 19% in the ARB-treated groups and increased pancreatic insulin secretion 64 and 113% in OLETF ARB and OLETF HG/ARB, respectively. ARB treatment in OLETF ARB and OLETF HG/ARB did not have an effect on insulin signaling proteins in skeletal muscle; however, it reduced pancreatic AT₁ protein expression 20 and 27%, increased pancreatic glucagon-like peptide-1 (GLP-1) receptor protein expression 41 and 88%, respectively, and increased fasting plasma GLP-1 approximately 2.5-fold in OLETF ARB. The results suggest that improvement of glucose intolerance is independent of an improvement in muscle insulin signaling, but rather by improved glucose-stimulated insulin secretion associated with decreased pancreatic AT₁ activation and increased GLP-1 signaling.

Topics: Adipose Tissue; Angiotensin II Type 1 Receptor Blockers; Animals; Blood Pressure; Dietary Supplements; Disease Models, Animal; Glucagon-Like Peptide-1 Receptor; Glucose; Glucose Intolerance; Insulin; Leptin; Male; Metabolic Syndrome; Muscle, Skeletal; Pancreas; Rats; Rats, Inbred OLETF; Rats, Inbred Strains; Receptor, Angiotensin, Type 1; Receptors, Glucagon; Triglycerides

Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA.

Topics: Acute-Phase Reaction; Adiponectin; Animals; Asbestos, Amphibole; Biomarkers; Inflammation; Leptin; Lipocalin-2; Lipocalins; Macroglobulins; Male; Metabolic Syndrome; Orosomucoid; Osteopontin; Proteomics; Rats; Rats, Inbred F344; Rats, Inbred SHR; Rats, Inbred WKY; Retrospective Studies

The links between obesity in parents and their offspring and the role of genes and a shared environment are not completely understood. Adipocytokines such as leptin and adiponectin play important roles in glucose and lipid metabolism. Therefore, we examined whether the offspring from dams exposed to a high-fat diet during pregnancy (OH mice) exhibited hypertension, insulin resistance, and hyperlipidemia along with epigenetic changes in the expression of adipocytokine genes. OH mice were significantly heavier than the offspring of dams exposed to a control diet during pregnancy (OC mice) from 14 wk of age after an increased caloric intake from 8 wk. OH mice exhibited higher blood pressure and worse glucose tolerance than the OC mice at 24 wk. Total triglyceride and leptin levels were significantly higher and the adiponectin level was significantly lower in OH compared with OC mice at 12 wk of age. This was associated with changes in leptin and adiponectin expression in white adipose tissue. There were lower acetylation and higher methylation levels of histone H3 at lysine 9 of the promoter of adiponectin in adipose tissues of OH mice at 2 wk of age as well as at 12 and 24 wk of age compared with OC mice. In contrast, methylation of histone 4 at lysine 20 in the leptin promoter was significantly higher in OH compared with OC mice. Thus, exposure to a high-fat diet in utero might cause a metabolic syndrome-like phenomenon through epigenetic modifications of adipocytokine, adiponectin, and leptin gene expression.

Topics: Acetylation; Adiponectin; Adipose Tissue; Animals; Animals, Newborn; Blood Pressure; Body Weight; Diet, High-Fat; Energy Intake; Epigenesis, Genetic; Female; Gene Expression; Glucose Tolerance Test; Histones; Insulin; Leptin; Male; Metabolic Syndrome; Methylation; Mice; Mice, Inbred ICR; Pregnancy; Prenatal Exposure Delayed Effects; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Triglycerides

Nutritional approaches are sought to overcome the limits of pioglitazone in metabolic syndrome and non-alcoholic fatty liver disease. Spirulina, a filamentous unicellular alga, reduces serum lipids and blood pressure while exerting antioxidant effects.. To determine whether Spirulina may impact macrophages infiltrating the visceral fat in obesity characterizing our metabolic syndrome mouse model induced by the subcutaneous injection treatment of monosodium glutamate.. Mice were randomized to receive standard food added with 5% Spirulina, 0.02% pioglitazone, or neither. We tested multiple biochemistry and histology (both liver and visceral fat) readouts at 24 weeks of age.. Data demonstrate that both the Spirulina and the pioglitazone groups had significantly lower serum cholesterol and triglyceride levels and liver non-esterified fatty acid compared to untreated mice. Spirulina and pioglitazone were associated with significantly lower leptin and higher levels, respectively, compared to the control group. At liver histology, non-alcoholic fatty liver disease activity score and lipid peroxide were significantly lower in mice treated with Spirulina.. Spirulina reduces dyslipidaemia in our metabolic syndrome model while ameliorating visceral adipose tissue macrophages. Human studies are needed to determine whether this safe supplement could prove beneficial in patients with metabolic syndrome.

Topics: Animals; Cell Aggregation; Cholesterol; Disease Models, Animal; Fatty Acids, Nonesterified; Fatty Liver; Food, Formulated; Hypoglycemic Agents; Insulin; Interleukin-6; Leptin; Lipid Peroxides; Liver; Macrophages; Male; Metabolic Syndrome; Mice; Pioglitazone; Random Allocation; Sodium Glutamate; Spirulina; Thiazolidinediones; Triglycerides; Tumor Necrosis Factor-alpha

The association between morbid obesity and hyperhomocysteinemia (HH) remains controversial and the nature of this relationship needs to be clarified as several metabolic, lipidic, inflammatory and anthropometric alterations that accompany morbid obesity may be involved. In 66 morbidly obese patients, 47 women and 19 men aged 41 ± 12 years and 66 normo-weight subjects, 43 women and 23 men, aged 45 ± 11 years, we determined homocysteine (Hcy) levels along with lipidic, anthropometric, inflammatory and insulin resistance markers. In addition, we investigated the effect of Metabolic Syndrome (MS) and its components on Hcy levels. Obese patients had statistically higher Hcy levels than controls: 12.76 ± 5.30 μM vs. 10.67 ± 2.50 μM; p = 0.006. Moreover, morbidly obese subjects showed higher waist circumference, glucose, insulin, HOMA, leptin, triglycerides, fibrinogen, C reactive protein (CRP) (p < 0.001, respectively), and lower vitamin B12 (p = 0.002), folic acid and HDL-cholesterol (p < 0.001, respectively). In the multivariate regression analysis, waist circumference, glucose, leptin and folic acid levels were independent predictors for Hcy values (p < 0.050). When obese patients were classified as having MS or not, no differences in Hcy levels were found between the two groups (p = 0.752). Yet when we analysed separately each MS component, only abdominal obesity was associated with Hcy levels (p = 0.031). Moreover when considering glucose >110 mg/dL (NCEP-ATPIII criteria) instead of glucose intolerance >100 mg/dl (updated ATPIII criteria), it also was associated with HH (p = 0.042). These results were confirmed in the logistic regression analysis where abdominal obesity and glucose >115 mg/dL constitute independent predictors for HH (OR = 3.2; CI: 1.23-13.2; p = 0.032, OR: 4.6; CI: 1.7-22.2; p = 0.016, respectively). The results of our study indicate that increased Hcy levels are related mostly with abdominal obesity and with insulin resistance. Thus, HH may raise atherothrombotic and thromboembolic risk in these patients.

Topics: Adult; Blood Glucose; Female; Homocysteine; Humans; Hyperhomocysteinemia; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity, Abdominal; Obesity, Morbid; Waist Circumference

In normal platelets, insulin inhibits agonist-induced Ca(2+) mobilization by raising cyclic AMP. Platelet from patients with type 2 diabetes are resistant to insulin and show increased Ca(2+) mobilization, aggregation and procoagulant activity. We searched for the cause of this insulin resistance.. Platelets, the megakaryocytic cell line CHRF-288-11 and primary megakaryocytes were incubated with adipokines and with plasma from individuals with a disturbed adipokine profile. Thrombin-induced Ca(2+) mobilization and signaling through the insulin receptor and insulin receptor substrate 1 were measured. Abnormalities induced by adipokines were compared with abnormalities found in platelets from patients with type 2 diabetes.. Resistin, leptin, plasminogen activator inhibitor-1 and retinol binding protein 4 left platelets unchanged but induced insulin resistance in CHRF-288-11 cells. Interleukin-6, tumor necrosis factor-α and visfatin had no effect. These results were confirmed in primary megakaryocytes. Contact with adipokines for 2 hours disturbed insulin receptor substrate 1 Ser(307)-phosphorylation, while contact for 72 hours caused insulin receptor substrate 1 degradation. Plasma with a disturbed adipokine profile also made CHRF-288-11 cells insulin-resistant. Platelets from patients with type 2 diabetes showed decreased insulin receptor substrate 1 expression.. Adipokines resistin, leptin, plasminogen activator-1 and retinol binding protein 4 disturb insulin receptor substrate 1 activity and expression in megakaryocytes. This might be a cause of the insulin resistance observed in platelets from patients with type 2 diabetes.

Topics: Adipokines; Blood Platelets; Calcium; Cell Line; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Leptin; Male; Megakaryocytes; Metabolic Syndrome; Plasminogen Activator Inhibitor 1; Resistin; Retinol-Binding Proteins, Plasma

It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction.

Topics: Animals; Blood Glucose; Diet, High-Fat; DNA, Mitochondrial; Eating; Female; Fetal Growth Retardation; Glucosephosphate Dehydrogenase; Glycogen; Insulin; Lactic Acid; Leptin; Male; Membrane Potentials; Metabolic Syndrome; Mitochondria; Mitochondrial Diseases; Muscle, Skeletal; Pregnancy; Proton-Translocating ATPases; RNA, Messenger; Swine; Triglycerides

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

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

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

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

Metabolic syndrome (MBS), a cluster of metabolic abnormalities and visceral fat accumulation, increases cardiovascular risks in postmenopausal women. In addition to visceral fat, perivascular adipose tissue has been recently found to play an important role in vascular pathophysiology. Hence, the present study investigates the effects of estrogen on both intra-abdominal fat (visceral fat) and periaortic fat (perivascular fat) accumulation as well as hypoxia in ovariectomized female rats. Female rats were divided into sham operation, ovariectomy and ovariectomy with 17β-estradiol supplementation groups. Twelve weeks later, we found that estrogen improved MBS via reducing body weight gain, the weight of periaortic and intra-abdominal fat, hepatic triglyceride, and total serum cholesterol levels. Estrogen also increased insulin sensitivity through restoring glucose and serum leptin levels. For periaortic fat, western blot showed estrogen inhibited hypoxia by reducing the levels of VEGF and HIF-1α, which is consistent with the results from immunohistochemical staining. The correlation analysis indicated that perivascular fat had a positive correlation with body weight, intra-abdominal fat or serum total cholesterol, but a negative correlation with insulin sensitivity index. For intra-abdominal fat, real-time fluorescent RT-PCR showed estrogen improved fat dysfunction via reducing the levels of relative leptin, MCP-1 but increasing adiponectin mRNA. Estrogen reduced the levels of VEGF and HIF-1α to inhibit hypoxia but restored the levels of PPARγ and Srebp-1c, which are important for lipid capacity function of intra-abdominal fat. These results demonstrated estrogen improved MBS through down-regulating VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.

Topics: Adiponectin; Animals; Blood Glucose; Body Weight; Chemokine CCL2; Cholesterol; Down-Regulation; Estrogens; Female; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Liver; Metabolic Syndrome; Organ Size; Ovariectomy; PPAR gamma; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Triglycerides; Uterus; Vascular Endothelial Growth Factor A

An unphysiologic accumulation of fat cells in many parts of the body including abdomen and joints results in increased production of pro-inflammatory cytokines which have adverse effects on serum lipids, glucose and on joint cartilage. The special extract of Cimicifuga racemosa CR BNO 1055 was shown to reduce the size of the abdominal fat depot. It was therefore tempting to test whether this extract, its saponin and its unpolar and polar fractions S- and R-fraction respectively (no quotation) also reduce fat depots and fat cell accumulation in a fat depot located in the lower hind leg (called paratibial fat depot = PFD), in joint fat pads (in the knee joint this is called Hoffa's fat pad) that occur in response to ovariectomy and whether this was accompanied by reduced serum lipids, glucose and improved cartilage features in the knee joint.. Rats (n = 10/group) were ovariectomized (ovx) and fed with CR BNO 1055, S- or R-fraction containing food (average intake 8.2, or 2.05 or 7.07 mg/day/animal) for 4 weeks. Ovx rats kept under no additive-containing food served as controls. The sizes of the PFD, of Hoffa's fat pad and of the cartilage thickness of the knee joints were determined by quantitative computer tomography and histomorphometrically. In the serum cholesterol, leptin and glucose levels were measured.. High load with fat tissue in the PFD and in the knee joints was present in the ovx rats. Treatment with CR BNO 1055 and its S-fraction reduced fat load of both, Hoffa's fat pad and of the PFD significantly and this resulted in reduced body weight which was significant under CR BNO 1055. Fat load in the PFD correlated significantly with the height of serum leptin and cholesterol. The fat load in the knee joint correlated inversely with the size of knee cartilage tissue.. High fat load of the body increases following ovx and this causes increased serum leptin, cholesterol and glucose levels. Following ovx the size of Hoffa's fat pad increases also significantly and this has adverse effects on knee cartilage tissue. Therefore, increased fat tissue in joints appears to belong to the Metabolic Syndrome. This effect can be largely prevented by CR BNO 1005 and its S- but not by its R-fraction. Hence, the saponins in CR BNO 1055 may be useful in preventing the Metabolic Syndrome and osteoarthritis.

Topics: Adipocytes; Animals; Body Weight; Cartilage, Articular; Cholesterol; Cimicifuga; Female; Hindlimb; Leptin; Metabolic Syndrome; Ovariectomy; Plant Extracts; Rats; Rats, Sprague-Dawley; Saponins; Triterpenes

The objective of the present study was to determine the suitability of a swine breed with leptin resistance and predisposition to obesity (the Iberian pig) as model for studies on metabolic syndrome and type 2 diabetes. Thus, six Iberian sows had ad libitum access to food enriched with saturated fat (SFAD group; food consumption was estimated to be 4.5 kg/animal/day) whilst four females acted as controls and were fed with 2 kg/animal/day of a commercial maintenance diet. After three months of differential feeding, SFAD animals developed central obesity, dyslipidemia, insulin resistance and impaired glucose tolerance, and elevated blood pressure; the five parameters associated with the metabolic syndrome. Thus, the current study characterizes the Iberian pig as a robust, amenable, and reliable translational model for studies on nutrition-associated diseases.

Topics: Animals; Diabetes Mellitus, Type 2; Dietary Fats; Disease Models, Animal; Female; Humans; Leptin; Metabolic Syndrome; Obesity; Species Specificity; Swine

Aim of this study was the investigation of feature of hormonal status in patients with metabolic syndrome (MetS). 111 reproductive age women were included in the study. According to diagnostic criteria for MetS of Society of Cardiology of the Russian Federation (2009) they were divided into two groups--study group (n=52) and control group (n=59). It was studied composition of body (fat mass, skeletal mass, lean mass, total, intracellular and extracellular fluid), parameter of lipid and carbohydrate metabolism, parameter of hormonal status. Study of hormonal status in reproductive age women with MetS showed a higher level of fasting and postprandial levels of insulin and C-peptide, hyperleptinemia and a reduced level of sex hormone-binding globulinn (SHBG). We suggest that serum leptin and SHBG levels may be used as an additional diagnostic criteria in these patients.

Topics: Adipose Tissue; Adolescent; Adult; Biomarkers; Blood Chemical Analysis; Body Composition; Body Mass Index; C-Peptide; Female; Gonadal Steroid Hormones; Health Status; Humans; Insulin; Leptin; Lipoproteins, HDL; Lipoproteins, LDL; Metabolic Syndrome; Middle Aged; Obesity; Reproduction; Risk Factors; Sex Hormone-Binding Globulin; Triglycerides; Waist-Hip Ratio

Rhodiola species are traditionally used as tonics and stimulants to treat asthenia, suggesting their possible regulatory effect on energy metabolism. Clinical trials have demonstrated their glucose-lowering effect in type 2 diabetes.. To examine the effects of Rhodiola on glucose and lipid metabolism in the metabolic syndrome and type 2 diabetes.. Zucker diabetic fatty (ZDF) rats were treated with Rhodiola crenulata root (RCR) powder (100 and 500 mg/kg, by gavage, once daily for 4 weeks). In addition, the effects of RCR on sucrose-induced acute hyperglycemia in mice and olive oil-induced hypertriglyceridemia in rats were also examined. Biochemical variables were determined enzymatically or by ELISA.. In ZDF rats, RCR treatment decreased the increased plasma insulin and triglyceride concentrations at baseline, the index of the homeostasis model assessment of insulin resistance (HOMA-IR) and excessive hepatic triglyceride accumulation. This treatment also inhibited abnormal increases in plasma glucose and insulin concentrations during oral glucose tolerance test. Furthermore, RCR reversed the increased adipose insulin resistance index, and accelerated the decline of plasma concentrations of non-esterified fatty acids after exogenous glucose stimulation. However, RCR minimally affected sucrose-induced acute hyperglycemia in mice and olive oil-induced acute hypertriglyceridemia in rats.. The present results demonstrate that RCR treatment improves metabolic derangements in animal model of the metabolic syndrome and type 2 diabetes. Our findings may provide new pharmacological basis of therapeutics for the adaptogenic plants to treat metabolic derangements-associated disorders, such as asthenia.

Topics: Animals; Blood Glucose; Cholesterol; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Hyperglycemia; Hypertriglyceridemia; Hypoglycemic Agents; Leptin; Lipid Metabolism; Liver; Male; Metabolic Syndrome; Mice; Phytotherapy; Plant Extracts; Plant Roots; Rats; Rats, Zucker; Rhodiola; Triglycerides

Our aim was to evaluate the relation of the sex hormone pattern and the serum level of the main adipokines with metabolic syndrome (MS) and its components in a cohort of pharmacologically untreated adult elderly subjects.. From the historical cohort of the Brisighella Heart Study we selected 199 adult healthy subjects aged 62.5 ± 12.4 years. Men and women included in the age class subgroups were matched for BMI, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. In these subjects we measured leptin, adiponectin, ghrelin, testosterone, estrone, and deydroepiandrosterone sulphate.. Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had a lower leptin level and leptin/adiponectin ratio than women with MS, but had significantly higher adiponectin, estrone, and deydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated with MS diagnosis (OR 3.36, 95% CI 1.40-8.08), while in women adiponectin alone appears to be a protective factor (OR 0.87, 95% CI 0.79-0.95).. In a sample of pharmacologically untreated adult elderly subjects, leptin/adiponectin ratio seems to be the factor that is more strongly associated with MS (especially in men) and its components, though this is true to a different degree in men and women.

Topics: Adiponectin; Aged; Biomarkers; Case-Control Studies; Cohort Studies; Dehydroepiandrosterone; Estrone; Female; Health Surveys; Humans; Italy; Leptin; Male; Metabolic Syndrome; Middle Aged; Sex Factors

Adipose tissue contributes to nonalcoholic fatty liver disease (NAFLD), being a source of fatty acids and cytokines such as leptin and adiponectin, and regulating ghrelin production. Their role in NAFLD pathogenesis remains controversial. We aimed to study the influence of those cytokines on the severity of NAFLD.. Morbidly obese individuals with biopsy-proven NAFLD were recruited. The NAFLD activity score was applied to liver histology. Serum concentrations of adiponectin, leptin, and ghrelin were determined.. Eighty-two patients were included, 13% with nonalcoholic steatohepatitis (NASH). Hypertriglyceridemia (P=0.018) and metabolic syndrome (P=0.040) were independent factors associated with NASH. Leptin associated positively and ghrelin associated negatively with BMI; adiponectin associated negatively with the waist to hip ratio. Adiponectin associated negatively with insulin resistance, hypertension, and metabolic syndrome; ghrelin associated positively with diabetes mellitus. Adiponectin below 23 ng/ml associated with NASH (odds ratio 12.95, P<0.001). Leptin increased progressively (P=0.032) and adiponectin decreased (P=0.004) with increasing severity of steatosis. Also, leptin increased progressively with more severe fibrosis (P=0.053). A formula incorporating the three cytokines yielded an AUROC of 0.789 (P=0.002), a sensitivity of 81.8%, and a specificity of 76.1% for NASH.. An imbalance in adiponectin, leptin, and ghrelin seems to be associated with more severe NAFLD. A formula combining the three cytokines showed good accuracy for NASH.

Topics: Adiponectin; Adult; Analysis of Variance; Bariatric Surgery; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Fatty Liver; Female; Ghrelin; Humans; Hypertriglyceridemia; Leptin; Male; Metabolic Syndrome; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity, Morbid; Prospective Studies; Regression Analysis; ROC Curve; Severity of Illness Index

To study the relationship between adipokines and metabolic syndrome (MS), and the predictive value of adipokines on diagnosis of MS.. According to the IDF consensus worldwide definition on MS in 2005, we divided the subjects into 4 groups: 115 in MS0 (with none of MS component); 118 in MS1 (with one MS component); 77 in MS2 (with two MS components) and 104 in MS3 (with none of MS component). Serum levels of leptin, visfatin adiponectin and resistin were measured in these groups, using the enzyme linked immunosorbent assay (ELISA) method. Retinol-binding protein 4 (RBP-4) was assessed by radioimmunoassay (RIA).. (1) Serum adiponectin level decreased while the serum level of leptin and RBP-4 increased in women with the number of MS components gathered. However, the level of visfatin obviously decreased only in the MS3 phase. The level of resistin showed no changes with MS components gathered. (2) Detection rates of the MS components such as high blood pressure, hyperglycemia, dyslipidemia, insulin resistance and obesity were significantly higher in the Q4 group with high level of leptin when compared to the Q1 group with lower level (odd ratio: Q4/Q1 is 1.3, 1.8, 1.6, 5.2, 3.0 respectively). (3) The higher level of serum RBP-4 was not only associated with greater risk for impaired glucose regulation (odd ratio: Q4/Q1=2.6), but also significantly with the risks for hyperglycemia (odd ratio: Q4/Q1=1.6) dyslipidemia (odd ratio: Q4/Q1=1.9), obesity (odd ratio: Q4/Q1=1.5) and MS (odd ratio: Q4/Q1=2.7). In the Q4 group with higher levels of RBP-4, the positive rates of MS reached 50%. (4) The detection rates of MS components such as dyslipidemia, obesity, hyperglycemia, and insulin resistance were significantly higher in the Q1 group with the lowest level of adiponectin when compared to the Q4 group with the highest level.. The levels of adipokines, serum adiponectin, leptin and RBP-4 showed significant associations with MS. Our findings suggested that these adipokines might serve as the key factors that participating in MS and could be used as markers for early prediction of MS as well as the new targets for therapy.

Topics: Adipokines; Adiponectin; Adult; Aged; Diabetes Mellitus; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Retinol-Binding Proteins, Plasma

The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On top of their diabetic cardiomyopathy, these patients experience frequent and severe cardiac ischemia-reperfusion (IR) insults, which further aggravate their degree of heart failure. Food restriction and angiotensin-converting enzyme inhibition (ACE-I) are standard therapies in these patients but the effects on cardiac IR injury have never been investigated. In this study, we tested the hypothesis that 1° food restriction and 2° ACE-I reduce infarct size and preserve cardiac contractility after IR injury in mouse models of diabetes and the metabolic syndrome.. C57Bl6/J wild type (WT) mice, leptin deficient ob/ob (model for type II diabetes) and double knock-out (LDLR-/-;ob/ob, further called DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome) were used. The effects of 12 weeks food restriction or ACE-I on infarct size and load-independent left ventricular contractility after 30 min regional cardiac ischemia were investigated. Differences between groups were analyzed for statistical significance by Student's t-test or factorial ANOVA followed by a Fisher's LSD post hoc test.. Infarct size was larger in ob/ob and DKO versus WT. Twelve weeks of ACE-I improved pre-ischemic left ventricular contractility in ob/ob and DKO. Twelve weeks of food restriction, with a weight reduction of 35-40%, or ACE-I did not reduce the effect of IR.. ACE-I and food restriction do not correct the increased sensitivity for cardiac IR-injury in mouse models of type II diabetes and the metabolic syndrome.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Caloric Restriction; Diabetes Mellitus, Type 2; Disease Models, Animal; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Receptors, LDL; Time Factors; Ventricular Function, Left; Ventricular Pressure

An experiment was conducted to study the protective effect of feeding extruded and unextruded blueberry pomace (BBP) on selected metabolic parameters associated with metabolic syndrome in a model of high fructose (HF)-fed growing Sprague-Dawley rats. Treatments were as follows: (1) control (modified AIN-based diet); (2) HF diet (AIN diet with 58% fructose); (3) HF diet with 1.5% unextruded BBP; (4) HF diet with 1.5% extruded BBP; (5) HF diet with 3% unextruded BBP; and (6) HF diet with 3% extruded BBP. Compared with the control, HF feeding increased fasting plasma insulin and fasting and postprandial plasma triglycerides as well as homeostatic scores of insulin resistance and β-cell function, but not weight gain, diet intake and efficiency, abdominal fat, oral glucose tolerance, and fasting and postprandial plasma glucose, cholesterol, and leptin levels. Inclusion of unextruded or extruded BBP was effective in minimizing or ameliorating the fructose-induced metabolic anomalies, except postprandial plasma triglycerides, especially at 3% of the diet. In addition, unextruded or extruded BBP at 3% of the diet was also able to reduce plasma cholesterol and abdominal fat relative to the HF control, which may impart additional health benefits. Compared with the control, inclusion of unextruded or extruded BBP at both 1.5% and 3% resulted in lower total fat weight, and animals fed a diet supplemented with 3% unextruded BBP in fasting state or 3% unextruded BBP in fed state had lower leptin levels than the control. This is the first study demonstrating the beneficial effects of feeding blueberry pomace on health.

Topics: Abdominal Fat; Adiposity; Animals; Antioxidants; Blueberry Plants; Dietary Supplements; Food-Processing Industry; Fructose; Fruit; Hypercholesterolemia; Hyperinsulinism; Industrial Waste; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Polyphenols; Random Allocation; Rats; Rats, Sprague-Dawley

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

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

Selenium (Se) is an essential trace element used for biosynthesis of selenoproteins and is acquired either through diet or cellular recycling mechanisms. Selenocysteine lyase (Scly) is the enzyme that supplies Se for selenoprotein biosynthesis via decomposition of the amino acid selenocysteine (Sec). Knockout (KO) of Scly in a mouse affected hepatic glucose and lipid homeostasis. Mice lacking Scly and raised on an Se-adequate diet exhibit hyperinsulinemia, hyperleptinemia, glucose intolerance, and hepatic steatosis, with increased hepatic oxidative stress, but maintain selenoprotein levels and circulating Se status. Insulin challenge of Scly KO mice results in attenuated Akt phosphorylation but does not decrease phosphorylation levels of AMP kinase alpha (AMPKα). Upon dietary Se restriction, Scly KO animals develop several characteristics of metabolic syndrome, such as obesity, fatty liver, and hypercholesterolemia, with aggravated hyperleptinemia, hyperinsulinemia, and glucose intolerance. Hepatic glutathione peroxidase 1 (GPx1) and selenoprotein S (SelS) production and circulating selenoprotein P (Sepp1) levels are significantly diminished. Scly disruption increases the levels of insulin-signaling inhibitor PTP1B. Our results suggest a dependence of glucose and lipid homeostasis on Scly activity. These findings connect Se and energy metabolism and demonstrate for the first time a unique physiological role of Scly in an animal model.

Topics: AMP-Activated Protein Kinases; Animals; Fatty Liver; Glucose Intolerance; Glutathione Peroxidase; Glutathione Peroxidase GPX1; Hypercholesterolemia; Hyperinsulinism; Leptin; Lyases; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Oxidative Stress; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Proto-Oncogene Proteins c-akt; Selenium; Selenoproteins

The alarming increase in obesity worldwide is of concern, owing to the associations of obesity with metabolic syndrome (MetS), which has been associated with a proinflammatory state characterized by elevated plasma concentrations of several markers of inflammation. The aim of this study was to assess levels of inflammatory markers and their association with MetS among adolescents.. A random sample of adolescents (n=362, 143 boys and 219 girls, 12-17 years) was interviewed, anthropometrically measured and provided a fasting blood sample. Circulating levels of adiponectin, leptin, tumour necrosis factor-alpha, plasminogen activator inhibitor 1 (PAI-1), interleukin-6 and high-sensitivity C-reactive protein were measured. The association between inflammatory markers and sex, age, body mass index (BMI) status, MetS, physical activity and blood pressure was also calculated.. Adiponectin levels are inversely associated and leptin levels are directly associated with MetS and BMI, but directly with gender (females show higher levels than boys), and PAI-1 levels are directly associated with MetS, among adolescents.. Leptin, adiponectin and PAI-1 may be used as biomarkers to predict MetS among adolescents.

Topics: Adiponectin; Adolescent; Biomarkers; Body Mass Index; C-Reactive Protein; Child; Cross-Sectional Studies; Down-Regulation; Female; Humans; Hypertension; Inflammation Mediators; Leptin; Male; Mediterranean Islands; Metabolic Syndrome; Overweight; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Prevalence; Spain; Up-Regulation

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

Previous studies have suggested that shiftwork can affect the prevalence of metabolic syndrome. This is thought to be related to disturbance of lipid parameters rather than their effects on glucose metabolism. Several complex mechanisms are suspected to be involved and notably insulin resistance, though the available data are limited. The objective of the present study was to provide further evidence for the effects of shiftwork on glucose and lipid metabolism with a specific focus on insulin resistance. A cross-sectional study has recruited 97 shiftworkers (SWs) (three shifts, 8 h) and 95 strictly day workers (DWs) from the same plant for 2001-2002. Several indices of insulin sensitivity or resistance were calculated, based on formulas of the homeostasis model assessment for insulin resistance (HOMA-IR), the Revised-Quicki, McAuley and Disse indices. The HOMA-β-cell index was used as a reflection of pancreatic secretion. Characteristics of the occupation, habitual diet and lifestyles were recorded. Logistic regression analysis in which pancreatic function or insulin sensitivity was the dependent variable was used to compare alternative models.. SWs were characterized as having significantly higher triglycerides and free fatty acids and normal but lower blood glucose. The risk of a high β-cell activity was increased almost three-fold in SWs. By adjusting for many confounding factors, SWs had significantly lower insulin sensitivity according to several indices, whereas HOMA-IR was not meaningfully different between shift and DWs. Lower insulin sensitivity and a compensatory pancreas response to maintain a normal glucose tolerance may suggest an intermediate state before development of frank insulin resistance in SWs. Early detection of these moderate alterations of the insulin/glucose balance could be important in the prevention of diabetes.

Topics: Adiponectin; Adult; Blood Glucose; Cross-Sectional Studies; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Leptin; Male; Metabolic Syndrome; Middle Aged; Risk Factors; Work Schedule Tolerance

The present study documents the increases in systolic arterial blood pressure, plasma leptin concentration and kidney proliferating cell nuclear antigen index, as well as the decreases in glutathione reductase, superoxide dismutase and catalase enzymatic activities in the liver, heart, kidney, soleus muscle and visceral adipose tissue homogenates of female rats exposed for 8 weeks to a diet containing 64% (w/w) D-fructose instead of 64% starch. In the fructose-fed rats, the partial substitution of sunflower oil by either safflower oil or salmon oil often opposed the fructose-induced changes in these variables. The present results, thus, extend to these functional, hormonal and enzymatic parameters the knowledge that the dietary supply of long-chain polyunsaturated ω6 fatty acids, mainly C18:2ω6, and long-chain polyunsaturated ω3 fatty acids opposes the undesirable features of the fructose-induced metabolic syndrome, with salmon oil demonstrating particular efficacy.

Topics: Adipose Tissue; Animals; Blood Pressure; Catalase; Dietary Supplements; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Fish Oils; Fructose; Glutathione Reductase; Heart; Kidney; Leptin; Liver; Metabolic Syndrome; Muscle, Skeletal; Myocardium; Plant Oils; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Safflower Oil; Sunflower Oil; Superoxide Dismutase

To analyze the relationship between leptin and obesity expressed as body mass index (BMI) and certain components of the metabolic syndrome (MS) in an adult population.. The study included 103 subjects, 42 men and 61 women, aged over 30 years, clinically defined as non-diabetic but with personal or family history of cardiovascular disease. All subjects underwent fasting blood measurements of leptin, insulin, glucose, glucose after ingestion of 75g glucose, HDL cholesterol and triglycerides, and insulin resistance (IR) and BMI were calculated.. BMI as an index of overall adiposity was strongly associated with serum leptin. BMI rose as serum leptin levels increased from the first to the third tertile; the correlation between leptin and BMI was strong, r=0.524 in men and r=0.603 in women, with high statistical significance (p<0.001); BMI was the best predictor of hyperleptinemia on ROC analysis, with area under the curve (AUC)=0.81 in men and 0.84 in women. The association between leptin and obesity (BMI ≥30kg/m(2)) showed high odds ratios (OR) in both sexes (10.11 in men, 6.00 in women) on univariate regression analysis and 9.30 in men and 8.21 in women on multivariate regression analysis. Hyperinsulinemia and IR strongly influenced hyperleptinemia. Leptin was the best predictor of IR in both sexes (AUC=0.89 in men and 0.85 in women), and IR in men (AUC=0.79) and hyperinsulinemia in women (AUC=0.78) were the best predictors of hyperleptinemia after BMI. The correlations between leptin and IR, and leptin and insulinemia, were strong in both sexes. With regard to MS components, increased serum levels of the study variables were observed as leptin concentrations rose from the first to the third tertile (with the exception of HDL cholesterol, which decreased).. Elevated serum leptin, particularly in obese individuals, should be taken as a warning sign of energy imbalance, poor diet, hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are strongly associated with cardiovascular disease and type 2 diabetes.

Topics: Adult; Body Mass Index; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged

Chronic partial sleep loss is associated with obesity and metabolic syndrome in humans. We used rats with lesions in the ventrolateral preoptic area (VLPO), which spontaneously sleep about 30% less than intact rats, as an animal model to study the consequences of chronic partial sleep loss on energy metabolism.. Adult male Sprague-Dawley rats (300-365 g).. We ablated the VLPO in rats using orexin-B-saporin and instrumented them with electrodes for sleep recordings. We monitored their food intake and body weight for the next 60 days and assessed their sleep-wake by 24-h EEG/EMG recordings on day 20 and day 50 post-surgery. On day 60, after blood samples were collected for metabolic profiling, the animals were euthanized and the brains were harvested for histological confirmation of the lesion site.. VLPO-lesioned animals slept up to 40% less than sham-lesioned rats. However, they showed slower weight gain than sham-lesioned controls, despite having normal food intake. An increase in plasma ghrelin and a decrease in leptin levels were observed, whereas plasma insulin levels remained unaffected. As expected from leaner animals, plasma levels of glucose, cholesterol, triglycerides, and C-reactive protein were reduced in VLPO-lesioned animals.. Chronic partial sleep loss did not lead to obesity or metabolic syndrome in rats. This finding raises the question whether adverse metabolic outcomes associated with chronic partial sleep loss in humans may be due to factors other than short sleep, such as circadian disruption, inactivity, or diet during the additional waking hours.

Topics: Animals; Blood Glucose; Body Weight; C-Reactive Protein; Energy Metabolism; Ghrelin; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Obesity; Rats; Sleep Deprivation; Weight Gain

Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.

Topics: Animals; Antibodies, Antinuclear; Biomarkers; Body Weight; Cytokines; Disease Models, Animal; Feeding Behavior; Female; Gene Expression Regulation; Humans; Insulin; Intra-Abdominal Fat; Leptin; Liver; Lupus Erythematosus, Systemic; Metabolic Syndrome; Mice; Proteinuria; TOR Serine-Threonine Kinases; Triglycerides

The objective of this study was to assess the association of serum leptin levels with insulin resistance (IR), metabolic syndrome (MetS), lipid levels, and glucose control in an Iranian type 2 diabetic population.. In this cross-sectional analysis, 132 type 2 diabetic patients (79 women) and 71 healthy non-diabetic and non-hypertensive individuals (40 women; as control subjects) were included. Homeostasis model assessment (HOMA) of insulin values ≥ 1.8 for females and 1.7 for males was regarded as the cut-point of IR. MetS was defined according to updated 2005 NCEP ATP III criteria. The leptin correlated with HOMA-IR values without adjustment (r = 0.24; p < 0.005) and with adjustment for sex and diabetes (r = 0.44; p < 0.005). Sex had significant effect on the BMI adjusted association of HOMA-IR (quintiles) and leptin (df = 4 F(12.7) = 3.5; p = 0.011). In diabetic women (but not men), leptin levels were different between those with and without IR (27.3 ± 1.9 vs. 18.2 ± 3.3; p < 0.05). BMI adjusted leptin values were different between subjects with and without MetS (22.2 ± 1.7 vs.14.8 ± 1.2; p < 0.001). No association was noticed between BMI-adjusted leptin with glycated hemoglobin or blood lipid levels.. In this study, plasma leptin concentration correlated with IR independent of the effect of obesity in female but not male diabetic subjects.

Topics: Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol, HDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Resistance; Iran; Leptin; Lipids; Male; Metabolic Syndrome; Obesity; Sex Factors; Triglycerides; Waist Circumference

Hyperprolactinemia might be related to weight gain, metabolic syndrome (MS), and insulin resistance (IR). Treatment with dopamine agonist (DA) has been shown to reduce body weight and improve metabolic parameters. The objectives of this study were to determine the prevalence of obesity, overweight, MS, and IR in patients with prolactinoma before and after therapy with DA and to evaluate the relation between prolactin (PRL), body weight, fat distribution, leptin levels, IR, and lipid profile before treatment. In addition, we investigated the correlation of the reduction in PRL levels with weight loss and metabolic profile improvement. Twenty-two patients with prolactinoma completed 6 months of treatment with DA. These patients were submitted to clinical (BMI, waist circumference, blood pressure (BP)), laboratory evaluation (leptin, glucose, low-density lipoprotein (LDL)-cholesterol, and triglyceride (TG) levels) and abdominal computed tomography (CT) before and after treatment. The statistical analyses were done by nonparametric tests. At the beginning of the study, the prevalence of obesity, overweight, MS, and IR was 45, 27, 27, and 18%, respectively. After 6 months of treatment with DA, PRL levels normalized, but no significant difference in BMI was observed. However, there was a significant decrease on homeostasis model assessment of insulin resistance (HOMA(IR)) index, glucose, LDL-cholesterol, and TG levels. This study suggests a possible involvement of prolactinoma on the prevalence of obesity. We should consider that DA may be effective on improving metabolic parameters, and we speculate that a period longer than 6 months of treatment is necessary to conclude whether this drug can interfere in the body weight of patients with prolactinoma.

Topics: Adult; Aftercare; Aged; Blood Glucose; Body Composition; Body Mass Index; Body Weight; Bromocriptine; Cabergoline; Cholesterol, HDL; Cholesterol, LDL; Dopamine Agonists; Ergolines; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Metabolome; Middle Aged; Obesity; Prevalence; Prolactinoma; Waist Circumference; Weight Gain; Young Adult

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

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

The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.

Topics: Abdominal Fat; Animals; Body Weight; Diabetes Mellitus, Experimental; Dietary Carbohydrates; Dietary Fats; Energy Intake; Fructose; Glucose Intolerance; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Liver; Male; Metabolic Syndrome; Obesity; Random Allocation; Rats; Rats, Wistar; Ventricular Remodeling

We examined the relationship between serum levels of leptin-binding protein (soluble leptin receptor [sOB-R]) and leptin with metabolic parameters at baseline and prospectively at 2-year follow-up in young healthy men. A total of 916 eighteen-year-old men were examined at baseline, with a subgroup of 91 participants examined again 2 years later. Anthropometric and metabolic measurements were performed at baseline and at follow-up. In the cross-sectional study, levels of sOB-R were significantly inversely correlated with all baseline measures of obesity and metabolic risk factors (blood pressure, total and low-density lipoprotein cholesterol, and fasting glucose), and significantly positively correlated with high-density lipoprotein cholesterol. After correcting for age, smoking status, and waist-to-hip ratio, the inverse correlation remained statistically significant for all measures of adiposity, fasting glucose, and the metabolic syndrome score. Correlations for leptin were similar in magnitude but opposite in direction to correlations for sOB-R. In prospective analyses, baseline levels of sOB-R were predictive at 2-year follow-up of fasting glucose, the metabolic syndrome score, and measures of adiposity in both unadjusted and adjusted models. Similarly, leptin was predictive of fasting glucose, the metabolic syndrome score, adiposity, and systolic blood pressure. We confirm correlations of leptin and sOB-R levels with measures of adiposity and metabolic risk factors at baseline, and demonstrate for the first time prospectively the role of sOB-R as an independent, although weak, predictor of metabolic syndrome and fasting glucose in young men.

Topics: Adiposity; Adolescent; Blood Glucose; Blood Pressure; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Humans; Leptin; Male; Metabolic Syndrome; Obesity; Prospective Studies; Receptors, Leptin; Risk Factors; Smoking; Waist-Hip Ratio; Young Adult

Insulin resistance (IR) plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS), but identification of insulin-resistant individuals is difficult. The homeostasis model assessment (HOMA), a surrogate marker of IR, is available in 2 computational models: HOMA1-IR (formula) and HOMA2-IR (computer program), which differ in incorporated physiological assumptions. This study evaluates the associations of the 2 models as markers of IR, the metabolic syndrome (MS), and PCOS.. Anthropometric, hormonal, and biochemical parameters were measured in 92 PCOS women and 110 controls. HOMA1 and HOMA2 were used to assess IR. Regression analyses were used to find the associations of the 2 models with different variables, MS, and PCOS.. The cutoff levels for definition of IR were HOMA1-IR ≥2.9 and HOMA2-IR ≥1.7. Mean HOMA1-IR (2.79) and HOMA2-IR (1.42) differed substantially. The difference (HOMA1-IR - HOMA2-IR) was significantly correlated with insulin, fasting plasma glucose, triglycerides, HDL cholesterol, waist circumference, leptin, and adiponectin (all P < 0.05). HOMA1-IR and HOMA2-IR were significantly associated with MS (odds ratio 5.7 and 4.2, respectively) and PCOS (odds ratio 3.7 and 3.5, respectively).. HOMA computational methods significantly affect the associations and cutoff values used for definition of IR. The correlations of the difference in the computational methods corroborate differences in captured physiological mechanisms. As precise identification of IR in PCOS patients is of practical importance, practitioners and researchers should be aware of these differences in the HOMA computational methods.

Topics: Adiponectin; Adolescent; Adult; Blood Glucose; Body Weights and Measures; Cholesterol, HDL; Computer Simulation; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Models, Biological; Polycystic Ovary Syndrome; Risk Assessment; Triglycerides; Young Adult

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

In an earlier study, we found a similar frequency of individuals with an abnormal correlation between serum leptin levels and body mass index (BMI) (outliers above or below the 95% confidence interval in the regression line) during treatment with antipsychotic drugs (n=301), other psychotropic drugs (n=65), and drug-free individuals (n=229). In this secondary analysis, we compare the frequency of the metabolic syndrome (International Diabetes Federation), its constituting variables, obesity, (BMI>30 kg/m), leptin and insulin serum levels, and an insulin-resistance index (homeostatic model assessment-insulin resistance) in outliers, nonoutliers distributed in their original treatment groups, and all the nonoutliers controlled by age, sex, and BMI. We identified 28 outliers, 24 above and four below the 95% confidence interval limits. Nine individuals were under antipsychotic treatment, four under other drug treatment, and 15 were drug-free. The outliers had a significantly higher frequency of metabolic syndrome and obesity, and higher values of waist circumference, triglycerides, insulin, and blood diastolic pressure. The outliers in the correlation between leptin and BMI may represent a population at high risk of metabolic dysfunction, irrespective of the specific psychotropic drug treatment administered.

Topics: Antipsychotic Agents; Blood Glucose; Body Composition; Body Mass Index; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Psychotic Disorders; Triglycerides; Waist Circumference

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

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

"At-risk" severely obese subjects are characterized by insulin resistance, and higher visceral fat and plasma lipid levels compared with metabolically healthy obese (MHO) subjects, although both groups have a high BMI and fat mass. The aim of this study was to measure several serum adipokines and gastrointestinal hormones in a young severely obese population from Southern Italy to identify biochemical markers of the "at-risk" insulin-resistant obese profile. We studied 160 unrelated white young adults (mean age = 25.2 years, mean BMI = 44.9 kg/m(2), 65% women) affected by obesity for at least 5 years. Serum concentrations of glucagon, ghrelin, gastric inhibitory peptide, glucagon like peptide-1, interleukin-6, tumor necrosis factor α, leptin, adiponectin, adipsin, and visfatin were measured. The leptin/adiponectin (L/A) ratio and fatty liver index (FLI) were calculated. We found a prevalence of 21.3% of MHO patients in our young severely obese patients. At univariate analysis, the "at-risk" group had higher mean levels of BMI (P < 0.0001), leptin (P = 0.039, men) and the L/A ratio (P = 0.003), and lower mean levels of visfatin (P = 0.026) than the MHO group. The L/A ratio, serum triglycerides, and male sex were significantly associated with "at-risk" obesity and accounted for 19.5% of insulin resistance at multivariate analysis. In conclusion, we demonstrate that a high serum L/A ratio and high levels of serum triglycerides may be markers of "at-risk" obesity, independent of waist circumference (WC) and BMI, in young severely obese population.

Topics: Adiponectin; Adult; Algorithms; Biomarkers; Cross-Sectional Studies; Cytokines; Fatty Liver; Female; Hospitals, University; Humans; Hypertriglyceridemia; Insulin Resistance; Italy; Leptin; Male; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Obesity, Morbid; Outpatient Clinics, Hospital; Prevalence; Risk Factors; Sex Factors; Young Adult

The mechanism of obesity leading to endothelial function is complex, and involves many adipokines and inflammatory cytokines. The data is especially lacking in obese patients without metabolic syndrome. We assessed the relationship among endothelial dysfunction, anthropometric indices, adipokines and inflammatory cytokines in this population.. Obese patients without metabolic syndrome were included in this study. The plasma resistin, leptin, retinol-binding-protein 4 and inflammatory cytokines were examined. Endothelial function was assessed by a fingertip peripheral arterial tonometry (PAT) device. Data are expressed as the natural logarithm (ln) of the PAT ratio. Endothelial dysfunction was defined by a ln (PAT ratio) <0.30.. A total of 35 patients were enrolled, 11 of whom were with endothelial dysfunction. There was a significant difference of ln leptin (p=0.007), ln [leptin/visceral fat thickness] (p=0.004) and ln [leptin/subcutaneous fat thickness] (p<0.001) between patients with and without endothelial dysfunction. Multivariate linear regression analyses showed that ln [leptin/subcutaneous fat thickness] was significantly related to the ln (PAT ratio) (p=0.002). Using ln [leptin/subcutaneous fat thickness] to detect endothelial dysfunction, the area of receiver operating characteristic curves was 0.843 (p=0.002). Using 6.10 as a cutoff point, the sensitivity and specificity to determine endothelial dysfunction were 91% and 78%, respectively.. Abnormal digital vascular function occurs in obese patients without metabolic syndrome. Low plasma leptin/subcutaneous fat ratio is associated with endothelial dysfunction in this population.

Topics: Adipose Tissue; Adult; Age Factors; Arteries; Body Mass Index; Cytokines; Endothelium, Vascular; Female; Humans; Inflammation; Leptin; Male; Manometry; Metabolic Syndrome; Obesity; Pilot Projects; Sex Factors

Obesity is associated with increased cardiovascular morbidity and mortality. We hypothesized that microvascular function may be impaired in obese subjects with metabolic syndrome (OB-MetSnd) compared to obese subjects without MetSnd (OB) and healthy subjects (HS). In this cross-sectional study, we evaluated skin capillary density (SCD) in OB-MetSnd (n=20, 12 women, BMI=36.5±1.1kg/m(2)), OB (n=25, 16 women, BMI=34.5±0.7kg/m(2)), and HS (n=30, 22 women, BMI=22.8±0.3kg/m(2)) groups. SCD was evaluated by intravital video-microscopy at rest and after post-occlusive reactive hyperemia (PORH) and venous congestion (VC). OB-MetSnd subjects exhibited significant differences in the values of MetSnd components and in leptin and HOMA-IR levels compared to OB and HS individuals. There were no differences in SCD among groups in resting conditions. The OB-MetSnd group failed to show a significant increase in the number of recruited capillaries during PORH and VC compared to the SCD evaluated at rest. A negative correlation of SCD with waist circumference, BMI, blood pressure, and HOMA-IR was observed after PORH and VC. When obese subjects were analyzed according to their HOMA-IR quartiles, a significant decrease in SCD was observed during POHR (P=0.02). Our findings showed that obese subjects have structural and functional alterations in skin microcirculation that are proportional to the increase in the degree of global and central obesity. In addition, in OB-MetSnd subjects, the cutaneous capillaries at rest are already maximally recruited, indicating an absence of functional capillary reserve. This may be related to the insulin resistance observed in OB-MetSnd individuals.

Topics: Adult; Blood Pressure; Body Mass Index; Capillaries; Female; Humans; Hyperemia; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Microcirculation; Microscopic Angioscopy; Obesity; Skin; Waist Circumference

Metabolic syndrome (MetS) and its components accelerate age-associated increases in arterial stiffness and thickness. We investigated whether specific proinflammatory cytokines contribute to arterial aging, independent of age, sex, MetS, and other traditional CV risk factors.. MetS components (ATP III criteria) and arterial properties were assessed in 6148 subjects, aged 14-102 in Sardinia, Italy. Common carotid artery (CCA) diameter, intima-media thickness (IMT), and aortic pulse wave velocity (PWV), adiponectin, leptin, high-sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein 1 (MCP1), and interleukin 6 (IL6) were measured.. While cytokine levels - except for MCP1 - were significantly higher (lower for adiponectin) in MetS than in control subjects, and the increased PWV and CCA IMT with aging were associated with MetS, this association was independent of cytokine levels (p<0.001 for both PWV and CCA IMT). Specific cytokines, however, were significantly associated with arterial stiffness (higher leptin, p<0.001, and higher hsCRP, p<0.001) or thickness (lower adiponectin, p<0.05, and higher IL6, p<0.001) - independent of age, sex, MetS and other traditional CV risk factors. The co-occurrence of both MetS and higher cytokines levels was associated with greater increases in arterial stiffness and thickness.. While MetS and specific cytokine patterns associated with arterial aging, the increases in arterial stiffness and thickness are greater when both MetS and higher cytokine levels are present, suggesting a possible synergistic effect of MetS and inflammation on the arterial wall.

Topics: Adiponectin; Adolescent; Adult; Aged; Aged, 80 and over; Aging; Arteries; Blood Flow Velocity; C-Reactive Protein; Carotid Artery, Common; Chemokine CCL2; Cytokines; Female; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Pulsatile Flow; Tunica Intima; Tunica Media; Vascular Resistance

The adipocyte/macrophage fatty acid-binding protein 4 (FABP4) has been described as a biomarker for adiposity and metabolic syndrome (MS). The aims of this study were to assess the relationship between FABP4 and inflammatory cytokines related to obesity, and to evaluate FABP4 mRNA expression in visceral and subcutaneous adipose tissue in non-diabetic morbidly obese women versus healthy lean women.. We analyzed circulating levels of FABP4 in 81 Spanish women: 38 lean (body mass index (BMI)<25 kg/m(2)) and 43 morbidly obese (BMI>40 kg/m(2)). We took 30 follow-up blood samples at 6 and 12 months after bariatric surgery. We assessed FABP4 gene expression in samples of subcutaneous abdominal and visceral adipose tissue. Adipose tissue mRNA expression was determined by real-time RT-PCR.. In morbidly obese women, plasma FABP4 levels were significantly higher than in non-obese patients. These levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin levels. Post-operative FABP4 levels decreased by a maximum of 30% after 12 months. We also found an inverse association between FABP4 and adiponectin levels, and positive correlations between FABP4 and circulating leptin, tumor necrosis factor (TNF) receptors, C-reactive protein (CRP) and interleukin 6 levels. Linear regression analysis revealed that FABP4 was more closely related to HOMA2-IR than adiponectin, CRP, TNF-RI, or leptin. Furthermore, high circulating FABP4 levels were associated with the presence of MS. FABP4 mRNA expression in visceral adipose tissue was related to its circulating levels in morbidly obese women.. Our results indicate that serum FABP4 is associated with inflammatory factors related to obesity and MS in non-diabetic morbidly obese women.

Topics: Adiponectin; Adult; C-Reactive Protein; Cytokines; Enzyme-Linked Immunosorbent Assay; Fatty Acid-Binding Proteins; Female; Humans; In Vitro Techniques; Inflammation; Leptin; Metabolic Syndrome; Obesity, Morbid; Receptors, Tumor Necrosis Factor, Type I

Maternal malnutrition during lactation programmes for overweight and central leptin resistance in adulthood. The inhibition of lactation by maternal treatment with bromocriptine (a prolactin inhibitor) programmes for obesity, hyperleptinaemia and leptin resistance. Here, we evaluated the short- and long-term effects of early weaning (EW) on body-weight regulation, leptin signalling, and hormone and lipid profiles in rats offspring. Lactating rats were separated into two groups: EW--dams were wrapped with a bandage to interrupt the lactation in the last 3 d of lactation; control--dams whose pups had free access to milk during all lactation (21 d). Data were significant at P < 0·05. At weaning, EW pups presented lower body weight (-10%), length (-4%), visceral fat (-40%), total fat (-30%), serum leptin (-73%), glycaemia (-10%), serum insulin (-20%) and insulin resistance index (IRI; -30 %), but higher total body protein content (+40%). At 180 d, EW offspring showed hyperphagia, higher length (+3%), body weight (+8%), visceral and total fat (+36 and 84%), serum TAG (+96%), glycaemia (+15%), leptinaemia (+185%) and IRI (+29%); however, they showed lower total protein content (-23%), leptin:body fat ratio (41%), prolactinaemia (-38%) and adiponectinaemia (-59%). Despite unchanged leptin receptor (OB-R) and signal transducer and activator of transcription 3 (STAT3), they displayed lower hypothalamic janus tyrosine kinase 2, phosphorylated STAT3 and a higher suppressor of cytokine signalling 3 levels, suggesting a central leptin resistance. Adult rats that were early weaned displayed higher adiposity, insulin resistance and dyslipidaemia, which are related to metabolic syndrome development. Our model reinforces the idea that neonatal malnutrition caused by shortening of the lactation period is important for metabolic programming of future diseases.

Topics: Aging; Animals; Blood Glucose; Body Composition; Body Size; Body Weight; Eating; Female; Genes, Homeobox; Hypothalamus; Lactation; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Rats; Signal Transduction; Time Factors; Weaning

The aim of this study was to investigate the associations of adiponectin and leptin with metabolic syndrome (MetS) and coronary heart disease (CHD) in patients with various coronary risk factors. We determined serum adiponectin, leptin, and metabolic syndrome components in 104 patients (59 men and 45 women; aged 40-86 years) with various coronary risk factors at a cardiovascular out-patient clinic. Natural logarithmic transformed (ln) leptin was lower in men and smokers, and positively correlated with body mass index (BMI) (r = 0.59, P < 0.0001), waist circumference (r = 0.60, P < 0.0001), and homeostasis model assessment of insulin resistance (HOMA-IR) levels (r = 0.24, P < 0.02). Ln adiponectin was higher in women and nonsmokers, and was correlated with age and high-density lipoprotein cholesterol (HDL-C). Patients with MetS (n = 69) had significantly higher BMI, HOMA-IR, and ln leptin and lower ln adiponectin than those without Mets (Ln leptin, 2.14 ± 0.08 versus 1.30 ± 0.11; Ln adiponectin, 2.29 ± 0.06 versus 2.54 ± 0.09). In contrast, patients with coronary heart disease (CHD: n = 40) had significantly lower serum ln adiponectin concentrations than non-CHD patients (n = 64) (1.79 ± 0.12 versus 1.91 ± 0.10) as well as lower HDL-C and a higher smoking percentage. Consistent results were obtained by multivariate analyses. In conclusion, this study disclosed factors associated with the increase in serum leptin and adiponectin. Serum levels of leptin may be associated positively with MetS, whereas adiponectin levels are associated negatively with MetS and CHD, even in patients with various coronary risk factors.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Algorithms; Analysis of Variance; Biomarkers; Body Mass Index; Coronary Disease; Female; Humans; Leptin; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Outpatients; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Waist Circumference

Little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and metabolic syndrome (MetS) in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on the relations.. Plasma HMW-adiponectin, leptin and sOB-R were measured among 1055 Chinese men and women (35∼54 yrs). Whole body and trunk fat mass were determined by Dual-energy X-ray absorptiometry. MetS was defined by the updated NCEP/ATPIII criterion for Asian-Americans.. HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR in the highest quartile= 0.30, 95%CI 0.18∼0.50, P<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR for the highest quartile = 0.78, 95%CI 0.47∼1.32, P = 0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR for the highest quartile= 2.64, 95%CI 1.35∼5.18, P = 0.006), although further adjustment for FMI abolished this association.. HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively.

Topics: Adiponectin; Adipose Tissue; Adult; Asian People; Biomarkers; Body Fat Distribution; Body Mass Index; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Molecular Weight; Receptors, Leptin; Risk Factors; Solubility

Nonalcoholic fatty liver disease (NAFLD) is a predominantly adult-diagnosed disorder. Knowledge regarding the epidemiology, phenotype, and metabolic risk factors, during adolescence is limited. We sought to determine the prevalence, phenotype, and predictors of NAFLD in 1170 community-based adolescents in the Western Australian Pregnancy Cohort (Raine) Study (the Raine Cohort) who underwent a cross-sectional assessment that included questionnaires, anthropometry, cardiovascular examinations, blood tests, and abdominal ultrasound examinations. Among the 1170 adolescents assessed, the prevalence of NAFLD was 12.8%. Females compared with males had a significantly higher prevalence of NAFLD (16.3% versus 10.1%, P = 0.004) and central obesity (33.2% versus 9.9%, P < 0.05). The severity of hepatic steatosis was associated with the body mass index, waist circumference, subcutaneous adipose tissue thickness (SAT), serum leptin level, homeostasis model assessment for insulin resistance score (P < 0.001 for all), and serum alanine aminotransferase level (P < 0.005) in both genders, but it was associated with increasing visceral adipose tissue thickness (VAT; P < 0.001) and decreasing serum adiponectin levels (P < 0.05) in males alone. Males and females with NAFLD had similar amounts of SAT (P > 0.05); however, in comparison with females with NAFLD, males with NAFLD had greater VAT, a more severe metabolic phenotype with higher glucose levels and systolic blood pressure and lower adiponectin and high-density lipoprotein cholesterol levels (P < 0.001 for all), and greater measures of liver injury (alanine aminotransferase and aspartate aminotransferase, P < 0.001 for all). Similarly, metabolic syndrome was more common in males than females with NAFLD (24% versus 8%, P = 0.01). Suprailiac skinfold thickness predicted NAFLD independently of the body mass index, insulin resistance, and VAT.. Gender differences in adolescent NAFLD are related to differences in adipose distribution and adipocytokines. The male phenotype of NAFLD is associated with more adverse metabolic features and greater visceral adiposity than the female phenotype despite the lower prevalence of NAFLD.

Topics: Adipokines; Adiponectin; Adolescent; Body Mass Index; Cohort Studies; Fatty Liver; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Prevalence; Sex Characteristics; Subcutaneous Fat; Waist Circumference; Western Australia

Leptin is strongly contributed to the clustering of metabolic syndrome (MetS) components and potentially can be regarded as a single predictor of MetS. This population-based study, for the first time, reports the diagnostic accuracy of different leptin cut-points for determining MetS. Further, the current study compares the predictive ability of the appropriate threshold of leptin with insulin resistance. Data of the individuals without history of known diabetes mellitus, aged 25-64 years, from the third national surveillance of risk factors of non-communicable diseases (SuRFNCD-2007) were analyzed. MetS was defined due to either adult treatment panel III (ATPIII) or the modified international diabetes federation (IDF) criteria. Receiver-operating characteristic (ROC) curves were depicted to define cut-off of serum leptin, using the maximum Youden index and the shortest distance methods. Further, the values of leptin cut-offs in prediction of MetS were compared with those of insulin resistance (defined as homeostasis model assessment of insulin resistance >1.775). In men, the optimal cut-offs of leptin for IDF- and ATPIII-defined MetS were 3.6 ng/ml (positive predictive value, PPV: 56.5%; negative predictive value, NPV: 72.7%) and 4.1 ng/ml (PPV: 49.6%; NPV: 78.1%), respectively. In women, the optimal threshold was equal to 11.0 ng/ml (PPV: 53.8%; NPV: 73.0% for IDF criteria and PPV: 60.1%; NPV: 64.9% for ATPIII criteria). The diagnostic accuracy of these values in identifying MetS was similar to that of insulin resistance. Therefore, leptin is comparable to insulin resistance in identifying MetS and can be used as single predictor of MetS.

Topics: Adult; Biomarkers; Female; Humans; Insulin Resistance; Iran; Leptin; Male; Metabolic Syndrome; Middle Aged; Population Surveillance; Predictive Value of Tests; Risk Factors; ROC Curve

The aim of this prospective study was too asses the frequency and clinical significance of metabolic syndrome (MS), insulin resistance (IR) and hepatic steatosis in 114 patients with chronic hepatitis C (HCV) genotype 1. MS was found in 47% and IR in 50% of the cases. Diagnosis of IR in patients without MC and marked fibrosis supported the role of HCV in the development of metabolic abnormalities. Hepatic steatosis was found in 38% of the patients and the degree of steatosis significantly correlated with that of fibrosis. Obesity, IR, steatosis and liver cirrhosis were independent negative predictors of the response to the treatment with peginterferon alpha and ribavirin.

Topics: Adult; Antiviral Agents; Fatty Liver; Female; Genome, Viral; Hepacivirus; Hepatitis C, Chronic; Hepatocytes; Humans; Insulin Resistance; Interferon alpha-2; Interferon-alpha; Leptin; Liver Cirrhosis; Male; Metabolic Syndrome; Middle Aged; Polyethylene Glycols; Prospective Studies; Recombinant Proteins; Ribavirin; Severity of Illness Index; Treatment Outcome

Several in vitro studies have suggested the effects of adipokines and insulin resistance on breast cancer cell proliferation and survival. However, little is known about the clinical significance of these findings.. We examined associations between breast cancer recurrence and adiponectin, leptin, insulin resistance, and metabolic syndrome (MetS) in a cohort of 747 patients from 2001 to 2004.. Adjusted hazard ratios showed an inverse trend across the quartiles for serum adiponectin concentration in estrogen receptor (ER)/progesterone receptor (PR) -negative patients (P for trend = 0.027) but not in ER/PR-positive patients. Compared to the highest quartile for adiponectin level, the lowest quartile showed a hazard ratio of 2.82 (1.03 to 7.68). Homeostasis model assessment for insulin resistance (HOMA-IR) showed a positive trend for recurrence in the ER/PR-negative group (P for trend = 0.087) and a negative trend in the ER/PR-positive group (P for trend = 0.081). Leptin did not show any associations (P for trend >0.05). A linear trend was observed with the number of components of MetS in ER/PR-negative patients (P for trend = 0.044). This association disappeared when adjusted for adiponectin and HOMA-IR.. Adiponectin and HOMA-IR have prognostic significance in breast cancer recurrence and interventions related to these factors may protect against recurrence in ER/PR-negative patients. These findings were not observed in the case of ER/PR-positive patients. Further evaluation of these insignificant associations is needed because it might be biased by adjuvant chemotherapy or other confounders.

Topics: Adiponectin; Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Cell Proliferation; Cohort Studies; Female; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Receptors, Estrogen; Receptors, Progesterone

To investigate how inflammation and metabolic syndrome (MetS) are associated with adipokine levels in patients with inflammatory arthritis.. Fifty-four female patients with arthritis were enrolled in the study. Twenty (37%) of these patients had MetS, which was diagnosed according to the definition of the International Diabetes Federation (IDF). Interleukin (IL)-6 and four adipokines (resistin, leptin, adiponectin, and adipsin) were determined by immunoassay. Healthy women with body mass index (BMI) between 22 and 25 kg/m(2) served as controls.. The patients with arthritis had higher levels of resistin than the healthy controls. This difference was clear in patients without MetS (17.4 in patients vs. 10.8 ng/mL in controls, p < 0.001), and even higher resistin levels were found in the patients with MetS (20.7 ng/mL; p < 0.001 vs. healthy controls; and p = 0.095 vs. patients without MetS). In the patients with arthritis and MetS, resistin correlated positively with IL-6 (Pearson's r = 0.5, p = 0.03). Leptin levels were increased in arthritis patients with MetS as compared to healthy controls, but not in patients without MetS. The statistically significant difference between patients with MetS and controls remained when leptin was adjusted with BMI. Accordingly, adiponectin levels were lower in patients with MetS than in healthy controls (p < 0.05). Leptin, adiponectin, and adipsin did not correlate with the inflammatory cytokine IL-6 or with C-reactive protein (CRP).. The results show that high resistin levels are associated with arthritis independently of MetS, whereas leptin is increased only in arthritis patients with MetS.

Topics: Adiponectin; Adult; Arthritis; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; Comorbidity; Complement Factor D; Female; Humans; Inflammation; Leptin; Metabolic Syndrome; Middle Aged; Resistin

Metabolic syndrome (MS) is associated with an increased risk of coronary artery disease (CAD) and type 2 diabetes mellitus (DM). In MS, adipose tissue has been shown to function as a paracrine and an endocrine organ secreting various adipocytokines. In the current study, adiponectin, tumor necrosis factor-α (TNF-α) and leptin gene expressions in the epicardial adipose tissue (EAT), paracardial adipose tissue (PAT) and subcutaneous adipose tissue (SAT) were investigated in MS patients with CAD and in non-MS patients without CAD.. Thirty-seven patients with MS undergoing coronary artery bypass grafting due to CAD (MS group) and twenty-three non-MS patients without CAD undergoing heart valve surgery (control group) were recruited prospectively to the study. Relative gene expressions of adiponectin, TNF-α and leptin in EAT, PAT and SAT were compared between two groups of patients. Adiponectin gene expression in EAT and PAT were significantly lower in MS group compared to the control group (p<0.0001, p=0.04, respectively) while SAT adiponectin gene expression did not differ significantly (p=0.64). TNF-α and leptin gene expressions were found to be statistically significantly higher in EAT, PAT and SAT of the MS group (p<0.0001, for all).. Our results demonstrate that TNF-α and leptin gene expressions increase prominently in the EAT, PAT and SAT while adiponectin gene expression decreases significantly in EAT and PAT in MS patients with CAD. These findings suggest that disturbances in expression of adiponectin, TNF-α and leptin in EAT, PAT and SAT might play an important role in MS patients with CAD.

Topics: Adiponectin; Adipose Tissue; Aged; Case-Control Studies; Coronary Artery Disease; Female; Gene Expression; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Pericardium; Prospective Studies; RNA, Messenger; Subcutaneous Fat; Tumor Necrosis Factor-alpha

Adiponectin and leptin are adipose tissue-derived hormones, shown to have opposing associations with the metabolic syndrome and coronary heart disease (CHD). This study evaluated the association between the leptin/adiponectin ratio and the components of the metabolic syndrome in a cohort with CHD. Methods and results This cross-sectional study included data from 105 subjects (men = 91), undergoing first-time elective coronary artery bypass grafting (CABG). Leptin and adiponectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Association was found between the leptin/adiponectin ratio and homeostatic model assessment (HOMA) (r(s) = 0.34, P = 0.0006), fasting insulin concentrations (r(s) = 0.37, P = 0.0001), fasting glucose concentrations (r(s) = 0.24, P = 0.01), systolic blood pressure (r(s) = 0.20, P = 0.05), diastolic blood pressure (r(s) = 0.24, P = 0.02), waist circumference (r(s) = 0.55, P < 0.0001), body mass index (BMI) (r(s) = 0.55, P < 0.0001) and waist/hip ratio (r(s) = 0.38, P = 0.0001). A significant difference was found in ratios between those with and without insulin resistance (HOMA > 3 and HOMA ≤ 3) (P = 0.029) and those with and without metabolic syndrome, defined by the International Diabetes Federation, (P < 0.001). However, using receiver operating characteristic (ROC) analysis and assessment of area under curve (AUC), the leptin/adiponectin ratio did not perform significantly better than its components.. In patients with severe CHD, the leptin/adiponectin ratio was not found to be a robust tool to distinguish patients with and without insulin resistance and those with and without the metabolic syndrome.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Pressure; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Statistics as Topic; Waist Circumference; Waist-Hip Ratio

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

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

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

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

The association of visfatin, an adipocytokine relevant to the development of inflammation and metabolic disorders, with juvenile obesity needs to be re-established as previously used tests occurred to be nonspecific.. To evaluate visfatin association with a metabolic profile of 88 overweight/obese and 26 lean children/adolescents as well as changes in its levels following weight reduction programme (diet + enhanced physical activity ± metformin).. A case-control and cohort study.. Visfatin was higher in obese than lean and overweight individuals (2·07 vs. 1·53 and 1·47 ng mL(-1) , P = 0·034). Of metabolic syndrome components, central obesity combined with either insulin resistance (IR) or hyperinsulinemia (HI) was associated with increases in circulating visfatin. In girls, visfatin correlated with leptin (r = 0·40, P = 0·009) and thiols (r = -0·36, P = 0·009), which explained 24% in visfatin variability. In boys, visfatin correlated with waist circumference (r = 0·36, P = 0·036), BMI% (r = 0·38, P = 0·025), whole body insulin sensitivity index (r = -0·36, P = 0·036), IL-6 (r = 0·38, P = 0·024) and thiobarbituric acid reactive substances (TBARS) (r = 0·52, P = 0·001), of which IL-6 and TBARS were independent predictors of visfatin elevation, explaining 42% in data variability. Visfatin was significantly lower following weight reduction programme than at baseline (1·43 vs. 1·83 ng mL(-1) , P = 0·033). Visfatin reduction correlated neither with changes in metabolic parameters nor was it affected by metformin. ΔVisfatin correlated exclusively with baseline visfatin (r = 0·612, P < 0·0001), which explained 38% in data variability.. Central obesity combined with HI/IR contributes to visfatin elevation. Visfatin association with metabolic/biochemical variables is gender dependent. Diet + enhanced physical activity are effective in visfatin reduction, the degree of which depends on baseline visfatin.

Topics: Adipokines; Adolescent; Age Factors; Body Mass Index; Case-Control Studies; Cohort Studies; Cytokines; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Obesity; Sex Factors; Statistics as Topic; Weight Loss

Psoriasis is a disorder with genetic and immunologic background. Leptin can regulate the T-helper response.. Our primary goal is to study the functional polymorphism (G-2548A) of the leptin (LEP) gene in the genetic predisposition of psoriasis, and our secondary goal is to examine factors affecting plasma leptin levels in psoriasis and to compare patients with and without metabolic syndrome (MS).. The study involved 94 patients with psoriasis and 100 healthy controls. Analysis of G-2548A polymorphism of the LEP gene was made by the PCR and restriction fragment length polymorphism technique. The relationship between LEP gene polymorphism and the clinical features of the patients was analysed. Plasma leptin levels and proportions of comorbidities in patients vs controls were compared.. In controls, the GA, AA and GG frequencies were 50%, 30% and 20%, respectively, while in patients, the distribution of genotypes was 42.5%, 20.2% and 38.3%, respectively, with significant difference (P = 0.014) between patients and controls. In patients with MS, the GG, GA and AA frequencies were 61.5%, 23.1% and 15.4%, respectively, while in patients without MS, the distribution of genotypes was 29.4%, 50% and 20.6%, respectively, with significant difference (P = 0.014) between both groups. Plasma leptin showed a significant higher levels in the patients versus the controls (P < 0.001), and among the different LEP genotypes (P < 0.001) in the patients' group.. LEP G-2548A polymorphism could be a predictor for higher plasma leptin and increased risk of psoriasis and could be used as a marker for psoriasis-related comorbidity risk.

Topics: Base Sequence; Biomarkers; Case-Control Studies; DNA Primers; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Humans; Leptin; Male; Metabolic Syndrome; Polymorphism, Single Nucleotide; Psoriasis; Risk Factors

Obesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/production either systemically (endocrine pathway) or locally (paracrine/autocrine pathway). Using quantitative PCR, mRNA expression of adiponectin (AdipoQ) and leptin (Ob) in mammary adipose tissue (MAT), intratumoral leptin and associated ligand receptors (ObR, AdipoR1, and AdipoR2) was examined in 77 patients with complete anthropomorphic and serological data. Expression of Ob in MAT, and ObR in matched tumor tissue was significantly higher in patients with MetS compared to obese only or normal weight cancer patients (P < 0.005). There was no difference in intratumoral leptin adiponectin or its ligand receptors in the same groups. Individual features of MetS correlated with Ob and ObR expression, but not obesity markers (BMI, waist circumference). mRNA expression of leptin (Ob) and ObR, in adipose tissue and matched tumor samples, respectively, appear to be associated with obesity status in breast cancer. Increasing insulin resistance is a predominant feature of this higher Ob/ObR expression observed. These novel data indicate that the MetS may be an amenable risk factor for breast cancer.

Topics: Adiponectin; Adipose Tissue; Adult; Aged; Aged, 80 and over; Breast; Breast Neoplasms; Cohort Studies; Female; Gene Expression Regulation, Neoplastic; Humans; Leptin; Metabolic Syndrome; Middle Aged; Receptors, Adiponectin; Receptors, Leptin; RNA, Messenger

Bisphenol A (BPA), a widely used environmental endocrine disruptor, has been reported to disrupt glucose homeostasis. BPA exposure may be a risk factor for type 2 diabetes. In this study, we investigated the effects of early-life BPA exposure on metabolic syndrome in rat offspring fed a normal diet and a high-fat diet. Pregnant Wistar rats were exposed to BPA (50, 250, or 1250 μg/kg · d) or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a normal diet or a high-fat diet after weaning. Body weight, parameters of glucose and lipid metabolism, morphology, and function of β-cells were measured in offspring. On a normal diet, perinatal exposure to 50 μg/kg · d BPA resulted in increased body weight, elevated serum insulin, and impaired glucose tolerance in adult offspring. On a high-fat diet, such detrimental effects were accelerated and exacerbated. Furthermore, severe metabolic syndrome, including obesity, dyslipidemia, hyperleptindemia, hyperglycemia, hyperinsulinemia, and glucose intolerance, was observed in high-fat-fed offspring perinatally exposed to 50 μg/kg · d BPA. No adverse effect of perinatal BPA exposure at 250 and 1250 μg/kg · d was observed no matter on a normal diet or a high-fat diet. These results suggest that perinatal exposure to BPA at reference dose, but not at high dose, impairs glucose tolerance in adult rat offspring on a normal diet and predisposes offspring to metabolic syndrome at adult on a high-fat diet. High-fat diet intake is a trigger that initiates adverse metabolic effects of BPA.

Topics: Aging; Animals; Benzhydryl Compounds; Body Weight; Dietary Fats; Energy Intake; Female; Fetus; Glucose; Homeostasis; Insulin-Secreting Cells; Leptin; Lipid Metabolism; Male; Metabolic Syndrome; Mitochondria; Phenols; Pregnancy; Rats; Rats, Wistar

To investigate the relationship of glucose metabolic rate (GMR) and plasma levels of adiponectin and leptin in patients with metabolic syndrome (MS).. A total of 30 MS subjects aged 36-60 years old were selected as MS group. And 20 normal adults were selected as control group. The GMR was evaluated by the technique of hyperinsulinemic euglycemia clamp. The plasma concentrations of adiponectin and leptin were detected by enzyme-linked immunosorbent assay (ELISA). Blood pressure, waist circumference (WC), body weight and body height were measured.. (1) During the steady state (last 30 min), the GMR was significantly lower in MS group than that in control Group [(4.13 ± 1.34) mg×kg(-1)×min(-1) vs (8.33 ± 1.59) mg·kg(-1)×min(-1), P < 0.01]. (2) The plasma level of adiponectin was significantly lower in MS group than that in control group [(5.15 ± 2.54) µg/ml vs (10.28 ± 5.50) µg/ml, P < 0.01]. The plasma level of leptin were significantly higher in MS group than that in control group [(189.37 ± 90.48) ng/ml vs (126.55 ± 72.70) ng/ml, P < 0.01]. (3) In MS group, glucose metabolic rate was associated with WC, BMI, TG, HDL-C FINS, leptin, and adiponectin, (all P < 0.05).. The technique of hyperinsulinemic euglycemic clamp shows that the BMR of MS patients significantly decreases. It may be associated with their lowered plasma levels of adiponectin and leptin.

Topics: Adiponectin; Adult; Case-Control Studies; Female; Glucose; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged

Knockout of the Cyp-19 gene (aromatase) renders mice to have insufficient endogenous estrogen production and contributes to the development of symptoms related the metabolic syndrome, including excess adiposity and insulin resistance. This study comparatively assessed the estrogen responsiveness in animal models of genetical versus surgical (ovariectomy) origin of estrogen deficiency. Evaluation of physiological parameters and gene expression pattern in response to estrogens revealed differences in estrogen responsiveness between aromatase deficient and castrated or intact wild-type mice. ArKO mice had a significantly higher bodyweight than matched ovariectomized wild-type mice. The weight of the completely regressed uterus following ovariectomy was higher than the uterine weight of ArKO mice. Further, alterations in metabolic parameters like increased serum leptin levels and decreased plasma glucose levels in genetically deficient mice became apparent. Finally, expression pattern of estrogen responsive genes differed in the two experimental models of estrogen deficiency. Both, in uterine and adipose tissues the regulation of expression of some genes either was inversed of regulation or considerably differed in the magnitude of the response in the two models. Our studies demonstrate that the cause of estrogen deficiency significantly impacts on estrogen responsiveness and may be of relevance for investigations on aspects of estrogen deficiency and metabolic and/or menopausal symptoms.

Topics: Animals; Aromatase; Base Sequence; Blood Glucose; Body Weight; DNA Primers; Estrogens; Female; Gene Expression Profiling; Leptin; Menopause; Metabolic Syndrome; Mice; Mice, Knockout; Organ Size; Ovariectomy; Real-Time Polymerase Chain Reaction; Uterus

Central fat distribution is significantly associated with an increased cortisol levels. We hypothesized that men with metabolic syndrome have a higher serum cortisol levels compared to women. The purpose of this study was to compare serum cortisol levels, and its correlation with serum leptin levels, between men and women with and without metabolic syndrome.. A cross sectional study was performed with 120 untreated patients with metabolic syndrome and 165 healthy volunteers as controls. Serum lipid profile, fasting blood sugar, insulin, cortisol and leptin levels were measured for both groups.. Men with metabolic syndrome had a higher serum cortisol levels, while serum leptin levels were significantly higher in women. The higher serum cortisol level in men with metabolic syndrome was significant after multiple adjustments for age, BMI and waist circumference (17.74±5.1 vs 14.07±4.3; p < 0.05) using general linear model; however, these difference were no longer significant when the waist-to-hip ratio was added as one of the adjustment factors (16.7±1.2 vs. 14.9±0.5; p < 0.2). Serum cortisol levels was significantly correlated with serum leptin (r=0.33, p < 0.05), cholesterol (r=0.35, p < 0.05), triglyceride (r=0.25, p < 0.05), waist circumference (r=0.41, p < 0.01) and waist-to-hip ratio (r=0.32, p < 0.01) in women with metabolic syndrome, after controlling for age and BMI.. Serum cortisol levels are significantly higher in men with metabolic syndrome. This effect is independent of waist circumference.

Topics: Adult; Female; Humans; Hydrocortisone; Leptin; Male; Metabolic Syndrome; Sex Factors; Waist Circumference; Young Adult

The present study investigated the relationships among metabolic risk factors, major lifestyle factors, and serum cytokines in a sample of Korean children. In a cross-sectional design, we studied a total of 275 children (130 boys and 145 girls) aged 12-13 years. Measured variables included anthropometrics, blood pressures (BP), VO2max, physical activity (PA), dietary intakes, lipids, glucose, and insulin. We explored the extent to which dietary intakes, VO2max, PA, and serum cytokines explained variance in a clustered risk score, which is a sum of Z scores for waist circumference, BP, TG, HDLC, and HOMA-IR, using a stepwise linear regression by blocks. VO2max, vigorous PA (VPA), and leptin were independent predictors for the clustered risk score while adjusting for age and Tanner stage. Our findings suggest that the clustered risk score is associated not only with low levels of VO2max and VPA, but also with elevated serum leptin in Korean children.

Topics: Acceleration; Adolescent; Analysis of Variance; Anthropometry; Blood Pressure; Child; Cluster Analysis; Confidence Intervals; Cross-Sectional Studies; Cytokines; Female; Health Status; Humans; Korea; Leptin; Life Style; Linear Models; Male; Metabolic Syndrome; Oxygen Consumption; Physical Fitness; Risk Factors

Transient environmental influences, such as perinatal nutritional stress, may induce deleterious metabolic symptoms that last for the entire life of individuals, implying that epigenetic modifications play an important role in this process. We have investigated, in mice, the consequences of maternal undernutrition during gestation and lactation on DNA methylation and expression of the leptin gene, which plays a major regulatory role in coordinating nutritional state with many aspects of mammalian biology. We show that animals born to mothers fed a low-protein-diet (F1-LPD group) have a lower body weight/adiposity and exhibit a higher food intake than animals born to mothers fed a control diet (F1-CD group). These modifications persisted throughout life and were associated with lower levels of leptin mRNA and protein in starved F1-LPD mice, emphasizing that maternal protein-undernutrition affects the balance between food intake and energy expenditure in adults. Moreover, this nutritional stress resulted in the removal of methyls at CpGs located in the promoter of leptin, causing a permanent specific modification in the dynamics of the expression of leptin, which exhibits a stronger induction in the F1-LPD than in F1-CD mice in response to a meal. This study is an example of a molecular rationale linking transient environmental influences to permanent phenotypic consequences.

Topics: Animals; Base Sequence; Body Composition; CpG Islands; Diet; Dietary Proteins; Female; Gene Expression Regulation; Humans; Leptin; Metabolic Syndrome; Mice; Mice, Inbred BALB C; Pregnancy; Prenatal Nutritional Physiological Phenomena; Promoter Regions, Genetic; RNA, Messenger

Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C - standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N - standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (+51%), catecholamine content (+37%), and serum 25-hydroxyvitamin D(3) (+76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (-37%) and higher in liver (+42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action.

Topics: Adiposity; Adrenal Glands; Animals; Animals, Newborn; Base Sequence; Calcium, Dietary; Catecholamines; Female; Hypothalamus; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Models, Animal; Nicotine; Pregnancy; Rats; Rats, Wistar; Receptors, Leptin; RNA, Messenger; Sirtuin 1; Tyrosine 3-Monooxygenase

Little evidence exists regarding the association of leptin with metabolic syndrome (MetS) as defined by conventional criteria. Moreover, the contribution of obesity to this relationship is not well understood. This study aimed to evaluate the association between leptin concentrations with MetS in obese and nonobese subjects.. Data from the Third National Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD) in Iran was used. In a cross-sectional study of 3045 adults (48.2% men) aged 25-64 years, anthropometric indices, blood pressure, fasting plasma glucose, fasting insulin, lipid profile [triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides], and fasting leptin were measured. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was also calculated.. Leptin concentrations were 2.6 fold higher in women compared with men. Subjects with MetS had significantly higher leptin concentrations. Leptin concentrations increased steadily with an increment in the number of MetS components (p <0.001). Leptin was significantly associated with MetS after adjustment for age, cigarette smoking, medication use, physical activity, HOMA-IR, and LDL-C. The significant association between leptin and MetS persisted after adjustment for body mass index (OR: 1.31, 95% CI: 1.09-1.58 in males and 1.17, 95% CI: 1.01-1.38 in females) and waist circumference (OR: 1.24 95% CI: 1.01-1.51 in men and 1.22, 95% CI: 1.04-1.43 in women). After dividing subjects into obese and nonobese, leptin concentrations were again significantly higher in subjects with MetS in both groups.. We demonstrated that leptin concentrations are significantly associated with International Diabetes Federation (IDF)-defined MetS, independent of overall and central obesity. Our findings point to an independent role for leptin in development of MetS.

Topics: Adult; Blood Glucose; Blood Pressure; Cross-Sectional Studies; Female; Humans; Iran; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Obesity; Risk Factors; Waist Circumference

Mechanisms of liver fibrosis are complex and varied. Among them, metabolic factors are particularly important in the development of fibrosis associated with nonalcoholic steatohepatitis (NASH). These factors are some of the "multiple parallel hits" responsible for liver damage during NASH. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Major profibrogenic protagonists, such as hepatic stellate cells and Kupffer cells, are activated by insulin resistance, apoptosis and local inflammation. Relations between steatosis, insulin resistance and fibrosis are complex. Initially, simple steatosis may be a way to store deleterious free fatty acid in neutral triglycerides. If the lipid storage threshold is exceeded, steatosis may become associated with lipotoxicity. Similarly, interindividual variations of adipose tissue expandability might explain various phenotypes, ranging from "metabolically obese patients with normal weight" to "metabolically normal morbidly obese patients". The metabolic abnormalities in subcutaneous and visceral adipose tissue are insulin resistance and low-grade inflammation, which are associated with increased release of free fatty acid flux and changes in adipocytokines production such as leptin, adiponectin and interleukin 6. The nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and the endocannabinoid system might have important roles in liver fibrogenesis and are potential therapeutic targets. Finally, with the development of new molecular tools, gut microbiota has been recently identified for its pleiotropic functions, including metabolism regulation. Better knowledge of these mechanisms should lead to new strategies for the treatment of metabolic factors that play a key role in liver injuries.

Topics: Adipokines; Adiponectin; Biomarkers; Body Mass Index; Cannabinoid Receptor Modulators; Fatty Liver; Hepatic Stellate Cells; Humans; Interleukin-6; Kupffer Cells; Leptin; Liver Cirrhosis; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; PPAR gamma; Risk Factors

Circulating leptin:adiponectin ratio (L:A) is a potential surrogate marker for cardiometabolic diseases; however, the relationship of the L:A with the occurrence of metabolic syndrome (MetS) has not yet been fully explored in the general Japanese population.. We enrolled 678 Japanese subjects (208 men and 470 women, mean age: 58.8±14.4 [SD] yr; mean body mass index: 23.6±3.3 kg/m(2)) in this study, and determined their MetS status by using the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP) recommendations with minor modifications for the Japanese population. Biochemical markers such as leptin and adiponectin present in blood were measured. The statistical analyses performed were gender-based.. A in subjects with MetS was significantly higher than that in subjects without MetS, regardless of gender. The L:A also showed a significant and gradual increase corresponding to the increase in the number of components of MetS present in both the genders (trend P<0.01). The cut-off level of the L:A to detect MetS was 0.59 (sensitivity: 0.72, specificity: 0.70) in men and 1.04 (sensitivity: 0.72, specificity: 0.69) in women.. These results suggest that the L:A can serve as a clinically useful marker for detecting MetS characteristics in the general Japanese population. The clinical application of this laboratory index for detecting MetS should be assessed in future studies.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Female; Humans; Japan; Leptin; Male; Metabolic Syndrome; Middle Aged; ROC Curve

In recent years, the number of patients suffering from diseases, such as cancer, apoplexy, osteoporosis, hypertension, and type 2 diabetes mellitus is increasing worldwide. Type 2 diabetes, a lifestyle-related disease, is recognized as a serious disease. Various types of pharmaceutics for diabetes have been used. Since the relationship between diabetes and biometals such as vanadium, copper, and zinc ions has been recognized for many years, we have been developing the anti-diabetic metal complexes as new candidates. We found that several zinc(II) (Zn) complexes exhibit glucose-lowering activity for treating type 2 diabetes. High doses of salicylates have been known to reverse hyperglycemia and hyperinsulinemia in type 2 diabetic patients. These findings strongly suggest that the combined use of Zn and salicylates achieves the synergism in treating type 2 diabetes. Because aspirin, acetyl salicylic acid, has a chelating ability, we used it as a ligand to Zn. Several Zn-salicylate complexes were prepared and their biological activities were examined in this study. The complexes with an electron-withdrawing group in the ligand exhibited higher in vitro insulinomimetic activity than those of Zn complexes with an electron-donating group in the ligand. When bis(aspirinato)Zn (Zn(asp)₂) complex was orally administered on KK-A(y) mice with hereditary type 2 diabetes, the diabetic state was improved. In addition, this complex exhibited normalizing effects on serum adiponectin level and high blood pressure in metabolic syndrome. In conclusion, Zn(asp)₂ complex is newly proposed as a potent anti-diabetic and anti-metabolic syndrome agent.

Topics: Adiponectin; Administration, Oral; Animals; Aspirin; Blood Pressure; Coordination Complexes; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Mice; Structure-Activity Relationship

Recent studies have reported that leptin and adiponectin are associated with metabolic syndrome. The leptin/adiponectin ratio has been suggested as an atherosclerotic index. The objective of this study was to compare the degree of association of metabolic syndrome with adiponectin levels, leptin levels, leptin/adiponectin ratio, and leptin/high-molecular-weight (HMW) adiponectin ratio. The study population included 3272 Koreans (men: 1915, women: 1357; age, 30-84 years), who had visited the Health Examination Center. Adipokines were divided into quartiles, and metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel-III (NCEP ATP III). A logistic regression model was fitted to establish the association between adipokines and metabolic syndrome. Adipokines, such as adiponectin, HMW adiponectin, and leptin, were found to be statistically related to metabolic syndrome. Compared to the lowest quartile, the leptin/HMW adiponectin ratio in the highest quartile was associated with a 5-fold increase in the probability of prevalent metabolic syndrome, which was independent of age, smoking status, exercise, low-density lipoprotein (LDL) cholesterol, and body mass index. There was a linear increase in the leptin/HMW adiponectin ratio as the number of metabolic syndrome components increased. The leptin/HMW adiponectin ratio had the highest odds ratio in women. In addition, compared to adiponectin or leptin alone, the AUC of the leptin/adiponectin ratio and leptin/HMW adiponectin ratio was higher for metabolic syndrome. We may suggest that the leptin/HMW adiponectin ratio is not superior to other adipokine markers, but is as effective as the leptin/total adiponectin ratio.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Female; Humans; Leptin; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Molecular Weight

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

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

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

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

To determine the effects of a [6]-gingerol analogue (6G), a major chemical component of the ginger rhizome, and its stable analogue after digestion in simulated gastric fluid, aza-[6]-gingerol (A6G), on diet-induced body fat accumulation, we synthesized 6G and A6G. Mice were fed either a control regular rodent chow, a high-fat diet (HFD), or a HFD supplemented with 6G and A6G. Magnetic resonance imaging adiposity parameters of the 6G- and A6G-treated mice were compared with those of control mice. Supplementation with 6G and A6G significantly reduced body weight gain, fat accumulation, and circulating levels of insulin and leptin. The mRNA levels of sterol regulatory element-binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase 1 in the liver were significantly lower in mice fed A6G than in HFD control mice. Our findings indicate that A6G, rather than 6G, enhances energy metabolism and reduces the extent of lipogenesis by downregulating SREBP-1c and its related molecules, which leads to the suppression of body fat accumulation.

Topics: Acetyl-CoA Carboxylase; Adiponectin; Adipose Tissue; Amides; Animals; Anti-Obesity Agents; Blood Glucose; Body Weight; Catechols; Dietary Fats; Energy Metabolism; Fatty Alcohols; Glucose Tolerance Test; Guaiacol; Insulin; Leptin; Lipogenesis; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred ICR; RNA, Messenger; Sterol Regulatory Element Binding Protein 1

Leptin and adiponectin are adipokines, shown to have opposing functions for fat metabolism and development of metabolic syndrome. We determined if the ratio of serum leptin to adiponectin (L/A ratio) adjunctively contributes to the risk of metabolic syndrome beyond the homeostasis model assessment of insulin resistance (HOMA-IR).. This study included 1532 men and 1856 women, aged 40-70 y assessed in the Korean Genomic Rural Cohort Study from 2005 to 2008. The serum concentrations of adiponectin and leptin were measured by radioimmunoassay. Area under the receiver operating characteristic curve (AUROC) analyses were used to describe the ability of L/A ratio and HOMA-IR to differentiate between subjects with and without metabolic syndrome.. There were no significant differences in the ability of L/A ratio and HOMA-IR to predict metabolic syndrome (AUROC of L/A ratio vs. HOMA-IR, 0.771 vs. 0.774, p=0.8006 for men; 0.677 vs. 0.691, p=0.3088 for women). There was a significant adjunctive contribution by the L/A ratio, beyond that of HOMA-IR, to the risk of metabolic syndrome in men (p<0.0001 with 0.028 increased AUROC) and women (p=0.025 with 0.017 increased AUROC).. The L/A ratio provides significant adjunctive information to the risk of metabolic syndrome beyond HOMA-IR alone. The L/A ratio could be a good surrogate marker to assess metabolic syndrome.

Topics: Adiponectin; Adult; Aged; Female; Homeostasis; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Republic of Korea

The metabolic syndrome (MetS) is associated with increased risk of diabetes and cardiovascular disease (CVD). Numerous groups have shown increased circulating biomarkers of inflammation in MetS. However, there are scanty data on the cellular sources contributing to this low-grade inflammation.. The aim of this study was to determine the role of sc adipose tissue (SAT) biology in nascent MetS without concomitant diabetes or CVD.. Subjects with MetS and controls were recruited after informed consent. Fasting blood was collected, and SAT was obtained by biopsy.. Circulating biomarkers of inflammation and insulin resistance, high-sensitivity C-reactive protein (hsCRP), IL-6, IL-1β, leptin, serum amyloid A, and retinol-binding protein-4 (RBP-4) concentrations were significantly higher in the MetS subjects than controls, whereas adiponectin concentrations were lower. In SAT, leptin, RBP-4, CRP, serum amyloid A, plasminogen activator inhibitor-1, IL-1, IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) levels were significantly higher in MetS than controls. These differences except for RBP-4 persisted after adjusting for waist circumference. In addition, there were significantly increased numbers of macrophages infiltrating the SAT of MetS and increased numbers of crown-like structures compared with controls. hsCRP correlated positively with homeostasis model assessment and SAT MCP-1 and negatively with adiponectin. Homeostasis model assessment correlated positively with plasminogen activator inhibitor-1, RBP-4, and SAT MCP-1.. We make the novel observation that SAT of MetS has increased macrophage recruitment with cardinal crown-like structure features and contributes to the increased cellular inflammation that produces increased levels of biomarkers that are correlated with both insulin resistance and low-grade inflammation. These aberrations could contribute to the progression of MetS and the increased risk for diabetes and CVD.

Topics: Adiponectin; Adipose Tissue; Adult; Biomarkers; C-Reactive Protein; Chemokines; Cytokines; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Waist Circumference

Topics: Adipose Tissue; Coronary Artery Disease; Female; Humans; Leptin; Male; Metabolic Syndrome; Tumor Necrosis Factor-alpha

The Berlin Fat Mouse BFMI860 is a polygenic obesity mouse model which harbors a natural major gene defect resulting in early onset of obesity. To elucidate adult bodily responses in BFMI860 mice that develop juvenile obesity, we studied features of the metabolic syndrome at 20 weeks.. We examined fat deposition patterns, adipokines, lipid profiles in serum, glucose homeostasis, and insulin sensitivity in mice that were fed either a standard maintenance (SMD) or a high-fat diet (HFD).. Like many obese humans, BFMI860 mice showed hyperleptinemia accompanied by hypoadiponectinemia already at SMD that was further unbalanced as a result of HFD. Furthermore, BFMI860 mice had high triglyceride concentrations. However, triglyceride clearance after an oral oil gavage was impaired on SMD but improved on HFD. The oral and intraperitoneal glucose as well as the insulin tolerance tests provided evidence for reduced insulin sensitivity under SMD and insulin resistance on HFD. BFMI860 mice can maintain normal glucose clearance over a wide range of feeding conditions according to an adaptation via increasing the insulin concentrations.. BFMI860 mice show obesity, dyslipidemia, and insulin resistance as three major components of the metabolic syndrome. As these mice develop the described phenotype as a result of a major gene defect, they are a unique model for the investigation of genetic and pathophysiological mechanisms underlying the observed features of the metabolic syndrome and to search for potential strategies to revert the adverse effects under controlled conditions.

Topics: Adipokines; Adiponectin; Animals; Blood Glucose; Diet, High-Fat; Dietary Fats; Disease Models, Animal; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Mice; Mice, Obese; Obesity; Triglycerides

Adiponectin and leptin play critical roles in the development of Metabolic Syndrome (MetS). This study was designed to assess the feasibility of using circulating levels of adiponectin and leptin for the early diagnosis of MetS.. A cross-sectional study was performed using data from 367 participants randomly selected from a well-characterized cohort of Mexican-Americans living at the US-Mexico border.. Significant differences in circulating levels of adiponectin and leptin were observed between males and females. Adiponectin/leptin correlated significantly with MetS in this population. A receiver-operator characteristic (ROC) analysis demonstrated that adiponectin/leptin showed a high sensitivity (70.9% for males, 78.9% for females) and specificity (90.2% for males and 69.8% for females) for the diagnosis of MetS, independent of BMI measurements.. These data support the central role of adiponectin and leptin in MetS, and demonstrated that adiponectin/leptin can be used as a highly sensitive and specific biomarker for MetS.

Topics: Adiponectin; Adult; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Metabolic Syndrome; Mexican Americans; Middle Aged; Sex Factors

Schizophrenic patients have a high prevalence of metabolic adversities. Previous studies have suggested some candidate genes for obesity- and metabolic-related traits, including the insulin-induced gene (INSIG2), melanocortin 4 receptor gene (MC4R), and leptin and leptin receptor genes (LEP and LEPR). We aimed to investigate the associations between these genes and metabolic disturbances in patients with schizophrenia in Taiwan.. Patients with a diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were recruited from 36 community psychiatric rehabilitation centers or hospitals in Taipei. A total of 650 subjects were enrolled, and 577 were included in the genetic analyses. The anthropometric (body mass index, waist circumference [WC], and blood pressure) and biochemical measurements (fasting plasma glucose, insulin, triglyceride, high-density lipoprotein cholesterol, and Homeostasis Model of Assessment - Insulin Resistance index [HOMA-IR]) were assessed. Seven loci in the 4 genes were genotyped using standard TaqMan assays. Genetic association analyses were conducted for binary and quantitative measurements of the previously mentioned traits. Obese patients with schizophrenia exhibited more metabolic disturbances than nonobese patients.. Our data showed that INSIG2 was significantly associated with fasting plasma glucose (for rs17587100, P < 0.0001), MC4R was associated with WC (for rs2229616, P = 0.005), and LEP was associated with body mass index and WC (for rs7799039, P < 0.01). In addition, these loci showed suggestive associations with traits including high-density lipoprotein cholesterol and triglyceride, metabolic syndrome, insulin level, and HOMA-IR index (P = 0.05). In addition to the effect from antipsychotic medications and an unhealthy lifestyle, genetic factors also contribute to the high prevalence of obesity and metabolic disturbances in patients with schizophrenia, especially genes involved in metabolic-related pathways.

Topics: Adult; Blood Glucose; Body Mass Index; Female; Genetic Association Studies; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Male; Membrane Proteins; Metabolic Syndrome; Middle Aged; Obesity; Polymorphism, Genetic; Psychotic Disorders; Receptor, Melanocortin, Type 4; Schizophrenia; Taiwan; Waist Circumference; Young Adult

To evaluate the relationship between metabolic syndrome (MetS) and the fasting serum leptin concentration in hemodialysis (HD) patients.. Fasting blood samples were obtained from 101 HD patients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation.. Forty-eight patients (47.5%) had MetS. Serum leptin concentrations were positively correlated with MetS (p<0.001). Serum leptin levels correlated with increasing numbers of MetS criteria in HD patients (p=0.001). Univariate linear regression analysis showed that the pre-HD body weight (p<0.001), waist circumference (p<0.001), body mass index (p=0.001), triglycerides (p=0.003), insulin level (p=0.043), and homeostasis model assessment of insulin resistance (p=0.003) positively correlated with serum leptin levels in HD patients and high-density lipoprotein-cholesterol (p=0.016) negatively correlated with serum leptin levels in HD patients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that pre-HD body weight (R(2)=0.175; p<0.001) was the independent predictor of the fasting serum leptin concentration.. Fasting serum leptin levels positively correlated with MetS and the pre-HD body weight could influence serum leptin in HD patients.

Topics: Aged; Body Weight; Fasting; Female; Humans; Hypertension, Renal; Insulin Resistance; Kidney Failure, Chronic; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Renal Dialysis; Risk Factors

Leptin, ghrelin, and adiponectin play important roles in the regulation of body weight, food intake, and energy homeostasis, and have been suggested to be important biomarkers of metabolic syndrome. In this study, we tried to simultaneously investigate the serum levels of leptin, ghrelin, and adiponectin in schizophrenic patients and healthy controls.. During a period of 2 years, we recruited 37 schizophrenic patients and 65 healthy controls. The levels of metabolic syndrome-related biomarkers including serum adiponectin, leptin, and ghrelin were measured with an enzyme-linked immunosorbent assay.. On applying analysis of covariance (ANCOVA) with age and body mass index adjustments, the leptin levels of schizophrenic patients (P = 0.038) were found to be higher than those of healthy controls. However, there were no significant differences in the serum levels of ghrelin or adiponectin between these two groups.. These results showed that serum leptin levels might be more sensitive than ghrelin or adiponectin levels between schizophrenic patients and healthy controls. However, studies with a large sample size are needed to confirm these results.

Topics: Adiponectin; Adult; Antipsychotic Agents; Case-Control Studies; Clozapine; Female; Ghrelin; Humans; Leptin; Male; Metabolic Syndrome; Peptide Hormones; Risperidone; Schizophrenia; Taiwan

Topics: Adiponectin; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Pulmonary Disease, Chronic Obstructive

Chronic obstructive pulmonary disease (COPD) and metabolic syndrome represent common causes of morbidity and mortality in ageing populations. The effect of the co-existence of COPD and metabolic syndrome on adipose tissue hormones and insulin resistance as well as the differences between COPD patients with and without metabolic syndrome have not been adequately studied. The prevalence of metabolic syndrome, based on Adult Treatment Panel III (ATP III) criteria, was evaluated in 114 male patients with COPD without significant co-morbidities. Pulmonary functions tests (PFTs), arterial blood gases, quality of life and BODE index were assessed. Blood samples were obtained for the assessment of adipose tissue hormones and insulin resistance. The overall prevalence of metabolic syndrome was 21%, being more prevalent in earlier stages of COPD. Patients with COPD and metabolic syndrome were younger with higher body-mass index (BMI), had better pulmonary function, less static hyperinflation and air-trapping, better diffusing capacity for carbon monoxide and BODE index. These patients had higher levels of leptin, lower levels of adiponectin and increased insulin resistance, as expressed by HOMA index, compared with patients without metabolic syndrome. Metabolic syndrome was more prevalent in younger patients with less severe COPD. These patients may constitute a specific COPD phenotype with greater leptin to adiponectin imbalance and insulin resistance, despite smaller impairment in PFTs. The prognosis and differences of these patients compared with other COPD phenotypes needs to be determined in prospective studies.

Topics: Adiponectin; Age Factors; Aged; Body Mass Index; Humans; Insulin Resistance; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Severity of Illness Index; Smoking

The possible relationship between cerebrospinal fluid (CSF) hypocretin and leptin levels, overweight, and association to risk factors for diabetes 2 in narcolepsy with cataplexy were compared to patients with idiopathic hypersomnia and controls.. 26 patients with narcolepsy, cataplexy, and hypocretin deficiency; 23 patients with narcolepsy, cataplexy, and normal hypocretin values; 11 patients with idiopathic hypersomnia; and 43 controls.. Body mass index (BMI), serum leptin, and HbA1C were measured in patients and controls; and CSF hypocretin 1 and leptin measured in all patients. Female and male patients with narcolepsy and hypocretin deficiency had the highest mean BMI (27.8 and 26.2, respectively), not statistically different from patients with narcolepsy and normal hypocretin or controls, but statistically higher than the patients with idiopathic hypersomnia (p < 0.001 and 0.011, respectively). The number of obese patients (BMI > 30) was increased in both narcolepsy groups. Serum and CSF leptin levels correlated positively to BMI in patients and controls, but not to CSF hypocretin concentrations. HbA1C was within normal levels and similar in all groups.. The study confirms a moderate tendency to obesity (BMI > 30) and overweight in patients with narcolepsy and cataplexy. Obesity was not correlated to hypocretin deficiency or reduced serum or CSF leptin concentrations. We suggest that overweight and possible metabolic changes previously reported in narcolepsy, may be caused by other mechanisms.

Topics: Adult; Aged; Body Mass Index; Case-Control Studies; Cataplexy; Causality; Comorbidity; Female; Humans; Idiopathic Hypersomnia; Intracellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Middle Aged; Narcolepsy; Neuropeptides; Obesity; Orexins; Overweight; Prognosis; Reference Values; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric

Along with the growing epidemic of overweight the risk of atherosclerosis, cardiovascular disease morbidity and mortality are increasing markedly. Metabolic syndrome (MS) is a condition clustering together several risk factors of those complications such as visceral obesity, glucose intolerance, arterial hypertension and dislipidemia. The risk of obesity in acute lymphoblastic leukemia (ALL) survivors is higher than in general population. We aimed to assess (1) the relationships between chosen adipokines and neuropeptides, chemotherapy, CRT, and body fatness and (2) evaluate adipokines and neuropeptides concentrations as a new markers of MS in children. We conducted cross-sectional evaluation of 82 ALL survivors (median age: 13.2 years; range: 4,8-26,2; median time from treatment: 3.2 years), including fasting laboratory testing: peptides (leptin, GLP-1, orexin, PYY, apelin), total cholesterol and its fractions, triglycerides; anthropometric measurements (weight, height), systolic and diastolic blood pressure. We estimated percentiles of body mass index and percentiles of blood pressure. Between 82 survivors overweight and diastolic hypertension was diagnosed in 31% of patients (35% in CRT group) and 15% respectively. At least one abnormality in lipids concentrations was found in 43%. Girls were more affected than boys. Statistically significant increased in leptin and apelin concentrations and decreased in soluble leptin receptor concentrations in the overweight group were observed compared to the non overweight subjects. Significant increase in orexin levels in females who had received CRT compared to those who had not received CRT was found. CRT is the main risk factor of elevated of body mass among survivors of childhood leukemia. Dyslipidemia and hypertension, along with increased adiposity indicate higher risk of MS development. Girls are more affected than boys. Leptin, orexin and apelin seem to be good markers of increased adiposity especially after CRT. Higher leptin levels may be related to central resistance to those peptides. Survivors of childhood acute lymphoblastic leukemia should be screened for markers of the metabolic syndrome.

Topics: Adipokines; Adolescent; Adult; Age Distribution; Biomarkers; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Hypertension; Intracellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Neuropeptides; Obesity; Orexins; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors; Young Adult

Melatonin, leptin, and insulin secretion was studied in 25 men with metabolic syndrome (MS) verified against IDF criteria (2005) (mean age 44 +/- 2 yr). The control group was constituted by 23 healthy men (mean age 45.1 yr). Melatonin secretion was estimated from 6-oxymelatonin sulfate (6-OMS) level in urine samples collected at 4 a.m. (in the darkness). It was shown to increase at this time in both groups but was lower in MS patients than in controls (t = 2, p < 0.05). The Pearson correlation analysis revealed moderate negative correlation between 6-SOMT level in urine and insulin and glucose levels in plasma (r = 0.95). Peak 6-SOMT level showed strong negative correlation with the leptin level. Multiple regression analysis demonstrated strong linear relationship of 6-OMS and insulin levels (r = 0.93) and 6SOMT and leptin levels (r = 0.95). The calculated odds ratio suggests that the risk of insulin resistance in patients displaying a peakless melatonin secretion profile is 3 times that in control subjects (OR = 3.0; 95% CI = 1.3-7). It is concluded that patients with MS present with disturbances of melatonin secretion manifest as the absence of its physiological elevation at night hours; they are characterized by negative correlation between melatonin, leptin and insulin levels and changes in melatonin secretion in relation to abnormal production of insulin and leptin.

Topics: Adult; Blood Glucose; Down-Regulation; Humans; Insulin; Insulin Secretion; Leptin; Male; Melatonin; Metabolic Syndrome; Middle Aged; Odds Ratio; Risk

Serum leptin has been reported to be associated in a sex-dependent manner with C-reactive protein (CRP), independently of adiposity. We tested the hypothesis that leptin is associated, independently of anthropometry indexes and in a sex-dependent way, with other inflammatory markers and variables related to metabolic syndrome (MS). In 384 healthy middle-aged adults (192 men and 192 women) total fat mass (FM), waist circumference (WC), serum leptin and 15 MS-related parameters (systolic and diastolic blood pressure, triglycerides, cholesterol, high density lipoprotein (HDL)-cholesterol, apo AI and B, fasting glucose, uric acid, CRP, orosomucoid and haptoglobin levels and aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities) were measured. After adjustment for age, alcohol and cigarette consumption, WC, and total FM, leptin concentration was significantly associated with serum triglycerides, total cholesterol, apo B, uric acid and haptoglobin concentrations and liver enzyme activity only in men, and with apo AI, HDL-cholesterol (only borderline) and CRP only in women. Sex interaction terms were significant for total cholesterol, apo B, HDL cholesterol, uric acid, ALAT and GGT, and borderline significant for triglycerides, apo AI and ASAT. In this healthy population, leptin is significantly associated with various MS factors, independently of WC and total FM, depending on gender. Our study provides further evidence of sex-related differences mediated by leptin in inflammatory mechanisms and other MS-related metabolic pathways.

Topics: Adiposity; Adult; Analysis of Variance; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Electric Impedance; Female; Follow-Up Studies; Humans; Leptin; Lipids; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Obesity; Regression Analysis; Risk Factors; Sex Factors; Uric Acid; Waist Circumference

To evaluate serum leptin concentration and its relation to metabolic syndrome (MSy) in non-diabetic patients with myotonic dystrophy type 1 (DM1).. This study included 34 DM1 patients, and the same number of healthy subjects matched for age, sex and body mass index (BMI).. DM1 patients had increased BMI and insulin resistance, and increased leptin and insulin concentrations, but the other features of MSy such as diabetes, glucose intolerance and hypertension were not detected in DM1 patients. Serum leptin levels were higher in patients with DM1 than in healthy controls (8.5 +/- 6.6 ng/ml vs 3.6 +/- 2.9 ng/ml in men, and 13.9 +/- 10.0 ng/ml vs 10.9 +/- 6.9 ng/ml in women, respectively). In DM1 patients, leptin levels correlated with BMI, fasting insulin and insulin resistance (HOMA) (P < 0.01).. The leptin overproduction correlated with insulin resistance in DM1 patients but the significance of this finding remains unclear.

Topics: Adult; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Myotonic Dystrophy; Sex Characteristics; Triglycerides

Leptin is mainly secreted from adipose tissue and is known to be associated with cardiovascular diseases. However, there are not many studies on the association between serum leptin and metabolic syndrome. The objective of this study was to determine the association between serum leptin and metabolic syndrome among the Korean adult population. The study population consisted of 3,272 Koreans (men: 1,915, women: 1,357) 30 to 84 years of age who had visited the Health Examination Center. Leptin levels were divided into quintiles and metabolic syndrome was defined by NCEP ATP III. The serum leptin levels increased as the number of components present for metabolic syndrome increased. Controlling for age, smoking, exercise, and LDL cholesterol, subjects with high leptin levels were more likely to have an elevated risk of metabolic syndrome than those with lower levels in both men and women. Subjects in the highest leptin quintile were found to have a higher risk of having metabolic syndrome than those in the lowest quintile (OR = 11.51 for men; OR = 4.65 for women). After further adjustment of the BMI, the risk of metabolic syndrome still increased slightly for men but not for women in increasing leptin categories. This association of leptin levels and metabolic syndrome did not change after stratification into obese and nonobese weight status. Serum leptin is associated with metabolic syndrome in Korean populations independent of body mass index. Thus, the reduction of circulating leptin may confer cardiovascular and metabolic protective effects regardless of weight status.

Topics: Abdominal Fat; Adult; Body Mass Index; Female; Humans; Hyperglycemia; Hypertension; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Odds Ratio; Republic of Korea; Triglycerides; Waist Circumference

Adipose tissue-derived inflammation may contribute to metabolic alterations and eventually to the metabolic syndrome (MetS). The purpose of this study was to: (1) examine the role of adipocytokines in the association between obesity and the MetS and (2) to determine whether the association is different in obese and non-obese persons.. Cross-sectional population-based InCHIANTI study.. A total of 944 community-dwelling adults aged 65 years and older living in Tuscany, Italy.. Obesity was defined as body mass index > or =30 kg/m2 and MetS as > or =3 of the ATP-III criteria. Circulating levels of C-reactive protein, interleukin (IL)-6, IL-1 receptor antagonist (IL-1ra), IL-18, tumour necrosis factor (TNF)-alpha R1, adiponectin, resistin and leptin were measured. Additionally, insulin resistance was determined using the homeostasis model assessment (HOMA-IR).. The prevalence of the MetS was 32%. Both overall and abdominal obesity were significantly associated with the MetS after adjusting for inflammatory cytokines, adipokines and lifestyle factors. After adjusting for multiple confounders and HOMA-IR, IL-1ra, TNF-alpha R1 and adiponectin (P < 0.05) remained significantly associated with the MetS. Having multiple cytokines in the highest tertile increased the likelihood of having the MetS in both obese (P for trend 0.002) and non-obese persons (P for trend 0.001) independent of insulin resistance.. Non-obese and obese individuals who develop an intense pro-inflammatory state may be more prone to develop the MetS than those with lower levels of inflammation.

Topics: Adipokines; Adiponectin; Aged; C-Reactive Protein; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Interleukin 1 Receptor Antagonist Protein; Interleukin-18; Interleukin-6; Leptin; Male; Metabolic Syndrome; Obesity, Abdominal; Receptors, Tumor Necrosis Factor, Type I; Resistin

Obesity causes complex metabolic and endocrine changes that may lead to adverse outcomes, including hypogonadism. We herein studied the reproductive axis function in male rats under a high-fat diet and analyzed the impact of changes in glycosylation of pituitary LH on the bioactivity of this gonadotropin. Rats were fed with a diet enriched in saturated fat (20% of total calories) and euthanized on days 90 or 180 of diet. Long-term (180 days), high-fat feeding rats exhibited a metabolic profile compatible with insulin resistance and metabolic syndrome; they concomitantly showed decreased intrapituitary and serum LH concentrations, low serum testosterone levels, and elevated serum 17beta-estradiol concentrations. A fall in biological to immunological ratio of intrapituitary LH was detected in 180 days control diet-treated rats but not in high-fat-fed animals, as assessed by a homologous in vitro bioassay. Chromatofocusing of pituitary extracts yielded multiple LH charge isoforms; a trend towards decreased abundance of more basic isoforms (pH 9.99-9.0) was apparent in rats fed with the control diet for 180 days but not in those that were fed the diet enriched in saturated fat. It is concluded that long-term high-fat feeding alters the function of the pituitary-testicular axis, resulting in hypogonadotropic hypogonadism. The alterations in LH function found in these animals might be subserved by changes in hypothalamic GnRH output and/or sustained gonadotrope exposure to an altered sex steroid hormone milieu, representing a distinctly different regulatory mechanism whereby the pituitary attempts to counterbalance the effects of long-term obesity on reproductive function.

Topics: Animals; Blood Glucose; Dietary Fats; Disease Models, Animal; Estradiol; Glycosylation; Hydrogen-Ion Concentration; Insulin Resistance; Leptin; Luteinizing Hormone; Male; Metabolic Syndrome; Obesity; Pituitary Gland, Anterior; Protein Isoforms; Rats; Rats, Wistar; Reproduction; Testosterone; Triglycerides

To determine the potential role of the transcriptional factor-activating enhancer-binding protein-2beta (TFAP2B) in the regulation of expression of adipokines, adiponectin, leptin, and interleukin-6 (IL-6) in vivo, we quantified the mRNA expression levels of these adipokines and TFAP2B in visceral (omental) and abdominal subcutaneous adipose tissues of 66 individuals with variable degree of adiposity and studied their correlations with BMI and their plasma concentrations. We found that BMI correlated negatively with plasma adiponectin levels and positively with those of leptin. Adiponection mRNA expression in subcutaneous fat correlated negatively with BMI, whereas leptin mRNA levels in the omentum correlated with plasma leptin levels and BMI. In contrast, IL-6 mRNA levels in subcutaneous and omental fat did not correlate with BMI. IL-6 mRNA levels in the omental fat correlated with plasma IL-6 levels. Whereas TFAP2B mRNA expression did not correlate with BMI, it correlated negatively with adiponectin expression in the subcutaneous adipose tissue. Furthermore, TFAP2B mRNA expression correlated negatively with leptin and positively with IL-6 expression in both subcutaneous and omental adipose tissues. These relationships are consistent with our in vitro observations and indicate that TFAP2B seems to regulate the expression of various adipokines in vivo.

Topics: Abdominal Fat; Adiponectin; Aged; Aged, 80 and over; Body Mass Index; Diabetes Mellitus, Type 2; Female; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Omentum; RNA, Messenger; Subcutaneous Fat; Transcription Factor AP-2

Visceral fat accumulation stimulates the production of adipocytokines in patients with metabolic syndrome. Excess body weight gain during pregnancy is a risk factor for preeclampsia. To evaluate whether the pathogenesis of preeclampsia is similar to that of metabolic syndrome, we measured plasma adipocytokine concentrations and investigated the association between plasma adiponectin concentrations and body weight gain or endothelial function in preeclamptic women. We investigated 15 preeclamptic and 17 women with uncomplicated pregnancies. Women with preeclampsia had significantly lower plasma concentrations of adiponectin (10.2+/-2.0 vs. 7.3+/-2.2 microg ml(-1), P<0.01), but higher concentrations of leptin, plasminogen activator inhibitor-1, interleukin-6, vascular cell adhesion molecule-1, E-selectin and C-reactive protein. Plasma triglyceride levels were significantly higher in preeclamptic patients, but the levels of other lipids did not differ significantly between the two groups. We found that flow-mediated vasodilation was significantly decreased in preeclamptic women compared with controls (10.6+/-6.4 vs. 3.8+/-2.0%, P<0.001). Plasma adiponectin concentrations correlated negatively with body mass index (r=-0.50, P<0.05) and body weight gain during pregnancy (r=-0.63, P<0.01), and positively with flow-mediated vasodilation (r=0.50, P<0.05) in preeclamptic women, but not in women with uncomplicated pregnancies. Similar to the patients with metabolic syndrome, we found that dysregulation of adipocytokines, such as low adiponectin levels and high levels of other adipocytokines, and excess body weight gain during pregnancy, may decrease plasma adiponectin concentrations that are associated with endothelial dysfunction in preeclamptic women.

Topics: Adipokines; Adiponectin; Body Weight; Case-Control Studies; Endothelium, Vascular; Female; Humans; Interleukin-6; Leptin; Metabolic Syndrome; Plasminogen Activator Inhibitor 1; Pre-Eclampsia; Pregnancy; Triglycerides; Vasodilation

Postmenopausal women develop often obesity which may be prevented by 20-OH-Ecdysone (Ecd). This was investigated in ovariectomized (ovx) rats. They were orally treated with 3 doses of Ecd (18, 56 or 116 mg/day/animal). Positive controls received 159 microg estradiol (E2). Quantitative computer tomography at the level of the abdomen and the metaphysis of the tibia allowed estimation of surface, fat depots and muscles. The highest dose of Ecd resulted in serum concentrations of 0.4 x 10(-6)M. Serum E2 concentrations in the positive controls were 73.3+/-24.41 pg/ml. E2 but not Ecd stimulated uterine weights. Under Ecd ovx animals gained less fat but had more muscle mass. Serum TSH, T4 and T3 levels remained unaffected while E2 treatment increases T4 but decreases T3 levels. Ecd at the lowest dose lowered serum LDL and did not result in increased serum triglycerides, an effect seen in the E2 treated rats. At the Ecd highest dose serum HDL was higher than in the controls. In conclusion Ecd has beneficial effects on fat and muscle tissue and may be able to prevent the metabolic syndrome and sarcopenia by a non-estrogenic mechanism.

Topics: Animals; Body Composition; Dose-Response Relationship, Drug; Ecdysterone; Estrogens; Female; Hindlimb; Intra-Abdominal Fat; Leptin; Lipids; Metabolic Syndrome; Obesity; Organ Size; Ovariectomy; Postmenopause; Rats; Rats, Sprague-Dawley; Sarcopenia; Thyroid Hormones; Thyrotropin; Uterus

The metabolic syndrome (MS) has become an epidemiological problem in Western countries. We developed a diet-induced obese rat model that mimics all the symptoms of MS in humans, but whose insulin resistance, hyperphagia and hyperleptinemia are caused by nutrition rather than genetic modifications.. Spontaneously hypertensive rats (SHR) were allowed for 12 weeks to choose between a cafeteria diet (CD, 20.3 kJ/g) and standard rat chow (11.7 kJ/g). Controls received rat chow.. Body weight (BW) exceeded control levels when SHR were fed with CD. The increase in BW was attributed to enhanced energy intake. The abundance of abdominal fat as well as the plasma levels of leptin and triglycerides increased concomitant with glucose, insulin and C-peptide. This prediabetic condition was further confirmed by a markedly increased insulin response following glucose challenge and by impaired glucose utilization after insulin tolerance tests.. Increases in food intake and BW despite hyperleptinemia indicate leptin resistance following CD feeding. CD-fed SHR feature leptin and insulin resistance, hypertension and obesity, thus mimicking the situation of MS patients. As such, our model is more suitable than the genetically modified rat models used to study human MS.

Topics: Abdominal Fat; Animals; Biomarkers; Blood Glucose; Blood Pressure; Body Weight; C-Peptide; Diet; Disease Models, Animal; Energy Intake; Heart Rate; Hyperphagia; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Triglycerides

Primary aldosteronism (PA) has been recently associated with an unfavorable cardiometabolic profile. However, whether pro- and antiinflammatory adipokines levels can vary in PA is unknown.. We evaluated the circulating levels of resistin, leptin, and adiponectin, echocardiographic left ventricle (LV) parameters, and the prevalence of metabolic syndrome (SM) in subjects with PA.. Seventy-five subjects with established diagnosis of PA and 232 consecutive individuals with known or suspected hypertension were enrolled.. Plasma adipokine levels and echocardiographic parameters were calculated. Prevalence of SM was also estimated.. Among the 75 PA subjects, 37 patients were affected by aldosterone-producing adenoma and 38 by idiopathic hyperaldosteronism; 40 subjects were affected by essential hypertension (EH) and SM (EH SM+); 152 subjects were affected by EH without SM (EH SM-); and 40 subjects were normotensive (NT). Subjects with PA had the highest plasma resistin levels among the four groups (P < 0.01). Plasma resistin concentration was significantly higher in PA subjects when compared with EH SM+ individuals (P < 0.01) and EH SM- subjects (P < 0.01). PA subjects showed the higher LV mass and left atrium than EH individuals, irrespectively of the presence of SM (P < 0.01 for both). Plasma resistin levels was significantly correlated with ejection fraction and LV end-diastolic volume. The prevalence of SM was higher in PA subjects than in those with EH (25.4 vs. 20.3%).. Our data suggest that elevated aldosterone levels is associated with elevated circulating resistin levels and cardiac morphological changes independently of the presence of SM.

Topics: Adenoma; Adiponectin; Adult; Aged; Aldosterone; Biomarkers; Blood Glucose; Blood Pressure; C-Reactive Protein; Cholesterol; Echocardiography; Female; Heart Ventricles; Humans; Hyperaldosteronism; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Resistin; Young Adult

Obesity is a risk factor for colorectal cancer and adenomatous polyps. The increased prevalence of neoplasia coupled with the observation that obesity may be associated with a suboptimal bowel preparation may diminish the adequate detection of adenomas for obese who undergo colonoscopy. The colonic complications of obesity are reviewed in this article.

Topics: Adenoma; Animals; Body Mass Index; Colonic Diseases; Colonoscopy; Colorectal Neoplasms; Comorbidity; Diverticulitis, Colonic; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Metabolic Syndrome; Obesity

Numerous clinical and experimental studies have linked stress to changes in risk factors associated with the development of physiological syndromes, including metabolic disorders. How different mediators of the stress response, such as corticosterone (CORT), influence these changes in risk remains unclear. Although CORT has beneficial short-term effects, long-term CORT exposure can result in damage to the physiological systems it protects acutely. Disruption of this important physiologic signal is observed in numerous disparate disorders, ranging from depression to Cushing's syndrome. Thus, understanding the effects of chronic high CORT on metabolism and physiology is of key importance. We explored the effects of 4-wk exposure to CORT dissolved in the drinking water on the physiology and behavior of male mice. We used this approach as a noninvasive way of altering plasma CORT levels while retaining some integrity in the diurnal rhythm present in normal animals. This approach has advantages over methods involving constant CORT pellets, CORT injections, or adrenalectomy. We found that high doses of CORT (100 microg/ml) result in rapid and dramatic increases in weight gain, increased adiposity, elevated plasma leptin, insulin and triglyceride levels, hyperphagia, and decreased home-cage locomotion. A lower dose of CORT (25 microg/ml) resulted in an intermediate phenotype in some of these measures but had no effect on others. We propose that the physiological changes observed in the high-CORT animals approximate changes observed in individuals suffering from the metabolic syndrome, and that they potentially serve as a model for hypercortisolemia and stress-related obesity.

Topics: Adipose Tissue, White; Adiposity; Adrenal Glands; Animals; Atrophy; Chemical Phenomena; Corticosterone; Disease Models, Animal; Dose-Response Relationship, Drug; Endocrine System; Glucose Intolerance; Hyperphagia; Insulin; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Motor Activity; Thymus Gland; Triglycerides; Weight Gain

Previous studies suggest that periodontitis is closely related to obesity and metabolic syndrome. Leptin, a pleiotrophic hormone produced by adipose tissue, has been reported to be related to periodontitis. This study investigates the effects of periodontal treatment on the serum levels of leptin and other cytokines in patients with chronic periodontitis (CP).. Serum samples were taken from 33 CP patients (22 non-smokers, 11 smokers) and 18 healthy subjects. The serum leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, and C-reactive protein (CRP) levels were measured before and after non-surgical periodontal treatment.. Significant differences between healthy and CP patients were found in serum leptin, IL-6, and CRP levels (P = 0.0018, P = 0.0064, and P = 0.0095, respectively). The serum leptin level was associated with mean probing depth, mean clinical attachment level, mean alveolar bone loss, and body mass index. There were significant associations between serum leptin levels and IL-6 and CRP levels. After non-surgical periodontal treatment, serum leptin, IL-6, and CRP levels were significantly decreased (mean +/- SD before and after, P value, respectively: leptin, 8.02 +/- 5.5, 7.10 +/- 4.4, P = 0.015; IL-6, 1.73 +/- 1.02, 1.36 +/- 0.73, P = 0.048; and CRP, 802.0 +/- 1065, 491.2 +/- 479.3, P = 0.047).. Periodontal treatment is effective in reducing serum leptin, IL-6, and CRP levels. The results suggest that leptin, IL-6, and CRP could be mediating factors that connect metabolic syndrome and periodontitis.

Topics: Adiponectin; Alveolar Bone Loss; Body Mass Index; C-Reactive Protein; Chronic Periodontitis; Dental Plaque Index; Dental Scaling; Female; Follow-Up Studies; Gingival Hemorrhage; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Oral Hygiene; Patient Education as Topic; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Root Planing; Smoking; Tumor Necrosis Factor-alpha

Interest in pharmacological intervention to combat metabolic syndrome and its complications is increasing as the prevalence of obesity is reaching epidemic proportions. The potential efficacy of drugs is often tested in animal models; however, the method of drug delivery is frequently overlooked and may act as a confounder due to stress. We hypothesized that long-term orogastric gavage would negatively influence the development of hepatic steatosis and the metabolic syndrome in a murine model of diet-induced obesity. C57BL/6J male mice were fed a high fat diet and were gavaged with a vehicle once or twice daily for 9 weeks. A group without orogastric gavaging served as control. A similar experiment was performed using leptin deficient ob/ob mice that were fed a standard diet for 4 weeks. Food intake was monitored, insulin resistance determined, and steatosis was assessed by histology and quantified via magnetic resonance spectroscopy. After 9 weeks, control C57BL/6J mice exhibited significantly more weight gain, insulin resistance and hepatic steatosis, compared to mice that were gavaged daily, or twice daily. This effect was likely due to decreased food consumption associated with gavage-induced stress. In contrast, the phenotype of leptin deficient ob/ob mice was not affected by orogastric gavage. Therefore, we concluded that orogastric gavage may lead to increased stress, thereby affecting food intake and the development of diet-induced obesity in a murine model. The effects of what may seem to be trivial laboratory routines, such as orogastric gavage, should be taken into account when designing animal studies for drug development.

Topics: Adiposity; Alanine Transaminase; Animals; Blood Glucose; Body Weight; Cholesterol; Dietary Fats; Eating; Energy Intake; Enteral Nutrition; Fasting; Fatty Liver; Insulin Resistance; Leptin; Liver; Magnetic Resonance Spectroscopy; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Organ Size; Phenotype; Severity of Illness Index; Stress, Physiological; Time Factors; Triglycerides; Weight Gain

Evidence suggests that telmisartan, an angiotensin II type 1 receptor (AT1) blocker and peroxisome proliferator-activated receptor-gamma partial agonist, has beneficial actions that limit development of the metabolic syndrome and diabetes. However, the role played by AT1 inhibition in metabolic effects elicited by telmisartan remains uncertain. Here we isolated the metabolic effects of telmisartan from AT1 antagonism.. Male At1a (also known as Agtr1a)-deficient mice were fed a standard diet or 60% high-fat diet; those on high-fat diet were co-administered telmisartan (3 mg kg(-1) day(-1) by oral gavage) or vehicle for 12 weeks.. In At1a-null mice, telmisartan prevented high-fat-diet-induced increases in (1) body weight, epididymal and inguinal white adipose tissue weight, adipocyte size and plasma leptin concentration; (2) plasma glucose and insulin concentrations and HOMA index; and (3) liver weight and triacylglycerol content. Insulin tolerance testing also indicated that telmisartan improved the high-fat-diet-induced reduction of glucose-lowering by insulin.. The present findings demonstrate beneficial, AT1-independent effects of the AT1 blocker telmisartan on dietary-induced obesity, insulin resistance and fatty liver in animals.

Topics: Adipocytes; Adipose Tissue, White; Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Benzoates; Blood Glucose; Cell Size; Diet, High-Fat; Fatty Liver; Insulin; Insulin Resistance; Leptin; Lipids; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Obesity, Abdominal; Organ Size; PPAR gamma; Receptor, Angiotensin, Type 1; Telmisartan; Triglycerides

Osteocalcin has been reported to influence insulin secretion in experimental animals. We investigated whether serum osteocalcin was associated with measures of insulin resistance, circulating adipokine levels, and the presence of metabolic syndrome (MetSyn).. Serum osteocalcin was measured by solid-phase sandwich immunoassay in 1284 blacks (64+/-9 years; 71% women) and 1209 non-Hispanic whites (59+/-10 years; 57% women) belonging to hypertensive sibships. MetSyn was defined per Adult Treatment Panel III criteria. The prevalence of MetSyn was 50% in blacks and 49% in non-Hispanic whites. In each ethnic group, after adjustment for age and gender, osteocalcin levels were inversely correlated with body mass index, fasting glucose and insulin, homeostasis model assessment of insulin resistance, triglycerides, and leptin, and positively correlated with adiponectin (P<0.001 for each variable). In multivariable regression analyses that adjusted for age, gender, smoking, serum creatinine, and statin and estrogen use, osteocalcin levels in the highest quartile (compared with the lowest quartile) were associated with a lower odds ratio (OR) of having MetSyn: OR (95% CI) in blacks, 0.33 (0.23 to 0.46); OR in non-Hispanic whites, 0.43 (0.31 to 0.63).. Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of MetSyn, suggesting a novel cross-talk between bone and adipose tissue.

Topics: Adipokines; Adiponectin; Aged; Biomarkers; Black or African American; Blood Glucose; Body Mass Index; Chi-Square Distribution; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Humans; Insulin; Insulin Resistance; Leptin; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Minnesota; Mississippi; Odds Ratio; Osteocalcin; Risk Assessment; Risk Factors; White People

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

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

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

Obesity induced, non-alcoholic fatty liver disease (NAFLD), is now the major cause in affluent countries, of the spectrum of steatosis-to-cirrhosis. Obesity and NAFLD rates in reproductive age women, and adolescents, are rising worldwide. Our hypothesis was that maternal obesity and lactation transmit to the offspring a pre-disposition to dysmetabolism, obesity and NAFLD.. Female mice were fed standard or obesogenic chow, before, throughout pregnancy, and during lactation. The critical developmental period was studied by cross-fostering offspring of lean and obese dams. Offspring were then weaned onto standard chow and studied at 3months. Read-outs included markers of metabolic dysfunction, biochemical and histological indicators of NAFLD, induction of liver fibrogenesis, and activation of pro-fibrotic pathways. Mechanisms involved in programming a dysmetabolic and NAFLD phenotype were investigated by assaying breast milk components.. Offspring of obese dams had a dysmetabolic, insulin resistant and NAFLD phenotype compared to offspring of lean dams. Offspring of lean dams that were suckled by obese dams showed an exaggerated dysmetabolic and NAFLD phenotype, with increased body weight, as well as increased levels of insulin, leptin, aspartate transaminase, interleukin-6, tumour necrosis factor-alpha, liver triglycerides, steatosis, hepatic fibrogenesis, renal norepinephrine, and liver alpha1-D plus beta1-adrenoceptors, indicative of sympathetic nervous system activation. Obese dams also had raised breast milk leptin levels compared to lean dams.. Maternal obesity programs development of a dysmetabolic and NAFLD phenotype, which is critically dependent on the early postnatal period and possibly involving alteration of hypothalamic appetite nuclei signalling by maternal breast milk and neonatal adipose tissue derived, leptin.

Topics: Actins; Adipose Tissue; Animals; Collagen; Collagen Type I; Fatty Liver; Female; Gene Expression; Interleukin-6; Lactation; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Milk; Obesity; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Receptors, Adrenergic, alpha-1; Signal Transduction; Tumor Necrosis Factor-alpha

The aim of this study was to investigate the influence of polygenetic polymorphisms, which play a role in the pathogenesis of metabolic syndrome, on the susceptibility to non-alcoholic fatty liver disease (NAFLD) of Chinese people.. The subjects were selected from an epidemiological survey in the Guangdong province of southern China. In each polymorphism study, 50-117 subjects who met the diagnostic criteria of NAFLD and had typical clinical and ultrasonographic findings were placed into the case group. Using a nested case-control design, the same numbers of matched people without NAFLD were included as controls. Single nucleotide polymorphisms (SNP) at nine positions in seven candidate genes were tested. These SNP were found to be associated with the pathogenesis of metabolic syndrome. Genetic analyses were performed using genomic DNA extracted from peripheral blood leukocytes. Polymerase chain reaction-restriction fragment length polymorphism was applied to detect SNP.. Most candidate genes' SNP were associated with susceptibility to NAFLD. Some showed positive relationships (increased risk): tumor necrosis factor-alpha-238, adiponectin-45, leptin-2548, peroxisome proliferator-activated receptors-161 and phosphatidyletha-nolamine N-methyltransferase-175. Other SNP demonstrated a negative association (decreased risk): adiponectin-276 and hepatic lipase-514. Only two were not associated: tumor necrosis factor-alpha-380 and peroxisome proliferator-activated receptors-gamma co-activator-1alpha-482.. Most candidate genes' SNP examined in metabolic syndrome patients were associated with susceptibility to NAFLD.

Topics: Adiponectin; Adult; Aged; Asian People; Case-Control Studies; Chi-Square Distribution; China; Fatty Liver; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Heat-Shock Proteins; Humans; Leptin; Lipase; Liver; Male; Metabolic Syndrome; Middle Aged; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phenotype; Phosphatidylethanolamine N-Methyltransferase; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; PPAR gamma; Prognosis; Risk Assessment; Risk Factors; Transcription Factors; Ultrasonography

The availability of useful animal models reflecting the human obesity syndrome is crucial in the search for novel compounds for the pharmacological treatment of obesity. In the current study, we have performed an extensive characterization of the obesity syndrome in a polygenetic animal model, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization including blood biochemistry and glucose homeostasis was examined at 2, 3, 6, and 9 months of age. Furthermore, in 6-month-old HE-fed DIO rats, the anti-obesity effects of liraglutide and sibutramine were examined in a 28-day study. Only HE-fed DIO rats developed visceral obesity, hyperleptinemia, hyperinsulinemia, and dyslipidemia, and showed a worsening of glucose tolerance over time. In line with the hyperlipidemic profile, a severe hepatic fat infiltration was observed in DIO rats at 6 months of age. The effects of liraglutide and sibutramine were tested in 6-month-old DIO rats. Both compounds effectively reduced food intake and body weight in DIO rats. Liraglutide furthermore improved glucose tolerance when compared with sibutramine. Our data highlights the usefulness of a polygenetic animal model for screening of compounds affecting food intake, body weight, and glucose homeostasis. Furthermore, the results underscore the effectiveness of GLP-1 mimetics both as anti-diabetes and anti-obesity agents.

Topics: Analysis of Variance; Animals; Appetite Depressants; Blood Glucose; Cyclobutanes; Diet; Disease Models, Animal; Eating; Enzyme-Linked Immunosorbent Assay; Feeding Behavior; Glucagon-Like Peptide 1; Insulin; Insulin Resistance; Leptin; Liraglutide; Metabolic Syndrome; Obesity; Rats; Rats, Sprague-Dawley

Elevated lipopolysaccharide-binding protein (LBP), a marker of subclinical endotoxemia, may be involved in the pathogenesis of obesity and metabolic risk. We aimed to investigate the association between plasma LBP and metabolic disorders in apparently healthy Chinese.. A population-based study including 559 overweight/obese (BMI >or=24.0 kg/m(2)) and 500 normal-weight (18.0

Topics: Acute-Phase Proteins; Adiponectin; Adult; Asian People; C-Reactive Protein; Carrier Proteins; Diabetes Mellitus, Type 2; Endotoxemia; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Leptin; Male; Membrane Glycoproteins; Metabolic Syndrome; Middle Aged; Obesity

Metabolic syndrome and abdominal obesity are the risk factors for cardiovascular diseases. The greater amount of adipose tissue the higher level of leptin, adipocytocin with potential proatherogenic properties.. was to evaluate the leptin level in patients with acute ischemic stroke and leptin's role in the pathogenesis of cerebrovascular diseases.. We examined 45 patients with acute ischemic stroke and 17 cases without CNS diseases, matched with age and gender. In all subjects we examined lipid pattern (cholesterol, HDL-cholesterol, LDL-cholesterol, triglicerydes), blood glucose level, blood pressure, BMI (body mass index) and central fat--measured by WC (waist circumference) and W/HR (waist to hip ratio). On the basis of these parameters we diagnosed the presence of metabolic syndrome, according to American Heart Association 2005. Leptin level was measured by an enzyme linked immunosorbent assay. Ultrasonographic scanning of the carotid artery was performed in every patient to evaluate the CIMT and arteriosclerosis.. Hyperleptiemia is more often present in patient with abdominal obesity (p < 0.001) and in subjects with metabolic syndrome (p < 0.01)--the constellation of risk factors predisposing to ischemic stroke. There is no independent association between increased leptin concentrations and glucose levels and presence of hypertension (p > 0.05). Hyperleptynemia is associated with CIMT--an early marker of asymptomatic atherosclerosis.. Leptin can be the stroke manifestation of obesity. There is necessary to further evaluation of leptin's role in the pathogenesis of cerebrovascular diseases and its potential role in prophylaxis of ischemic stroke.

Topics: Adult; Aged; Aged, 80 and over; Brain Infarction; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity, Abdominal

Factors released by perivascular adipose tissue (PVAT) disrupt coronary endothelial function via phosphorylation of endothelial NO synthase by protein kinase C (PKC)-beta. However, our understanding of how PVAT potentially contributes to coronary disease as a complication of obesity/metabolic syndrome (MetS) remains limited. The current study investigated whether PVAT-derived leptin impairs coronary vascular function via PKC-beta in MetS.. Coronary arteries with and without PVAT were collected from lean or MetS Ossabaw miniature swine for isometric tension studies. Endothelial-dependent vasodilation to bradykinin was significantly reduced in MetS. PVAT did not affect bradykinin-mediated dilation in arteries from lean swine but significantly exacerbated endothelial dysfunction in arteries from MetS swine. PVAT-induced impairment was reversed by inhibition of either PKC-beta with ruboxistaurin (Eli Lilly and Company, Indianapolis, Ind) or leptin receptor signaling with a recombinant, pegylated leptin antagonist. Western blot and immunohistochemical analyses demonstrated increased PVAT-derived leptin and coronary leptin receptor density with MetS. Coronary PKC-beta activity was increased in both MetS arteries exposed to PVAT and lean arteries exposed to leptin. Finally, leptin-induced endothelial dysfunction was reversed by ruboxistaurin.. Increases in epicardial PVAT leptin exacerbate coronary endothelial dysfunction in MetS via a PKC-beta-dependent pathway. These findings implicate PVAT-derived leptin as a potential contributor to coronary atherogenesis in MetS.

Topics: Adipose Tissue; Animals; Coronary Vessels; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Leptin; Male; Metabolic Syndrome; Pericardium; Phenotype; Protein Kinase C; Protein Kinase C beta; Protein Kinase Inhibitors; Receptors, Leptin; Signal Transduction; Swine; Swine, Miniature; Up-Regulation; Vasodilation; Vasodilator Agents

Topics: Adiponectin; Biomarkers; Cohort Studies; Humans; Hypertension; Insulin Resistance; Leptin; Metabolic Syndrome; Sleep Apnea, Obstructive

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

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

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

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

The link between obesity and insulin resistance largely accounts for the pathogenesis of metabolic syndrome and diabetes mellitus, in which adipokine expression plays a key role. Puerarin, a major active isoflavone extracted from the traditional Chinese medicine Radix Puerariae, has been studied for its comprehensive biological actions. However, its effect on high-fat diet (HFD)-induced insulin resistance and adipokine expression in rat has not been well investigated. In the present study, male Sprague-Dawley rats were fed on a normal control diet (NCD) or HFD for 6 weeks, followed by administration of puerarin (100 and 200 mg/kg) for up to 8 weeks. Compared to NCD, HFD feeding for 6 weeks led to increased body weight gain and impaired glucose/insulin tolerance manifested by oral glucose/intraperitoneal insulin tolerance tests in rats. These exacerbations prolonged through HFD feeding, but were effectively reversed by puerarin administration. Enzyme-linked immunosorbent assay demonstrated that, serum levels of leptin and resistin, but not that of adiponectin, were markedly augmented by HFD and retarded by puerarin treatment. Real-time reverse transcription polymerase chain reaction results showed that, in agreement with the circulating levels, mRNA expression of leptin and resistin in epididymal white adipose tissue was modified by HFD and improved by puerarin in the same pattern. Collectively, we revealed that puerarin could improve body weight gain, glucose/insulin intolerance and adipokine expression in HFD-induced insulin resistant rats, indicating its potential value for treatment of metabolic syndrome.

Topics: Adipokines; Adiponectin; Adipose Tissue, White; Animals; Anti-Obesity Agents; Dietary Fats; Dose-Response Relationship, Drug; Glucose Intolerance; Insulin Resistance; Isoflavones; Leptin; Male; Metabolic Syndrome; Obesity; Random Allocation; Rats; Rats, Sprague-Dawley; Resistin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To investigate the role of hormones and the types of FB in the development of morbid obesity (MO), to develop a treatment policy for MO to examine the diagnostic predictive value of the FB hormones and FB modifications.. Were investigated 67 patients: 28 (42%) males and 39 (58%) female aged 18 to 60 years under the scheme: medical history, questionnaire on the questionnaire SF-36, score types of FB, the study of the anthropometric data (OT/OB, BMI), the definition of the FB hormones with subsequent control of BMI, OT/OB dynamics, types and FB hormones.. In patients older than 50 years were dominated abdominal FB, in patients younger than 50 years - all three types of FB in approximately equal proportions. After the decline in MT was observed pattern between the FB modification and age of the patient. There was an increase of leptin and ghrelin and decrease in serotonin at all three types of FB. After weight correction was a decreased leptin, ghrelin, and increased serotonin, but the achievement of normal numbers are not marked. The paradoxical result is related to a violation of reciprocal relations of hormones.. In patients with MO FB hormone levels (Leptin, Ghrelin) elevated to normal values, reduced levels of serotonin, there is an infringement of their reciprocal correlations. The approach to patients should be lengthy and complex, involving multidisciplinary team aimed at FB correcting the with the rejection of improper food stereotype. In the treatment of MO must used different methods: reducing diet, physiotherapy effects, drug therapy and their combination with the selection of individual programs, taking into contraindications account. For the above techniques inefficiency is necessary to use surgical treatment. Correction of FB in patients older than 50 years is the most difficult task (due to the presence of concomitant diseases). Necessary to draw attention and to start treatment at a young age.

Topics: Adolescent; Adult; Age Factors; Feeding Behavior; Female; Ghrelin; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Serotonin

Baboons (Papio hamadryas Sp.) develop features of the cardiometabolic syndrome and represent a clinically-relevant animal model in which to study the aetiology of the disorder. To further evaluate the baboon as a model for the study of the cardiometabolic syndrome, we developed a high sugar high fat diet and hypothesized that it could be used to induce adiposity gain and affect associated circulating biomarkers.. We developed a diet enriched with monosaccharides and saturated fatty acids that was composed of solid and liquid energy sources. We provided a group of baboons (n = 9) ad libitum access to this diet for 8 weeks. Concurrently, a control group (n = 6) was maintained with ad libitum access to a low sugar low fat baseline diet and normal water for 8 weeks. Body composition was determined by dual-energy X-ray absorptiometry and circulating metabolic biomarkers were measured using standard methodology before and after the 8 week study period.. Neither body composition nor circulating biomarkers changed in the control group. Following the 8 weeks, the intervention group had a significant increase in fat mass (1.71 ± 0.98 vs. 3.23 ± 1.70 kg, p = 0.004), triglyceride (55 ± 13 vs. 109 ± 67 mg/dL, p = 0.006,), and leptin (1.19 ± 1.40 vs. 3.29 ± 2.32 ng/mL, p = 0.001) and a decline in adiponectin concentrations (33530 ± 9744 vs. 23330 ± 7863 ng/mL, p = 0.002). Percentage haemoglobin A1C (4.0 ± 0.3 vs. 6.0 ± 1.4, p = 0.002) also increased in the intervention group.. Our findings indicate that when exposed to a high sugar high fat diet, young adult male baboons develop increased body fat and triglyceride concentrations, altered adipokine concentrations, and evidence of altered glucose metabolism. Our findings are in keeping with observations in humans and further demonstrate the potential utility of this highly clinically-relevant animal model for studying diet-induced metabolic dysregulation.

Topics: Absorptiometry, Photon; Adiponectin; Adiposity; Animals; Biomarkers; C-Reactive Protein; Dietary Fats; Dietary Sucrose; Energy Intake; Energy Metabolism; Glycated Hemoglobin; Insulin; Leptin; Male; Metabolic Syndrome; Obesity; Papio hamadryas; Time Factors; Triglycerides

Metabolic syndrome (MetS), manifested by insulin resistance, dyslipidemia, central obesity, and hypertension, is conceived to be associated with hyperleptinemia and physical activity. The aim of this study was to elucidate the factors underlying components of MetS and also to test the suitability of leptin and physical activity as additional components of this syndrome. Data of the individuals without history of diabetes mellitus, aged 25-64 years, from third national surveillance of risk factors of non-communicable diseases (SuRFNCD-2007), were analyzed. Performing factor analysis on waist circumference, homeostasis model assessment of insulin resistance, systolic blood pressure, triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) led to extraction of two factors which explained around 59.0% of the total variance in both genders. When TG and HDL-C were replaced by TG to HDL-C ratio, a single factor was obtained. In contrast to physical activity, addition of leptin was consistent with one-factor structure of MetS and improved the ability of suggested models to identify obesity (BMI≥30 kg/m2, P<0.01), using receiver-operator characteristics curve analysis. In general, physical activity loaded on the first identified factor. Our study shows that one underlying factor structure of MetS is also plausible and the inclusion of leptin does not interfere with this structure. Further, this study suggests that physical activity influences MetS components via modulation of the main underlying pathophysiologic pathway of this syndrome.

Topics: Adult; Blood Pressure; Female; Homeostasis; Humans; Insulin Resistance; Iran; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Motor Activity; Population Surveillance; Predictive Value of Tests; Risk Assessment; Risk Factors; Waist Circumference

TNF--α is one of the most important factors in the development and course of inflammation. It is suggested that polymorphism located in the 5'regulatory region of the TNF-α gene at position 308 (guanine [G]→adenine[A]) may increase the expression of this cytokine in fat tissue and influence the fat mass and insulin resistance.. To investigate whether the G-308A polymorphism of the TNF-α gene may influence obesity, insulin resistance, fasting plasma lipids, serum leptin levels, and the incidence of metabolic syndrome.. The obese group included 124 children with simple obesity (72 girls and 52 boys) aged 10-18 (mean age 15 years) with SDS of BMI ≥2.0. A control group consisted of 56 healthy non-obese children (36 girls and 20 boys) aged 11-18 (mean age 14 years) with SDS of BMI <1.0. Polymorphism identification was performed in total genomic DNA, using PCR-RFLP method.. Carriers of A (AG+AA) allele among the obese children were significantly more frequent than in the control group (OR = 2.29, 95% CI 1.2-4.4, χ⊃2 = 6.24, P<0.05). Carriers of A alleles showed a higher concentrations of fasting glucose (81.3 ±10.5 vs. 77.4 ±10.3 mg/dl; P<0.05), but lower values of fasting insulin (15.1 ±7.3 vs. 19.0 ±9.5 μIU/ml; P<0.05), lower values of HOMA index (3.0 ±1.5 vs. 3.7 ±2.0; P <0.05). In the group of boys, carriers of A alleles showed a tendency for lower concentrations of HDL (43.8 ±12.6 vs. 48.3 ±11.8 mg/dl; P<0.05). Blood pressure and leptin level did not differ between the obese children with gene polymorphism and those of wild homozygous. The incidence of the full metabolic syndrome (MetS) in the children, according to the IDF definition, was 33%. The presence of the MetS in children with wild homozygous GG and carriers of A allele of TNF-α polymorphism gene did not show statistical differences (OR = 1.38; 95% CI 0.6-3.1, χ⊃2 = 0.58).. 1/ Polymorphism G-308A of the TNF-α gene is more common in children with obesity; and 2/ Polymorphism G-308A of the TNF-α gene does not seem to be associated with the grade of obesity, insulin resistance, lipid profile, leptin levels, and the incidence of metabolic syndrome in obese children.

Topics: Adolescent; Child; Cholesterol, HDL; Female; Genotype; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Polymorphism, Genetic; Tumor Necrosis Factor-alpha

Leptin plays an important role in the regulation of body weight and operates by inhibiting food intake and stimulating energy expenditure. The purpose of the present study was to ascertain the relationship between serum leptin levels and the lipid profile, insulin resistance, and metabolic risk factors in North Indian adult women. In a transactional case-control study of 390 women, subjects were 186 women with metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) guidelines and 204 healthy control women without metabolic syndrome, all of whom were between 20-40 years of age. Circulating leptin levels were determined by sandwich enzyme-linked immunosorbent assay, insulin resistance was determined by homeostasis model assessment for insulin resistance (HOMA-IR), and the lipid profile was determined using an enzymatic method. Results indicated that circulating leptin (13.38 ± 9.00 vs. 8.16 ± 6.31 ng/mL, p < 0.001), HOMA-IR (2.68 ± 2.05 vs. 1.72 ± 1.20, p < 0.001), the lipid profile, and other metabolic risk factors (waist circumference, waist-to-hip ratio, body mass index, and fasting plasma insulin) were significantly higher in women with metabolic syndrome than in women without the syndrome (p < 0.001). Further, in women with metabolic syndrome serum leptin was significantly (p < 0.05 or p < 0.001) and positively correlated with HOMA-IR (p = 0.000) and other metabolic risk factors but negatively correlated with fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol. Circulating leptin was found to be significantly associated with hyperlipidemia, insulin resistance, and other metabolic risk factors in North Indian adult women.

Topics: Adult; Anthropometry; Blood Pressure; Enzyme-Linked Immunosorbent Assay; Female; Humans; India; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Risk Factors

To estimate the incidence and clinical value of metabolic syndrome, insulin resistance, and steatosis in patients with chronic hepatitis C (CHC) caused by its virus genotype 1.. One hundred and fourteen patients (67 men and 47 women; mean age 44.9 +/- 13.3 years) were examined.. There were high incidence rates of metabolic syndrome (47.2%) and insulin resistance (50%), in the genesis of which the host-virus interaction is discussed. There was an independent correlation of the insulin resistance and elevated leptin levels with abdominal obesity and hepatic steatosis; however, these indicators did not correlate with the stage of fibrosis. At the same time hepatic steatosis (found in 38% of the patients) and its degree correlated with the stage of fibrosis. Thirty-four of 66 (54.5%) patients receiving antiviral therapy achieved a stable virological response.. Obesity, hyperglycemia, and significant insulin resistance along with the stage of hepatic cirrhosis are independent cofactors that determine no treatment response.

Topics: Adult; Antiviral Agents; Diabetes Mellitus, Type 2; Fatty Liver; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Incidence; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Prospective Studies; Treatment Outcome

Topics: Breast Neoplasms; Female; Humans; Insulin; Leptin; Metabolic Syndrome; Risk Factors

Serum adipocyte fatty acid-binding protein (FABP) concentrations are linked to human obesity and other features of metabolic syndrome. Whether FABP associates with metabolic alterations in chronic malnutrition is unknown. In the present study, we measured fasting serum levels of FABP, leptin, soluble leptin receptor, adiponectin, resistin, C-reactive protein (CRP), insulin, glucose, cholesterol and triglycerides in 19 patients with a restrictive type of anorexia nervosa (AN) and in 16 healthy age-matched control women (C). Body mass index, serum leptin, and CRP concentrations were significantly lower, while serum adiponectin and soluble leptin receptor levels were significantly higher in AN relative to C group. Serum insulin, glucose, cholesterol and triglyceride levels did not differ between the groups studied. Serum FABP levels were unchanged in patients with AN and were not related to any of parameters studied. We conclude that, in contrast to patients with obesity where FAPB is a prominent marker of metabolic alterations, chronic malnutrition in AN does not significantly affect its serum levels.

Topics: Anorexia Nervosa; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholesterol; Fatty Acid-Binding Proteins; Female; Humans; Leptin; Lipid Metabolism; Metabolic Syndrome; Nutritional Status; Obesity; Receptors, Leptin; Young Adult

Pigment epithelium-derived factor (PEDF) inhibits endothelial cell injury. Further, serum levels of PEDF are elevated in the metabolic syndrome. These observations suggest that PEDF may be elevated as a counter-system against vascular cell damage in the metabolic syndrome. However, little is known about the regulation of PEDF in patients with diabetes. In order to clarify the determinants of serum PEDF, here, we examined the relationship between the 1-year changes in PEDF levels and those in anthropometric and metabolic variables in type 2 diabetic patients.. Eighty-six consecutive outpatients with type 2 diabetes underwent a complete history and physical examination, determination of blood chemistries, and serum levels of PEDF at baseline and 1 year after. PEDF gene expression in cultured subcutaneous or omental adipocytes were analysed by quantitative real-time reverse transcription-polymerase chain reactions.. Multiple regression analyses revealed that waist circumference, triglycerides, creatinine, and TNF-alpha were independently associated with PEDF. Further, the percent changes in serum levels of PEDF during 1-year observational periods were positively correlated with those of BMI. In addition, PEDF mRNA levels in cultured adipocytes were increased in parallel to the BMI values of subjects from whom adipocytes were derived, especially in omental adipocytes.. These results demonstrated that serum levels of PEDF were positively associated with metabolic components and TNF-alpha in Japanese patients with type 2 diabetes. Our present study suggests that PEDF may be generated from adipose tissues and play some role in visceral obesity in type 2 diabetic patients.

Topics: Adipocytes; Adipose Tissue; Aged; Body Mass Index; Diabetes Mellitus, Type 2; Eye Proteins; Female; Follow-Up Studies; Humans; Japan; Leptin; Male; Metabolic Syndrome; Middle Aged; Nerve Growth Factors; Obesity; Regression Analysis; RNA, Messenger; Serpins; Serum Amyloid A Protein; Time Factors; Viscera

Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high- or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or "junk food" diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance.

Topics: Adiposity; Age Factors; Aging; Animal Nutritional Physiological Phenomena; Animals; Behavior, Animal; Blood Pressure; Body Weight; Conditioning, Operant; Dietary Fats; Disease Models, Animal; Feeding Behavior; Female; Hybridization, Genetic; Hyperphagia; Hypertension; Insulin; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Motivation; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred SHR; Rats, Wistar; Reward; Weaning

Over the last decade there has been a steady rise in obesity and co-morbidity, but little is known about the rate of metabolic dysfunction among young adults in the United Arab Emirates. Various factors have been implicated as biomarkers of metabolic syndrome. The objective of this study was to analyze the relationships of leptin, C-reactive protein (CRP), adiponectin, insulin, and uric acid to the metabolic syndrome components in lean, overweight, and obese young females.. This was a cross-sectional study of 69 apparently healthy young females, who were classified according to their body mass index (BMI) (kg/m(2)) into three groups: lean (25 and <30), and obese (>or=30). Estimated biomarkers were: leptin, insulin, adiponectin, high-sensitivity [hs]-CRP, uric acid, blood sugar, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides (TG). Anthropometric measures, blood pressure, and homeostasis model assessment-insulin resistance (HOMA-IR) were also measured.. Serum leptin, hs-CRP, insulin, and uric acid increased significantly (p < 0.01) with increased BMI. Only one significant correlation (p < 0.05) between the biomarkers and the metabolic syndrome components was found in lean subjects (leptin vs. waist circumference r = 0.48) as opposed to six in the obese group (hs-CRP vs. waist circumference and systolic blood pressure [SBP], r = 0.45 and r = -0.41, respectively; insulin vs. diastolic blood pressure [DBP], r = 0.47; adiponectin vs. blood sugar, r = -0.44; and uric acid vs. waist circumference and TG, r = 0.5 and r = 0.51, respectively).. Estimation of the levels of studied biomarkers could be an important tool for early detection of metabolic syndrome before the appearance of its frank components. Uric acid seems to be the most reliable biomarker to identify obese subjects with metabolic syndrome.

Topics: Adiponectin; Adolescent; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Cross-Sectional Studies; Early Diagnosis; Female; Humans; Insulin; Leptin; Metabolic Syndrome; Obesity; Overweight; Predictive Value of Tests; Thinness; United Arab Emirates; Up-Regulation; Uric Acid; Waist Circumference; Young Adult

This study was designed to test whether Alpinia pricei (AP), a member of the ginger family indigenous to Taiwan, reduced metabolic syndrome induced by sucrose-containing drinking water in C57BL/6J mice. Mice given a chow diet were divided into a control group (C) or a test group given 30% sucrose water (SW) to drink ad libitum. After 22 weeks, mice in the SW group were subdivided into SW and SW + AP groups, the latter receiving a chow diet with an ethanol extract of AP (1500 mg/kg dosage). Four weeks later, bio-indexes associated with metabolic syndrome were measured. Compared with the C group, the SW group had significantly higher body weight, visceral fat weights, serum and tissue lipid, serum insulin level and the area under the curve for blood glucose of the insulin tolerance test (p < 0.05). These indicators in the SW + AP group were lower than in the SW group except for serum lipid, although slightly higher than the C group. The SW + AP group also showed significantly lower serum levels of leptin and tumor necrosis factor-alpha and a significantly higher level of adiponectin than the SW group. These results indicated that visceral adiposity and insulin resistance induced by sucrose water drinking might be alleviated by AP supplementation.

Topics: Adiponectin; Alpinia; Animals; Blood Glucose; Body Weight; Dietary Sucrose; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipids; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Plant Extracts; Sucrose; Tumor Necrosis Factor-alpha

To study concentrations of adipokines in patients with systemic lupus erythematosus (SLE) and the relationship among adipokines, the metabolic syndrome (MeS), and cardiovascular disease (CVD) risk factors.. We enrolled 50 SLE patients and 26 controls, all women. Leptin, resistin, visfatin, and adiponectin were measured by commercial ELISA kits.. MeS prevalence was increased among subjects with SLE. Leptin levels were higher in patients with SLE than controls. Among SLE patients, independent determinants of leptin were insulin levels (p < 0.0001), triglycerides (p = 0.03), body mass index (p = 0.02), corticosteroid dosage (p = 0.02), and SLE Disease Activity Index (p = 0.005). Other adipokines did not differ between SLE patients and controls.. Leptin was increased in SLE patients and could play a role in SLE-related cardiovascular diseases.

Topics: Adipokines; Adiponectin; Adrenal Cortex Hormones; Adult; Biomarkers; Body Mass Index; Comorbidity; Cytokines; Female; Humans; Immunosuppressive Agents; Insulin; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Predictive Value of Tests; Resistin; Triglycerides; Up-Regulation

The aim of this study was to compare the strength of association between metabolic syndrome (MetS) and adiponectin, leptin and leptin to adiponectin ratio (L/A) in older Chinese. This study included 950 males (220 with MetS) and 1096 females (452 with MetS), aged 60-96 years from 18 major cities of the 2002 China National Nutrition and Health Survey. The associations of adiponectin, leptin and L/A with components of MetS and MetS were examined using logistic regression and the receiver operating characteristic (ROC) curves. The correlation coefficients of MetS components except fasting glucose with leptin were similar to those with L/A and higher than those with adiponectin. After adjusting for age and BMI, the odds ratio for MetS corresponding to 1 SD change in L/A was higher than those for leptin and adiponectin. L/A had highest area under the curve (AUC) for MetS. However, there was no statistically significant difference in AUC between leptin and L/A, and both indices produced a significantly higher AUC than adiponectin. In conclusion, L/A and leptin may be better diagnostic markers for MetS than adiponectin. After adjusting for BMI, L/A has better ability for correctly classifying subjects with and without MetS than adiponectin or leptin alone.

Topics: Adiponectin; Age Factors; Aged; Aged, 80 and over; Asian People; Body Mass Index; China; Data Collection; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Sex Factors

The study assessed anthropometric and laboratory variables, in particular testosterone (T) in a group of obese men of <40 years. Of 60 men with a body mass index (BMI) of >27 kg m(-2), 34 met the criteria of the metabolic syndrome (MS). Twenty men <40 years (with a BMI <25 kg m(-2)) were studied for comparison. It was found that with increasing BMI, levels of serum leptin, triglycerides, insulin, the ratio high-density lipoprotein (HDL) cholesterol/low-density liporotein (LDL) cholesterol, the waist circumference (WC), the area of visceral fat and systolic/diastolic blood pressure were higher, whereas insulin sensitivity (HOMA) and serum T were lower. Obesity (BMI 27-30 kg m(-2)) was associated with a decline in plasma T, but not with a decline in plasma sex hormone-binding globulin (SHBG). The latter was the case in more severe obesity (>30 kg m(-2)) qualifying as MS. In patients with MS, 58% variability of T levels could be predicted by combination of independent factors - SHBG, ratio LDL/HDL, insulin and leptin. On the other hand, in men with MS, 80% variance of concentrations of SHBG were predicted by triglycerides, HDL, glucose, leptin and surface of visceral adipose tissue. It is concluded that plasma T is significantly correlated with a number of features of the MS and, therefore, plasma T could serve as a marker of the MS.

Topics: Adult; Biomarkers; Blood Pressure; Body Mass Index; Cholesterol, HDL; Humans; Insulin; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Obesity; Sex Hormone-Binding Globulin; Testosterone; Triglycerides; Waist Circumference

Topics: HIV Infections; Humans; Leptin; Lipodystrophy; Metabolic Syndrome; Pilot Projects; Recombinant Proteins; Triglycerides

Metabolic syndrome (MS) encompasses a clustering of risk factors for cardiovascular disease, including obesity, insulin resistance, and dyslipidemia. We characterized a new mouse model carrying a dominant mutation, C57BL/6J-Nmf15/+ (B6-Nmf15/+), which develops additional complications of MS such as adipose tissue inflammation and cardiomyopathy. A backcross was used to genetically map the Nmf15 locus. Mice were examined in the comprehensive laboratory animal monitoring system, and dual energy X-ray absorptiometry and blood chemistry analyses were performed. Hypothalamic LEPR, SOCS1, and STAT3 phosphorylation were examined. Cardiac function was assessed by echo- and electrocardiography. Adipose tissue inflammation was characterized by in situ hybridization and measurement of Jun kinase activity. The Nmf15 locus mapped to distal mouse chromosome 5 with an LOD (logarithm of odds) score of 13.8. Nmf15 mice developed obesity by 12 weeks of age. Plasma leptin levels were significantly elevated in pre-obese Nmf15 mice at 8 weeks of age and an attenuated STAT3 phosphorylation in the hypothalamus suggests a primary leptin resistance. Adipose tissue from Nmf15 mice showed a remarkable degree of inflammation and macrophage infiltration as indicated by expression of the F4/80 marker and increased phosphorylation of JUN N-terminal kinase 1/2. Lipidosis was observed in tubular epithelial cells and glomeruli of the kidney. Nmf15 mice demonstrate both histological and pathophysiological evidence of cardiomyopathy. The Nmf15 mouse model provides a new entry point into pathways mediating leptin resistance and obesity. It is one of few models that combine many aspects of MS and can be useful for testing new therapeutic approaches for combating obesity complications, particularly cardiomyopathy.

Topics: Adipose Tissue; Animals; Blood Glucose; Cardiomyopathies; Chromosome Mapping; Disease Models, Animal; Female; Hypothalamus; Inflammation; Leptin; Lipidoses; Male; Metabolic Syndrome; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Oxygen Consumption; Quantitative Trait Loci

Leptin is correlated with several features of metabolic syndrome; however, possible confounders (eg, obesity) of this association are not known. This study evaluated the relationship between leptin, metabolic syndrome, and insulin resistance in an Iranian population and further investigated whether this relationship is confounded by obesity or central obesity.. A total of 387 participants (18-65 years old) who referred to a large university general hospital for routine health examinations were categorized into 2 groups with (n = 130) and without (n = 257) metabolic syndrome. Fasting plasma glucose, insulin, lipids, and leptin levels were measured and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria.. Age- and sex-adjusted leptin levels were significantly higher in patients with than those without metabolic syndrome (29.62 +/- 1.67 vs. 18.50 +/- 1.21 ng/mL, P < 0.001). After adjustment for age, sex, and body mass index (BMI), leptin values were significantly correlated with HOMA-IR (P < 0.001), metabolic syndrome, and its components (P < 0.05). After adjustment for waist circumference, however, these associations were no longer statistically significant.. We demonstrated that high leptin levels are associated with insulin resistance and metabolic syndrome independent of BMI but these associations are significantly mediated through the effects of central obesity.

Topics: Adolescent; Adult; Aged; Asian People; Biomarkers; Blood Glucose; Body Mass Index; Confounding Factors, Epidemiologic; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Iran; Leptin; Lipids; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Models, Biological; Obesity, Abdominal; Risk Assessment; Risk Factors; Waist Circumference; Young Adult

Metabolic syndrome and coronary artery disease (CAD) are increasing in urban black South Africans during their transition from a rural to a western lifestyle. Inflammation is frequently associated with metabolic syndrome and CAD. This study evaluated markers of inflammation in black CAD patients, some of whom had metabolic syndrome.. Metabolic syndrome was defined according to International Diabetes Federation criteria. Inflammatory markers leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) were measured in 40 patients and 20 control subjects.. Metabolic syndrome was present in 23 patients and absent in 17 patients. Leptin was the only significantly higher marker in patients with metabolic syndrome compared to patients without metabolic syndrome (P < 0.01). Leptin was higher in women than men (P < 0.01) and higher in both genders with metabolic syndrome (P < 0.03 and P < 0.04, respectively). Leptin levels rose significantly with increasing metabolic syndrome criteria (P < 0.05). hs-CRP concentrations were elevated in both patient groups. Positive correlations were found between leptin and body mass index (BMI) (r = 0.7107; P < 0.0001), waist circumference (WC) (r = 0.4981; P <0.002), and hs-CRP (r = 0.3886; P < 0.02).. Leptin differentiated between CAD patients with and without metabolic syndrome and determined metabolic syndrome status in women and men. Leptin was the only marker that increased with additional metabolic syndrome criteria. Elevated hs-CRP concentrations may indicate a low-grade inflammatory state in CAD patients. Association of leptin with BMI, WC, and hs-CRP revealed a close link with metabolic syndrome, obesity, and inflammation in urban black South African CAD patients.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Fasting; Female; Humans; Inflammation Mediators; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Sex Characteristics; South Africa; Urban Population; Waist Circumference

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-/anovulation, and polycystic ovarian morphology and is a complex endocrine disorder that also presents with features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia. These latter symptoms form cardiometabolic risk factors predisposing individuals to the development of type 2 diabetes and cardiovascular disease (CVD). To date, animal models to study PCOS in the context of the metabolic syndrome and CVD risk have been lacking. The aim of this study was to investigate the JCR:LA-cp rodent as an animal model of PCOS associated with the metabolic syndrome. Metabolic indices were measured at 6 and 12 wk, and reproductive parameters including ovarian morphology and estrous cyclicity were assessed at 12 wk or adulthood. At 6 wk of age, the cp/cp genotype of the JCR:LA-cp strain developed visceral obesity, insulin resistance, and dyslipidemia (hypertriglyceridemia and hypercholesterolemia) compared with control animals. Serum testosterone concentrations were not significantly different between groups at 6 wk of age. However, at 12 wk, the cp/cp genotype had higher serum testosterone concentrations, compared with control animals, and presented with oligoovulation, a decreased number of corpora lutea, and an increased number of total follicles, in particular atretic and cystic follicles. The cardiometabolic risk factors in the cp/cp animals were exacerbated at 12 wk including obesity, insulin resistance, and dyslipidemia. The results of this study demonstrate that the JCR:LA-cp rodent may be a useful PCOS-like model to study early mechanisms involved in the etiology of cardiometabolic risk factors in the context of both PCOS and the metabolic syndrome.

Topics: Animals; Blood Glucose; Disease Models, Animal; Estrous Cycle; Fasting; Female; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Liver; Metabolic Syndrome; Ovary; Polycystic Ovary Syndrome; Rats; Receptors, Leptin; Risk Factors; Triglycerides

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are well-recognized complications of obesity. This study was designed to evaluate the role of the UCP1 -3826 A>G polymorphism, adiponectin levels, leptin/adiponectin ratio (L/A), and main biochemical parameters in 102 unrelated severely obese adults [61 females and 41 males, median body mass index (BMI) = 47.8 kg/m2] with NAFLD, with (MS+) or without MS (MS-) from Southern Italy.. The UCP1 polymorphism was tested by the TaqMan method, main biochemical parameters by routinary methods, adiponectin, and leptin serum levels by enzyme-linked immunosorbent assay. MS was diagnosed according to the American Heart Association criteria, liver steatosis was detected by ultrasound.. MS was present in 53% male and 66% female obese patients. Only total cholesterol (p=0.04 males and p=0.002 females) and L/A ratio (p=0.03 males) differed between MS+ and MS- obese patients. At multivariate analysis, severe liver steatosis was significantly associated with: UCP1 (AG+GG) genotypes [odds ratio-confidence interval (OR-CI): 4.25; 1.12-16.13], MS (OR-CI: 8.47; 1.78-40.25), low adiponectin levels (OR-CI: 0.92; 0.87-0.98), high alanine aminotransferase levels (OR-CI: 1.03; 1.00-1.06), age (ORCI: 1.08; 1.00-1.15), and male gender (OR-CI: 10.78; 1.61- 71.96).. In addition to traditional factors, total cholesterol and L/A ratio appear to contribute to MS characterization in severe obesity. Furthermore, the UCP1 (AG+GG) genotypes and low adiponectin levels could predispose to a more severe liver steatosis independently of MS presence. Based on our data, polymorphic UCP1 (AG+GG) obese patients with low adiponectin levels appear to be high-risk subjects for worsening of liver steatosis, a NAFLD, possibly requiring a second-step evaluation by liver biopsy.

Topics: Adiponectin; Adolescent; Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Blood Glucose; Cholesterol; Fatty Liver; Female; gamma-Glutamyltransferase; Humans; Insulin; Ion Channels; Italy; Leptin; Male; Metabolic Syndrome; Middle Aged; Mitochondrial Proteins; Obesity, Morbid; Polymorphism, Single Nucleotide; Statistics, Nonparametric; Triglycerides; Uncoupling Protein 1; Young Adult

TNF-alpha signals through two receptors, TNFR1 and TNFR2. Our goals were: 1) determine the role of TNFRs in obesity and metabolic disease and 2) investigate whether TNFRs contribute to the link between obesity and adipose tissue macrophage infiltration and polarization. R1(-/-)R2(-/-) (RKO) and wild-type (WT) mice were fed standard chow or a high-fat/high-sucrose diet (HFHS) over 14 wk. Body composition, food intake, and energy expenditure were measured. Oral glucose tolerance and insulin sensitivity tests assessed glucose homeostasis. Adipose tissue and systemic inflammatory status were evaluated by quantifying plasma adipokine levels and macrophage-specific gene expression in fat. RKO mice were heavier (10%) and fatter (18%) than WT controls at 4 wk of age and were 26% heavier and 50% fatter than WT after 14 wk of HFHS diet feeding. Age- and diet-adjusted 24-h oxygen consumption, activity, and respiratory exchange ratio were significantly reduced in RKO mice. Obese RKO mice were markedly insulin resistant, suggesting that intact TNFR signaling is not required for the effect of obesity to impair glucose metabolism. Adipose tissue from HFHS-fed RKO mice exhibited increased macrophage infiltration, but compared with WT mice, macrophage phenotypic markers featured a predominance of antiinflammatory M2 over proinflammatory M1 cells. TNFRs play a physiological role to limit body weight and adiposity by modestly increasing metabolic rate and fatty acid oxidation, and they are required for obesity-induced activation of adipose tissue macrophages. Despite these effects, TNFRs are not required for obesity-induced insulin resistance.

Topics: Adipokines; Adipose Tissue; Animals; Insulin Resistance; Leptin; Macrophages; Male; Metabolic Syndrome; Mice; Mice, Knockout; Obesity; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha

Topics: Antipsychotic Agents; Apoptosis; Central Nervous System; Humans; Leptin; Metabolic Syndrome; Neuroprotective Agents; Psychotic Disorders; Schizophrenia; Weight Gain

Chemerin is a recently discovered adipokine that regulates adipocyte differentiation and modulates chemotaxis and activation of dendritic cells and macrophages. Given the convergence of adipocyte and macrophage function, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis in humans. We sought to examine the relationship of i) chemerin and markers of inflammation, ii) chemerin and components of the metabolic syndrome, and iii) chemerin and coronary atherosclerotic plaque burden and morphology.. Serum chemerin levels were determined in 303 patients with stable typical or atypical chest pain who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed, or non-calcified.. Chemerin levels were highly correlated with high sensitivity C-reactive protein (r=0.44, P<0.0001), interleukin-6 (r=0.18, P=0.002), tumor necrosis factor-alpha (r=0.24, P<0.0001), resistin (r=0.28, P<0.0001), and leptin (r=0.36, P<0.0001) concentrations. Furthermore, chemerin was associated with components of the metabolic syndrome including body mass index (r=0.23, P=0.0002), triglycerides (r=0.29, P<0.0001), HDL-cholesterol (r=-0.18, P=0.003), and hypertension (P<0.0001). In bivariate analysis, chemerin levels were weakly correlated with coronary plaque burden (r=0.16, P=0.006) and the number of non-calcified plaques (r=0.14, P=0.02). These associations, however, were lost after adjusting for established cardiovascular risk factors (odds ratio, OR 1.17, 95% confidence interval (CI) 0.97-1.41, P=0.11 for coronary plaque burden; OR 1.06, 95% CI 0.96-1.17, P=0.22 for non-calcified plaques).. Chemerin is strongly associated with markers of inflammation and components of the metabolic syndrome. However, chemerin does not predict coronary atherosclerosis.

Topics: Aged; C-Reactive Protein; Chemokines; Cholesterol; Cohort Studies; Coronary Artery Disease; Female; Humans; Hypertension; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Regression Analysis; Resistin; Triglycerides; Tumor Necrosis Factor-alpha

Apolipoprotein (apo) M may exert anti-atherogenic properties in experimental studies. Its hepatic gene expression may be linked to glucose and lipid metabolism. Plasma apoM is decreased in obese mouse models. We hypothesized that plasma apoM is lower in metabolic syndrome (MetS) subjects, and determined whether intima media thickness (IMT) is associated with apoM.. In 19 non-diabetic subjects with and 60 non-diabetic subjects without MetS (NCEP, ATP III criteria), the relationships of plasma apoM with obesity, glucose, insulin, lipids and adipokines, as well as with IMT were determined.. Plasma apoM was on average 15% lower in subjects with MetS compared to subjects without MetS (p=0.036). ApoM correlated inversely with body mass index and waist circumference (p<0.001), and positively with total cholesterol, LDL cholesterol and apoA-I (p<0.05). ApoM was not significantly correlated with glucose, insulin, leptin, adiponectin or resistin (p>0.20). Age- and sex adjusted IMT was lower in subjects with MetS (p<0.05), but was unrelated to apoM (p=0.68). In a multiple linear regression model that included the presence of both MetS and apoM, IMT was only related to MetS (p=0.05).. Plasma apoM is reduced in MetS. In this study, apoM did not predict subclinical atherosclerosis.

Topics: Adiponectin; Analysis of Variance; Apolipoproteins; Apolipoproteins M; Case-Control Studies; Female; Humans; Leptin; Linear Models; Lipocalins; Male; Metabolic Syndrome; Middle Aged; Resistin; Tunica Intima

We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin and visfatin were measured in 109 patients with SLE and 78 control subjects. Coronary calcification was measured using electron beam-computed tomography, and insulin resistance was defined by the homeostasis model assessment index. Concentrations of adiponectin (28.7 +/- 17.9 vs 22.0 +/- 15.3 microg/mL, P = 0.003), leptin (41.1 +/- 49.9 vs 19.8 +/- 24.6 ng/mL, P < 0.001) and visfatin (7.5 +/- 10.5 vs 4.5 +/- 2.8 ng/mL, P < 0.001) were higher in patients with SLE than in controls. These differences remained significant after adjustment for age, race, sex and body mass index (BMI; all P values < 0.02). Concentrations of resistin (10.7 +/- 7.6 vs 9.1 +/- 5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (rho = 0.80, P < 0.001), insulin resistance (rho = 0.46, P < 0.001) and C-reactive protein (CRP) (rho = 0.30, P = 0.002), whereas adiponectin was negatively associated with the same factors (rho = -0.40, P < 0.001; rho = -0.38, P < 0.001; rho = -0.22, P = 0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE.

Topics: Adipokines; Adiponectin; Adult; Body Mass Index; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Insulin Resistance; Leptin; Lupus Erythematosus, Systemic; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Resistin; Risk Factors

WOKW (Wistar Ottawa Karlsburg W) rats develop metabolic syndrome closely resembling human disorder. In crossing studies between disease-prone WOKW and disease-resistant DA (Dark Agouti) rats, several quantitative trait loci (QTLs) were mapped. To prove the in vivo relevance of QTLs, congenic DA.WOKW rats, briefly termed DA.3aW, DA.3bW, DA.5W, DA.10W, and DA.16W, were generated by transferring chromosomal regions of WOKW chromosomes 3, 5, 10, and 16 onto DA genetic background. Male (n=12) and female (n=12) rats of each congenic strain and their parental strain DA were characterized for adiposity index (AI), serum leptin, and serum insulin as well as serum cholesterol and serum triglycerides as single facets of metabolic syndrome at the age of 30 weeks. The data showed a significant higher AI for male and female DA.3aW and female DA.16W compared with DA. Serum leptin was significantly elevated in male and female DA.3aW, DA.10W, and DA.16W rats in comparison with DA. Rats of both sexes of DA.10W and female DA.16W showed significantly elevated serum insulin in comparison to DA. Female rats of all congenics had significantly higher serum cholesterol compared with DA, while males did not differ. Finally, triglycerides were only elevated in male DA.16W. The results demonstrate an involvement of WOKW chromosomes 3, 5, 10, and 16 in developing facets of the metabolic syndrome.

Topics: Adiposity; Animals; Animals, Congenic; Cholesterol; Chromosomes, Mammalian; Crosses, Genetic; Disease Models, Animal; Female; Genetic Predisposition to Disease; Insulin; Leptin; Male; Metabolic Syndrome; Phenotype; Quantitative Trait Loci; Rats; Rats, Inbred Strains; Sex Factors; Species Specificity; Time Factors; Triglycerides

It has been shown that the renin-angiotensin system participates in the development of the metabolic syndrome. This study aimed to show whether the angiotensin II type 1 receptor blocker, irbesartan, exerts a protective effect against metabolic and cardiovascular abnormalities in rats fed a high fat diet (HFD).. Wistar rats (n = 30) were divided into three groups: (1) rats fed a standard diet for 7 weeks were used as a control group; (2) rats fed a HFD (33.5% fat) for 7 weeks; and (3) rats fed a HFD (33.5% fat) treated with irbesartan (0.1 mg/kg per day) for 7 weeks. Body weight, white and brown adipose tissue weight, plasma concentrations and protein expression of leptin and adiponectin in white adipose tissue, and glucose metabolism were investigated. Vascular reactivity in aortic rings and heart function were also evaluated.. HFD rats showed increased (P < 0.05) body, epididymal and lumbar adipose tissue weights, but did not experience a change in brown adipose tissue weight. Irbesartan attenuated (P < 0.05) all of these parameters, but increased brown adipose tissue weight. The leptin/adiponectin ratio of plasma concentrations and protein expression in lumbar adipose tissue increased (P < 0.05) in HFD rats, and were normalized by irbesartan. Along with these changes, irbesartan improved (P < 0.05) insulin sensitivity and exaggerated responses to angiotensin I and II in the aorta.. Irbesartan reduced body and white adipose tissue weights, improved glucose metabolism and vascular function in the aorta. The correction of leptin-adiponectin imbalance may be an important mechanism participating in the protective effect of irbesartan in HFD rats.

Topics: Adiponectin; Adipose Tissue; Angiotensin II Type 1 Receptor Blockers; Animal Feed; Animals; Aorta; Biphenyl Compounds; Glucose; Irbesartan; Leptin; Male; Metabolic Syndrome; Models, Biological; Rats; Rats, Wistar; Renin-Angiotensin System; Tetrazoles

We examined mechanisms leading to the impairment of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)-dependent vasorelaxation in response to acutely administered leptin in rats with the metabolic syndrome.. Effects of leptin on blood pressure and NO and cGMP in the aortic wall were studied in four groups of rats: (1) lean control, (2) obese, fed "cafeteria diet" for 3months (hyperleptinemia and hyperinsulinemia), (3) hyperleptinemia induced by administration of exogenous leptin for 8days, and (4) fructose-fed, receiving 20% fructose in the drinking water for 8weeks (hyperinsulinemia with slightly elevated leptin).. Stimulatory effect of leptin on NO and cGMP production in the aortic wall was impaired in obese and hyperleptinemic groups but not in the fructose group. In contrast, EDHF-mimetic effect of leptin was impaired in obese and fructose-fed but not in the hyperleptinemic group. Leptin increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in the aortic wall, and this effect was impaired in obese and fructose-fed animals. The EDHF-mimetic effect of leptin was abolished by phosphoinositide 3-kinase inhibitor, wortmannin, whereas its effect on NO was not. In addition, IRS-1 phosphorylation at Ser(307) and Ser(612) was enhanced in obese and fructose-fed but not in hyperleptinemic rats.. These results indicate that: (1) long-term hyperleptinemia induces resistance to acute vascular NO-mimetic effect of leptin in obesity/metabolic syndrome, (2) leptin stimulates EDHF in IRS-1 and PI3K-dependent manner, and this effect is impaired in obesity due to excessive serine phosphorylation of IRS-1.

Topics: Animals; Aorta; Biological Factors; Blood Pressure; Cyclic GMP; Disease Models, Animal; Endothelium, Vascular; Insulin; Leptin; Male; Metabolic Syndrome; Nitric Oxide; Obesity; Phosphorylation; Rats; Rats, Wistar; Recombinant Proteins; Vasodilation

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

Insulin resistance (IR) and hypertension are common in overweight children, and the adipocyte-derived hormones resistin, adiponectin, and leptin may modulate IR and blood pressure (BP). Few data exist in children on dietary determinants of IR, BP, or leptin, and no data exist on dietary determinants of resistin and adiponectin. Therefore, the objective of this study was to investigate dietary determinants of IR, BP, resistin, adiponectin, and leptin concentrations, as well as the interrelationship among these variables, in normal and overweight children.. In 6- to 14-year-old Swiss children (n=79), nutritional intake was assessed using two 24-hour-recalls and a one-day dietary record. Body mass index (BMI), body fat percentage (BF%), waist/hip ratio (W/H ratio), BP, glucose, insulin, resistin, adiponectin, and leptin were determined. IR was calculated using the quantitative insulin sensitivity check index (QUICKI).. BMI, BF%, and W/H ratio were significant predictors of leptin and insulin, QUICKI, and systolic BP, but not resistin or adiponectin. Of the overweight and obese children, 40% were diagnosed pre-hypertensive or hypertensive. Total energy, fat, saturated fat, and protein intakes were significant predictors of fasting insulin and QUICKI, and total fat, saturated fat, and monounsaturated fat intakes were significant predictors of systolic BP, independent of BMI standard deviation score (BMI-SDS) and age. There were no associations between these dietary factors and leptin, adiponectin, or resistin.. In children, dietary macronutrient composition is a predictor of IR and systolic BP, but not resistin, adiponectin, or leptin concentrations. Resistin and adiponectin concentrations are not correlated with IR or BP in this age range.

Topics: Adiponectin; Adiposity; Adolescent; Algorithms; Analysis of Variance; Blood Glucose; Blood Pressure; Body Mass Index; Child; Databases, Factual; Diet; Diet Records; Diet Surveys; Dietary Fats; Fasting; Female; Humans; Insulin Resistance; Leisure Activities; Leptin; Male; Metabolic Syndrome; Motor Activity; Nutrition Policy; Obesity; Overweight; Regression Analysis; Resistin; Surveys and Questionnaires

To contribute to the anthropometric and metabolic phenotyping of orexin-A-deficient narcoleptic patients, and to explore a possible risk of their developing a metabolic syndrome.. We performed a cross-sectional study comparing metabolic alterations in patients with narcolepsy with cataplexy (NC) and patients with idiopathic hypersomnia without long sleep time.. University hospital.. Fourteen patients with narcolepsy with cataplexy and 14 sex and age-matched patients with idiopathic hypersomnia without long sleep time.. N/A.. Metabolic parameters were evaluated by measuring body mass index (BMI), waist circumference (also with abdominal computed tomography), blood pressure, and daily calorie intake (3-day diary). Chronotypes were assessed through the morningness-eveningness questionnaire. Lumbar puncture for cerebrospinal fluid orexin-A determination and HLA typing were performed. Patients with narcolepsy with cataplexy (all HLA DQB1*0602 positive and with cerebrospinal fluid orexin-A levels < 110 pg/mL) had a higher BMI and BMI-independent metabolic alterations, namely waist circumference, high-density lipoprotein cholesterol, and glucose/insulin ratio (an insulin resistance index), with respect to patients with idiopathic hypersomnia without long sleep time (cerebrospinal fluid orexin-A levels > 300 pg/mL). Despite lower daily food intake, patients with narcolepsy with cataplexy displayed significant alterations in metabolic parameters resulting in a diagnosis of metabolic syndrome in more than half the cases.. BMI-independent metabolic alterations and the relative hypophagia of patients with narcolepsy with cataplexy, as compared with patients with idiopathic hypersomnia without long sleep time, suggest that orexin-A influences the etiology of this phenotype. Moreover, considering that these dysmetabolic alterations are present from a young age, a careful metabolic follow-up of patients diagnosed with narcolepsy with cataplexy is mandatory.

Topics: Adult; Blood Glucose; Body Mass Index; Case-Control Studies; Cataplexy; Cross-Sectional Studies; Energy Intake; Female; Histocompatibility Testing; HLA-DQ Antigens; HLA-DQ beta-Chains; Humans; Idiopathic Hypersomnia; Insulin; Intracellular Signaling Peptides and Proteins; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Neuropeptides; Orexins

Adipokines have been implicated in the pathogenesis of metabolic syndrome (MetS) and insulin resistance. We investigated the association between these conditions and serum levels of visfatin, adiponectin and leptin.. 175 overweight and obese boys and girls aged 3-17 years. MetS was defined as presence of at least three of the following: triglycerides >or= 1.24 mmol/L, high-density lipoprotein cholesterol or= 6.1 mmol/L, elevated waist circumference and systolic or diastolic blood pressure >or= 90th percentile.. After adjustment for age and gender visfatin levels were significantly higher (median 19.0 [25th, 75th percentiles 11.9 , 37.1] vs. 15.2 [11.6 , 21.1] ng/ml; p(adjusted) = 0.02) in subjects with MetS (n = 41) compared to subjects without (n = 134). There were no significant differences in adiponectin or leptin levels between the two groups after adjustment for age and gender. Visfatin levels increased proportionally with number of MetS components (beta = 0.16, 95%CI 0.04, 0.28; p(adjusted) = 0.01), and adiponectin levels decreased proportionally with number of components (beta = -0.11, 95%CI -0.18, -0.04; p(adjusted) = 0.002). Leptin levels were not related to number of components of MetS. Unlike visfatin, both adiponectin (beta = -0.24, 95%CI -0.33, -0.15; p adjusted < 0.001) and leptin (beta = 0.14, 95%CI 0.01, 0.28; p adjusted = 0.03) were associated with insulin resistance.. The elevation of visfatin observed in children and adolescents with MetS was proportionate to number of components of MetS but was not associated with insulin resistance. The increase in visfatin may contribute to low-grade systemic inflammation associated with MetS.

Topics: Adiponectin; Adolescent; Child; Child, Preschool; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Obesity

To evaluate the associations between leptinemia and the components of metabolic syndrome (MetS).. Fifty-one obese adults (9 men; 36.7 +/- 10.0 years; body mass index (BMI) 46.2 +/- 10.0 kg/m(2)) were submitted to clinical examination, determinations of body fat mass (BF, bioimpedance) and resting energy expenditure (REE, indirect calorimetry), and to hormonal and biochemical analysis. Patients were categorized into three groups, according to the number of criteria for MetS: Group I: none or 1; Group II: 2; and Group III: 3 or 4 criteria.. Absolute leptinemia (LepA; 37.5 +/- 16.9 ng/mL) was directly correlated with BMI (r = 0.48; p = 0.0004), waist circumference (r = 0.31; p = 0.028) and BF (r = 0.52; p = 0.0001). Leptinemia adjusted for BF (LepBF) was inversely correlated with weight (r = -0.41; p=0.027), REE (r = -0.34; p = 0.01) and number of MetS criteria (r = -0.32; p = 0.02). There was no difference in LepA among the groups. LepBF in Group III (0.58 +/- 0.27 ng/mL/kg) was significantly lower compared to Group I (0.81 +/- 0.22 ng/mL/kg; p = 0.03) and Group II (0.79 +/- 0.30 ng/mL/kg; p = 0.02).. Leptin production by the adipose tissue is decreased in obese subjects fulfilling three or more criteria of MetS, suggesting a state of relative leptin deficiency in obesity associated with advanced stages of MetS.

Topics: Adipose Tissue; Adult; Body Mass Index; Body Weight; Energy Metabolism; Epidemiologic Methods; Female; Humans; Leptin; Male; Metabolic Syndrome; Obesity; Risk Factors; Waist Circumference

The aim of the study was to investigate whether the G-174C polymorphism of the IL-6 gene is related to obesity and the incidence of the metabolic syndrome (MetS) according to IDF definition in children.. The examined group included 124 obese children with BMI > or = 2 SDS, and the control group consisted of 56 non-obese children with BMI <1.0 SDS. Polymorphism identification was performed in total genomic DNA using PCR-RFLP method.. In the obese children, carriers of C allele in homozygotic and heterozygotic genotypes were more frequent than in the control group. The carriers of C alleles presented with lower thickness of subcutaneous tissue and higher concentrations of HDL-C than the wild type. The incidence of MetS was 33% of the group of obese children. Analysis of the presence of MetS factors showed that there is more frequent MetS in the group with the wild homozygous genotype type.. Polymorphism 174G>C in the IL-6 gene does not seem to be associated with obesity and with the incidence of MetS in children.

Topics: Adolescent; Alleles; Child; Cholesterol, HDL; Female; Genotype; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Obesity; Polymorphism, Single Nucleotide

This study aimed (a) to investigate the relationship between the degree of obesity and serum adiponectin, tumor necrosis factor (TNF)-α, leptin, insulin levels and the lipid profile; (b) to clarify the relationship between insulin resistance/glucose tolerance and adipocytokine levels; and (c) to investigate the value of adipocytokine levels as a marker of metabolic syndrome (MS).. We studied 151 obese children and adolescents (86 boys and 65 girls; mean age was 12.3±2.4 years). We defined obesity as a body-mass index (BMI) z-score more than 2 SD above the mean for age and sex. The control group consisted of 100 children (48 boys, 52 girls, mean age 12.4±2.5 years). Fasting glucose, insulin levels and lipid profiles were measured in all cases and controls after a 12-hour fast. Adiponectin, TNF-α, and leptin levels were measured in the subjects who participated in the adipocytokine branch of the study. An oral glucose tolerance test (OGTT) was also performed in all obese patients. Obese patients were grouped into three subgroups according to their glucose tolerance and insulin sensitivity assessment, and also according to whether they were grouped as MS or not.. Serum levels of total cholesterol, LDL and VLDL cholesterol, log triglyceride, insulin, leptin and TNF-α were higher, whereas HDL and square root adiponectin levels were lower in the obese group when compared with controls. Multiple regression analysis among BMI-z score, LDL, triglyceride, HOMA-IR, leptin and TNF-α as determinants of adiponectin revealed that BMI-z score was the only determinant for adiponectin (r:-0.45, p<0.0001). Adiponectin levels in hyperinsulinemic and impaired glucose tolerance groups (IGT) tended to be lower than in normoinsulinemic obese children, however, the difference was not significant. There was a weak negative correlation between adiponectin levels and increasing severity of insulin resistance (r=-0.23, p=0.005) in the groups of obese subjects. Mean serum adiponectin level in subjects with MS was lower than in subjects without MS (p=0.008).. Evaluation of serum adiponectin levels might contribute to an early intervention in obese children with MS.

Topics: Adiponectin; Adolescent; Biomarkers; Blood Glucose; Body Mass Index; Case-Control Studies; Child; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Obesity; Tumor Necrosis Factor-alpha

Leptin is a peptide hormone secreted by adipocytes. It has been shown to modulate production and clearance of amyloid beta (Abeta) in rodent models. We sought to determine if serum leptin was associated with cognitive decline in the elderly. We studied 2871 well-functioning elders, aged 70-79, who were enrolled in a prospective study. Serum leptin concentrations were measured at baseline and analyzed by mean+/-1S.D. Clinically significantly cognitive decline over 4 years was defined as > or =5-point drop on the Modified Mini Mental State Exam (3MS). Compared to those in the lower leptin groups, elders in the high leptin group had less cognitive decline, 20.5% versus 24.7% (OR=0.79; 95% CI 0.61-1.02, p=0.07). After adjustment for demographic and clinical variables, including body mass index and total percent body fat, those in the high leptin group had significantly less likelihood of cognitive decline, OR=0.66 (95% CI 0.48-0.91). We conclude that in elderly individuals, higher serum leptin appears to protect against cognitive decline, independent of comorbidites and body fat.

Topics: Adipose Tissue; Aged; Aging; Biomarkers; Body Mass Index; Cognition Disorders; Dementia; Disease Progression; Humans; Leptin; Metabolic Syndrome; Neuropsychological Tests; Obesity; Prospective Studies

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

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

Obesity and metabolic syndrome are significant problems for patients taking antipsychotic drugs. Evidence is emerging of genetic risk factors.. To investigate the influence of two candidate genes, smoking and drug treatment on obesity and metabolic syndrome in patients with schizophrenia.. Patients (n=134) were assessed for measures of obesity, other factors contributing to metabolic syndrome, and two genetic polymorphisms (5-HT(2C) receptor -759C/T and leptin -2548A/G).. Neither genotype nor smoking was significantly associated with measures of obesity. However, both leptin genotype and smoking were significantly associated with metabolic syndrome. Significant interaction occurred between the genetic polymorphisms for effects on obesity, whereby a genotype combination increased risk. Drug treatment showed significant effects on measures of obesity and triglyceride concentrations; risperidone was associated with lower values than olanzapine or clozapine.. The findings suggest interacting genetic risk factors and smoking influence development of metabolic syndrome in patients on antipsychotic drugs.

Topics: Adult; Alleles; Antipsychotic Agents; Body Mass Index; Cross-Sectional Studies; Female; Genetic Variation; Genotype; Humans; Leptin; Male; Metabolic Syndrome; Obesity; Polymorphism, Genetic; Promoter Regions, Genetic; Receptor, Serotonin, 5-HT2C; Risk Factors; Schizophrenia; Smoking; Time Factors

Obesity is a risk factor for esophageal adenocarcinoma, with a pathway through inflammation and metaplasia secondary to reflux the dominant hypothesis. The proinflammatory impact of adipocytokines associated with the metabolic syndrome of central adiposity may also be relevant. The objective of this study was to explore this profile in Barrett esophagus.. Patients with specialized intestinal metaplasia were invited to attend the metabolic syndrome screening where they underwent anthropometry, segmental bioelectrical impedance analysis, and blood pressure measurement, and had blood taken for quantification of fasting lipids, insulin, glucose, C-reactive protein, and adipocytokines.. One hundred two patients were studied. Forty-six percent of Barrett patients had metabolic syndrome and 78% were centrally obese. Patients with metabolic syndrome were significantly more obese by body mass index, had a 9.4 cm greater waistline, were more hypertensive, and were insulin resistant with 25% having fasting hyperinsulinemia compared with Barrett patients without metabolic syndrome. Metabolic syndrome was associated with elevated C-reactive protein, leptin, and a trend toward decreased adiponectin levels. Sixty percent of patients with long-segment Barrett had metabolic syndrome, and 92% were centrally obese compared with 23.8% and 62%, respectively (P = 0.007 and 0.005) in short-segment Barrett. Long-segment Barrett was associated with hyperinsulinemia and significantly increased levels of interleukin-6 compared with short-segment Barrett.. The prevalence of metabolic syndrome in Barrett far exceeds population norms, and the syndrome was significantly associated with the length of specialized intestinal metaplasia. The data do suggest that the metabolic syndrome may be relevant to the continuum of metaplasia within the Barrett cohort.

Topics: Adiponectin; Adiposity; Analysis of Variance; Anthropometry; Barrett Esophagus; Blood Glucose; Blood Pressure Determination; C-Reactive Protein; Chi-Square Distribution; Cytokines; Electric Impedance; Enzyme-Linked Immunosorbent Assay; Female; Humans; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Phenotype; Prevalence; Resistin

We evaluated the hypothesis that plasma levels of adiponectin and leptin are independently but oppositely associated with coronary artery calcification (CAC), a measure of subclinical atherosclerosis. In addition, we assessed which biomarkers of adiposity and insulin resistance are the strongest predictors of CAC beyond traditional risk factors, metabolic syndrome, and plasma C-reactive protein (CRP).. Adipokines are fat-secreted biomolecules with pleiotropic actions that converge in diabetes and cardiovascular disease.. We examined the association of plasma adipocytokines with CAC in 860 asymptomatic, nondiabetic participants in the SIRCA (Study of Inherited Risk of Coronary Atherosclerosis).. Plasma adiponectin and leptin levels had opposite and distinct associations with adiposity, insulin resistance, and inflammation. Plasma leptin was positively (top vs. bottom quartile) associated with higher CAC after adjustment for age, gender, traditional risk factors, and Framingham risk scores (tobit regression ratio 2.42 (95% confidence interval [CI]: 1.48 to 3.95; p = 0.002) and further adjustment for metabolic syndrome and CRP (tobit regression ratio: 2.31; 95% CI: 1.36 to 3.94; p = 0.002). In contrast, adiponectin levels were not associated with CAC. Comparative analyses suggested that levels of leptin, interleukin-6, and soluble tumor necrosis factor receptor-2, as well as the homeostasis model assessment of insulin resistance (HOMA-IR) index, predicted CAC scores, but only leptin and HOMA-IR provided value beyond risk factors, metabolic syndrome, and CRP.. In SIRCA, although both leptin and adiponectin levels were associated with metabolic and inflammatory markers, only leptin was a significant independent predictor of CAC. Of several metabolic markers, leptin and the HOMA-IR index had the most robust, independent associations with CAC.

Topics: Adipokines; Adiposity; Adult; Aged; Biomarkers; C-Reactive Protein; Calcinosis; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Risk Assessment; Risk Factors

The role of adiponectin, a marker of the metabolic syndrome, on the pathogenesis of hypertension in comparison with markers of adipose tissue mass (leptin) and inflammation (high-sensitivity C-reactive protein [hs-CRP]) remains to be clarified. The eligible study population consisted of 2,045 residents aged > or =40 years who had participated in a community-based survey and had complete data for serum adiponectin, leptin, and hs-CRP, and for whom homeostasis model assessment of insulin resistance (HOMA-IR) had been calculated from insulin and plasma glucose. Among all eligible participants, as well as in the subgroup of nondiabetic normotensives (blood pressure <140/90 mmHg and without antihypertensive medication), all three markers were significantly correlated with systolic blood pressure (negative correlation for adiponectin and positive correlations for leptin and hs-CRP). Among all participants, systolic blood pressure and the presence of hypertension were determined mainly by age, sex, body mass index, and waist circumference. None of the markers further contributed to the multivariate linear regression or logistic regression models. In contrast, adiponectin, but not leptin, hs-CRP, or HOMA-IR, was significantly associated with systolic blood pressure and the presence of pre-hypertension (blood pressure within 120-139/80-89 mmHg) after adjustment for age, sex, body mass index, and waist circumference in the nondiabetic normotensive subgroup. Similarly, adiponectin was independently associated with diastolic blood pressure in the nondiabetic normotensive subgroup but not in the whole population. In conclusion, adiponectin, but not leptin or hs-CRP, was independently associated with blood pressure in a nondiabetic normotensive subgroup.

Topics: Abdominal Fat; Adiponectin; Adult; Aged; Biomarkers; Blood Pressure; C-Reactive Protein; Cross-Sectional Studies; Female; Health Surveys; Humans; Hypertension; Inflammation; Leptin; Linear Models; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Obesity

Aldoketoreductase 1C3 (AKR1C3) is a functional prostaglandin F synthase and a negative modulator of the availability of ligands for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma). AKR1C3 expression is known to be associated with adiposity, one of the components of the metabolic syndrome. The aim of this study was to characterize the expression of AKR1C3 in the adipose tissue and adipocytes and to investigate its potential role in the metabolic syndrome. Using microarray analysis and realtime PCR, we studied the expression of AKR1C3 in adipose tissue samples from obese subjects with or without metabolic complications, during very low calorie diet-induced weight loss, and its expression in isolated human adipocytes of different sizes. The adipose tissue AKR1C3 expression levels were marginally lower in obese subjects with the metabolic syndrome compared with the levels in healthy obese subjects when analyzed using microarray (p = 0.078) and realtime PCR (p < 0.05), suggesting a secondary or compensatory effect. The adipose tissue mRNA levels of AKR1C3 were reduced during and after dietinduced weight-loss compared to the levels before the start of the diet (p < 0.001 at all time-points). The gene expression of AKR1C3 correlated with both adipose tissue mRNA levels and serum levels of leptin before the start of the diet (p < 0.05 and p < 0.01, respectively). Furthermore, large adipocytes displayed a higher expression of AKR1C3 than small adipocytes (1.5-fold, p < 0.01). In conclusion, adipose tissue AKR1C3 expression may be affected by metabolic disease, and its levels are significantly reduced in response to dietinduced weight loss and correlate with leptin levels.

Topics: 3-Hydroxysteroid Dehydrogenases; Adipose Tissue; Adult; Aldo-Keto Reductase Family 1 Member C3; Diet, Reducing; Female; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Humans; Hydroxyprostaglandin Dehydrogenases; Leptin; Male; Metabolic Syndrome; Middle Aged; Molecular Sequence Data; Obesity; Oligonucleotide Array Sequence Analysis; Tissue Distribution; Weight Loss

Atherosclerotic vascular diseases such as cerebrovascular and cardiovascular diseases are major causes for fatality of hemodialysis (HD) patients. Since adipocytokines are key players for arteriosclerosis in the concept of metabolic syndrome (MetS), we aimed to determine whether circulating levels of major three adipocytokines, adiponectin, TNF-alpha, and leptin, could be associated with various parameters and clinical events in HD patients who are diagnosed as MetS using a new criteria designed for the Japanese population.. We enrolled 53 very stable patients under maintenance HD at Minami-Senju Hospital. Basically, clinical and laboratory data were taken just before HD therapy. HD sessions were performed regularly and all the participants took oral administration and injection as usual. A cross-sectional study was performed to evaluate clinical and laboratory data related to three major adipocytokines, adiponectin, TNF-alpha and leptin.. We observed no significant differences of three adipocytokines when the participants were divided in accordance with existence of MetS or past cerebrocascular/cardiovascular diseases. Only the serum adiponectin levels were significantly different in two groups categorized by existence of diabetes mellitus. Serum triglycerides (TG) were significantly correlated with two circulating adipocytokines, adiponectin (r=-0.328, p<0.016) and leptin (r=0.397, p<0.003), when we analyzed all 53 patients together.. Plasma adiponectin and leptin are expected as contributors related to dyslipidemia, suggesting these may be targets of prevention of vascular diseases in maintenance HD patients.

Topics: Adipokines; Adiponectin; Aged; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Metabolic Syndrome; Middle Aged; Renal Dialysis; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha

We evaluated the effects of GW501516, a specific peroxisome proliferator-activated receptor beta/delta (PPARdelta) agonist in metabolic syndrome mice, obtained by perinatal injection of monosodium L-glutamate, to investigate the efficacy of GW501516 against metabolic syndrome and the effectiveness of PPARdelta activation as therapeutic target for metabolic syndrome. After 14 days treatment, GW501516 effectively improved the glucose intolerance, normalized the fasted blood glucose, and increased the serum high-density lipoprotein cholesterol (HDL-C) level. Postprandial blood glucose, serum insulin, leptin, free fatty acid (FFA) levels, and total cholesterol/HDL-C ratio were also significantly decreased. Moreover, semiquantitative reverse transcription-polymerase chain reaction results indicated that the above phenotypes might be due to (i) enhancement of fatty acid oxidation in muscle, adipose tissue and the liver; (ii) improvement of insulin-stimulated glucose transportation in skeletal muscle and adipose tissue; and (iii) reduced local glucocorticoid synthesis. Therefore, GW501516 could significantly ameliorate dyslipidaemia and insulin resistance in monosodium L-glutamate mice and activation of PPARdelta could be envisioned as a useful strategy against human metabolic syndrome and related diseases.

Topics: Animals; Animals, Newborn; Blood Glucose; Cholesterol, HDL; Dyslipidemias; Fatty Acids; Gene Expression; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Mice; Mice, Obese; Oxidation-Reduction; PPAR delta; Sodium Glutamate; Thiazoles

Epidemiological evidence together with experimental models shows a direct relationship between fetal and early postnatal growth patterns and an increased risk of adult metabolic disease. Maternal health and nutrition are key determinants in influencing infant growth but the precise molecular mechanisms underlying this relationship are unclear, although it is evident that there are critical time windows when these effects are important. Animal models show mechanistic parallels with human populations and highlight that the early environment represents a therapeutic window for protection from obesity and metabolic disease. The observation that developmental programming can be reversed has been demonstrated in studies in which both maternal and neonatal leptin treatment prevents the induction of the adverse metabolic phenotype. Given that orally administered peptides are absorbed intact by the new born, the prospect of providing supplemental leptin either as drops or in milk deserves serious consideration as a means of reducing or reversing the obesity and type 2 diabetes epidemic.

Topics: Adult; Animals; Disease Models, Animal; Feeding Behavior; Female; Humans; Infant; Infant, Newborn; Leptin; Metabolic Syndrome; Obesity; Pregnancy; Prenatal Exposure Delayed Effects

Hearts of NaCl-induced hypertensive-glucose intolerant (HGI) rats develop reduced infarcts after ischemia-reperfusion injury (IRI) than their hypertensive (H) counterparts. Because high intake of saturated fat is a major risk factor for ischemic heart disease, we tested the hypothesis that chronic (18 weeks) consumption of a high saturated fat diet increases susceptibility to IRI, an effect more marked in the HGI rats than in the H rats. The fat-fed H (HFAT) rat displayed significantly higher body weight and plasma leptin content compared to the H, HGI, or fat-fed HGI (HGIFAT) rats which all showed similar values. In contrast, plasma triglyceride concentration was significantly higher in the HGIFAT rat than in the other three groups. Plasma insulin concentration was similar in the two H groups but higher than that of the two HGI groups. Compared to the H rat, the HGI rat was markedly glucose intolerant, with fat feeding causing comparable worsening of glucose intolerance in each group. The HGIFAT rats displayed a reduction in baseline myocardial contractility and relaxation and a higher end-diastolic pressure compared to the other three groups. Infarct size was significantly lower in the HGI rats than in the H rats. Although fat feeding did not affect infarct size of the H rat, it worsened that of the HGIFAT rat thereby abrogating the differential that existed between the H and HGI rats. In conclusion, excess fat feeding impairs myocardial function of HGI rats and increases their susceptibility to IRI. These findings are of relevance to the metabolic syndrome that manifests as a cluster of insulin resistance, dyslipidemia, and systemic hypertension.

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Dietary Fats; Disease Models, Animal; Glucose Intolerance; Hypertension; Insulin; Leptin; Male; Metabolic Syndrome; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Rats; Rats, Inbred WKY; Sodium Chloride, Dietary; Streptozocin; Time Factors; Triglycerides; Ventricular Pressure

Leptin has been linked to adiposity, insulin resistance, and coronary artery disease (CAD). We examined whether the leptin concentrations are associated with the risk of CAD and metabolic syndrome (MS). The plasma leptin concentrations were measured in 556 diabetic patients (341 men and 215 women). The odds ratio (OR) of CAD and MS were increased on moving from the lowest quartile (Q1) of leptin concentration to the highest quartile (Q4) and remained significant after adjusting for age, sex, BMI, concentrations of total cholesterol, triglyceride, or high-sensitivity C-reactive protein (hsCRP), and treatment modalities for hyperglycemia. The frequency of CAD was highest in the insulin resistant group (Q4 of homeostasis model assessment-insulin resistance index [HOMA-IR]) at Q4 of leptin concentration (34.5%), compared with that of Q4 of leptin (26.4%) or HOMA-IR (21.9%). In multivariate analysis, plasma leptin concentration was identified as the most significantly independent predictor for CAD (OR 10.24, 95% CI 3.01 to 45.05). Other variables with associated with CAD were age, sex, hypertension, low-HDL cholesterolemia, and hsCRP. In conclusion, hyperleptinemia might be an independent risk factor for CAD and MS in diabetic subjects. And the simultaneous measurement of insulin resistance and leptin concentration might be helpful for screening subjects with a high-risk of CAD.

Topics: Adult; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Odds Ratio; Prevalence; Risk Factors

Previous reports indicate that both distribution and amount of body fat confers susceptibility to metabolic syndrome. However, the relative contributions of these two different parameters of body fat to the various components of the metabolic syndrome have not been well defined.. Dual-energy X-ray absorptiometry (DXA) was used to measure and compare the relative amounts of total body fat, truncal fat, and lower body fat in a representative sample of 2587 black, white, and Hispanic men and women from the Dallas Heart Study (DHS). The relationships among these variables and fasting plasma levels of lipids, glucose, insulin, C-reactive protein (CRP), and leptin as well as blood pressure were analyzed.. Beyond total body fat, fat distribution had the greatest impact on plasma triglycerides in all subjects and on high-density lipoprotein cholesterol (HDL-C) levels in women only. An intermediate effect of fat distribution was observed for homeostasis model assessment of insulin resistance (HOMA-IR) and for blood pressure. Plasma CRP levels were much more sensitive to body fat content than to body fat distribution and leptin levels were determined almost exclusively by body fat content. Although there were minor differences among the different ethnic groups, the major relationship patterns between these variables were similar.. For most metabolic risk factors, both body fat content and distribution independently contributed to levels, although significant differences were seen between the relative contributions of each variable to individual risk factors.

Topics: Absorptiometry, Photon; Adult; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Female; Humans; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Risk Factors; Sex Factors

The purpose of this work was to determine whether, in children with metabolic syndrome and sleep-disordered breathing, metabolic markers separate them from children with metabolic syndrome without sleep-disordered breathing and whether treatment of sleep-disordered breathing with continuous positive airway pressure is associated with an improvement in metabolic derangement.. Subjects aged 7 to 19 years old with metabolic syndrome and a positive validated sleep questionnaire were recruited. Subjects underwent overnight polysomnography, during which sympathetic nervous system activity was assessed via 8-hourly measurements of norepinephrine and epinephrine, together with leptin. The next morning, a fasting 3-hour oral glucose-tolerance test was performed to calculate whole-body insulin sensitivity. A fasting lipid panel interleukin 6, adiponectin, and C-reactive protein levels were also measured. Children with sleep-disordered breathing were placed on continuous positive airway pressure for 3 months and studied again. Sleep-disordered breathing and no sleep-disordered breathing groups were compared by using Fisher's exact test and t test for independent samples with analysis of covariance to adjust for age and BMI.. Of 34 children studied, 25 had sleep-disordered breathing (apnea-hypopnea index: >1.5). Mean hourly norepinephrine and leptin levels were higher in the group with sleep-disordered breathing compared with the group without sleep-disordered breathing (P < .005), with no difference in whole-body insulin sensitivity. Eleven subjects with sleep-disordered breathing completed 3 months of nightly continuous positive airway pressure treatment. In the follow-up study, mean hourly leptin levels were significantly lower than in the initial study, with no change in BMI z score or other measurements.. Our findings support the hypothesis that sleep-disordered breathing in children with metabolic syndrome is associated with increased sympathetic nervous system activity and leptin levels but not worsening of insulin resistance. Treatment of sleep-disordered breathing with continuous positive airway pressure led to a significant decrease in leptin levels.

Topics: Adolescent; Biomarkers; Child; Continuous Positive Airway Pressure; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Leptin; Male; Metabolic Syndrome; Polysomnography; Respiration; Sleep Wake Disorders; Treatment Outcome

Oxidative stress, that is, overproduction of reactive oxygen species and reduced antioxidant system activity, is implicated in the pathogenesis of diabetic complications; and therefore, superoxide dismutase (SOD) mimetic tempol should be protective in diabetic kidney. However, the effects of tempol in metabolic syndrome-associated renal injury have not been thoroughly examined. In this study, we examined the effects of 9 weeks of treatment with tempol on metabolic status, renal oxidative stress, and kidney function and structure in obese, diabetic, hypertensive ZSF(1) rats and their nondiabetic, hypertensive, lean littermates. The obese rats had significantly reduced total SOD and catalase activity, increased peroxidase activity and lipid peroxidation, and higher level of protein oxidation in renal cortical tissue compared with their lean littermates. These changes were accompanied by renal injury (proteinuria; reduced excretory function; and markedly increased glomerular and interstitial inflammation, proliferation, and collagen IV synthesis). Tempol treatment slightly increased total SOD activity, significantly reduced lipid peroxidation and peroxidase activity, but had no effect on catalase and protein oxidation. Tempol had no effects on blood pressure, renal hemodynamics and excretory function, and proteinuria in obese rats, yet improved insulin sensitivity and reduced renal inflammatory, proliferative, and fibrotic changes. Because tempol possesses no catalase activity and, in diabetes, not only SOD but also catalase is inhibited, it is possible that the toxicity of hydrogen peroxide (H(2)O(2)) remains unaltered under tempol treatment. This study suggests that superoxide and H(2)O(2) may have distinct roles in the pathogenesis of diabetic renal injury, with superoxide mainly being involved in inflammatory, proliferative, and fibrotic changes, and H(2)O(2) in glomerular hemodynamics and proteinuria.

Topics: Animals; Antioxidants; Blood Glucose; Blood Pressure; Catalase; Cyclic N-Oxides; Hydrogen Peroxide; Immunohistochemistry; Insulin; Kidney Diseases; Leptin; Male; Metabolic Syndrome; Oxidative Stress; Peroxidase; Rats; Rats, Zucker; Spin Labels; Superoxide Dismutase; Superoxides

Despite a better overall tolerance as compared to classical antipsychotics, atypical antipsychotics are not devoid of side-effects, notably metabolic factors (weight gain, alteration of lipid and glucose profile). These side-effects are very troubling concerning long term morbidity and mortality and may also influence compliance towards drugs. The department of psychiatry of the Hospital University Centre has established a guideline on the clinical monitoring of patients receiving atypical antipsychotics, based on recently published consensus, which will be presented here. In addition, recent studies show that weight gain and metabolic alterations induced by this type of medication may be influenced by the genetic background of the patients. Such studies should allow, in the near future, to adapt the treatment for each patient.

Topics: Antidepressive Agents, Second-Generation; Glucose Intolerance; Humans; Leptin; Metabolic Syndrome; Pharmacogenetics; Receptors, Leptin; Weight Gain

The aim of this study was to investigate serum leptin, adiponectin and paraoxonase1 levels in adult females receiving pharmacotherapy for various psychiatric disorders.. The study group consisted of 32 obese females (mean age 40.53 +/- 11.00 years, mean body mass index 35.44 +/- 5.33 kg/m(2)) who were receiving treatment for psychiatric disorders, and the control group included 22 obese females (mean age 35.95 +/- 9.16 years, mean body mass index 30.78 +/- 3.33 kg/m(2)) who were free of psychiatric disorders. Analyses were performed using a bioelectrical impedance device. Fasting blood samples were obtained for complete blood count and various biochemical tests, including determination of leptin, adiponectin and paraoxonase1 activity.. Body mass index, waist and hip circumference, body fat percentage, fasting blood glucose, insulin, glycosylated hemoglobin, homeostasis model assesement of insulin resistance, alanine transaminase, aspartate tarnsaminase, and leptin levels were significantly higher in the study group than in controls. Although body weight was positively correlated with leptin levels in both groups, body weight was negatively correlated with adiponectin levels in the control group and positively correlated with adiponectin levels in the study group. In the study group, body mass index and hip circumference correlated positively with leptin levels, hip circumference correlated positively with adiponectin levels, and waist to hip ratio correlated positively with paraoxonase levels. In the control group, body mass index as well as waist and hip circumferences were positively correlated with leptin levels. Weight, body mass index, and hip circumference were also negatively correlated with the adiponectin/leptin ratio in the control group.. This study indicates a higher risk for obesity-related disorders, particularly metabolic syndrome, diabetes and cardiovascular disease, in patients treated with psychiatric drugs.

Topics: Adiponectin; Adult; Antidepressive Agents; Aryldialkylphosphatase; Biomarkers; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Mental Disorders; Metabolic Syndrome; Obesity; Waist-Hip Ratio

Obstructive sleep apnea syndrome (OSAS) is frequently complicated by metabolic syndrome, including diabetes and hypertension. Both OSAS and metabolic syndrome are strongly associated with obesity. Recently, adiponectin and leptin, which are secreted by adipose tissue, have been considered to play important roles in the progression of these diseases. Thus, to examine the association between leptin, adiponectin and OSAS, we measured the serum level of these adipocytokines in the same OSAS patients.. Sixty-eight consecutive Japanese men, who recorded all-night polysomnography, were enrolled in this study, and were divided into three groups, control (n=15), moderate OSAS (n=21) and severe OSAS (n=32). We measured serum levels of adiponectin and leptin by ELISA.. Serum leptin levels were positively correlated with apnea hypopnea index (AHI) (r=0.552, p<0.001), the percentage of time with less than 90% hemoglobin saturation level in total sleep time (%T<90) (r=0.399, p<0.001) and body mass index (BMI) (r=0.807, p<0.0001). These parameters were suggested as the determinant factor for the serum leptin level by stepwise multiple regression analysis. On the other hand, serum adiponectin levels showed a positive correlation with age (r=0.361, p=0.005) and HDL-cholesterol level (r=0.274, p=0.039). Although there was no significant correlation between serum adiponectin levels and AHI or %T<90, serum adiponectin levels were chosen at a determinant factor of %T<90.. These results suggested that the increasing severity of OSAS induces an increase in setum leptin concentration, but the serum adiponectin levels may be regulated independently of the degree of OSAS, obesity and serum leptin levels in patients with OSAS.

Topics: Adipokines; Adiponectin; Adult; Body Mass Index; Cholesterol, HDL; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Polysomnography; Sleep Apnea, Obstructive

To evaluate the role of leptin, a 16-kDa adipocyte-derived hormone, in the development of metabolic dysregulation of psoriasis.. Case-control study.. Referral centers. Patients Seventy-seven patients with psoriasis and 81 age- and sex-matched control subjects were included in the study. Intervention Enzyme-linked immunoassay of serum samples from study subjects.. Serum leptin levels and proportions of comorbidities (including hypertension, diabetes mellitus, metabolic syndrome, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol concentrations) in cases vs controls were compared using chi(2) and Mann-Whitney tests. The clinical significance of leptin in psoriasis was analyzed using logistic regression models.. Significantly more obesity (odds ratio [OR], 2.67) and hypertension (2.17) (P =.04 for both) were observed in subjects with psoriasis. High serum leptin levels (>or=7397.43 pg/mL) were found in female subjects (OR, 6.05; P < .001) and in subjects with obesity (3.45; P =.01), hypertension (2.19; P =.04), metabolic syndrome (3.58; P =.008), and psoriasis (2.25; P =.02). On multivariate analysis, psoriasis (OR, 4.57; P =.009) was significantly associated with hyperleptinemia independent of female sex (26.36; P < .001), metabolic syndrome (4.37; P =.04), and obesity (2.83; P =.12). Finally, patients with psoriasis who had hyperleptinemia tended to be female (P < .001) and manifested obesity (P =.002) and metabolic syndrome (P =.003).. Hyperleptinemia is associated with psoriasis independent of female sex and other conventional cardiovascular risk factors such as obesity and metabolic syndrome. Hyperleptinemia in psoriasis may contribute to metabolic syndrome.

Topics: Adult; Aged; Case-Control Studies; Female; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Psoriasis; Risk Factors; Sex Factors

High leptin and low ghrelin are associated with the metabolic syndrome (MS).. Ghrelin, leptin (RIA kits), and insulin-like growth factor I (IGF-I) (ELISA kit) concentrations of the population-based cohort of 1045 subjects and their interactions with metabolic parameters were analysed. Intima-media thickness (IMT) was measured with carotid ultrasound.. The interaction between leptin and ghrelin on the MS was significant (P = 0.011). An additive effect of high leptin and low ghrelin on metabolic disturbances was observed: low ghrelin concentration (adjusted for age and sex) (P < 0.001) was associated with the MS and type 2 diabetes in the highest but not in the lower leptin quartiles. In the highest leptin quartile, ghrelin concentrations decreased linearly when the number of International Diabetes Federation MS criteria met (P < 0.01) increased. Ghrelin-leptin relation was independently associated with carotid IMT (P < 0.005). The independent positive association (P < 0.01) between the plasma ghrelin quartile and the carotid IMT was evident in the lowest IGF-I quartile.. Low ghrelin is associated with MS and type 2 diabetes in the presence of insulin and leptin resistance. Ghrelin-leptin relation is associated with early atherosclerosis. The interaction between IGF-I and ghrelin modifies the association of ghrelin with early atherosclerosis.

Topics: Adult; Carotid Artery Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Ghrelin; Humans; Insulin-Like Growth Factor I; Leptin; Male; Metabolic Syndrome; Middle Aged; Tunica Intima; Tunica Media

To examine the relation of well-known factors of the metabolic syndrome (MetS) as well as related circulating factors, with risk of colorectal cancer.. We performed a case control study of 306 colorectal cancer cases and 595 matched controls nested in the Northern Sweden Health and Disease Cohort. Levels of C-peptide, glycated haemoglobin (HbA1c), leptin and adiponectin were measured in cryopreserved samples. Body mass index (BMI), systolic and diastolic blood pressure and fasting and post-load plasma glucose, had been measured in a subcohort. Conditional logistic regression was used to calculate odds ratios (OR) of disease, including risk assessments for the MetS factors: obesity (BMI>30 kg m(-2)), hypertension (blood pressure > or =140/90 mmHg or use of anti-hypertensive drugs) and hyperglycaemia (fasting glucose > or =6.1 mmol l(-1) or post-load glucose in capillary plasma > or =8.9 mmol l(-1)).. None of the studied variables were significantly associated with risk across quartiles. Presence of obesity, hypertension and hyperglycaemia significantly increased the risk of colorectal cancer; OR for three vs null factors was 2.57 (95% Confidence Interval [CI] 1.20-5.52; P (trend)=0.0021), as compared to a 30 to 70% increased risk for the factors in single. Similarly, top decile levels of C-peptide, HbA1c and leptin/adiponectin ratio were associated with an increased risk; ORs for top vs deciles 1-9 were 1.56 (95% CI 0.93-2.62; P=0.090), 1.83 (95% CI 1.00-3.36; P=0.051) and 1.50 (95% CI 0.83-2.71; P=0.18), respectively.. Our study support the view that components of the MetS increase risk of colorectal cancer, and further suggests that only very high levels of metabolic factors confer an increased risk.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Colorectal Neoplasms; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Sweden

Prior studies report slightly lower prostate-specific antigen (PSA) levels among obese men. To understand this effect, we investigated the association between PSA and blood HbA1c, C-peptide, leptin and adiponectin levels in African-American (AA) (n=121) and Caucasian (CA) (n=121) men. Among AA men, PSA levels decreased with increasing C-peptide levels (PSA=0.99, 0.93, 0.75 and 0.53 ng ml(-1) across quartiles of C-peptide, respectively; P(trend)=0.005). Among CA men, PSA levels decreased with increasing HbA1c (PSA=0.84, 0.73, 0.77 and 0.45 ng ml(-1) across quartiles of HbA1c, respectively; P(trend)=0.005). This may suggest that metabolic disturbances related to metabolic syndrome or diabetes affect the ability to detect early-stage prostate cancer.

Topics: Adiponectin; Adult; Aged; Black or African American; Body Mass Index; C-Peptide; Cohort Studies; Diabetes Complications; Early Diagnosis; Glycated Hemoglobin; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; White People

Retinol binding protein 4 (RBP4) is a novel adipokine which might be involved in the development of insulin resistance. The aim of the study was to investigate the expression of RBP4 mRNA in subcutaneous and visceral fat depots and the relationship between RBP4 plasma and mRNA levels relative to indices of adiposity and insulin resistance. In 59 Caucasian women (BMI 20 to 49 kg/m(2)) paired samples of subcutaneous and visceral fat were obtained for RBP4, leptin and GLUT 4 mRNA analysis using reverse transcription-quantitative PCR. Euglycemic hyperinsulinemic clamp and computed tomography scans were performed. RBP4 mRNA levels as well as GLUT 4 mRNA and leptin mRNA levels were lower (P<0.001, P<0.01 and P<0.001, respectively) in visceral compared to subcutaneous fat. No differences were found in RBP4 mRNA expression in the two fat depots or in RBP4 plasma levels between subgroups of non-obese subjects (n=26), obese subjects without metabolic syndrome (n=17) and with metabolic syndrome (n=16). No correlations between RBP4 mRNA or plasma levels relative to adiposity, glucose disposal rate and GLUT 4 mRNA expression in adipose tissue were found. There was a weak positive correlation between plasma RBP4 and plasma triglycerides (r = 0.30, p<0.05) and between plasma RBP4 and blood glucose (r = 0.26, p<0.05). Regardless of the state of adiposity or insulin resistance, RBP4 expression in humans was lower in visceral than in subcutaneous fat. We found no direct relationship between either RBP4 mRNA or its plasma levels and the adiposity or insulin resistance.

Topics: Adiposity; Adult; Aged; Blood Glucose; Female; Glucose Transporter Type 4; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Retinol-Binding Proteins, Plasma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Subcutaneous Fat; Tomography, X-Ray Computed; Young Adult

The ability of the Adult Treatment Panel III (ATP III) criteria of metabolic syndrome to identify insulin-resistant subjects at increased cardiovascular risk is suboptimal, especially in the absence of obesity and diabetes. Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and is emerging as an independent cardiovascular risk factor. We compared the strength of the associations of ATP III criteria and of NAFLD to insulin resistance, oxidative stress, and endothelial dysfunction in nonobese nondiabetic subjects.. Homeostasis model assessment of insulin resistance (HOMA-IR) >2, oxidative stress (nitrotyrosine), soluble adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin), and circulating adipokines (tumor necrosis factor-alpha, leptin, adiponectin, and resistin) were cross-sectionally correlated to ATP III criteria and to NAFLD in 197 unselected nonobese nondiabetic subjects.. NAFLD more accurately predicted insulin resistance than ATP III criteria: sensitivity 73 vs. 38% (P = 0.0001); positive predictive value: 81 vs. 62% (P = 0.035); negative predictive value 87 vs. 74% (P = 0.012); positive likelihood ratio 4.39 vs. 1.64 (P = 0.0001); and negative likelihood ratio 0.14 vs. 0.35 (P = 0.0001). Adding NAFLD to ATP III criteria significantly improved their diagnostic accuracy for insulin resistance. Furthermore, NAFLD independently predicted HOMA-IR, nitrotyrosine, and soluble adhesion molecules on logistic regression analysis; the presence of NAFLD entailed more severe oxidative stress and endothelial dysfunction, independent of adiposity or any feature of the metabolic syndrome in insulin-resistant subjects.. NAFLD is more tightly associated with insulin resistance and with markers of oxidative stress and endothelial dysfunction than with ATP III criteria in nonobese nondiabetic subjects and may help identify individuals with increased cardiometabolic risk in this population.

Topics: Adiponectin; Adult; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Fatty Liver; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Tumor Necrosis Factor-alpha

The metabolic syndrome is a group of disorders including obesity, insulin resistance, atherogenic dyslipidemia, hyperglycemia, and hypertension. To date, few animal models have been described to recapitulate the phenotypes of the syndrome. In this study, we generated and characterized two lines of triple-knockout mice that are deficient in either apolipoprotein E (Apoe(-/-)) or low-density lipoprotein receptor (Ldlr(-/-)) and express no leptin (Lep(ob/ob)) or apolipoprotein B-48 but exclusively apolipoprotein B-100 (Apob(100/100)). These two lines are referred to as Apoe triple-knockout-Apoe 3KO (Apoe(-/-)Apob(100/100)Lep(ob/ob)) and Ldlr triple-knockout-Ldlr 3KO (Ldlr(-/-)Apob(100/100)Lep(ob/ob)) mice. Both lines develop obesity, hyperinsulinemia, hyperlipidemia, hypertension, and atherosclerosis. However, only Apoe 3KO mice are hyperglycemic and glucose intolerant and are more obese than Ldlr 3KO mice. To evaluate the utility of these lines as pharmacological models, we treated both with leptin and found that leptin therapy ameliorated most metabolic derangements. Leptin was more effective in improving glucose tolerance in Ldlr 3KO than Apoe 3KO animals. The reduction of plasma cholesterol by leptin in Ldlr 3KO mice can be accounted for by its suppressive effect on food intake. However, in Apoe 3KO mice, leptin further reduced plasma cholesterol independently of its effect on food intake, and this improvement correlated with a smaller plaque lesion area. These effects suggest a direct role of leptin in modulating VLDL levels and, likewise, the lesion areas in VLDL-enriched animals. These two lines of mice represent new models with features of the metabolic syndrome and will be useful in testing therapies targeted for combating the human condition.

Topics: Animals; Apolipoprotein B-48; Apolipoproteins E; Disease Models, Animal; Hyperglycemia; Hyperlipidemias; Hypertension; Insulin Resistance; Leptin; Lipoproteins, VLDL; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Phenotype; Receptors, LDL

Serum retinol-binding protein (RBP4) is secreted by liver and adipocytes and is implicated in systemic insulin resistance in rodents and humans. RBP4 normally binds to the larger transthyretin (TTR) homotetramer, forming a protein complex that reduces renal clearance of RBP4. To determine whether alterations in RBP4-TTR binding contribute to elevated plasma RBP4 levels in insulin-resistant states, we investigated RBP4-TTR interactions in leptin-deficient ob/ob mice and high-fat-fed obese mice (HFD). Gel filtration chromatography of plasma showed that 88-94% of RBP4 is contained within the RBP4-TTR complex in ob/ob and lean mice. Coimmunoprecipitation with an RBP4 antibody brought down stoichiometrically equal amounts of TTR and RBP4, indicating that TTR was not more saturated with RBP4 in ob/ob mice than in controls. However, plasma TTR levels were elevated approximately fourfold in ob/ob mice vs. controls. RBP4 injected intravenously in lean mice cleared rapidly, whereas the t(1/2) for disappearance was approximately twofold longer in ob/ob plasma. Urinary fractional excretion of RBP4 was reduced in ob/ob mice, consistent with increased retention. In HFD mice, plasma TTR levels and clearance of injected RBP4 were similar to chow-fed controls. Hepatic TTR mRNA levels were elevated approximately twofold in ob/ob but not in HFD mice. Since elevated circulating RBP4 causes insulin resistance and glucose intolerance in mice, these findings suggest that increased TTR or alterations in RBP4-TTR binding may contribute to insulin resistance by stabilizing RBP4 at higher steady-state concentrations in circulation. Lowering TTR levels or interfering with RBP4-TTR binding may enhance insulin sensitivity in obesity and type 2 diabetes.

Topics: Animals; Blotting, Western; Body Weight; Diabetes Mellitus, Type 2; Dietary Fats; Female; Injections, Intravenous; Insulin Resistance; Leptin; Metabolic Syndrome; Mice; Mice, Obese; Obesity; Prealbumin; Retinol-Binding Proteins, Plasma

The agouti viable yellow (A vy) spontaneous mutation generates an unusual mouse phenotype of agouti-colored coat and adult-onset obesity with metabolic syndrome. Persistent production of agouti signaling protein in A vy mice antagonizes melanocortin receptors in the hypothalamus. To determine how this disruption of neuroendocrine circuits affects leptin transport across the blood-brain barrier (BBB), we measured leptin influx in A vy and B6 control mice after the development of obesity, hyperleptinemia, and increased adiposity. After iv bolus injection, (125)I-leptin crossed the BBB significantly faster in young (2 month old) B6 mice than in young A vy mice or in older (8 month old) mice of either strain. This difference was not observed by in situ brain perfusion studies, indicating the cause being circulating factors, such as elevated leptin levels or soluble receptors. Thus, A vy mice showed peripheral leptin resistance. ObRa, the main transporting receptor for leptin at the BBB, showed no change in mRNA expression in the cerebral microvessels between the age-matched (2 month old) A vy and B6 mice. Higher ObRb mRNA was seen in the A vy microvasculature with unknown significance. Immunofluorescent staining unexpectedly revealed that many of the ObR(+) cells were astrocytes and that the A vy mice showed significantly more ObR(+) astrocytes in the hypothalamus than the B6 mice. Although leptin permeation from the circulation was slower in the A vy mice, the increased ObR expression in astrocytes and increased ObRb mRNA in microvessels suggest the possibility of heightened central nervous system sensitivity to circulating leptin.

Topics: Adipose Tissue; Age of Onset; Animals; Biological Transport; Blood-Brain Barrier; Body Weight; Disease Models, Animal; Glial Fibrillary Acidic Protein; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C3H; Mice, Obese; Obesity; Polymerase Chain Reaction; Receptors, Leptin; RNA

Serum amyloid A (SAA) is a novel link between increased adipose tissue mass and low-grade inflammation in obesity. Little is known about the factors regulating its serum concentration and mRNA levels. We investigated the association between SAA and leptin in obese and normal weight subjects and analyzed the effect of weight reduction on serum SAA concentration and gene expression in adipose tissue of the obese subjects.. Seventy-five obese subjects (60+/-7 years, body mass index (BMI) 32.9+/-2.8 kg/m(2), mean+/-s.d.) with impaired fasting plasma glucose or impaired glucose tolerance and other features of metabolic syndrome, and 11 normal weight control subjects (48+/-9 years, BMI 23.7+/-1.9 kg/m(2)) were studied at the baseline. Twenty-eight obese subjects underwent a 12-week intensive weight reduction program followed by 5 months of weight maintenance. Blood samples and abdominal s.c. adipose tissue biopsies were taken at the baseline and after the follow-up. Gene expression was studied using real-time quantitative PCR.. The gene expressions in women and serum concentrations of leptin and SAA were interrelated independently of body fat mass in the obese subjects (r=0.54, P=0.001; r=0.24, P=0.039 respectively). In multiple linear regression analyses, leptin mRNA explained 38% of the variance in SAA mRNA (P=0.002) in the obese women. Weight loss of at least 5% increased SAA mRNA expression by 48 and 36% in men and women, but serum SAA concentrations did not change.. The association between SAA and leptin suggests an interaction between these two adipokines, which may have implications in inflammatory processes related to obesity and the metabolic syndrome.

Topics: Adipocytes; Adipose Tissue; Aged; Body Weight; Female; Gene Expression; Glucose Intolerance; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; RNA, Messenger; Serum Amyloid A Protein; Weight Loss

Overweight and obesity have been associated with better survival in patients with chronic obstructive pulmonary disease (COPD). On the other hand, excess body weight is associated with abnormal metabolic and inflammatory profiles that define the metabolic syndrome and predispose to cardiovascular diseases. This study was undertaken to evaluate the impact of overweight and obesity on the prevalence of the metabolic syndrome and on the metabolic and inflammatory profiles in patients with COPD.. Twenty-eight male patients with COPD were divided into an overweight/obese group [ n = 16, body mass index (BMI) = 33.5 +/- 4.2 kg/m(2)] and normal weight group (n = 12, BMI = 21.1 +/- 2.6 kg/m(2)). Anthropometry, pulmonary function and body composition were assessed. The metabolic syndrome was diagnosed according to waist circumference, circulating levels of triglyceride and high-density lipoprotein cholesterol levels, fasting glycemia and blood pressure. C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), leptin and adiponectin plasma levels were measured.. Airflow obstruction was less severe in overweight/obese compared with normal weight patients (forced expiratory volume(1): 51 +/- 19% versus 31 +/- 12% predicted, respectively, P < 0.01). The metabolic syndrome was diagnosed in 50% of overweight/obese patients and in none of the normal weight patients. TNF-alpha, IL-6 and leptin were significantly higher in overweight/obese patients whereas the adiponectin levels were reduced in the presence of excess weight.. The metabolic syndrome was frequent in overweight/obese patients with COPD. Obesity in COPD was associated with a spectrum of metabolic and inflammatory abnormalities.

Topics: Adiponectin; Aged; Body Composition; C-Reactive Protein; Comorbidity; Humans; Inspiratory Capacity; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Pulmonary Disease, Chronic Obstructive; Risk Factors; Tumor Necrosis Factor-alpha

Microalbuminuria increases cardiovascular risk and is considered a metabolic disorder. Low glomerular filtration rate is also associated with increased cardiovascular risk, but the relation of low glomerular filtration rate to metabolic disorders is not well understood.. Designed as a cross-sectional, epidemiologic study, the Insulin Resistance Atherosclerosis Study was conducted in four centers: San Antonio (Texas), San Luis Valley (Colorado), and Oakland and Los Angeles (California). The Modification of Diet in Renal Disease equation was used to classify individuals without diabetes and with normoalbuminuria (n = 856; age 40 to 69 yr) by the presence or absence of low glomerular filtration rate (<60 ml/min per 1.73 m(2)). A direct marker of insulin resistance, the insulin sensitivity index, was measured by the frequently sampled intravenous glucose tolerance test.. Low glomerular filtration rate was related to hypertension and the metabolic syndrome. Low glomerular filtration rate was associated with fasting insulin concentration and insulin sensitivity index. Low glomerular filtration rate was also associated with insulin concentration after adjustment for potential determinants of glomerular filtration rate but was not associated with insulin sensitivity index.. Low glomerular filtration rate is associated with increased insulin concentration in individuals without diabetes and with normoalbuminuria. Longitudinal analyses are needed to determine whether insulin concentration (insulin resistance) precedes the deterioration of renal function.

Topics: Adult; Aged; Albuminuria; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus; Fasting; Glomerular Filtration Rate; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Southwestern United States

The aim of the study is to reveal hormonal disintegration in patients with metabolic syndrome (MS). The examination of 27 healthy persons and 38 patients with metabolic syndrome was performed with assistance of Clamp-test and computer tomography. The dynamics of insulin, leptin, cortisol, testosterone and estradiol levels was studied. Influence of hyperinsulinemia and insulin resistance, leptin and cortisol levels fluctuation on MS development is shown. Probable mechanisms of hormonal interaction being in the base of the pathological process are proposed. Influence of sensitivity to insulin on the activity of sympathetic nervous system and increase of arterial pressure is demonstrated.

Topics: Adipose Tissue; Adult; Aged; Biomarkers; Estradiol; Female; Follow-Up Studies; Humans; Hydrocortisone; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Radiography; Severity of Illness Index; Testosterone

Various adipose tissue factors have been implicated as biomarkers of the metabolic syndrome (MS). The objective of this study was to assess which specific adipose tissue factors would discriminate the presence of MS in a strictly obese population meeting waist circumference (WC) criteria for the MS.. This was a cross-sectional study of 148 subjects recruited from a university-based weight loss program prior to starting the program. Patients were eligible if they had a BMI more than 25 kg/m(2) and had WC more than 40 and 35 inches in males and females, respectively. Biomarkers measured included high sensitivity C-reactive protein (hs-CRP), leptin, adiponectin, and total insulin.. Of the total population, 33.8% satisfied criteria for the MS. Insulin was the only biomarker to consistently differentiate between presence and absence of MS in this obese population (P = 0.0001 in males, P = 0.006 in females). All biomarkers measured with the exception of leptin had a statistically significant relationship with increasing criteria for the MS.. In a population where an excess amount of adipose tissue exists, insulin is the only reliable biomarker to differentiate MS status. We surmise that differences in hs-CRP, leptin, and adiponectin are a reflection of their measurements in individuals with statistically different amounts of adipose tissue.

Topics: Adiponectin; Adult; Biomarkers; Body Fat Distribution; C-Reactive Protein; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Prevalence; Waist-Hip Ratio

Genetic variation in the beta2 (ADRB2) and beta3 (ADRB3) adrenergic receptor genes are associated with obesity and insulin resistance. To further elucidate the role of these genes in the pathophysiology of obesity the present study investigated associations between certain polymorphisms in ADRB2 and ADRB3 and parameters of carbohydrate and lipid metabolism in a population of African origin.. Data of 102 black South African women obtained in the POWIRS (Profile of Obese Women with the Insulin Resistance Syndrome) study were used. Endpoint measurements included several anthropometric variables, resting blood pressure, plasma glucose, insulin, free fatty acids (FFA), ghrelin, leptin and lipids, and insulin resistance as estimated by the homeostasis model assessment (HOMA-IR) index. Polymorphisms were analyzed via PCR based methods.. The percentage body fat was significantly lower (p< or =0.05) and the FFA significantly higher (p< or =0.05) in lean subjects (BMI< or =25 kg/m2) with the Glu27 variant allele compared to subjects with the Gln27 wildtype allele of the ADRB2 gene. In contrast, the variant allele of the ADRB2 gene was significantly positive associated (p< or =0.05) with the HOMA-IR-index in overweight black African women (BMI>25 kg/m2). No significant differences in parameters of the metabolic syndrome were apparent between subjects with the wildtype and variant alleles in the ADRB3 gene.. The presence of the Glu27 and Arg64 polymorphisms of the ADRB2 and ADRB3 genes are not directly related to indices of the metabolic syndrome.

Topics: Adipose Tissue; Adult; Black People; Blood Pressure; Body Mass Index; Fatty Acids, Nonesterified; Female; Humans; Leptin; Metabolic Syndrome; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Receptors, Adrenergic, beta-3; Thinness

Ectonucleotide pyrophosphatase phosphodiesterase (ENPP1) is a positional candidate gene at chromosome 6q23 where we previously detected strong linkage with fasting-specific plasma insulin and obesity in Mexican Americans from the San Antonio Family Diabetes Study (SAFDS). We genotyped 106 single-nucleotide polymorphisms (SNPs) within ENPP1 in all 439 subjects from the linkage study, and measured association with obesity and metabolic syndrome (MS)-related traits. Of 72 polymorphic SNPs, 24 were associated, using an additive model, with at least one of eight key metabolic traits. Three traits were associated with at least four SNPs. They were high-density lipoprotein cholesterol (HDL-C), leptin, and fasting plasma glucose (FPG). HDL-C was associated with seven SNPs, of which the two most significant P values were 0.0068 and 0.0096. All SNPs and SNP combinations were analyzed for functional contribution to the traits using the Bayesian quantitative-trait nucleotide (BQTN) approach. With this SNP-prioritization analysis, HDL-C was the most strongly associated trait in a four-SNP model (P=0.00008). After accounting for multiple testing, we conclude that ENPP1 is not a major contributor to our previous linkage peak with MS-related traits in Mexican Americans. However, these results indicate that ENPP1 is a genetic determinant of these traits in this population, and are consistent with multiple positive association findings in independent studies in diverse human populations.

Topics: Adult; Aged; Aged, 80 and over; Bayes Theorem; Blood Glucose; Cholesterol, HDL; Diabetes Mellitus, Type 2; Fasting; Female; Gene Expression Regulation, Enzymologic; Gene Frequency; Genetic Linkage; Genetic Predisposition to Disease; Humans; Leptin; Male; Metabolic Syndrome; Mexican Americans; Middle Aged; Models, Genetic; Obesity; Phenotype; Phosphoric Diester Hydrolases; Polymorphism, Single Nucleotide; Pyrophosphatases; Risk Factors; Texas

The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown.. The objective of the study was to study the cross-sectional relations of these adipokines to cardiometabolic risk factors in a community-based sample.. We measured circulating ghrelin, leptin, and sOB-R in 362 participants (mean age 45 yr; 54% women) of the Framingham Third Generation Cohort.. Body mass index, waist circumference (WC), blood pressure, lipid measures, fasting glucose, smoking, and metabolic syndrome (MetS) were measured.. Ghrelin and leptin concentrations were significantly higher in women (P < 0.0001). In multivariable models, ghrelin was inversely associated with age and systolic blood pressure, and leptin was positively related to body mass index and WC. sOB-R was positively associated with age, total cholesterol, and fasting glucose and inversely with WC and high-density lipoprotein cholesterol. Ghrelin and sOB-R concentrations were significantly lower with number of MetS components (P for trend = 0.022 and < 0.0001, respectively), whereas leptin concentrations were higher (P for trend = 0.0001). Relating all adipokines to MetS conjointly, higher ghrelin and leptin concentrations were associated with decreased and increased odds of MetS (odds ratio 0.55, P < 0.0001; odds ratio 4.44, P = 0.0002, per 1 sd increase of respective log adipokine).. In our community-based sample, we observed a sexual dimorphism in circulating ghrelin and leptin concentrations. Ghrelin, leptin, and sOB-R were associated with number of MetS components cross-sectionally, consistent with the hypothesis that these adipokines may have a central role in cardiometabolic risk.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Energy Metabolism; Female; Ghrelin; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Receptors, Leptin; Risk Factors; Sex Characteristics

Obesity and hyperlipidemia are common findings 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 > 30 kg/m2) with dyslipidemia. We compared findings of a new therapeutic regimen 1 year (at baseline) and 2 years after renal transplantation. Using the Subjective Global Assessment, at the end of the first year an Individualized Hypoenergetic-Hypolipidemic diet was initiated. Subsequently, after withdrawal of corticosteroids IHHD was regularly supplemented 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<0.25) and an increase in adiponectin levels (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). Insulin clearance mean systolic and diastolic blood pressure, proteinuria and apo-lipoprotein E isoforms did not differ significantly. Based on our results, we can assume that obesity and hyperlipidemia after renal transplantation can be effectively treated by modified immunosuppression (corticosteroid withdrawal), statins and long-term diet (IHHD). The increased levels of adiponectin may be a marker of reduced atherosclerosis and chronic allograft nephropathy.

Topics: Adiponectin; Adult; Aged; Female; Humans; Hyperlipidemias; Kidney Transplantation; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity

Obesity and the metabolic syndrome have emerged as clinical and public health crises in many populations, but not all obese patients have the syndrome. As adipocytes produce several adipokines that modulate insulin action as well as glucose and lipid metabolism, we postulate that estimation of adipokines may be useful addition to the criteria used to identify obese individuals with the metabolic syndrome.. To evaluate the determinants and associations of plasma adiponectin in relation to the metabolic syndrome in patients with Type 2 diabetes.. Cross-sectional study.. General Teaching Hospital.. One hundred and thirty five (57 M, 78 F) patients with Type 2 diabetes mellitus.. Adiponectin, leptin, high-sensitivity C-reactive protein (hs-CRP), fasting plasma insulin, glucose, glycated hemoglobin and full lipid profile. Patients were classified on the basis of the degree of adiposity, insulin resistance (IR) (homeostasis model assessment of insulin resistance (HOMA-IR)) and the number of the American Heart Association and the National Heart, Lung and Blood Institute criteria of the metabolic syndrome.. Adiponectin levels were inversely correlated with age, indices of obesity, IR and hs-CRP. Overweight/obese and non-obese insulin-sensitive patients had significantly higher (P<0.05) adiponectin levels than those with IR despite similar body mass index and waist circumference. Therefore, within each category of obesity stratification, lower adiponectin levels were associated with IR. Adiponectin showed stepwise decrease with increasing number of the criteria for diagnosis of the metabolic syndrome. Using multiple logistic regression, the odds ratio of the metabolic syndrome as predicted by adiponectin was 0.73 (95% confidence interval 0.53-0.96; P=0.04). At cutoff point of 18 ng/ml, the diagnostic sensitivity and specificity of adiponectin for the metabolic syndrome were 83 and 65%, respectively, in male patients and 92 and 41%, respectively, in female patients. Receiver operating characteristic analysis showed that adiponectin had significantly higher area under the curve compared with leptin, leptin:adiponectin ratio and triglycerides for the detection of the metabolic syndrome.. In patients with Type 2 diabetes, adiponectin concentrations are closely related to IR and the components of the metabolic syndrome. Adiponectin concentration may be a useful addition to the criteria used for identifying obese subjects with the metabolic syndrome.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Sensitivity and Specificity

In order to find orally active Zn(II) complexes that can treat diabetes mellitus (DM) at low doses, four new Zn(II)-dithiocarbamate complexes with Zn(II)-sulfur coordination bonds were prepared and their in vitro insulinomimetic activity and in vivo anti-diabetic ability were evaluated. Among the Zn(II)-dithiocarbamate complexes, the bis(pyrrolidine-N-dithiocarbamate)zinc(II) (Zn(pdc)(2)) complex was found to be the most effective in terms of inhibiting free fatty acid-release and enhancing glucose-uptake in adipocytes. After oral administration of the Zn(pdc)(2) complex to KK-A(y) mice with obesity and type 2 DM, we observed that the high blood glucose levels in the mice were lowered from approximately 500 mg/dL to 350 mg/dL within 6 days, and the effect was maintained during the administration period. Also, indicators of insulin resistance such as serum insulin, leptin, and triglyceride levels were also reduced compared with those in untreated mice. Moreover, the Zn(pdc)(2) complex improved not only the hypertension in the mice, but also the adiponectin level in the serum. On the basis of the results, the Zn(pdc)(2) complex is proposed to improve hyperglycemia and insulin resistance in type 2 DM animals on daily oral administrations.

Topics: Adipocytes; Adiponectin; Administration, Oral; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose; Glucose Tolerance Test; Hypoglycemic Agents; Insulin; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Organometallic Compounds; Thiocarbamates; Triglycerides; Zinc Sulfate

Primary hyperparathyroidism (PHPT) has been associated with high cardiovascular morbidity and mortality; its pathogenesis is not fully understood. Moreover, many metabolic abnormalities are frequently present in patients with PHPT. Several substances (such as leptin and adiponectin) are secreted from adipocytes, which may contribute to regulate energy homeostasis and the development of cardiovascular diseases. We examined the relationship between leptin and adiponectin levels and metabolic disorders in 67 newly diagnosed never-treated patients with PHPT and in 46 healthy subjects (HS). Twenty (29.8%) patients with PHPT presented a metabolic syndrome (as defined by Adult Treatment Panel III criteria). Serum leptin and adiponectin levels in HS were 6.28 +/- 3.3 ng/mL (range, 1.7-19.2 ng/mL) and 6.65 +/- 1.7 microg/mL (range, 3.72-10.86 microg/mL), respectively. In all patients with PHPT, the mean leptin levels (34.28 +/- 20.4 ng/mL) were significantly higher than those of HS (P < .01) and, in particular, in PHPT patients with metabolic syndrome (52.63 +/- 31.2 ng/mL) and positively correlated with body mass index, waist circumference, and cholesterol. The mean adiponectin level was significantly lower (4.34 +/- 3.5 mug/mL) only in PHPT patients with metabolic syndrome (P < .005) and negatively correlated with waist circumference and fasting glucose. We concluded that increased serum level of leptin and decreased serum level of adiponectin coexist in patients with PHPT and may represent a pathogenetic factor for cardiovascular disease in this condition.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Mass Index; Calcium; Cardiovascular Diseases; Cholesterol; Female; Heart Rate; Humans; Hyperparathyroidism; Leptin; Magnesium; Male; Metabolic Syndrome; Middle Aged; Parathyroid Hormone; Phosphorus; Uric Acid

To evaluate the prevalence of beta(3)-adrenergic receptor (ADRB3) Trp64Arg polymorphism and its relationship with the metabolic syndrome in severe obesity.. Cross-sectional outpatients study.. In 265 (100 men) severely obese non-diabetic subjects and 78 (25 men) healthy volunteers, genomic DNA was isolated from peripheral leukocytes. In obese patients, plasma concentrations of leptin, lipids, glucose and insulin, the homeostasis model assessment index and blood pressure have been measured. The Trp64Arg mutation was identified with the real-time TaqMan method.. Neither genotype distribution nor allele frequency differed between the two groups. The metabolic syndrome prevalence was 59% in obese subjects, and was higher in men than in women (65 vs 55%: P=0.03). The body mass index (BMI) was related to age tertiles (beta=0.08; P<0.001; multiple linear regression) in Trp64Arg-positive obese subjects.. We confirm the high prevalence of the metabolic syndrome among severely obese subjects. ADRB3 polymorphism was significantly related to insulin resistance only in obese male subjects. Moreover, increased BMI was related to age in obese subjects with the ADRB3 polymorphism.

Topics: Adult; Age Factors; Blood Glucose; Body Mass Index; Cross-Sectional Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Insulin; Italy; Leptin; Leukocytes; Linear Models; Lipids; Male; Metabolic Syndrome; Mutation; Obesity, Morbid; Polymorphism, Genetic; Receptors, Adrenergic, beta-3; Sex Factors

Arginine-vasopressin (AVP) is known to be involved in maintaining glucose homeostasis, and AVP-resistance is observed in poorly controlled non-insulin-dependent diabetes mellitus subjects, resulting in a lowered plasma volume. Recently we reported that V1a vasopressin receptor-deficient (V1aR(-/-)) mice exhibited a decreased circulating blood volume and hypermetabolism of fat accompanied with impaired insulin-signaling. Here we further investigated the roles of the AVP/V1a receptor in regulating glucose homeostasis and plasma volume using V1aR(-/-) mice. The plasma glucose levels at the baseline or during a glucose tolerance test were higher in V1aR(-/-) than wild-type (WT) mice. Moreover, a hyperinsulinemic-euglycemic clamp revealed that the glucose infusion rate was significantly lower in V1aR(-/-) mice than in WT mice and that hepatic glucose production was higher in V1aR(-/-) mice than WT mice. In contrast to the increased hepatic glucose production, the liver glycogen content was decreased in the mutant mice. These results indicated that the mutant mice had impaired glucose tolerance. Furthermore, feeding V1aR(-/-) mice a high-fat diet accompanied by increased calorie intake resulted in significantly overt obesity in comparison with WT mice. In addition, we found that the circulating plasma volume and aldosterone level were decreased in V1aR(-/-) mice, although the plasma AVP level was increased. These results suggested that the effect of AVP on water recruitment was disturbed in V1aR(-/-) mice. Thus, we demonstrated that one of the AVP-resistance conditions resulting from deficiency of the V1a receptor leads to decreased plasma volume as well as impaired glucose homeostasis, which can progress to obesity under conditions of increased calorie intake.

Topics: Animals; Arginine Vasopressin; Blood Glucose; Body Weight; Dietary Fats; Energy Intake; Feeding Behavior; Glycogen; Homeostasis; Insulin; Leptin; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Plasma Volume; Receptors, Vasopressin

Chronic kidney disease coexists with metabolic syndrome and this relationship may be apparent before overt manifestations of cardiovascular disease. To investigate early stages of the natural history of associations between renal function and metabolic syndrome, we phenotyped 1572 young (mean age=18.4 years), apparently healthy men for metabolic risk factors and estimated their creatinine clearance based on the Cockcroft-Gault equation. High metabolic risk (clustering of at least three metabolic risk factors) was revealed in 8.7% (137) of the subjects and was associated with a 6.9-fold increase in the odds of glomerular hyperfiltration (95% confidence interval (CI): 3.9-11.5) when compared to reference (from none to two metabolic risk factors). Overweight, elevated blood pressure, and low high-density lipoprotein (HDL) cholesterol increased the multivariate-adjusted odds ratio of glomerular hyperfiltration to 6.6 (95% CI: 3.8-11.6), 1.8 (95% CI: 1.0-3.0), and 2.5 (95% CI: 1.5-4.3), respectively. Systolic and diastolic blood pressures clustered together with leptin in the factor analysis and this blood pressure-adiposity component correlated with estimated creatinine clearance (r=0.329, P<0.0001) and explained on its own 10.2% of the variance in the estimated renal function. Our data reveal the silent epidemics of metabolic risk among young, apparently healthy men. Furthermore, the results indicate that high metabolic risk is associated with glomerular hyperfiltration before overt manifestations of cardiovascular disease.

Topics: Adolescent; Adult; Age Factors; Biomarkers; Creatinine; Glomerular Filtration Rate; Humans; Hyperglycemia; Kidney Diseases; Leptin; Male; Metabolic Syndrome; Prevalence; Risk Factors

The metabolic syndrome, characterized by obesity, insulin resistance and dyslipidemia, is a major cause of cardiovascular disease. The origins of the syndrome have been hypothesized to lie in continuous availability of energy dense foods in modern societies. In contrast, human physiology has evolved in an environment of sporadic food supply and frequent food deprivation. Intermittent food restriction in rats has previously been shown to lead to reduction of cardiovascular risk and a greater life span. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG) is taken up by cells and induces pharmacological inhibition of metabolism of glucose. We hypothesized that intermittent inhibition of glucose metabolism, a metabolic deprivation, may mimic intermittent food deprivation and ameliorate metabolic and pathophysiological aspects of the metabolic syndrome.. Insulin resistant, atherosclerosis-prone JCR:LA-cp rats were treated with 2-DG (0.3% w/w in chow) on an intermittent schedule (2 days treated, one day non-treated, two days treated and two days non-treated) or continuously at a dose to give an equivalent averaged intake.. Intermittent 2-DG-treatment improved insulin sensitivity, which correlated with increased adiponectin concentrations. Further, intermittent treatment (but not continuous treatment) reduced plasma levels of leptin and the inflammatory cytokine IL-1 beta. Both 2-DG treatments reduced micro-vascular glomerular sclerosis, but only the intermittent schedule improved macro-vascular dysfunction.. Our findings are consistent with reduction in severity of the metabolic syndrome and protection against end stage micro- and macro-vascular disease through intermittent metabolic deprivation at a cellular level by inhibition of glucose oxidation with 2-DG.

Topics: Acetylcholine; Adiponectin; Animals; Blood Glucose; Body Weight; Deoxyglucose; Dose-Response Relationship, Drug; Eating; Female; In Vitro Techniques; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Nitroprusside; Obesity; Phenylephrine; Rats; Rats, Inbred Strains; Rats, Mutant Strains; Renal Circulation; Time Factors; Vascular Diseases; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents

Hyperandrogenism in postmenopausal women is due to ovarian hyperthecosis or an androgen-secreting ovarian/adrenal tumor. Making the correct diagnosis might be complicated due to the possible existence of an adrenal neoplasm secreting testosterone only, ectopic ovarian tissue or ectopic luteinizing hormone/human chorionic gonadotropin receptors in the adrenals, as well as the relatively low sensitivity of imaging techniques (computed tomography, magnetic resonance imaging) and vein catheterization for this type of pathology. We present the case of an obese postmenopausal woman with metabolic syndrome, hyperandrogenism (high testosterone levels, suppressed gonadotropins), adrenal macronodular hyperplasia and Leydig-cell ovarian tumor. At presentation she had low leptin levels despite high body fat content. After a catheter study left adrenalectomy was carried out but hyperandrogenism persisted. Then, bilateral oophorectomy with hysterectomy was performed and a small Leydig-cell tumor was found in the left ovary. Postoperatively, testosterone and gonadotropin levels were normal (postmenopausal) and leptin level became elevated without change in body mass index or body fat content. In conclusion, we speculate that low leptin levels in obese hyperandrogenic women might be a marker for androgen-secreting tumors.

Topics: Adrenal Glands; Alopecia; Biomarkers; Female; Hirsutism; Humans; Hyperandrogenism; Hyperplasia; Leptin; Leydig Cell Tumor; Metabolic Syndrome; Middle Aged; Obesity; Ovarian Neoplasms

To evaluate serum leptin levels in obese Indian children and its correlation to anthropometric and biochemical parameters.. Cohort study.. Referral tertiary hospital.. Leptin levels were measured in 36 children (26 boys, age 1.5 to 15 years) and 37 adults (21 men, age 25 to 69 years) with obesity and 29 normal weight controls (15 children and 14 adults).. Leptin levels were higher than controls in obese children (19.4 +/- 6.4 ng/mL against 5.4 +/- 1.7 ng/mL, p = 0.0001) and obese adults (18.9 +/- 6.4 ng/mL against 7.8 +/- 5.6 ng/mL, p = 0.0001). Leptin levels were higher than males in obese girls (23.5 +/- 1.7 ng/mL against 18.0 +/-7.6 ng/mL, p = 0.040) and women (21.3 +/- 4.4 ng/mL against 15.8 +/- 7.4 ng/mL). Leptin levels correlated with body mass index, waist circumference and waist to-hip ratio. A positive correlation was observed between serum leptin and cholesterol, triglycerides and LDL-cholesterol. No correlation was seen with fasting blood glucose and HDL-cholesterol.. Leptin levels correlate significantly with anthropometric and laboratory parameters in obese children. There is a need for further studies on the role of leptin in childhood obesity and metabolic syndrome.

Topics: Adolescent; Adult; Aged; Anthropometry; Body Mass Index; Case-Control Studies; Child; Child, Preschool; Female; Humans; India; Infant; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors

This study investigates the impact of uric acid (UA) on the risk factors associated with metabolic syndrome. In addition, this study explores the relationship between UA and insulin resistance and serum leptin levels in metabolic syndrome. A total of 470 subjects (252 women and 218 men) were recruited from the Department of Health Management at Chang Gung Medical Center (Linkou, Taiwan). Metabolic syndrome was defined using a modified Adult Treatment Panel III (ATP III) definition. The formula for the homeostasis model assessment of insulin resistance (HOMA-IR) is as follows: fasting serum insulin (microU/mL) x fasting plasma glucose (mmol/L)/22.5. Diabetes mellitus was diagnosed in 45 subjects (9.6%); 82 subjects (17.4%) had hypertension. Hyperuricemia was diagnosed in 144 subjects (30.6%). Of these subjects, 115 (63 females and 52 males) (24.5%) were diagnosed as having metabolic syndrome. Patients with hyperuricemia had increased body mass index, waist-to-hip ratio, and triglyceride (Tg) level. The subjects also had lower high-density lipoprotein and greater hypertension. Hormone assays showed an elevation of leptin, immunoreactive insulin (IRI), and HOMA-IR in the hyperuricemia group. Uric acid appeared to be better correlated with Tg, blood pressure (both systolic and diastolic), obesity, immunoreactive insulin, and HOMA-IR. Uric acid did not correlate with leptin or blood glucose levels. Metabolic syndrome and Tg/high-density lipoprotein ratio showed a statistically significant difference in HOMA-IR using 3.8 as a cutoff value. Otherwise, there was no difference in leptin value. In conclusion, serum UA is significantly related to risk factors of metabolic syndrome except for blood glucose. Waist-to-hip ratio and HOMA-IR were statistically different in subjects with and without metabolic syndrome.

Topics: Adult; Aged; Body Mass Index; Female; Humans; Insulin Resistance; Leptin; Lipoproteins, HDL; Male; Metabolic Syndrome; Middle Aged; Risk Factors; Uric Acid; Waist-Hip Ratio

Associations between SDB, the metabolic syndrome, and circulating levels of adipokines have emerged in adults but have not been examined in snoring children, who, in contradistinction to adults, display insulin resistance and lipid abnormalities as a function of adiposity rather than SDB. Therefore, we aimed to examine associations between circulating adipokines levels, insulin resistance, and measures of SDB in children.. Prospective study.. Polysomnographic evaluation and assessment of plasma levels of leptin, adiponectin, resistin, glucose, insulin, and CRP.. 130 children (mean age 8.2 +/- 2.8 years; 39% obese) were studied.. Log adiponectin levels were lower in obese than nonobese children (3.8 +/- 0.31 vs 4.0 +/- 0.30 corresponding to 8,381.4 +/- 5,841.0 vs 12,853.2 +/- 7,780.2 ng/ml, P < 0.0001) and were inversely correlated with BMI Z scores (r = -0.47, P < 0.0001) but not with log AHI. Log leptin concentrations were higher in the obese group than the nonobese group (4.2 +/- 0.32 vs 3.4 +/- 0.57 corresponding to 19,542.6 +/- 13,643.6 vs 5,875.5 +/- 8,425.7 pg/ml, P < 0.0001), correlated with BMI Z scores (r = 0.64, P < 0.0001), and were significantly lower in children with AHI < or = 1/hr than children with AHI > 1/hr (P = 0.006) and in children with SpO2 nadir > or = 90% than children with SpO2 nadir < 90%, even after controlling for BMI Z score (P < 0.03). No significant differences were found in log resistin levels as a function of obesity or AHI. Significant correlations between log adiponectin levels and log Insulin/Glucose (I/G) ratios (-0.28, P = 0.006) and between log leptin levels and log I/G ratios (r = 0.66, P < 0.0001) emerged.. In close agreement with the absence of a measurable effect of SDB on insulin resistance in children, circulating adipokines levels are primarily attributable to the ponderal index. However, SDB and associated hypoxemia may contribute to the elevation of leptin levels.

Topics: Adolescent; Blood Glucose; Body Mass Index; C-Reactive Protein; Child; Child, Preschool; Female; Humans; Infant; Insect Hormones; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Oligopeptides; Polysomnography; Pyrrolidonecarboxylic Acid; Resistin; Risk Factors; Sleep Apnea, Obstructive; Statistics as Topic

Women with epilepsy (WWE) tend to have hormonal and metabolic abnormalities, raising concerns about an increased risk of cardiovascular disorders. This study was performed to determine whether epilepsy itself and/or antiepileptic drug (AED) medication cause metabolic abnormalities.. WWE in premenopausal state aged 18 to 45 years old, currently on AED monotherapy for more than six months, were recruited for this study. The subjects checked their oral temperature each morning, and tested serum levels for lipid profiles, insulin, glucose, and leptin. A HOMA-index was used as a marker for insulin resistance.. Of the 54 total patients, 18 women were diagnosed with primary generalized epilepsy (PGE) and the other 36 were diagnosed with localization-related epilepsy (LRE). Among the subjects, 19 women were on carbamazepine (CBZ), 12 on valproate (VPA), 12 on lamotrigine (LTG), and 11 on topiramate (TPM). Body mass index increased and HDL-cholesterol decreased in patients on VPA monotherapy compared with CBZ, LTG, or TPM (p=0.046 and 0.002). Metabolic syndrome was more frequently associated with VPA-treated patients (41.7%) than CBZ (5.3%), LTG (0%), or TPM group (0%) (p=0.005). There were no differences in hormonal and metabolic indices between PGE and LRE groups.. WWE on VPA monotherapy are more obese and more frequently suffer from metabolic syndrome. LTG or TPM may be safer when prescribed to the patients with high risk of cardiovascular disease.

Topics: Adolescent; Adult; Anticonvulsants; Blood Glucose; Body Mass Index; Carbamazepine; Comorbidity; Epilepsy; Female; Humans; Insulin; Insulin Resistance; Lamotrigine; Leptin; Lipids; Metabolic Syndrome; Obesity; Risk Factors; Sex Factors; Triazines; Valproic Acid

The purpose of this study was to investigate whether cholesterol metabolism is associated with serum adipokines and inflammatory markers.. In fifty-eight subjects with impaired fasting glucose or impaired glucose tolerance and features of the metabolic syndrome cholesterol metabolism was assayed with serum non-cholesterol sterol ratios to cholesterol, surrogate markers of synthesis (cholesterol precursors) and dietary absorption % of cholesterol (cholestanol and plant sterols) and related them to serum adiponectin, leptin, high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).. Adiponectin was negatively related to synthesis markers (e.g. desmosterol r=-0.371, P<0.01), and positively to absorption markers (e.g. cholestanol r=0.269, P<0.05). Leptin was associated with synthesis markers (e.g. desmosterol r=0.271, P<0.05) and negatively with absorption markers (e.g. sitosterol r=-0.278, P<0.05). Hs-CRP was negatively associated with absorption markers (e.g. sitosterol r=-0.407, P<0.001). IL-6 and TNF-alpha were not related to cholesterol metabolism. When dividing the subjects into tertiles by the serum desmosterol/cholestanol ratio, the I tertile (high synthesis/low absorption) was associated with low adiponectin concentrations, high BMI and serum leptin concentrations (P<0.05 for all).. Adiponectin, leptin and hs-CRP were associated with variables of cholesterol metabolism. A high ratio of cholesterol synthesis to absorption is characterized by high serum leptin and low adiponectin concentrations.

Topics: Adipocytes; Adiponectin; Biomarkers; C-Reactive Protein; Cholesterol; Cytokines; Female; Humans; Inflammation; Leptin; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged

Fischer-344 (F344) rats exhibit proteinuria and insulin resistance in the absence of hypertension as they age. We determined the effects of long-term (1 yr) treatment with the angiotensin (ANG) II type 1 (AT(1)) receptor blocker L-158,809 on plasma and urinary ANG peptide levels, systolic blood pressure (SBP), and indexes of glucose metabolism in 15-mo-old male F344 rats. Young rats at 3 mo of age (n = 8) were compared with two separate groups of older rats: one control group (n = 7) and one group treated with L-158,809 (n = 6) orally (20 mg/l) for 1 yr. SBP was not different between control and treated rats but was higher in young rats. Serum leptin, insulin, and glucose levels were comparable between treated and young rats, whereas controls had higher glucose and leptin with a similar trend for insulin. Plasma ANG I and ANG II were higher in treated than untreated young or older rats, as evidence of effective AT(1) receptor blockade. Urinary ANG II and ANG-(1-7) were higher in controls compared with young animals, and treated rats failed to show age-related increases. Protein excretion was markedly lower in treated and young rats compared with control rats (young: 8 +/- 2 mg/day vs. control: 129 +/- 51 mg/day vs. treated: 9 +/- 3 mg/day, P < 0.05). Long-term AT(1) receptor blockade improves metabolic parameters and provides renoprotection. Differential regulation of systemic and intrarenal (urinary) ANG systems occurs during blockade, and suppression of the intrarenal system may contribute to reduced proteinuria. Thus, insulin resistance, renal injury, and activation of the intrarenal ANG system during early aging in normotensive animals can be averted by renin-ANG system blockade.

Topics: Aging; Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Blood Glucose; Blood Pressure; Imidazoles; Insulin; Kidney; Leptin; Male; Metabolic Syndrome; Metabolism; Rats; Rats, Inbred F344; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Tetrazoles

The study aimed to examine if dysmetabolic subjects (MetS+) have lower adiponectin gene expression and lower circulating adiponectin levels than non-dysmetabolic obese subjects (MetS-) at baseline, if adiponectin expression and adiponectin concentration rise more in the dysmetabolic group during weight loss, and if v-SNARE Vti1a (vesicle transport soluble NSF attachment protein receptor vps10p tail interacting 1a) expression increases during the weight loss, as a mechanism for increased adiponectin secretion. Twenty-one obese MetS+ and 19 obese MetS- subjects underwent a very low-energy diet for 16 weeks followed by 2 weeks of refeeding. Abdominal subcutaneous adipose tissue biopsies and blood samples were taken before, during, and after dieting for DNA microarray, reverse transcriptase-polymerase chain reaction, and biochemical analyses. Serum adiponectin was also assessed in a sex- and age-matched healthy, nonobese reference group. Weight decreased by 26.3+/-9.8 kg in the MetS+ group and 28.2+/-8.4 kg in the MetS- group with concomitant reductions in insulin, hemoglobin A1c, and triglycerides that were more pronounced in the MetS+ group. Initially, the MetS+ subjects had lower serum adiponectin, but the differences disappeared at week 8, with a continuous increase in serum adiponectin throughout the study in both groups to a level that was higher than in the reference group. The expression of adiponectin and v-SNARE Vti1a did not differ between the groups or over time. In conclusion, obese subjects with the metabolic syndrome had lower circulating adiponectin than subjects without the syndrome. Weight loss increased serum levels of adiponectin without a parallel increase in adiponectin gene expression. The mechanisms involved in the regulation of adiponectin levels merits further investigation.

Topics: Adiponectin; Adipose Tissue; Adult; Body Weight; Diet, Reducing; Energy Intake; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Glycated Hemoglobin; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA; SNARE Proteins; Triglycerides; Weight Loss

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

Because high circulating plasma leptin is associated with many features of the metabolic syndrome (MS), such as abdominal obesity, insulin resistance and high blood pressure (BP), we analysed the ability of plasma leptin concentration to predict the risk of developing MS in a prospective investigation of adult male participants of the Olivetti Heart Study (OHS).. Three hundred and sixty out of 907 men participating in the 1994-95 and 2002-04 OHS examinations (mean age at baseline 50.4 years, range 25-73 years) were free of MS at first visit according to NCEP-ATP III criteria (modified for the lack of high-density lipoprotein cholesterol measurement at baseline). During an average follow-up period of 8 years, there were 52 incident cases of MS (14.5%) due, in particular, to a rise in the prevalence of high BP (+42.4%), abdominal obesity (+16.4%) and impaired fasting glucose (IFG, +6.1%). In multivariate analyses, a one standard deviation difference in baseline plasma leptin concentration was associated with a 1.58-fold greater risk of developing MS (95% confidence interval = 1.10-2.30, P = 0.016) accounting for age, waist circumference, homeostatic assessment model index, smoking, alcohol consumption and physical activity. In particular, plasma leptin was positively associated with the risk of developing high BP (0.006) and IFG (0.014), after adjustment for confounders.. In this sample of an adult male population free of MS at baseline, circulating plasma leptin was a significant predictor of the risk of MS and, in particular, of its high BP and IFG components, independently of potential confounders.

Topics: Adult; Follow-Up Studies; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Risk Factors

The diagnostic criteria and the clinical usefulness of the metabolic syndrome (MetSy) are currently questioned. The objective was to describe the structure of MetSy and to evaluate its components for prediction of diabetes type 2 (T2DM).. This was a case-referent study nested within a population-based health survey. Among 33,336 participants, we identified 177 initially non-diabetic individuals who developed T2DM after 0.1 to 10.5 years (mean, 5.4 years), and, for each diabetes case, two referents matched for sex, age, and year of health survey. Baseline variables included oral glucose tolerance test, BMI, blood pressure, blood lipids, adipokines, inflammatory markers, insulin resistance, and beta-cell function. Exploratory and confirmative factor analyses were applied to hypothesize the structure of the MetSy. The prediction of T2DM by the different factors was evaluated by multivariate logistic regression analysis.. A hypothetical five-factor model of intercorrelated composite factors was generated. The inflammation, dyslipidemia, and blood pressure factors were predicitive only in univariate analysis. In multivariable analyses, two factors independently and significantly predicted T2DM: an obesity/insulin resistance factor and a glycemia factor. The composite factors did not improve the prediction of T2DM compared with single variables. Among the original variables, fasting glucose, proinsulin, BMI, and blood pressure values were predictive of T2DM.. Our data support the concept of a MetSy, and we propose five separate clusters of components. The inflammation and dyslipidemia factors were not independently associated with diabetes risk. In contrast, obesity and accompanying insulin resistance and beta-cell decompensation seem to be two core perturbations promoting and predicting progression to T2DM.

Topics: Adult; Analysis of Variance; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Diabetes Mellitus; Dyslipidemias; Female; Health Surveys; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Middle Aged; Predictive Value of Tests; Proinsulin; Risk Factors; Sweden

The adipocyte influences eating behavior and metabolism via cytokine secretion. We report our findings of adipokine secretion in a cohort of diabetic and nondiabetic morbidly obese patients before and after Roux-en-Y gastric bypass (RYGB).. Ten morbidly obese subjects who underwent uncomplicated RYGB were studied: five were diabetic and nine were female. Nonfasting plasma levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha were determined preoperatively and 6 mo postoperatively. C-reactive protein (CRP) was followed as a marker of the metabolic syndrome.. The patient age was 42 +/- 11 y, and the preoperative BMI was 50 +/- 6 kg/m(2). The 6 mo BMI fell to 33 +/- 5 kg/m(2) (P < 0.0001), and there were no differences between diabetics and nondiabetics with respect to amount of weight loss. In nondiabetic patients, there were significant increases compared with preoperative levels for adiponectin, resistin, and tumor necrosis factor-alpha; leptin was significantly decreased while CRP was unchanged. CRP and leptin levels were both significantly lower (P < 0.05), while all other protein levels were unchanged in diabetic patients.. At 6 mo postoperation, RYGB significantly altered most adipokine levels for nondiabetic patients. Only CRP and leptin were changed in diabetic patients. All patients lost a significant amount of weight over 6 mo, suggesting a different metabolic effect between nondiabetic and diabetic patients after RYGB.

Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Hormones; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity, Morbid; Pilot Projects; Resistin; Tumor Necrosis Factor-alpha; Weight Loss

Concentrations of adiponectin, an adipocytokine with insulin-sensitizing actions, may vary according to ethnic group. This study aimed to determine whether fasting adiponectin levels of Caucasian and African women differ. A second objective was to determine which components of the metabolic syndrome are more closely related to adiponectinemia in both groups.. A cross-sectional study including 102 urban African and 115 Caucasian women with a wide range of obesity aged 20-55 years.. Anthropometric measurements were taken, namely weight, height, body mass index, waist circumference, and hip circumference. Cardiovascular measurements included blood pressure and arterial compliance. Fasting blood samples were taken to determine glucose, insulin, C-peptide, leptin, adiponectin, and lipid levels.. Mean adiponectin levels of the whole groups did not differ, but normal weight African women (N = 38) showed marginally lower adiponectin levels than their Caucasian counterparts (N = 41; P = 0.047). No differences in adiponectin were shown for overweight and obese women. Separate multiple regression analyses for ethnic groups showed that only homeostasis model assessment-insulin resistance (HOMA-IR) significantly contributed to the variance in adiponectin levels of African women, whereas leptin, triacylglycerol levels and HOMA-IR contributed significantly to adiponectin variance in Caucasian women. An additional multiple regression analysis in a combined ethnic group (N = 217) showed ethnicity to be a significant contributor to variances in adiponectin levels.. Even though adiponectin levels of these ethnic groups are similar, different associations of adiponectin with leptin and triacylglycerol levels might indicate that there are ethnic differences regarding the mechanistic functions of adiponectin within the scope of the metabolic syndrome.

Topics: Adiponectin; Adult; Anthropometry; Black People; Blood Pressure; Body Mass Index; Female; Heart Rate; Humans; Leptin; Lipids; Metabolic Syndrome; Obesity; South Africa; White People

High-sensitivity C-reactive protein (hsCRP) and leptin, known to interact at the molecular level, have been associated with the metabolic syndrome (MS). We examined the independent and joint effects of high leptin and hsCRP levels on the development of MS in a population-based cohort of middle-aged subjects (N = 1035). Leptin and hsCRP levels increased with an increase in the number of metabolic abnormalities (P < .001). However, additional adjustment for body mass index diluted the association of leptin with MS in women. In men, the association of high leptin with insulin resistance and waist circumference (P < .001), and in women, the association of high hsCRP with insulin resistance (P = .029) and waist circumference (P = .009) persisted in the multivariate logistic regression models. High leptin in men and high hsCRP in women were significant predictors of MS in logistic regression analysis (P < .001). The highest prevalence of MS (86% in men and 71% in women) was observed in the subjects who belonged to the highest quartile in both leptin and hsCRP. MS is associated independently with high leptin in men and with hsCRP in women, whereas individuals with both of these markers belong to the highest risk of metabolic cluster. The study suggests sex-specific interplay between metabolic and inflammatory markers in the pathogenesis of MS.

Topics: Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Case-Control Studies; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Sex Characteristics; Waist-Hip Ratio

The aim of this study was to assess the suitability of A/J and C57BL/6J mice of both sexes as models of some components of the human metabolic syndrome (MetS) under nutritional conditions more comparable with the actual worldwide diet responsible for the increased incidence of the MetS.. We fed large cohorts (n = 515) of two strains of mice, A/J and the C57BL/6J, and of both sexes a high-fat diet (HFD; 60% fat) that, in contrast with most previous reports using saturated fats, was enriched in mono- and polyunsaturated fatty acids, thus more closely mimicking most Western diets, or a control diet (10% fat), for 20 weeks.. In sharp contrast to previous reports, weight gain and hyperleptinemia were similar in both strains and sexes. Hyperinsulinemia, glucose tolerance, insulin resistance, and hypercholesterolemia were observed, although with important differences between strains and sexes. A/J males displayed severely impaired glucose tolerance and insulin resistance. However, in contrast with C57BL6/J mice, which displayed overt type 2 diabetes, A/J mice of both sexes remained normoglycemic.. With important differences in magnitude and time course, the phenotypic and metabolic characteristics of both strains and both sexes on this HFD demonstrate that these models are very useful for identifying the mechanisms underlying progression or resistance to subsequent type 2 diabetes.

Topics: Animals; Blood Glucose; Body Composition; Body Weight; Cholesterol; Cohort Studies; Diabetes Mellitus, Type 2; Dietary Fats; Disease Models, Animal; Eating; Fatty Acids, Monounsaturated; Female; Glucose Tolerance Test; Insulin; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Pregnancy; Specific Pathogen-Free Organisms; Triglycerides

Recently, we found that poly(gamma-glutamic acid)oxovanadium(IV) complex (VO(gamma-pga)) exhibits a potent antidiabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice. This result prompted us to examine its ability to treat the type 2 diabetic model KKA(y) mice with insulin resistance. We studied the in vivo antidiabetic activity of VO(gamma-pga), compared with that of vanadium(IV) oxide sulfate (VS) as control. Both compounds were orally administered at doses of 5-10 mg (0.1-0.2 mmol) V kg(-1) body mass to the KKA(y) mice for 30 days. VO(gamma-pga) normalized the hyperglycemia within 21 days, whereas VS lowered the blood glucose concentration only by a small degree. In addition, the glucose intolerance, HbA(1c) level, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia were significantly improved in VO(gamma-pga)-treated KKA(y) mice compared with those treated with VS. Based on these observations, VO(gamma-pga) is proposed to be the first orally active oxovanadium(IV)-polymer complex for the efficacious treatment of not only type 2 diabetes but also metabolic syndrome in animals.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Glucose Tolerance Test; Hyperglycemia; Insulin; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Polyglutamic Acid; Vanadates

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

To explore the relationship between serum level of leptin and the components of metabolic syndrome in a group of mid-aged Chinese population.. 345 adults (184 men and 161 women) aged 46 - 53 were enrolled from Fetal Origin of Adult Disease (FOAD) cohort to participate the clinic examination including anthropometry, measurements of blood pressure, fasting and 2 hr plasma levels of glucose and insulin, serum levels of lipid and leptin. HOMA-IR index was calculated to estimate individual insulin resistance. Metabolic syndrome (MS) was diagnosed according to the definition criteria issued by the International Diabetes Federation (IDF) in 2005.. The prevalences of central obesity, higher serum level of triglyceride (TG), lower serum level of high-density lipoprotein (HDL-C), IFG, higher blood pressure and MS were 53.0%, 47.5%, 34.2%, 26.7%, 33.9%, 31.9% in this mid-aged population, respectively. Serum geometric mean level of leptin was higher in females than in males. Serum level of leptin increased with the prevalence of MS and components of abnormal metabolism. The serum level of leptin compared with central obesity, higher blood pressure, higher serum level of triglyceride (TG), lower serum level of high-density lipoprotein cholesterol (HDL-C), IFG and MS was significantly higher respectively (P < 0.05) without HDL-C in males. The serum level of leptin increased with the number of components of abnormal metabolism subjects had (P < 0.001).. The serum level of leptin in this population is significantly associated with MS and components of MS. Hyperleptinemia could be a new component of metabolic syndrome. It might be a target in selection of MS and relative diseases.

Topics: China; Cholesterol, HDL; Cohort Studies; Female; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity

Adipocyte fatty acid-binding protein (A-FABP) has been reported to be increased in obese adults and to be related to metabolic syndrome. Because studies concerning A-FABP in weight loss are limited and studies in obese children are missing, we analyzed A-FABP in obese children before and after weight loss. Fasting serum A-FABP, leptin, insulin, glucose, triglycerides, low-and high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and tumor necrosis factor alpha concentrations as markers of the metabolic syndrome, and weight status (body mass index and percentage body fat based on skinfold measurements) were determined in 30 obese children (median age, 11.9 years) before and after participating in a 1-year obesity intervention. Furthermore, A-FABP levels were measured in 10 nonobese children of similar age, sex, and pubertal stage. Obese children had significantly (P < .001) higher A-FABP concentrations compared with nonobese children. In backward multivariate linear regression analysis, A-FABP correlated significantly (P < .05) with percentage body fat and leptin, but not with any of the markers of the metabolic syndrome. Changes of A-FABP concentrations correlated significantly with changes of percentage body fat (r = 0.53, P = .001) and leptin (r = 0.55, P < .001), but not with any changes of parameters of the metabolic syndrome. Substantial weight loss in 10 children led to a significant (P < .05) decrease in A-FABP levels in contrast to the 20 children without change of weight status. In cross-sectional as well as longitudinal analyses, A-FABP levels were related to weight status and leptin levels. Further longitudinal studies are necessary to study the relationship between A-FABP concentrations and parameters of the metabolic syndrome.

Topics: Adipose Tissue; Adolescent; Blood Pressure; Body Mass Index; C-Reactive Protein; Child; Cross-Sectional Studies; Fatty Acid-Binding Proteins; Female; Humans; Leptin; Longitudinal Studies; Male; Metabolic Syndrome; Multivariate Analysis; Obesity; Regression Analysis; Tumor Necrosis Factor-alpha; Weight Loss

Obstructive sleep apnea (OSA), often concomitant with obesity, increases the risk for the metabolic syndrome. One mechanism that may participate in this association is upregulation of inflammatory pathways. We used structural equation modeling to assess the interrelations between childhood obesity, OSA, inflammation, and metabolic dysfunction. One hundred and eighty-four children (127 boys, mean age: 8.5 +/- 4.1 years) had height and weight measured, underwent overnight polysomnography and had fasting blood taken. The blood was analyzed for insulin, glucose, lipids, leptin, and cytokines [interferon (IFN)-gamma, granulocyte macrophage-colony stimulating factor, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha]. Structural equation modeling (SEM) was used to evaluate associations between the outcomes of interest including hypoxia, arousal (related to respiratory and spontaneous), obesity, metabolic dysfunction, and inflammatory markers. Two cytokine factors and one metabolic factor were derived for the SEM. These factors provided good fit in the structural equation model (chi(2)/df = 2.855; comparative fit index = 0.90, root mean squared error of approximation = 0.10) and all factor loadings were significantly different from zero (P < or = 0.01). Overall, our results indicate that while obesity (as measured by body mass index z-score) has a major influence on the metabolic dysfunction associated with OSA, arousal indices, and cytokine markers may also influence this association. Our results support the hypothesis that OSA is a contributor to the mechanisms that link sleep, systemic inflammation and insulin resistance, and show that the interrelations may begin in childhood.

Topics: Adolescent; Arousal; Blood Glucose; Child; Child, Preschool; Cytokines; Female; Humans; Infant; Inflammation; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Models, Statistical; Obesity; Oxygen; Polysomnography; Signal Processing, Computer-Assisted; Sleep Apnea, Obstructive; Software

The prevalence of metabolic syndrome is high and is increasing in parallel with increasing incidences of breast and prostate cancers. The combination of soy with tea was shown to have synergistic effects on preventing breast and prostate tumors, but the effects of soy and tea combinations on metabolic syndrome-related elements have not been investigated.. We aimed to determine the effects of soy and tea components, alone and in combination, on abdominal adipose mass and serum concentrations of adipokines, growth factors, and sex hormones in male and female mice.. Male and female FVB/N mice were treated with soy, tea components, or both. Food intake and body weight were monitored weekly. At the end of the experiment, abdominal white adipose tissue was weighed, and serum concentrations of biomarkers were measured.. Whole teas, but not the tea polyphenol extracts, significantly reduced abdominal white adipose tissue by 43-60% in female mice and by 65-70% in male mice. The combination of soy phytochemical concentrate and green tea reduced serum insulin-like growth factor-I concentrations in both male and female mice in a synergistic manner. The soy phytochemical concentrate and tea combinations reduced serum estrogen concentrations in female mice in a synergistic manner. Soy phytochemical concentrate and teas also significantly reduced serum leptin concentrations in both male and female mice and testosterone concentrations in male mice.. Further research is warranted to investigate whether soy and tea combinations may prevent breast or prostate cancer in a synergistic manner in part by alleviating metabolic disorders.

Topics: Abdominal Fat; Adiponectin; Animals; Breast Neoplasms; Diet; Drug Synergism; Estrogens; Female; Humans; Insulin-Like Growth Factor I; Leptin; Male; Metabolic Syndrome; Mice; Prostatic Neoplasms; Random Allocation; Soybean Proteins; Tea; Testosterone

Obesity is an independent risk factor for the development of cardiovascular disease frequently associated with hypertension, dyslipemia, diabetes, and insulin resistance. Higher homocysteine (Hcy) levels are observed in the hyperinsulinemic obese adults and suggest that Hcy could play a role in the higher risk of cardiovascular disease in obesity. We analyzed total Hcy levels in obese prepubertal children and their possible association with both metabolic syndrome and various inflammatory biomarkers and leptin. We studied 43 obese children (aged 6-9 years) and an equal number of nonobese children, paired by age and sex. The obese subjects presented significantly elevated values for insulin (P = .003), C-reactive protein (P = .033), and leptin (P < .001). No significant differences were found in Hcy levels between the obese and nonobese children. However, Hcy concentration was significantly higher in the hyperinsulinemic obese children than in the normoinsulinemic group (P = .002). Using multivariant regression analysis, in the obese group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .001) and leptin (P partial = .02) are independent predictive factors for Hcy. In the control group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .005) and leptin (P partial = .031) also are independent predictive factor for Hcy. Increased plasma Hcy, particularly in hyperinsulinemic obese children, may be causally involved in the pathogenesis of atherosclerosis and/or cardiovascular disease, both of which are common in obesity.

Topics: Anthropometry; Biomarkers; Body Weight; Case-Control Studies; Child; Female; Fluorescence Polarization Immunoassay; Homocysteine; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Puberty

Metabolic syndrome (MBS) is a significant health care problem in postmenopausal women and is driven largely by obesity. We wished to assess the prevalence of insulin resistance (IR), diagnosed using practical methods, and whether several adipocyte factors (adiponectin, leptin, resistin) or the gastric peptide ghrelin, associated with cardiovascular risk, might be abnormal and may relate to IR.. We evaluated 37 obese postmenopausal women with MBS and 34 matched obese premenopausal controls, as well as 14 non-obese premenopausal controls. We measured fasting glucose and insulin, performed 75 g 2 hr oral glucose tolerance and intravenous insulin tolerance tests to assess IR, and measured fasting lipids, adiponectin, leptin, resistin and ghrelin.. The kinetic decline in glucose after insulin (kITT) as a marker of IR was the most frequently abnormal test (abnormal in 81%), with QUICKI, HOMA, and a modification of the Matsuda-DeFronzo index (ISIM) abnormal in 76, 73, and 68%, respectively. The GIR was abnormal in only 35% of subjects. Leptin and resistin were elevated and adiponectin and ghrelin were decreased in the postmenopausal women, compared to both groups of premenopausal controls. BMI correlated strongly with markers of insulin resistance as well as adipocytokine values. After controlling for BMI, only leptin was predictive of ISIM.. Being overweight after menopause results in worsening IR and elevations in adipocytokine levels. While BMI is the most important factor, abnormal adipocytokine secretion may enhance IR and increase cardiovascular risk in postmenopausal women.

Topics: Adiponectin; Adult; Body Mass Index; Case-Control Studies; Female; Ghrelin; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Obesity; Peptide Hormones; Postmenopause; Premenopause; Resistin

Endogenously formed reactive oxygen species continuously damage cellular constituents including DNA. These challenges, coupled with exogenous exposure to agents that generate reactive oxygen species, are both associated with normal aging processes and linked to cardiovascular disease, cancer, cataract formation, and fatty liver disease. Although not all of these diseases have been definitively shown to originate from mutations in nuclear DNA or mitochondrial DNA, repair of oxidized, saturated, and ring-fragmented bases via the base excision repair pathway is known to be critical for maintaining genomic stability. One enzyme that initiates base excision repair of ring-fragmented purines and some saturated pyrimidines is NEIL1, a mammalian homolog to Escherichia coli endonuclease VIII. To investigate the organismal consequences of a deficiency in NEIL1, a knockout mouse model was created. In the absence of exogenous oxidative stress, neil1 knockout (neil1-/-) and heterozygotic (neil1+/-) mice develop severe obesity, dyslipidemia, and fatty liver disease and also have a tendency to develop hyperinsulinemia. In humans, this combination of clinical manifestations, including hypertension, is known as the metabolic syndrome and is estimated to affect >40 million people in the United States. Additionally, mitochondrial DNA from neil1-/- mice show increased levels of steady-state DNA damage and deletions relative to wild-type controls. These data suggest an important role for NEIL1 in the prevention of the diseases associated with the metabolic syndrome.

Topics: Animals; DNA Damage; DNA Glycosylases; DNA, Mitochondrial; Fatty Liver; Female; Gene Deletion; Hyperinsulinism; Hyperlipidemias; Kidney; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Pedigree

Obesity is associated with metabolic syndrome and increased incidence of and mortality from myocardial infarction. The aim of the present study was to develop an animal model with metabolic syndrome and examine how that influences size of myocardial infarcts induced by occlusion and reperfusion of the left anterior descending coronary artery. Sprague-Dawley rats (n = 105) were fed either LF (low-fat) or MHF (moderately high-fat) diets for 13 weeks before coronary occlusion for 45 min, followed by reperfusion for 60 min. Compared with LF-fed and lean MHF-fed rats, obese MHF-fed rats developed metabolic disturbances similar to those seen in the metabolic syndrome, including being overweight by 24% (compared with lean MHF-fed rats), having 74% more visceral fat (compared with LF-fed rats), 15% higher blood pressure (compared with LF-fed rats), 116% higher plasma insulin (compared with lean MHF-fed rats), 10% higher fasting plasma glucose (compared with LF-fed rats), 35% higher non-fasting plasma glucose (compared with lean MHF-fed rats), 36% higher plasma leptin (compared with lean MHF-fed rats) and a tendency to lower plasma adiponectin and higher plasma non-esterified fatty acids. Infarct size was similar in the three groups of rats (36+/-14, 42+/-18 and 41+/-14% in obese MHF-fed, lean MHF-fed and LF-fed rats respectively). In conclusion, rats fed a MHF diet developed metabolic syndrome, but this did not influence myocardial infarct size.

Topics: Adiponectin; Animals; Blood Glucose; Cholesterol; Fatty Acids, Nonesterified; Insulin; Leptin; Male; Metabolic Syndrome; Models, Animal; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Rats; Rats, Sprague-Dawley

Fenofibrate, a selective (1)PPAR-alpha activator, is prescribed to treat human dyslipidemia. The aim of this study was to delineate the mechanism of fenofibrate-mediated reductions in adiposity, improvements in insulin sensitivity, and lowering of triglycerides (TG) and free fatty acids (FFA) and to investigate if these favorable changes are related to the inhibition of lipid deposition in the aorta. To test this hypothesis we used male LDLr deficient mice that exhibit the clinical features of metabolic syndrome X when fed a high fat high cholesterol (HF) diet. LDLr deficient mice fed HF diet and simultaneously treated with fenofibrate (100 mg/kg body weight) prevented development of obesity, lowered serum triglycerides and cholesterol, improved insulin sensitivity, and prevented accumulation of lipids in the aorta. Lowering of circulating lipids occurred via down-regulation of lipogenic genes, including fatty acid synthase, acetyl CoA carboxylase and diacyl glycerol acyl transferase-2, concomitant with decreased liver TG and cholesterol, and TG output rate. Fenofibrate also suppressed liver apoCIII mRNA levels and markedly increased lipoprotein lipase mRNA levels, known to enhance serum TG catabolism. In addition, fenofibrate profoundly reduced epididymal fat and mesenteric fat mass to the levels seen in lean mice. The reductions in body weight were associated with elevation of hepatic uncoupling protein 2 (UCP2) mRNA, a concomitant increase in the ketone body formation, and improved insulin sensitivity associated with tumor necrosis factor-alpha reductions and phosphoenol pyruvate carboxykinase down-regulation. These results demonstrate that fenofibrate improves lipid abnormalities partly via inhibition of TG production and partly via clearance of TG-rich apoB particles by elevating LPL and reduced apoCIII. The prevention of obesity development occurred via energy expenditure. Fenofibrate-mediated hypolipidemic effects together with improved insulin sensitivity and loss of adiposity led to the reductions in the aortic lipid deposition by inhibiting early stages of atherosclerosis possibly via vascular cell adhesion molecule-1 (VCAM-1) modulation. These results suggest that potent PPAR-alpha activators may be useful in the treatment of syndrome X.

Topics: Adiposity; Animals; Aorta; Coronary Artery Disease; Diet, Atherogenic; Energy Metabolism; Fenofibrate; Gluconeogenesis; Hypercholesterolemia; Hypertriglyceridemia; Insulin; Insulin Resistance; Leptin; Ligands; Lipid Metabolism; Lipids; Lipogenesis; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; PPAR alpha; Receptors, LDL; Triglycerides; Weight Gain

To study the relationships between nontraditional cardiovascular (CV) risk factors and components of the metabolic syndrome in Native Canadian children, a population at risk of future CV disease.. CV risk factors were evaluated in a population-based study of a Canadian Oji-Cree community, involving 236 children aged 10 to 19 years.. Using an age- and sex-specific case definition, 18.6% of the children met criteria for pediatric metabolic syndrome. As the number of metabolic syndrome component criteria increased, C-reactive protein, leptin, and ratio of apolipoprotein B to apolipoprotein A1 levels rose (all P < .0001) and adiponectin concentration decreased (P = .0006). Principal factor analysis using both traditional and nontraditional CV risk factors revealed 5 underlying core traits, defined as follows: adiposity, lipids/adiponectin, inflammation, blood pressure, and glucose.. Nontraditional CV risk factors accompany the accrual of traditional risk factors early in the progression to pediatric metabolic syndrome. Furthermore, inclusion of these factors in factor analysis suggests that 5 core traits underlie the early development of an enhanced CV risk factor profile in Native children.

Topics: Adiponectin; Adolescent; Adult; Apolipoprotein A-I; Blood Glucose; Blood Pressure; Body Constitution; C-Reactive Protein; Canada; Cardiovascular Diseases; Child; Cholesterol, HDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Factor Analysis, Statistical; Fasting; Female; Humans; Interleukin-6; Leptin; Male; Metabolic Syndrome; Risk Factors; Serum Amyloid A Protein; Sex Factors; Triglycerides

Survivors of childhood-onset (CO) acute lymphoblastic leukemia (ALL) treated with prophylactic cranial radiotherapy often exhibit GH deficiency (GHD), which is associated with increased prevalence of cardiovascular risk factors and cardiac dysfunction.. The objective of the study was to evaluate the effect of GH replacement on cardiovascular risk factors and cardiac function in former CO ALL patients.. Eighteen former CO ALL patients (aged 19-32 yr) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and with confirmed GHD were studied at baseline and after 12 (n = 18) and 24 months (n = 13) of GH treatment (median 0.5 mg/d). A group of 18 age- and sex-matched subjects served as controls.. After 12 months of GH treatment, a significant decrease in serum leptin (P = 0.002), leptin per kilogram fat mass (FM) (P = 0.01), plasma glucose (P = 0.004), FM (P = 0.002), and hip (P = 0.04) and waist (P = 0.02) circumference and increased muscle mass (P = 0.004) were recorded in the patients. Before GH treatment six patients had a metabolic syndrome, but after 12 months only one had it and after 24 months none. After 24 months of GH treatment, an increase in left ventricular mass index (P = 0.06) and significant improvements in cardiac systolic function, measured as fractional shortening (P = 0.03) and ejection fraction (P = 0.03), were recorded.. Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome were recorded after 2 yr of GH replacement in former CO ALL patients with GHD. Long-term follow-up is highly warranted.

Topics: Absorptiometry, Photon; Adult; Body Composition; Body Mass Index; Body Weight; Child; Echocardiography, Doppler; Exercise; Female; Growth Hormone; Heart; Heart Function Tests; Heart Rate; Human Growth Hormone; Humans; Leptin; Lipoproteins; Male; Metabolic Syndrome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors; Survivors; Waist-Hip Ratio

Highly active antiretroviral therapy (HAART) for HIV-1 infection has been associated with a metabolic syndrome characterized by insulin resistance, hyperlipidemia, and redistribution of body fat (lipodystrophy). A subset of patients with predominant lipoatrophy has low levels of the adipocyte-secreted hormone leptin.. The objective of the study was to assess whether administration of recombinant methionyl human leptin (r-metHuLeptin) improves insulin resistance and other metabolic abnormalities in HIV+ leptin-deficient subjects with HAART-induced lipoatrophy.. We conducted a randomized, placebo-controlled, double-blinded, crossover study from 2002 to 2004 in seven HIV+ men with HAART-induced lipoatrophy, serum leptin level less than 3 ng/ml, and fasting triglyceride level greater than 300 mg/dl, who were administered placebo for 2 months before or after administration of r-metHuLeptin at physiological doses for an additional 2 months.. Insulin resistance, lipid levels, inflammatory markers, body composition, and HIV control were measured.. Compared with placebo, r-metHuLeptin therapy improved fasting insulin levels, insulin resistance (as expressed by the homeostasis model assessment index and an insulin suppression test), and high-density lipoprotein. Body weight and fat mass decreased on r-metHuLeptin, mainly due to a decrease in truncal fat but not peripheral fat or lean body mass. r-metHuLeptin was well tolerated, and HIV control was not adversely affected.. r-metHuLeptin replacement at physiological doses in HIV+ leptin-deficient patients with HAART-induced lipoatrophy improves insulin resistance, high-density lipoprotein, and truncal fat mass. Future larger and more long-term studies in HAART-induced lipoatrophy, including patients with more severe metabolic abnormalities, are warranted to evaluate the physiological and potentially therapeutic role of r-metHuLeptin for this condition and to fully clarify the underlying mechanisms of action.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Antiretroviral Therapy, Highly Active; Body Composition; Body Mass Index; Cross-Over Studies; Double-Blind Method; HIV-1; HIV-Associated Lipodystrophy Syndrome; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Lipids; Lipoproteins, HDL; Male; Metabolic Syndrome; Placebos; Recombinant Proteins

To characterize microvascular function, candidate risk pathways, and metabolic syndrome prevalence in women with cardiac syndrome X, 52 nondiabetic women with angiographically normal epicardial arteries but >1 mm of planar ST depression during exercise testing (patients) and 24 healthy controls of similar age were recruited. In addition to fasting blood samples and anthropometric measurements, forearm cutaneous microvascular function after iontophoresis of acetylcholine and sodium nitroprusside was assessed by laser Doppler imaging. Despite body mass index correction and a larger proportion on statin therapy, patients had high levels of insulin (p=0.016), triglycerides (p=0.018), intercellular adhesion molecule-1 (p=0.021), von Willebrand factor (p=0.005), and leptin (p=0.005) and lower levels of high-density lipoprotein cholesterol (p=0.042) compared with controls. Consistent with these data, 30% of patients but only 8% of controls fulfilled criteria for the metabolic syndrome as defined by the National Cholesterol Education Program (p=0.015). Endothelium-dependent and -independent microvascular functions were markedly impaired in patients (p<0.001), and the odds ratio for cardiac syndrome X was 7.38 (95% confidence interval 2.2 to 24.7) if the acetylcholine response was <8,710 flux units. In conclusion, women with cardiac syndrome X more commonly have metabolic syndrome and related adiposity, metabolic, and inflammatory derangements. They also have significantly impaired skin microvascular function as assessed by laser Doppler imaging, consistent with generalized vascular dysfunction, a finding with potential diagnostic implications.

Topics: Acetylcholine; Biomarkers; Blood Pressure; Body Mass Index; Case-Control Studies; Cholesterol, HDL; Exercise Test; Female; Humans; Insulin; Intercellular Adhesion Molecule-1; Iontophoresis; Laser-Doppler Flowmetry; Leptin; Metabolic Syndrome; Microcirculation; Microvascular Angina; Middle Aged; Risk Factors; ROC Curve; Skin; Triglycerides; Vasodilator Agents; von Willebrand Factor

The aim of our investigation was the detection of endocrine-metabolic disorders in patients with hyperplastic processes of endomyometrium, uterine cervix and mammary glands. 88 patients of reproductive age with several gynaecological complaints have been investigated. 72 patients with hyperplastic processes in endomyometrium, uterine cervix (hyperplasia, polyposis, myoma) and mammary glands (fibroadenomatosis, adenomatosis) were selected in main group. Control group consisted of 16 patients without any hyperplastic processes of reproductive organs. Metabolic syndrome in main group was revealed in 28% of cases, in control - 18,8% (chi(2)=3,95, p=0,047); insulin resistance - 37,5% and 18,7% (chi(2)=4,59, p=0,033), respectively; obesity - 52,8% and 25,0% (chi(2)=4,05, p=0,045), respectively; dyslipidemia - 52,8% and 0,0%; hypertension - 26,4% and 12,5% (chi(2)=1,88, p=NS), respectively. Blood leptin level in main group was - 13,7+/-10,9 ng/ml, and in control - 5,0+/-2,9 ng/ml (p=0,005). Our results suggest that metabolic syndrome and its components significantly influences the formation of hyperplastic processes of endomyometrium, uterine cervix and mammary glands. Blood leptin level is significantly increased in patients with hyperplastic pathologies.

Topics: Adult; Breast Neoplasms; Cervix Uteri; Endocrine System Diseases; Female; Humans; Hyperplasia; Leptin; Mammary Glands, Human; Metabolic Syndrome; Reproduction; Uterine Cervical Neoplasms

The aim of our investigation was the study of blood adiponectin and leptin levels in patients with menopausal metabolic syndrome (MMS) and their correlation with the parameters of MMS features. 40 females with menopause have been investigated. In 38 cases diabetes mellitus type 2 has been registered, and in 2 - impaired glucose tolerance. Mean duration of postmenopausal period was 11,1+/-7,4. Control group consisted of 10 females of postmenopausal age. The blood content of adiponectin and leptin was measured by ELISA. For MMS diagnostics WHO classification (2002) was applied. In basic group MMS was revealed in 37 patients, in control group - in 3 cases (chi(2)=19,53, p<0,001). It was not observed significant difference in blood adiponectin levels of basic and control groups (16,4+/-7,6 vs. 16,3+/-6,1, p=NS), but blood leptin level was significantly higher in study group in comparison with controls (166,7+105,3 vs. 60,3+/-51,0, p<0,001). Significant correlations of blood adiponectin and leptin levels with the parameters of MMS features were observed. Obtained results show that blood adiponectin level in MMS does not differ from the values in control group, although blood leptin level is significantly higher than the one among controls. They significantly correlated with the parameters of MMS features.

Topics: Adiponectin; Aged; Control Groups; Female; Humans; Leptin; Menopause; Metabolic Syndrome; Middle Aged

Lipodystrophy (lipo) and metabolic derangements associated with an increased cardiovascular risk are observed frequently in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral treatment (ART). The objective of the study was to provide detailed biochemical information about metabolic syndrome in this condition. One hundred forty-six HIV-infected male and female patients on ART for more than 6 months were compared with 156 body mass index (BMI)-matched healthy subjects. Lipodystrophy was diagnosed upon patient and physician concordance. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Plasma adiponectin (AD) and leptin were measured by radioimmunoassay. Insulin resistance (IR) was assessed by the homeostasis model assessment (HOMA). The prevalence of metabolic syndrome was higher in HIV-infected patients on ART than in non-HIV-infected healthy controls (15.8% vs 3.2%; P < .001). Patients with metabolic syndrome are older (44.6 +/- 6 vs 39.8 +/- 8 years; P = .004), have an increased BMI (24.9 +/- 3.8 vs 22.9 +/- 9.8 kg/m(2); P = .01), present with a reduced AD-to-leptin ratio log(10) (-0.19 +/- 0.4 vs 0.5 +/- 0.4; P = .04), and show increased IR (HOMA, 5.6 +/- 2.7 vs 3.8 +/- 2.2; P = .001; plasma fasting insulin, 22.9 +/- 9.8 vs 16.6 +/- 9.7 ng/mL; P < .001). In multivariate analysis, the diagnosis of lipo and HOMA were independently and significantly related to metabolic syndrome. In conclusion, the prevalence of metabolic syndrome is significantly increased in HIV-infected patients on ART and its presence is associated with lipo, increased age and BMI, IR, and a reduced plasma AD-to-leptin ratio.

Topics: Adiponectin; Adult; Anti-HIV Agents; Female; HIV Infections; Humans; Insulin Resistance; Leptin; Lipodystrophy; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis

Physical activity has beneficial effects on symptoms of the metabolic syndrome and low-grade inflammation in adults. These associations have rarely been studied in adolescents. Moreover, it has not been established whether they depend on adiposity, fat localisation and adipokines.. We used cross-sectional data of 640 12-year-old adolescents participating in the Intervention Centred on Adolescents' Physical Activity and Sedentary Behaviour Study (ICAPS). Weight, height, body fat mass and WHR were measured. Metabolic syndrome components, two inflammatory markers (IL-6 and C-reactive protein), plasma leptin, adiponectin and soluble TNF-alpha receptor 1 (sTNF-alpha R1) were determined. Insulin resistance was estimated by homeostasis model assessment (HOMA) and energy expenditure due to organised leisure-time physical activity (PAE) assessed by questionnaire.. The metabolic syndrome was present in 5.8% of the adolescents. After adjustment for sex, sexual maturity and socio-economic status, a beneficial relationship between PAE and all metabolic syndrome features was found, but only the associations with HOMA and IL-6 were independent of body fat mass and WHR. Adjusted means from the lowest to the highest tertile of PAE were 1.99, 1.80 and 1.78 for HOMA (p=0.04), and 0.88, 0.69 and 0.70 pg/ml for IL-6 (p=0.02). PAE was inversely associated with leptin, independently of body fat mass and WHR (p<10(-2)), but not with adiponectin or sTNF-alpha R1. Further adjustment for adipokines did not change the relationships of PAE with HOMA and IL-6.. In adolescents, physical activity is inversely related to HOMA and IL-6, independently of adiposity and fat localisation. These relationships are not accounted for by adipokines.

Topics: Adipocytes; Adiponectin; Adiposity; Body Weight; C-Reactive Protein; Child; Cross-Sectional Studies; Female; Humans; Inflammation; Interleukin-6; Least-Squares Analysis; Leptin; Male; Metabolic Syndrome; Motor Activity; Receptors, Tumor Necrosis Factor, Type I; Socioeconomic Factors; Surveys and Questionnaires

The relationships between adipocytokines, sex steroids and the GH/IGF-I axis is poorly studied and subject to controversy in healthy elderly male subjects. We investigated the association between both adiponectin and leptin, and the metabolic syndrome (MetS), lipid parameters, insulin sensitivity, sex steroids and IGF-I in healthy non-diabetic Lebanese men.. In this cross-sectional study, a total of 153 healthy non-diabetic men aged 50 and above (mean age 59.3 +/- 7 years) had a detailed clinical and biological evaluation. Subjects were classified according to the National Cholesterol Education Program criteria of the MetS. Insulin sensitivity was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI).. Subjects with the MetS had lower adiponectin and higher leptin levels (P < 0.0001 for both variables) compared with individuals without the MetS. Adiponectin was significantly correlated with waist size, triglycerides, high-density lipoprotein (HDL) cholesterol and QUICKI (r = -0.33, -0.26, 0.45 and 0.36 respectively, P < 0.0001 for all variables). The relation between adiponectin and HDL cholesterol, triglycerides and QUICKI remained significant after adjustment for age and body mass index (BMI). Also, leptin was strongly correlated with waist size and QUICKI (r = 0.63 and -0.63 respectively, P < 0.001 for both variables). However, its relation to the lipid profile was weak (for cholesterol r = 0.16, P < 0.05; for triglycerides r = 0.17, P < 0.05) and disappeared after adjustment for BMI. Adiponectin was positively correlated with sex hormone-binding globulin (SHBG) (r = 0.39, P < 0.001) and inversely correlated with free-androgen index (r = -0.24, P < 0.01), estradiol and dehydroepiandrosterone sulfate (r = -0.165, P < 0.05; r = -0.21, P < 0.01 respectively). This difference remained significant for SHBG after adjustment for age and BMI (r = 0.20, P < 0.005). Finally, leptin was inversely correlated with total testosterone and SHBG (r = -0.44, P < 0.001; r = -0.30, P < 0.001 respectively); the relation with testosterone remained significant after adjustment for BMI. No significant relationship of either adiponectin or leptin with GH or IGF-I values was observed. In a stepwise multiple regression analysis, the independent predictors of adiponectin were HDL cholesterol, QUICKI, age and BMI (P < 0.0001, P = 0.005, P = 0.002 and P = 0.047 respectively) while for leptin, it was QUICKI, waist size and testosterone (P < 0.0001, P < 0.0001 and P = 0.004 respectively). The adjusted R2 values were 0.34 and 0.55.. Our results show that in a healthy elderly male population, both adiponectin and leptin are related to insulin sensitivity, independent of age and BMI. While adiponectin is independently related to triglycerides and HDL cholesterol, the weak relationship of leptin to the lipid profile is completely mediated by BMI. In addition, and more interestingly, both adipocytokines are strongly associated with sex steroids. We speculate that SHBG is regulated by adiponectin and that there is an inhibitory effect of testosterone on the adiponectin gene. Further studies are needed to fully elucidate these relationships.

Topics: Adipocytes; Adiponectin; Aged; Androgens; Biomarkers; Cholesterol, HDL; Cytokines; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Lebanon; Leptin; Male; Metabolic Syndrome; Reference Values; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone

The metabolic syndrome (MS) describes a cluster of metabolic disturbances including type 2 diabetes and/or insulin resistance, hypertension, dyslipidemia and obesity, which predict a high risk of cardiovascular disorders. The associated hyperinsulinemia and hyperleptinemia may contribute to the cardiovascular risk. However, the operational value of the MS in elderly patients is questionable. We therefore investigated the prevalence and significance of the MS in geriatric care. In a survey of 98 consecutive admissions of diabetic patients, <40% had a MS; this is a low value compared to younger diabetic adults, due to a low prevalence of obesity and dyslipidemia. We found a high prevalence of low BMI (<20 kg/m2), hypoalbuminemia and low total cholesterol levels, suggesting that the MS may be modified by undernutrition. The interplay between the MS and undernutrition was further studied in 30 non-diabetic patients. Both leptinemia and insulin resistance indexes (HOMA-IR and QUICKI) were strongly associated with BMI and body fat (measured by Bioelectrical impedance Analysis). BMI, leptinemia and insulin resistance indexes were associated with the Mini Nutritional Assessment (MNA) score. Thus, undernutrition is associated with low leptin and insulin levels and may obscure the association of these parameters with cardiovascular risk. In conclusion, the MS has a low prevalence in our population of elderly diabetic patients, and is of questionable prognostic value. It can be oveshadowed by undernutrition, which is associated with low body weight, leptinemia and insulin resistance indexes. Prevention of undernutrition and/or adjustment to its consequences should receive higher priority in the care of elderly diabetic patients.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Hospitals, Special; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Malnutrition; Metabolic Syndrome; Nutrition Assessment; Risk Factors

Topics: Adult; Aged; Aged, 80 and over; Areca; Female; Humans; Leptin; Leukocyte Count; Male; Mastication; Metabolic Syndrome; Middle Aged; Taiwan; Tumor Necrosis Factor-alpha

This study was conducted to explore the association between nonalcoholic fatty liver disease and glucose metabolism as well as insulin resistance using the homeostasis model assessment method (HOMA).. From July 2003 to June 2004, 23 patients with ultrasound-proved fatty liver and either normal (10 patients) or abnormal (13 patients) serum aminotransferase levels were enrolled. Blood tests included a routine biochemistry, a 75-g glucose oral glucose tolerance test (OGTT) with blood sampled at 30-minute intervals during a 120-minute period. Fasting and 120-minute serum leptin, insulin, and C-peptide concentrations were also measured.. Using the Mann-Whitney U test, significant differences were found in gamma glutamyl transpeptidase (28.6+/-7.9 vs. 65.1+/-65.9 U/L, P=0.008), fasting insulin (FI) (13.11+/-7.53 vs. 31.76+/-42.95 muU/mL, P=0.02), fasting C-peptide (3.82+/-3.00 vs. 2.17+/-0.43 ng/mL, P=0.01), fasting leptin (10.34+/-4.05 vs. 24.27+/-24.97 ng/mL, P=0.01), HOMA-IR (3.34+/-1.06 vs. 8.81+/-13.18, P=0.02), and HOMA beta-cell function (120.32+/-52.50 vs. 242.20+/-247.29, P=0.02) between normal and abnormal ALT/AST function groups. From the 75-g OGTT, no significant difference of plasma glucose was noted at 0, 30, 60, and 90 minutes but significant change was noted in 120-minute plasma glucose (99.3+/-21.5 vs. 131.4+/-27.3 mg/dL, P=0.004) of 2 groups.. In conclusion, patients with fatty liver proved by ultrasound sonography might be at high risk of developing type 2 diabetes, especially when they had elevated liver enzymes. OGTT is warranted for the early diagnosis of these high risk patients.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; C-Peptide; Fatty Liver; Female; Food Deprivation; Glucose Tolerance Test; Homeostasis; Humans; Hyperglycemia; Insulin; Leptin; Liver Function Tests; Male; Metabolic Syndrome; Postprandial Period; Ultrasonography

Polycystic ovary syndrome (PCOS) patients are abdominally obese and are at increased risk of developing the metabolic syndrome. Low adiponectin and ghrelin levels in PCOS patients could be caused by insulin resistance as well as high testosterone levels.. Adiponectin and ghrelin levels were evaluated in 51 hirsute PCOS patients referred to the outpatient clinic of an academic, tertiary care medical centre and in 63 weight-matched female controls. Relationships between adiponectin, ghrelin, leptin, body composition, testosterone and insulin were examined.. Measurements of body composition including waist-hip-ratio (WHR), body mass index (BMI) and whole body dual-energy X-ray absorptiometry scan measures of body fat mass. Measurements of fasting levels of adiponectin, ghrelin, leptin, androgen status, oestradiol, lipid variables and insulin during follicular phase.. Adiponectin levels were significantly decreased in obese PCOS patients compared with weight-matched controls (geometric mean (-2 to 2 s.d.) 5.3 (2.5-11.1) vs 7.3 (3.0-17.4) mg/l, P<0.05). Mean ghrelin was significantly lower in hirsute PCOS patients than in controls (0.6 (0.3 to 1.4) vs 0.8 (0.4 to 1.7) microg/l, P<0.001) and this remained significant after subdividing subjects according to waist circumference and BMI. During multiple regression analysis, testosterone correlated positively with adiponectin and negatively with ghrelin independent of BMI, WHR and total fat mass.. Obese hirsute PCOS patients demonstrated significantly lower adiponectin levels than weight-matched controls suggesting a very high risk for the metabolic syndrome. Furthermore, ghrelin levels were decreased in hirsute PCOS patients and showed a significant, negative correlation with testosterone independent of body composition.

Topics: Absorptiometry, Photon; Adiponectin; Biomarkers; Body Constitution; Body Mass Index; Female; Ghrelin; Hirsutism; Homeostasis; Humans; Insulin; Leptin; Metabolic Syndrome; Peptide Hormones; Polycystic Ovary Syndrome; Regression Analysis; Risk Factors; Testosterone; Waist-Hip Ratio

Obesity and its complications including metabolic syndrome has been increased in children and adolescents recently. Leptin is known to play an important role in the pathogenesis of obesity.. The objective of this study was to evaluate the relationship of leptin and metabolic syndrome in obese Iranian children. A cross sectional study was carried out in 65 primary schools in Tehran. The children with waist circumferences equal or above 90th percentile for their height and age were chosen for further evaluations. 505 children aged 7-12 years participated in the study. Anthropometric variables measurements, blood pressure, fasting plasma glucose, triglyceride, high-density lipoprotein cholesterol and serum leptin were obtained from the study sample.. Serum leptin levels were significantly higher in girls in comparison to the boys (with median 11.0 Vs 8.25 ng/dl; P value = 0.007). Serum level of leptin were higher in children with metabolic syndrome (median 11.3 Vs 8.9 ng/dl; P value = 0.045). However, after adjustment for sex, this association was removed.. Leptin did not appear to have a major role in metabolic syndrome, even though it was strongly associated with obesity parameters. More studies evaluating the relationship between leptin and metabolic syndrome in various ethnic groups are recommended.

Topics: Anthropometry; Child; Cross-Sectional Studies; Female; Humans; Leptin; Male; Metabolic Syndrome; Obesity

The metabolic syndrome, closely associated with cardiovascular disease, is characterized by increased insulin resistance (IR). Although accelerated atherosclerosis is frequently observed in systemic lupus erythematosus (SLE), the prevalence and significance of IR remain to be elucidated. We evaluated IR in association with plasma concentrations of adipocytokines in patients with SLE.. Outpatients with SLE (n = 37) and healthy controls (n = 80) were studied. A value of the homeostasis model assessment index (HOMA-IR) > 2.0 was considered to be IR. Plasma concentrations of adiponectin and tumor necrosis factor-a (TNF-a) were measured by ELISA and leptin by radioimmunoassay.. HOMA-IR indices of the SLE patients were significantly higher than those of controls (2.3 +/- 2.3 vs 1.3 +/- 1.0, respectively; p < 0.01), although both groups exhibited a similar body mass index. The prevalence of hypertension and diabetes mellitus was significantly higher in patients with SLE compared with controls (48.6% vs 8.8% and 10.8% vs 0%). Twelve SLE patients (32%) with IR exhibited significantly higher incidence of hypertension and current proteinuria than SLE patients without IR. Plasma leptin, TNF-a, and, unexpectedly, adiponectin levels were higher in SLE patients than controls (adiponectin, 13.7 +/- 5.0 vs 9.5 +/- 3.9 microg/ml). Among the SLE patients, patients with IR showed significantly lower adiponectin levels than patients without IR (10.9 +/- 4.6 vs 15.4 +/- 4.4 microg/ml). Serum levels of adiponectin were significantly correlated inversely with HOMA-IR in SLE patients.. Elevated levels of adiponectin in SLE, despite inverse correlation with IR, suggest the possible involvement of adiponectin in IR and alterations in its effect on insulin sensitivity.

Topics: Adiponectin; Adult; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Leptin; Lupus Erythematosus, Systemic; Male; Metabolic Syndrome; Outpatients; Radioimmunoassay; Tumor Necrosis Factor-alpha

To investigate the relationship of early obesity to metabolic syndrome during sex hormonal imbalances in mutant female mice at different ages.. Hormonal imbalances, accumulation and nature of adipose tissue, food intake, glucose tolerance, and expression of candidate genes and markers of inflammation were studied by comparing wild-type, null, and haploinsufficient follitropin receptor knockout female mice at different ages.. Follitropin receptor deletion in mice produced null females that are infertile and haploinsufficient mice that undergo accelerated biological aging. Both types of mutants with sex hormonal imbalances have central obesity without hyperphagia, but circulating leptin is elevated. Adipocyte hyperplasia and hypertrophy is attributed to elevated peroxisome proliferator-activated receptor gamma expression. Adiponectin protein levels increase in fat tissue and plasma. Only mutants but not controls acquire age-dependent decline in glucose tolerance with high insulin and altered pancreatic beta cells. Changes in inflammation markers, decreased muscle insulin receptor phosphorylation, and increase of the enzyme protein tyrosine phosphatase 1B indicate insulin resistance.. In this animal model, the chronological appearance of early obesity induced by hormonal imbalances culminates in characteristics that are attributable to metabolic syndrome, including cardiovascular abnormalities. Dissection of the depot-specific alterations and defining molecular interrelationships could help in developing targeted remedies and resolving complications and controversies related to health benefits and adversities of current hormone replacement therapy.

Topics: Adiponectin; Adipose Tissue; Aging; Animals; Disease Models, Animal; Female; Follicle Stimulating Hormone; Gene Expression Regulation; Glucose Tolerance Test; Gonadal Steroid Hormones; Inflammation; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Mice; Mice, Knockout; Obesity; PPAR gamma; Receptors, FSH

Accumulating data indicate that metabolic syndrome is an inflammatory condition. Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with nephritis and cardiovascular disease. Evidence suggests that individuals with SLE are at risk for developing insulin resistance; however, this has not been directly examined. Using an established mouse strain with SLE (NZBWF1), we examined whether SLE is associated with increased body weight and fat deposition. Mean arterial pressure was significantly increased (140+/-4 versus 114+/-2 mm Hg; n > or = 5) in SLE mice by 36 weeks of age compared with control mice (NZW/LacJ). Body weight in SLE mice was higher at each age compared with controls by 12%, 22%, and 34% (n > 30). Visceral adipose tissue weight was increased in SLE by 44%, 74%, and 117% at 8, 20, and 36 weeks, respectively (n > or = 12). Plasma leptin was increased in SLE mice (8.6+/-1.0 versus 24.7+/-2.2 ng/mL; n = 5), and renal and adipose tissue exhibited macrophage infiltration. Fasted insulin was higher in SLE mice (0.6+/-0.1 versus 1.4+/-0.3 ng/mL; n > or = 10), but fasted glucose was not different (94+/-5 versus 80+/-9; n > or = 9). A glucose tolerance test caused a significantly greater and longer increase in blood glucose from mice with SLE compared with control mice. Food intake was not different between control and SLE mice. However, mice with SLE demonstrated lower levels of nighttime activity than controls. These data show that the NZBWF1 strain may be an important model to study the effects of obesity and insulin resistance on SLE-associated hypertension.

Topics: Animals; Disease Models, Animal; Female; Hypertension; Insulin Resistance; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome; Mice; Mice, Inbred NZB; Obesity

Liver regeneration after partial hepatectomy (PH) is impaired in leptin-deficient ob/ob mice. Here, we tested whether exogenous leptin and/or correction of the obese phenotype (by food restriction or long-term leptin administration) would rescue hepatocyte proliferation and whether the hepatic progenitor cell compartment was activated in leptin-deficient ob/ob livers after PH. Because of the high mortality following 70% PH to ob/ob mice, we performed a less extensive (55%) resection. Compared to lean mice, liver regeneration after 55% PH was deeply impaired and delayed in ob/ob mice. Administration of exogenous leptin to ob/ob mice at doses that restored circulating leptin levels during the surgery and postsurgery period or for 3 weeks prior to the surgical procedure did not rescue defective liver regeneration. Moreover, correction of obesity, metabolic syndrome and hepatic steatosis by prolonged administration of leptin or food restriction (with or without leptin replacement at the time of PH) did not improve liver regeneration in ob/ob mice. The hepatic progenitor cell compartment was increased in ob/ob mice. However, after PH, the number of progenitor cells decreased and signs of proliferation were absent from this cell compartment. In this study, we have conclusively shown that neither leptin replacement nor amelioration of the metabolic syndrome, obese phenotype and hepatic steatosis, with or without restitution of normal circulating levels of leptin, was able to restore replicative competence to ob/ob livers after PH. Thus, leptin does not directly signal to liver cells to promote hepatocyte proliferation, and the obese phenotype is not solely responsible for impaired regeneration.

Topics: Animals; Cell Proliferation; Dose-Response Relationship, Drug; Fatty Liver; Female; Food Deprivation; Hepatectomy; Hepatocytes; Injections, Intraperitoneal; Injections, Subcutaneous; Leptin; Liver; Liver Regeneration; Metabolic Syndrome; Mice; Mice, Obese; Obesity

Recent deorphanization efforts have paired the G-protein-coupled receptors GPR40, GPR41 and GPR43 with fatty acids as endogenous ligands. While carboxylic acids have been historically known to serve as fuel sources and biomarkers of disease, these studies demonstrate that fatty acids can act as signalling molecules at the cell-surface level. This receptor subfamily shares approx. 30% identity among members, with some limited cross-over between ligand activities. Generalized expression patterns within the pancreatic beta-cell, adipose depots and the gastrointestinal tract infer involvement in energy source recognition, absorption, storage and/or metabolism. GPR40, activated by medium and long-chain fatty acids, has been shown to potentiate insulin secretion at the beta-cell, and has been hypothesized to participate in the detrimental effects of chronic fatty acid exposure on beta-cell function. GPR41 and GPR43 have been reported to stimulate leptin release and adipogenesis respectively via activation by short-chain fatty acids. These common themes implicate GPR40, GPR41 and GPR43 in playing significant roles in metabolic diseases, such as diabetes, obesity and the metabolic syndrome.

Topics: Animals; Diabetes Mellitus; Humans; Leptin; Metabolic Syndrome; Obesity; Receptors, Cell Surface; Receptors, G-Protein-Coupled

A prospective clinical intervention study was performed to estimate the metabolic risk factors in patients with very severe obesity (VSO) vs. severe obesity (SO).. Two hundred twenty-eight VSO (BMI > or = 50 kg/m(2)) and 221 SO patients (BMI = 40 to 49.9 kg/m(2)) participated in the study (367 women and 82 men). Metabolic measurements included plasma lipids, glucose and insulin, hemoglobin A(1c), leptin, and sex hormones, as well as hepatic steatosis in a subgroup of patients. Subgroups of patients with non-insulin-dependent diabetes and hyperlipidemia (HLP) were examined.. The most unexpected result of our study was that VSO men showed significantly better lipid profiles than SO men. Furthermore, 18% of VSO men had no metabolic aberrations, whereas all SO men did. The advantageous metabolic status of VSO men was associated with sex hormone changes that favor gynoid fat distribution. The beneficial metabolic situation with VSO seems to be sex specific for men.. This study shows that the metabolic situation in VSO is not more severe than in the less obese cohort. These findings distinctly differ from the positive associations that have previously been reported between BMI, lipids, and other metabolic indices among individuals whose BMI is <40 kg/m(2).

Topics: Adult; Blood Glucose; Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2; Estradiol; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Obesity, Morbid; Progesterone; Prospective Studies; Risk Factors; Sex Factors; Testosterone

To determine whether low levels of testosterone, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and dehydroepiandrosterone sulfate (DHEAS) and high levels of cortisol and leptin would be associated with metabolic syndrome (MS).. Cross-sectional.. Population-based sample of older Italian men.. Four hundred fifty-two men aged 65 and older enrolled in the Invecchiare in Chianti (InCHIANTI) study.. Complete data on testosterone, cortisol, DHEAS, SHBG, fasting insulin, IGF-1 and leptin. MS was defined according to Adult Treatment Panel III criteria.. MS was present in 73 men (15.8% of the sample). After adjusting for confounders, total testosterone (P < .05) and log (SHBG) (P < .001) were inversely associated, whereas log (leptin) was positively associated with MS (P < .001). Independent of age, log (SHBG) was positively associated with high-density lipoprotein cholesterol (P < .05) and negatively associated with abdominal obesity (P < .001) and triglycerides (P < .001). Log (leptin) was significantly associated with each component of MS. Cortisol, DHEAS, free and bioavailable testosterone, and IGF-1 were not associated with MS. Having three or more hormones in the lower (for hormones lower in MS) or the upper (for hormones higher in MS) quartile was associated with three times the risk of being affected by MS (odds ratio = 2.8, 95% confidence interval = 1.3-6.9) (P = .005), compared with not having this condition.. Total testosterone and SHBG are negatively and leptin is positively associated with MS in older men. Whether specific patterns of hormonal dysregulation predict the development of MS should be tested in longitudinal studies.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Italy; Leptin; Male; Metabolic Syndrome; Testosterone

The aim of this study was to investigate adiponectin, leptin, and metabolic syndrome as predictors of the severity of obesity-related steatosis. By ultrasonography steatosis-positive (cases) subjects (n = 141) were compared with controls (n = 111). Demographic and anthropometric data and serum concentrations of adiponectin, leptin, and insulin were measured. The impact of several criteria of metabolic syndrome, serum adiponectin concentrations, and serum leptin concentrations were tested using a multivariate logistic regression analysis. The frequency of metabolic syndrome was higher in cases (44.0% versus 9.2%; P < .0001). Cases were older and had higher insulin resistance, waist circumference, and lower concentrations of adiponectin (all P < .001). The upper adiponectin quartile was associated with a lesser grade of steatosis. Metabolic syndrome and adiponectin concentrations were independently associated with the probability of steatosis. In conclusion, adipokines and metabolic syndrome are useful indices for the prediction of the severity of obesity-related steatosis.

Topics: Adiponectin; Adult; Case-Control Studies; Cross-Sectional Studies; Fatty Liver; Female; Humans; Leptin; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Obesity; Severity of Illness Index; Ultrasonography

Thirty-four children were assessed for body composition, blood pressure, lipids, glucose tolerance, markers of insulin resistance, oxidative stress, and adipokines. Children were divided into 3 groups: (1) normal weight, (2) overweight but otherwise healthy, and (3) overweight with the metabolic syndrome. There were no differences among any of the groups for age or Tanner stage, and anthropometric variables were similar between the overweight and the overweight with the metabolic syndrome groups. Differences across groups were found for high-density lipoprotein cholesterol (P < .001), triglycerides (P < .01), fasting insulin (P < .001), homeostasis model assessment (P < .01), adiponectin (P < .05), leptin (P < .0001), C-reactive protein (P < .0001), interleukin 6 (P < .0001), and 8-isoprostane (P < .001). In children, oxidative stress and adipokine levels worsen throughout the continuum of obesity and especially in the presence of components of the metabolic syndrome. Overweight children with components of the metabolic syndrome may be at elevated risk for future cardiovascular disease.

Topics: Adiponectin; Adolescent; Biomarkers; Blood Glucose; Blood Pressure; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Child; Cholesterol, HDL; Dinoprost; Female; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Syndrome; Minnesota; Obesity; Oxidative Stress; Risk Assessment; Risk Factors; Triglycerides

We previously reported that prenatal and suckling exposure to a maternal diet rich in animal fat leads to cardiovascular dysfunction in young adult rat offspring with subsequent development of dyslipidemia and hyperglycemia. We have further investigated glucose homeostasis in adult female offspring by euglycemic-hyperinsulinemic clamp and by dynamic assessment of glucose-stimulated insulin secretion in isolated, perifused pancreatic islet cells. Additionally, given the link between reduced mitochondrial DNA (mtDNA) content and the development of type 2 diabetes mellitus, we have measured mtDNA in organs from young adult animals. Sprague-Dawley rats were fed a diet rich in animal fat or normal chow throughout pregnancy and weaning. Infusion of insulin (5 mU.kg(-1).min(-1)) resulted in a higher steady-state plasma insulin concentration in 1-year-old offspring of fat-fed dams (OHF, n = 4) vs. offspring of control dams (OC, n = 4, P < 0.01). Glucose-stimulated insulin secretion in isolated islets from 9-mo-old OHF was significantly reduced compared with OC (n = 4, P < 0.05). Transmission electron micrography showed altered insulin secretory granule morphology in OHF pancreatic beta-cells. Kidney mtDNA was reduced in 3-mo-old OHF [16S-to-18S gene ratio: OC (n = 10) 1.05 +/- 0.19 vs. OHF (n = 10) 0.66 +/- 0.06, P < 0.05]. At 6 mo, gene chip microarray of OHF aorta showed reduced expression of the mitochondrial genome. Prenatal and suckling exposure to a diet rich in animal fat leads to whole body insulin resistance and pancreatic beta-cell dysfunction in adulthood, which is preceded by reduced tissue mtDNA content and altered mitochondrial gene expression.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Dietary Fats; Female; Gene Expression; Homeostasis; Insulin; Insulin Resistance; Islets of Langerhans; Leptin; Lipids; Metabolic Syndrome; Mitochondria; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Rats; Rats, Sprague-Dawley

Adipose tissue is a major source of inflammatory and thrombotic cytokines. This study investigated the relationship of abdominal subcutaneous adipose tissue cytokine gene expression to body composition, fat distribution, and metabolic risk during obesity. We determined body composition, abdominal fat distribution, plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF-alpha, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 +/- 0.8 kg/m2; age, 57 +/- 1 yr). A subset of these women without diabetes (n = 15) also underwent an OGTT. In all women, visceral fat volume was negatively related to leptin (r = -0.46, P < 0.05) and tended to be negatively related to adiponectin (r = -0.38, P = 0.09) gene expression. Among the nondiabetic women, fasting insulin (r = 0.69, P < 0.01), 2-h insulin (r = 0.56, P < 0.05), and HOMA index (r = 0.59, P < 0.05) correlated positively with TNF-alpha gene expression; fasting insulin (r = 0.54, P < 0.05) was positively related to, and 2-h insulin (r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area (r = -0.56, P < 0.05) was negatively related to, and insulin area (r = -0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression. Also, adiponectin gene expression was significantly lower in women with vs. without the metabolic syndrome (adiponectin-beta-actin ratio, 2.26 +/- 0.46 vs. 3.31 +/- 0.33, P < 0.05). We conclude that abdominal subcutaneous adipose tissue expression of inflammatory cytokines is a potential mechanism linking obesity with its metabolic comorbidities.

Topics: Abdomen; Absorptiometry, Photon; Adiponectin; Adipose Tissue; Aged; Blood Glucose; Body Composition; Cholesterol, HDL; Cytokines; Exercise; Female; Gene Expression Regulation; Glucose Tolerance Test; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Metabolic Syndrome; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Triglycerides; Tumor Necrosis Factor-alpha

In humans, a hyperactivity of glucocorticoid metabolism was postulated to be involved in the intrauterine programming of the metabolic syndrome in adulthood. We studied in rats the effects of overfeeding, obtained by reducing the size of the litter in the immediate postnatal period, a time crucial for neuroendocrine maturation such as late gestation in humans. Overfeeding induced early-onset obesity and accelerated the maturation of the hypothalamo-pituitary-adrenal (HPA) axis together with an upregulation of adipose tissue glucocorticoid receptor (GR) mRNA. In adulthood, neonatally overfed rats presented with moderate increases in basal and stress-induced corticosterone secretion and striking changes in visceral adipose tissue glucocorticoid signaling, that is, enhanced GR and 11beta-hydroxysteroid dehydrogenase type 1 mRNA levels. The above-mentioned alterations in the endocrine status of overfed rats were accompanied by a moderate overweight status and significant metabolic disturbances comparable to those described in the metabolic syndrome. Our data demonstrate for the first time that postnatal overfeeding accelerates the maturation of the HPA axis and leads to permanent upregulation of the HPA axis and increased adipose tissue glucocorticoid sensitivity. Thus, the experimental paradigm of postnatal overfeeding is a powerful tool to understand the pathophysiology of glucocorticoid-induced programming of metabolic axes.

Topics: Adipose Tissue; Aging; Animals; Blood Glucose; Body Weight; Diet; Disease Models, Animal; Fatty Acids, Nonesterified; Glucocorticoids; Insulin; Leptin; Metabolic Syndrome; Obesity; Rats; Rats, Wistar; Weaning

The disruption between the brain and the spinal cord leads to a decentralized sympathetic nervous system in people with chronic, cervical spinal cord lesions. These tetraplegic subjects are prone to disorders of energy metabolism and osteoporosis, and they experience alterations in their body composition with a relative accumulation of fat. The adipocyte-derived cytokine leptin is a key signal in caloric intake and energy expenditure, and it might modify bone remodelling, possibly regulated by sympathetic neuronal signalling. In able-bodied subjects leptin exhibits circadian variations, possibly mediated via sympathetic neurones. We have examined the plasma concentration of leptin among tetraplegics, to determine whether plasma leptin in these subjects exhibits circadian variations.. Blood samples were collected during a 24-h study period from tetraplegic subjects (n = 6) and from able-bodied controls (n = 8). Fasting, tetraplegic subjects had mean plasma concentrations of leptin about four times those of able-bodied controls (P < 0.05). In tetraplegia, plasma leptin was negatively correlated with total lean mass (r =-0.88, P < 0.05) but correlated positively with total fat mass (r = 0.89, P < 0.05). A marked circadian variation in plasma leptin concentrations was more evident in tetraplegia than in able-bodied controls.. Plasma leptin is markedly elevated and it shows more prominent circadian variations in tetraplegia compared with able-bodied subjects. Possibly the regulation of leptin metabolism is impaired among these patients. This might distort thermogenesis and energy expenditure, thus explaining the enhanced risk of the metabolic syndrome and of osteoporosis among tetraplegic subjects.

Topics: Adult; Body Composition; Case-Control Studies; Circadian Rhythm; Humans; Leptin; Male; Metabolic Syndrome; Osteoporosis; Quadriplegia; Risk

Metabolic syndrome is a common disorder in Taiwan. For this study 431 subjects were randomly selected from visitors to the Department of Health Management. Blood pressure, blood glucose, lipid, uric acid levels and anthropometric measurements with immunoreactive insulin (IRI) and leptin levels were all correlated. We randomly selected 431 subjects who visited the Department of Health Management. Whole body three-dimensional (3-D) laser scanner scans were employed for the anthropometric measurements. The metabolic index (MI) was designed using anthropometric parameters. Of the 431 subjects, 50% had displayed a body mass index (BMI) equal to or exceeding 25 kg/m2. Pearson correlation coefficient and multiple regression analysis revealed that MI constituted another index for correlating metabolic parameters by comparing MI with BMI and waist circumference to hip circumference ratio (WHR). Most data related to metabolic syndrome showed statistically significant differences between high and low IRI groups, comprising uric acid, total cholesterol, fasting plasma glucose, triglyceride, LDL, Chol/HDL ratio, and LDL/HDL ratio. Both IRI and leptin revealed statistical association with BMI, WHR, waist cross section area to hip cross section area ratio (WHAR), and MI in the study. Hypercholesterolemia appeared in 14.6% of the subjects. Elevated low-density lipoprotein (> or = 130 mg/dL) affected 36.9% of the subjects. In conclusion, MI calculated from 3-D body scanner correlated with many important metabolic risk factors and associated with clinical disorders like DM, hyperlipidemia, hyperuricemia and hypertension.

Topics: Adult; Aged; Aged, 80 and over; Anthropometry; Body Mass Index; Body Weights and Measures; Female; Humans; Hyperlipidemias; Imaging, Three-Dimensional; Incidence; Insulin; Lasers; Leptin; Male; Metabolic Syndrome; Middle Aged; Risk Factors; Waist-Hip Ratio

To determine the concentration levels of C-reactive protein (CRP), leptin and adiponectin in obese pre-pubertal children, and their possible relation with metabolic syndrome, fibrinogen and plasminogen activator inhibitor-1.. A study was carried out in 51 obese children (aged 6 to 9 years) and the same number of non-obese children (control group), matched by age and sex. (Cross-sectional study of obese children). Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined for each child. Serum CRP, leptin, adiponectin, glucose, insulin, lipid profile, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were all measured.. The levels of CRP serum (1.67+/-0.222 vs 0.92+/-0.16 mg/l) and leptin (15.56+/-1.27 vs 4.68+/-0.62 ng/ml) were significantly higher in obese children. The adiponectin level was significantly higher in non-obese children (11.58+/-0.63 vs 9.64+/-0.49 microg/dl). In the obese group, log. CRP showed a positive correlation with BMI, insulin, homeostasis model assessment (HOMA), triglycerides, alanine aminotransferase (ALT), uric acid, PAI-1, fibrinogen and interleukin 6 (IL-6), and correlated negatively with apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-C). The leptin was positively correlated with BMI, insulin, HOMA, triglycerides and PAI-1 and negatively with Apo A-I and HDL-C. Adiponectin correlated negatively with BMI, insulin, HOMA, and triglycerides.. Low-grade systemic inflammation, elevated leptin concentration and low adiponectin level are described in very young obese children, correlating with a range of variables of metabolic syndrome. Inflammation and adipocytokines can play an important role in the etiopathogeny of metabolic syndrome.

Topics: Adiponectin; Blood Glucose; Blood Pressure; C-Reactive Protein; Child; Cross-Sectional Studies; Female; Fibrinogen; Homeostasis; Humans; Inflammation; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Lipids; Male; Metabolic Syndrome; Obesity; Plasminogen Activator Inhibitor 1

Fatty liver is extremely common in insulin-resistant patients with either obesity or lipodystrophy and it has been proposed that hepatic steatosis be considered an additional feature of the metabolic syndrome. Although insulin resistance can promote fatty liver, excessive hepatic accumulation of fat can also promote insulin resistance and could contribute to the pathogenesis of the metabolic syndrome. We sought to create a new nonobese rat model with hypertension, hepatic steatosis, and the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein (SREBP-1a) in the spontaneously hypertensive rat (SHR). SREBPs are transcription factors that activate the expression of multiple genes involved in the hepatic synthesis of cholesterol, triglycerides, and fatty acids. The new transgenic strain of SHR overexpressing a dominant-positive form of human SREBP-1a under control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter exhibited marked hepatic steatosis with major biochemical features of the metabolic syndrome, including hyperglycemia, hyperinsulinemia, and hypertriglyceridemia. Both oxidative and nonoxidative skeletal muscle glucose metabolism were significantly impaired in the SHR transgenic strain and glucose tolerance deteriorated as the animals aged. The SHR transgenic strain also exhibited reduced body weight and reduced adipose tissue stores; however, the level of hypertension in the transgenic SHR was similar to that in the nontransgenic SHR control. The transgenic SHR overexpressing SREBP-1a represents a nonobese rat model of fatty liver, disordered glucose and lipid metabolism, and hypertension that may provide new opportunities for studying the pathogenesis and treatment of the metabolic syndrome associated with hepatic steatosis.

Topics: Adiponectin; Adipose Tissue; Aging; Animals; Animals, Genetically Modified; Blood Pressure; CCAAT-Enhancer-Binding Proteins; Disease Models, Animal; DNA-Binding Proteins; Fatty Liver; Gene Expression; Humans; Hypertension; Intercellular Signaling Peptides and Proteins; Leptin; Liver; Metabolic Syndrome; Rats; Rats, Inbred SHR; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Transgenes

The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. We found that homozygous Clock mutant mice have a greatly attenuated diurnal feeding rhythm, are hyperphagic and obese, and develop a metabolic syndrome of hyperleptinemia, hyperlipidemia, hepatic steatosis, hyperglycemia, and hypoinsulinemia. Expression of transcripts encoding selected hypothalamic peptides associated with energy balance was attenuated in the Clock mutant mice. These results suggest that the circadian clock gene network plays an important role in mammalian energy balance.

Topics: Adipocytes; Animals; Body Weight; Brain; Circadian Rhythm; CLOCK Proteins; Dietary Fats; Energy Intake; Energy Metabolism; Feeding Behavior; Hepatocytes; Hyperglycemia; Hyperlipidemias; Insulin; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Motor Activity; Mutation; Neuropeptides; Obesity; Trans-Activators; Weight Gain

Both environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Over 18 weeks, the 129 strain developed features of the metabolic syndrome, notably obesity, hyperinsulinemia, and glucose intolerance only on the high-fat diet; the B6 strain on the other hand developed these features on both diets. High-fat feeding of both strains led to decreased serum triglycerides, hepatic steatosis, and hypercholesterolemia; however, B6 mice developed worse steatosis and a larger increase in LDL cholesterol. Both B6 background and high-fat feeding increased sterol regulatory element-binding protein-1c (SREBP-1c), a key regulator of lipogenic gene transcription, and its downstream targets. Stearoyl-CoA desaturase 1 (SCD1), an enzyme that regulates monounsaturated fatty acid (MUFA) synthesis, was also increased at the mRNA and enzyme activity levels by both high-fat feeding and B6 background. Furthermore, lipid analysis revealed increased hepatic triglycerides and MUFAs in B6 and high-fat-fed mice. Thus, dietary fat and genetic background act through SREBP-1c and SCD1 to affect hepatic lipid metabolism contributing to the development of the metabolic syndrome.

Topics: Animals; Blood Glucose; Body Weight; CCAAT-Enhancer-Binding Proteins; Diet, Fat-Restricted; Dietary Fats; DNA-Binding Proteins; Hypercholesterolemia; Insulin; Leptin; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Stearoyl-CoA Desaturase; Sterol Regulatory Element Binding Protein 1; Transcription Factors

The levels of the liporegulatory hormone leptin are increased in obesity, which contributes to the metabolic syndrome; the latter is associated with elevated cardiovascular risk and morbidity. Leptin may play a role in the metabolic syndrome since correlations have been observed between serum leptin levels and several components of the metabolic syndrome. The association of leptinemia and hypertension or diabetes is inconsistent. Leptin levels are higher in females versus males and obese versus lean individuals. We investigated if correlations exist between leptin levels and several indices of the metabolic syndrome in obese and lean Moroccan subjects with (63 males, 129 females) and without (123 males, 234 females) diabetes and/or hypertension. Plasma glucose and insulin and systolic and diastolic blood pressures were higher in obese versus lean individuals. Obesity had no effect on lipid profile, plasma IGF-1, or C-peptide levels. Leptin levels were higher in females versus males and in obese versus lean individuals. The levels correlated significantly with body mass index. Serum leptin concentration did not correlate with either systolic or diastolic blood pressure, although there was a trend for higher blood pressure with increased leptin levels in females. There was no significant difference in leptin levels between NIDDM patients and healthy controls. However, in hypertensive patients, leptin levels were significantly higher in both lean males and females with diabetes as compared to those without diabetes. Similarly, the higher leptin levels paralleled elevated insulin levels in obese nondiabetic males and females, and in male and female diabetics with hypertension. Correlations were observed between leptin levels and C-peptide (an estimate of endogenous insulin secretion), but not with serum IGF-1. The calculated values of HOMA-IR, a marker of insulin resistance, were somewhat higher, parallel with elevated leptin levels, in obese male and female individuals compared to their lean counterparts. There was no relationship between leptin levels and serum lipids. There was a trend for increased serum uric acid levels with higher leptin concentrations. Thus, leptinemia is related to some components of metabolic syndrome, and in turn, it may contribute to the syndrome. This study is novel in that relationships were determined between leptin levels and various indices of metaboli syndrome in a large population of the same ethnic/regional background.

Topics: Aged; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Morocco; Obesity; Sex Characteristics; Uric Acid

This study determined the effects of adding monosodium glutamate (MSG) to a standard diet and a fiber-enriched diet on glucose metabolism, lipid profile, and oxidative stress in rats.. Male Wistar rats (65 +/- 5 g, n = 8) were fed a standard diet (control), a standard diet supplemented with 100 g of MSG per kilogram of rat body weight, a diet rich in fiber, or a diet rich in fiber supplemented with 100 g of MSG per kilogram of body weight. After 45 d of treatment, sera were analyzed for concentrations of insulin, leptin, glucose, triacylglycerol, lipid hydroperoxide, and total antioxidant substances. A homeostasis model assessment index was estimated to characterize insulin resistance.. Voluntary food intake was higher and feed efficiency was lower in animals fed the standard diet supplemented with MSG than in those fed the control, fiber-enriched, or fiber- and MSG-enriched diet. The MSG group had metabolic dysfunction characterized by increased levels of glucose, triacylglycerol, insulin, leptin, and homeostasis model assessment index. The adverse effects of MSG were related to an imbalance between the oxidant and antioxidant systems. The MSG group had increased levels of lipid hydroperoxide and decreased levels of total antioxidant substances. Levels of triacylglycerol and lipid hydroperoxide were decreased in rats fed the fiber-enriched and fiber- and MSG-enriched diets, whereas levels of total antioxidant substances were increased in these animals.. MSG added to a standard diet increased food intake. Overfeeding induced metabolic disorders associated with oxidative stress in the absence of obesity. The fiber-enriched diet prevented changes in glucose, insulin, leptin, and triacylglycerol levels that were seen in the MSG group. Because the deleterious effects of MSG, i.e., induced overfeeding, were not seen in the animals fed the fiber-enriched diets, it can be concluded that fiber supplementation is beneficial by discouraging overfeeding and improving oxidative stress that is induced by an MSG diet.

Topics: Animals; Blood Glucose; Dietary Fiber; Energy Intake; Food Additives; Insulin; Leptin; Lipid Metabolism; Male; Metabolic Syndrome; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Sodium Glutamate; Triglycerides

The complex pathology of disease has sparked the development of novel protein expression profiling techniques that require validation in clinical settings. This study focuses on multiplexed analyses of adipocytokines and biomarkers linked to the metabolic syndrome, diabetes, and cardiovascular disease.. Multiplexed immunoassays using fluorescent microspheres and the Luminex-100 system were performed on plasma from 80 obese patients (40 with the metabolic syndrome) before and after 6-8 weeks of diet-induced weight loss. Leptin, insulin, C-peptide, monocyte chemoattractant protein-1 (MCP-1), eotaxin, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and IL-6 concentrations measured with multiplex panels from 3 different manufacturers were compared with results from commercial ELISAs. Detection limits and between- and within-run imprecision were determined for each analyte. Bland-Altman analysis was used to determine agreement between multiplexed immunoassays and ELISAs.. Correlation between the Luminex multiplexed assays and ELISAs was good for leptin (Linco), insulin (Linco), MCP-1 (Biosource and Upstate), and eotaxin (Biosource) with correlation coefficients of 0.711-0.895; fair for eotaxin (Upstate) and C-peptide (Linco) with correlation coefficients of 0.496-0.582; and poor for TNF-alpha, IL-8, and IL-6 (Linco, Biosource, Upstate, and R&D) with correlation coefficients of -0.107 to 0.318. Within- and between-run imprecision values for the multiplex method were generally <15%. Relative changes in plasma leptin and insulin concentrations after diet-induced weight loss were similar whether assessed by multiplex assay or ELISA.. Although this technology appears useful in clinical research studies, low assay sensitivity and poor correlations with conventional ELISA methods for some analytes with very low plasma concentrations should be considered when using the Luminex platform in clinical studies.

Topics: Adipose Tissue; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Cytokines; Female; Fluorescent Dyes; Humans; Immunoassay; Insulin; Interleukin-6; Interleukin-8; Leptin; Male; Metabolic Syndrome; Microspheres; Middle Aged; Obesity; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss

Obesity is frequently reported in patients treated for childhood leukaemia. Obesity, particularly abdominal obesity, is one of the main characteristics of the metabolic syndrome and a risk factor for cardiovascular disease and non-insulin-dependent diabetes mellitus (NIDDM).. All patients treated for acute lymphoblastic leukaemia (ALL) before the onset of puberty in the region of western Sweden, between 1973 and 1985, and in first remission, were included. 35 out of 47 patients aged 20-32 years participated. 19 patients had received cranial radiotherapy, and the median follow-up time was 20 years. The focus of this report was to study body composition and signs of the metabolic syndrome and correlate the findings to spontaneous growth hormone (GH) secretion.. Body composition was assessed using dual-energy X-ray absorbtiometry (DEXA). We analyzed serum concentrations of insulin, glucose, leptin and lipids.. No patient was obese according to World Health Organization criteria (body mass index, BMI > or = 30 kg/m2) but one-third were overweight (BMI 25-29.9 kg/m2). The maximal GH peak during 24 h (GHmax) was correlated to percentage of total body fat (r = -0.42; P = 0.017), trunk fat (r = -0.5; P = 0.005) and fat-free mass (r = 0.42; P = 0.017). GHmax was also correlated to s-triglycerides (r = -0.54; P = 0.001), low-density lipoprotein-cholesterol (r = -0.382; P = 0.024) and high-density lipoprotein-cholesterol (r = 0.45; P = 0.007).. We found little effect on BMI but an increased percentage of total body fat, especially trunk fat, and a tendency for an unfavourable lipid profile in adult survivors of childhood leukaemia. These findings were related to low endogenous GH secretion due to cranial irradiation.

Topics: Adipose Tissue; Adult; Body Composition; Body Mass Index; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Obesity; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Risk Factors; Survivors; Waist-Hip Ratio

Previous observations by us have clarified that proteins modified by advanced glycation end products (AGEs) are recognized as effective ligands by CD36-overexpressed CHO cells and undergo receptor-mediated endocytosis. CD36, a member of the class B scavenger receptor family, also acts as a fatty acid transporter in adipocytes. Oxidized low-density lipoprotein (Ox-LDL), a ligand for CD36, is known to upregulate CD36 by activating peroxisome proliferator-activated receptor gamma (PPAR-gamma) in macrophages, whereas PPAR-gamma ligands such as troglitazone and 15-deoxy-delta12,14-prostaglandin J2 decrease leptin secretion from adipocytes. The purpose of this study was to examine effects of AGE ligands on leptin expression in adipocytes. Glycolaldehyde-modified bovine serum albumin (GA-BSA) decreased leptin expression at both the protein and mRNA levels in 3T3-L1 adipocytes and mouse epididymal adipocytes. The binding to and subsequent endocytic degradation of GA-BSA by 3T3-L1 adipocytes were effectively inhibited by a neutralizing anti-CD36 antibody. These results indicate that the ligand interaction of GA-BSA with CD36 leads to downregulation of leptin expression in 3T3-L1 adipocytes, suggesting that AGE-induced leptin downregulation is linked to reduction of the insulin sensitivity in metabolic syndrome.

Topics: 3T3 Cells; Acetaldehyde; Adipocytes; Animals; CD36 Antigens; Cell Culture Techniques; Gene Expression Regulation; Leptin; Metabolic Syndrome; Mice; PPAR gamma; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Serum Albumin, Bovine

Leptin regulates energy balance and body weight by activating its receptor LEPRb and multiple downstream signaling pathways, including the STAT3 and the IRS2/PI 3-kinase pathways, in the hypothalamus. Leptin stimulates activation of LEPRb-associated JAK2, which initiates cell signaling. Here we identified SH2-B, a JAK2-interacting protein, as a key regulator of leptin sensitivity, energy balance, and body weight. SH2-B homozygous null mice were severely hyperphagic and obese and developed a metabolic syndrome characterized by hyperleptinemia, hyperinsulinemia, hyperlipidemia, hepatic steatosis, and hyperglycemia. The expression of hypothalamic orexigenic NPY and AgRP was increased in SH2-B(-/-) mice. Leptin-stimulated activation of hypothalamic JAK2 and phosphorylation of hypothalamic STAT3 and IRS2 were significantly impaired in SH2-B(-/-) mice. Moreover, overexpression of SH2-B counteracted PTP1B-mediated inhibition of leptin signaling in cultured cells. Our data suggest that SH2-B is an endogenous enhancer of leptin sensitivity and required for maintaining normal energy metabolism and body weight in mice.

Topics: Adaptor Proteins, Signal Transducing; Animals; Body Weight; DNA-Binding Proteins; Enzyme Activation; Female; Homeostasis; Hypothalamus; Insulin Receptor Substrate Proteins; Intracellular Signaling Peptides and Proteins; Janus Kinase 2; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Phosphoproteins; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Signal Transduction; STAT3 Transcription Factor; Trans-Activators

The term metabolic syndrome (MS) describes a cluster of cardiovascular risk factors including dyslipidemia, glucose intolerance, insulin resistance, and hypertension. Obesity increases the risk of MS, but as obesity is neither necessary nor sufficient to cause the syndrome, there is considerable interest in identifying obesity-independent pathways. One such pathway may involve the actions of the adipokine leptin, which is associated cross-sectionally with MS and prospectively with coronary heart disease and stroke, independently of obesity. Our goal was to test the hypothesis that leptin predicts the development of the features of MS independently of obesity.. This study used a prospective population-based cohort of 748 middle-aged whites in whom baseline measures of leptin and repeated measurement of the subcomponents of the MS at 5 and 10 years were available. The features of the MS were characterized as five factors (obesity, dyslipidemia, elevated blood pressure, glucose intolerance, and insulin resistance), which were combined to create an MS summary score.. Baseline leptin significantly predicted the development of obesity (p = 0.001) and, after adjustment for BMI, development of glucose intolerance (p = 0.016) and insulin resistance (p < 0.0001). Leptin levels did not independently predict a change in lipids or blood pressure. Leptin levels significantly predicted the development of the MS (p = 0.036), independently of baseline BMI.. Leptin predicts the development of the MS independently of baseline obesity. This association is specifically related to the development of glucose intolerance and insulin resistance. The extent to which these relationships are explained through residual confounding by obesity remains to be determined.

Topics: Adult; Cohort Studies; Female; Humans; Leptin; Male; Metabolic Syndrome; Obesity; Prospective Studies; Risk Factors

The aim of this study was to further elucidate the relationship between resistin and insulin sensitivity, body fat distribution and the metabolic syndrome in humans.. We measured plasma resistin levels in 177 non-diabetic subjects (75 male, 102 female; age 32-75 years). BMI, waist circumference, blood pressure, lipids, glucose, plasminogen-activator inhibitor 1 (PAI-1), adiponectin and leptin levels were also measured. The insulin sensitivity index (S(I)) was quantified using Bergman's minimal model. Intra-abdominal fat (IAF) and subcutaneous fat (SQF) areas were quantified by CT scan. Presence of metabolic syndrome criteria was determined using the National Cholesterol Education Program Adult Treatment Panel III guidelines.. When subjects were divided into categories based on BMI (< or > or =27.5 kg/m(2)) and S(I) (< or > or = 7 x 10(-5) min(-1) [pmol/l](-1)), resistin levels did not differ between the lean, insulin-sensitive (n=53, 5.36+/-0.3 ng/ml), lean, insulin-resistant (n=67, 5.70+/-0.4 ng/ml) and obese, insulin-resistant groups (n=48, 5.94+/-0.4 ng/ml; ANOVA p=0.65). Resistin correlated with age (r=-0.22, p<0.01), BMI (r=0.16, p=0.03) and SQF (r=0.19, p=0.01) but not with S(I) (p=0.31) or IAF (p=0.52). Resistin did not correlate with the number of metabolic syndrome criteria or any of the individual metabolic syndrome criteria. In contrast, adiponectin, PAI-1 and leptin each correlated with IAF, SQF and S(I). Additionally, the number of metabolic syndrome criteria correlated with adiponectin (r=-0.32, p<0.001), leptin (r=0.31, p<0.001) and PAI-1 (r=0.26, p=0.001).. In contrast to other adipokines, resistin is only weakly associated with body fat and is unlikely to be a major mediator of insulin resistance or the metabolic syndrome in humans.

Topics: Adiponectin; Adult; Age Factors; Aged; Body Fat Distribution; Body Mass Index; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Regression Analysis; Resistin

The metabolic syndrome mostly represented by obesity and hyperinsulinaemia connected with insulin resistance, presents the main mechanism in the pathogenesis of cardiovascular disease. The aim of this study was to analyze the interrelations between several metabolic variables (including leptin) and factors related to insulin resistance in groups of both normal and non-diabetic hyperlipemic postmenopausal women and men of appropriate age, and to attempt to elucidate the gender differences. Two groups of patients (20 men, 20 women) with hypertriglyceridemia were compared with 30 individuals (10 men, 20 women) with normal serum triacylglycerols. Fasting serum leptin concentration, lipid parameters (triacylglycerols, HDL cholesterol, LDL cholesterol) and BMI were measured and compared with changes in insulin parameters influencing insulin resistance (HOMA IR, insulin, intact proinsulin, C-peptide). Statistical analysis was performed using SAS/STAT software including unpaired Student's t-test, Kolmogorov-Smirnov's test, Spearman's rank-order correlation and multiple regression analysis. In men, the insulin sensitivity correlates with leptin only. In women insulin sensitivity is markedly influenced by a complex of factors: leptin and lipid parameters. Increased insulin resistance in men is followed mainly by the increased correlations between leptin, HOMA IR and insulin parameters. In women correlations between leptin, HOMA IR and insulin parameters were smaller, but the inverse correlation with HDL cholesterol was stronger. In postmenopausal women and also in men, serum leptin concentration contributes to insulin resistance. However in women the effect of increase in serum triacylglycerols in contribution of insulin resistance seems to be more dominant.

Topics: Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged

The aim of the study was to establish the best cut-off value for the homeostatic model assessment (HOMA) index in identifying children and adolescents with the metabolic syndrome. The study included 72 non-obese and 68 obese children aged 7 to 16 years. Obesity is defined using the criteria proposed by Cole et al., being included as metabolic syndrome variables waist circumference, systolic blood pressure, diastolic blood pressure and seric values of glucose, uric acid, fasting insulin, leptin, triglycerides and HDL-cholesterol. Children were considered as having the metabolic syndrome when four or more characteristics showed abnormal values. The HOMA index was calculated as the product of the fasting plasma insulin level (microU/mL) and the fasting plasma glucose level (mmol/L), divided by 22.5. HOMA index cut-offs from the 5th to the 95th percentile were used. A receiver operating characteristic (ROC) curve was generated using the different HOMA cut-offs for the screening of the metabolic syndrome. The areas under the ROC curve, 95% confidence intervals, and the point to the ROC curve closest to 1, were calculated. The area under the ROC curve was 0.863 (95% C.I.: 0.797, 0.930). The point closest to 1 corresponds to the 60th percentile of the HOMA index distribution in our sample. HOMA index value at the 60th percentile was 2.28. Cut-off values corresponding to a range of HOMA index from the 50 to the 75 percentile, showed similar distances to 1. HOMA index values for percentiles 50 to 75 ranged from 2.07 to 2.83. In conclusion, HOMA index could be a useful tool to detect children and adolescents with the metabolic syndrome. HOMA cut-off values need to be defined in the paediatric population; however, values near to 3 seem to be adequate.

Topics: Adolescent; Anthropometry; Blood Glucose; Blood Pressure; Body Composition; Body Height; Body Mass Index; Body Weight; Child; Cholesterol, HDL; Fasting; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; ROC Curve; Sensitivity and Specificity; Triglycerides; Uric Acid

Protein tyrosine phosphatase-1B negatively regulates leptin and insulin signaling, potentially contributing to hormonal resistance. We selected six tagging single nucleotide polymorphisms (SNPs) representing 18 common variants in the protein tyrosine phosphatase-1B gene (PTPN1) and tested their effect on serum leptin, body fat, and measures of insulin sensitivity and the metabolic syndrome in a large sample of normal female Caucasian twins (n = 2,777; mean age, 47.4 +/- 12.5 years) from the St. Thomas' U.K. Adult Twin Registry. SNP rs718049 was significantly associated with waist circumference (P = 0.008) and central fat (P = 0.035) and also with Avignon's insulin sensitivity index (SiM) (P = 0.007), fasting insulin (P = 0.004), fasting glucose (P = 0.022), triglyceride (P = 0.023), and systolic blood pressure (P = 0.046). SNPs rs2282146 and rs1885177 were associated with SiM (P = 0.049 and P = 0.013, respectively), and 1484insG was associated with triglyceride (P = 0.029). A risk haplotype (7.3%) was associated with lower SiM (P = 0.036) and a protective haplotype (5.2%) with higher SiM (P = 0.057), with mean values in homozygotes differing by >1 SD (P = 0.003). The protective haplotype also showed lower triglyceride (P = 0.045) and lower systolic blood pressure (P = 0.006). Fine mapping analyses predicted significant associations with SiM and fasting insulin for several ungenotyped SNPs. PTPN1 variants appear to contribute to central fat and metabolic syndrome traits, secondary to their effect on insulin sensitivity.

Topics: Adipose Tissue; Adult; Fasting; Female; Genetic Predisposition to Disease; Haplotypes; Humans; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Physical Chromosome Mapping; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Registries

Despite major advances in understanding monogenic causes of morbid obesity, the complex genetic and environmental etiology of idiopathic metabolic syndrome remains poorly understood. One hypothesis suggests that similarities between the metabolic disease of plasma glucocorticoid excess (Cushing's syndrome) and idiopathic metabolic syndrome results from increased glucocorticoid reamplification within adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1). Indeed, 11beta-HSD-1 is now a major therapeutic target. Because much supporting evidence for a role of adipose 11beta-HSD-1 comes from transgenic or obese rodents with single-gene mutations, we investigated whether the predicted traits of metabolic syndrome and glucocorticoid metabolism were coassociated in a unique polygenic model of obesity developed by long-term selection for divergent fat mass (Fat and Lean mice with 23 vs. 4% fat as body weight, respectively). Fat mice exhibited an insulin-resistant metabolic syndrome including fatty liver and hypertension. Unexpectedly, Fat mice had a marked intra-adipose (11beta-HSD-1) and plasma glucocorticoid deficiency but higher liver glucocorticoid action. Furthermore, metabolic disease was exacerbated only in Fat mice when challenged with exogenous glucocorticoids or a high-fat diet. Our data suggest that idiopathic metabolic syndrome might associate with such a novel pattern of glucocorticoid action and sensitivity in humans, with implications for tissue-specific therapeutic targeting of 11beta-HSD-1.

Topics: Adipose Tissue; Animals; Blood Glucose; Corticosterone; Crosses, Genetic; Cushing Syndrome; Epididymis; Glucocorticoids; Insulin; Leptin; Liver; Male; Metabolic Syndrome; Mice; Mice, Obese; Models, Genetic; Obesity; RNA; Skin; Triglycerides

Topics: Fatty Liver; Humans; Insulin Resistance; Leptin; Liver; Liver Cirrhosis; Metabolic Syndrome

Familial partial lipodystrophy (FPLD) and obesity are both associated with increased risks of type 2 diabetes and cardiovascular disease. Although adipokines have been implicated, few data exist in subjects with FPLD; therefore we investigated a family with FPLD due to a lamin A/C mutation in order to determine how abnormalities of the plasma adipokine profile relate to insulin resistance and the metabolic syndrome.. Plasma levels of adiponectin, leptin, resistin, IL-1beta, IL-6 and TNF-alpha in 30 subjects (ten patients, 20 controls) were correlated with indices of metabolic syndrome.. Compared with controls, FPLD patients had significantly lower plasma levels of adiponectin (3.7+/-1.0 in FDLP cases vs 7.1+/-0.72 mug/ml in controls, p=0.02), leptin (1.23+/-0.4 vs 9.0+/-1.3 ng/ml, p=0.002) and IL-6 (0.59+/-0.12 vs 1.04+/-0.17 pg/ml, p=0.047) and elevated TNF-alpha (34.8+/-8.1 vs 13.7+/-2.7 pg/ml, p=0.028), whereas IL-1beta and resistin were unchanged. In both groups, adiponectin levels were inversely correlated with body fat mass (controls, r=-0.44, p=0.036; FDLP, r=-0.67, p=0.025), insulin resistance (controls, r=-0.62, p=0.003; FDLP, r=-0.70, p=0.025) and other features of the metabolic syndrome. TNF-alpha concentrations were positively related to fat mass (controls, r=0.68, p=0.001; FDLP, r=0.64, p=0.048) and insulin resistance (controls, r=0.86, p=0.001; FDLP, r=0.75, p=0.013). IL-6, IL-1beta and resistin did not demonstrate any correlations with the metabolic syndrome in either group.. Low adiponectin and leptin and high TNF-alpha were identified as the major plasma adipokine abnormalities in FPLD, consistent with the hypothesis that low adiponectin and high TNF-alpha production may be mechanistically related, and perhaps responsible for the development of insulin resistance and cardiovascular disease in FPLD.

Topics: Adiponectin; Adult; Case-Control Studies; Diabetes Mellitus, Lipoatrophic; Female; Homeostasis; Humans; Insulin Resistance; Interleukin-1; Interleukin-6; Laminin; Leptin; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Mutation; Obesity; Resistin; Tumor Necrosis Factor-alpha

Obesity and multiple pituitary hormone deficiency are common complications after surgery for childhood craniopharyngioma. We hypothesized that post craniopharyngioma surgery, children are at high risk for the metabolic syndrome, including insulin resistance due to excess weight gain and GH deficiency. This study characterized body composition (anthropometry and dual energy x-ray absorptiometry) and metabolic outcomes in 15 children (10 males and 5 females; age, 12.2 yr; range, 7.2-18.5 yr) after surgical removal of craniopharyngioma. In 9 subjects, outcomes were compared with those of healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Insulin sensitivity was measured by 40-min iv glucose tolerance test. Seventy-three percent of subjects were overweight or obese. Sixty-six percent had normal growth velocity without GH treatment. Subjects had increased abdominal adiposity (P = 0.008) compared with controls. However, there was no significant difference in total body fat. Subjects had higher fasting triglycerides (P = 0.02) and lower high density lipoprotein cholesterol to total cholesterol ratio (P = 0.015). Insulin sensitivity was equally reduced for subjects and controls (P = 0.86). After craniopharyngioma removal, patients had more features of the metabolic syndrome compared with controls. This could be a result of hypothalamic damage causing obesity and GH deficiency. Further studies exploring predictors of the metabolic syndrome after craniopharyngioma surgery are required.

Topics: Abdomen; Adipose Tissue; Adolescent; Blood Glucose; Body Composition; Body Mass Index; Child; Cholesterol; Cholesterol, HDL; Craniopharyngioma; Fasting; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Male; Metabolic Syndrome; Obesity; Pituitary Neoplasms; Postoperative Complications; Triglycerides

Topics: Adiponectin; Aged; Aging; Animals; Female; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Life Expectancy; Longevity; Male; Metabolic Syndrome; Papio; Proteins; Risk Assessment; Sensitivity and Specificity

Topics: Adiponectin; Biomedical Research; Diabetes Mellitus, Type 2; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Proteins; Resistin

Leptin has been shown to be linked to adiposity and insulin resistance in middle-aged participants. However, the association between leptin and metabolic syndrome independently of body fat and body fat distribution has not been evaluated in healthy elderly people.. We studied the independent relation between leptin and the components of the metabolic syndrome in 107 women aged 67-78 years with body mass index (BMI) ranging from 18.19 to 36.16 kg/m2. In all participants, we evaluated BMI, waist and hip circumferences, body composition by dual energy X-ray absorptiometry, fasting, and 2-hour glucose, lipids, insulin, homeostasis model assessment of insulin resistance (HOMA), systolic (SBP), diastolic blood pressure (DBP), and leptin.. Significant correlation was found between leptin, BMI, waist circumference, fat mass, DBP, SBP, cholesterol, triglycerides, insulin, and HOMA. After adjusting for age and waist circumference, as well for age and fat mass, leptin was significantly related to insulin levels, HOMA, and cholesterol. In a stepwise multiple regression analysis using insulin levels or HOMA as dependent variables and age, waist circumference, fat mass, leptin, SBP, DBP, cholesterol, and triglycerides as independent variables, leptin entered the regression first, waist circumference second, and age third.. Our study shows that leptin is significantly related to indices of adiposity in elderly women, and leptin is significantly associated with insulin levels, HOMA, and cholesterol independent of age, body fat, and fat distribution. Leptin, waist circumference, and age together explained 31% and 33% of insulin levels and HOMA variance, respectively, in healthy elderly women.

Topics: Age Factors; Aged; Anthropometry; Body Composition; Body Weight; Female; Humans; Insulin; Leptin; Metabolic Syndrome; Regression Analysis

Impaired vascular endothelial function may be an important mechanism linking obesity to increased cardiovascular risk. We investigated whether short-term weight loss improves conduit artery endothelial dysfunction in overweight adults. Forty-three otherwise healthy overweight patients with a body mass index > or =27 kg/m(2) completed an open-label 3-month trial consisting of a calorie-restricted diet and 120 mg of orlistat taken 3 times daily with meals. Endothelial function and parameters of the metabolic syndrome were measured before and after intervention. Subjects lost 6.6 +/- 3.4% of their body weight. Low-density lipoprotein cholesterol, low-density lipoprotein concentration, fasting insulin, and leptin decreased significantly (all p <0.009), and C-reactive protein decreased (p = 0.22). Conduit vascular function did not change as assessed by flow-mediated dilation (3.86 +/- 3.54 vs 3.74 +/- 3.78%, p = 0.86) and nitroglycerin-mediated dilation (17.18 +/- 5.89 vs 18.87 +/- 7.11%, p = 0.13) of the brachial artery. A moderate degree of weight reduction over 3 months improved the metabolic syndrome profile but not the vascular dysfunction associated with uncomplicated obesity.

Topics: Adolescent; Adult; Anti-Obesity Agents; C-Reactive Protein; Cholesterol, LDL; Diet, Reducing; Endothelium, Vascular; Female; Humans; Insulin; Lactones; Leptin; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Weight Loss

The incidence of obesity, with its associated health risks, is on the increase throughout the western world affecting all age groups, including children. The typical western diet is high in fat and sugar and low in complex carbohydrates. This study looks at the effects of feeding an equivalent high-energy (HE) diet to growing rats. Juvenile male Sprague-Dawley rats that were fed an HE (18.9 kJ/g) diet starting approximately 10 d after weaning gained less weight than littermates fed a nonpurified (14 kJ/g) diet. Despite an initial hyperphagia following the change in diet, HE rats also consumed less energy. Although they exhibited reduced weight gain, HE rats were relatively obese; fat pad weights were elevated for all 4 dissected depots. HE-fed rats exhibited symptoms of developing metabolic syndrome with elevated plasma concentrations of glucose, triglycerides, nonesterified fatty acids, insulin, and leptin. In addition, leptin receptor gene expression in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus of HE rats was reduced. Consistent with the elevated serum leptin and other peripheral signals in HE rats, hypothalamic gene expression for the orexigenic neuropeptides, neuropeptide Y (ARC and dorsomedial nucleus), and agouti-related peptide (AgRP), was reduced. This reduction in orexigenic signaling and decline in energy intake is consistent with an apparent attempt to counter the further development of an obese state in rats consuming an energy-dense diet. The juvenile Sprague-Dawley rat has potential in the development of a model of childhood diet-induced obesity.

Topics: Agouti-Related Protein; Animals; Animals, Newborn; Body Weight; Energy Intake; Gene Expression; Hypothalamus; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Neuropeptide Y; Obesity; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, Leptin

Topics: Adiponectin; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Obesity; Plasminogen Activator Inhibitor 1; Protein Biosynthesis; Tumor Necrosis Factor-alpha

Severe obesity increases the prevalence of the metabolic syndrome, and moderate acute weight loss with a very low-calorie diet in obese subjects with the metabolic syndrome leads to significant metabolic benefits. Adiponectin has been implicated in both the pathogenesis of obesity-related insulin resistance and increased inflammation. We analyzed the relationship of the adipocyte-derived hormone adiponectin with indices of inflammation, adiposity, and insulin resistance in obese subjects with (MS+, n = 40) and without (MS-, n = 40) the metabolic syndrome and examined the acute effects of rapid weight loss. MS+ subjects had significantly lower adiponectin (7.6 +/- 0.6 vs. 10.4 +/- 0.6 microg/ml; P = 0.003) and significantly higher TNF-alpha (3.3 +/- 0.2 vs. 2.8 +/- 0.3 pg/ml; P = 0.004) levels compared with MS- subjects matched for age and body mass index. Plasma adiponectin and TNF-alpha levels were inversely related to the number of metabolic syndrome factors in a stepwise manner. After 4-6 wk of weight loss, there was marked improvement in glucose, insulin, leptin, and triglycerides, whereas adiponectin and TNF-alpha concentrations did not change. Thus, increases in plasma levels of adiponectin or reductions in TNF-alpha are not required for marked improvements in glucose/insulin and lipid metabolism with acute weight loss.

Topics: Adiponectin; Blood Glucose; Diet, Reducing; Energy Intake; Female; Humans; Inflammation; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Proteins; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss

This study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), tumor necrosis factor-alpha (TNF-alpha)); iii) thermogenesis and free fatty acid (FFA) transport/catabolism (uncoupling protein-1 (UCP1), lipoprotein lipase (LPL), beta2- and beta3-adrenergic receptor (beta2AR, beta3AR), fatty acid transport protein-1 (FATP-1) and iv) lipoproteins (apoliprotein E (apoE), apo CIII). The 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated. The single gene mutations such as C105 T OB and Pro115 Gln PPAR-gamma2 linked to morbid obesity were not detected in our group. A weak correlation between obesity and certain gene polymorphisms was observed. Being overweight (25 < BMI > or = 30 kg/m2) significantly correlated with worse FFA tolerance in male PPAR-gamma2 12Pro, LPL-H (G) allele carriers. Insulin resistance was found in female PPAR-gamma2 Pro12, TNF-alpha (-308A) and LPL-H (G) allele carriers. Hypertension linked to the PPAR-gamma2 Pro allele carriers was characterized by high leptin output during OLTT. We conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.

Topics: Adult; Age Factors; Apolipoprotein C-III; Apolipoproteins C; Apolipoproteins E; Blood Pressure; Body Mass Index; Carrier Proteins; Dietary Fats; Fatty Acid-Binding Proteins; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Humans; Hypertension; Insulin; Insulin Resistance; Ion Channels; Leptin; Lipoprotein Lipase; Male; Membrane Proteins; Metabolic Syndrome; Middle Aged; Mitochondrial Proteins; Obesity; Poland; Polymorphism, Genetic; PPAR gamma; Receptor, Melanocortin, Type 3; Receptors, Adrenergic, beta; Receptors, Dopamine D2; Risk Factors; Tumor Necrosis Factor-alpha; Uncoupling Protein 1

To evaluate relationship between serum level of leptin and the components of risk factors for metabolic syndrome and to analyze the characteristics and laws of clustering of the risk factors.. Totally, 795 non-diabetic adult Chinese subjects (691 men and 104 women, aged 40 - 75 years) from a diabetes prevalence survey in 2000 were involved in this study. Measurements included serum levels of true insulin (TI), leptin, fasting lipids, fasting glucose (FBG) and 2 h postchallenge glucose, as well as seated blood pressure (BP), body mass index (BMI), ratio of waist circumference to hip circumference (WHR), calculated quantitative insulin sensitivity check index (QUICKI), etc. Relationship between serum level of leptin and all the variables mentioned above was studied by statistical methods such as factor analysis, etc.. Serum level of leptin in the study subjects increased with the number of components of abnormal metabolism they had. Detection rates of obesity, hypertension, dyslipidemia and metabolic syndrome were significantly higher in those with the upper tertile of serum leptin level than in those with the lower tertile. Factor analysis revealed that variation of the 11 variables including serum level of leptin was affected by the three factors, i.e., the central factor associated with BMI, WHR, FTI, QUICKI and higher serum level of triglyceride (TG) and lower serum level of high-density lipoprotein-cholesterol (HDL-C), the glucose intolerance factor loaded with blood glucose level, FTI, QUICKI and higher serum level of TG (in women only) and the hypertension factor loaded with blood pressure and BMI (in men only), which could explain 62.0% and 66.7% of total variance in men and women, respectively, and higher serum level of TI and insulin resistance also loaded with both the central factor and glucose tolerance factor.. Serum level of leptin was significantly associated with the key markers of metabolic syndrome. Hyperleptinaemia could be a new component of metabolic syndrome. Clustering of the risk factors for metabolic syndrome could be affected by many factors, and although insulin resistance played an important role in it, insulin resistance alone could not explain its etiology.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; China; Cluster Analysis; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors

Topics: C-Reactive Protein; Cardiovascular Diseases; Electron Spin Resonance Spectroscopy; Female; Humans; Inflammation; Leptin; Male; Membrane Fluidity; Metabolic Syndrome; Nitric Oxide; Obesity; Reference Values

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Humans; Hyperinsulinism; Leptin; Metabolic Syndrome; Risk Factors

Adiponectin, secreted specifically from adipocytes, is thought to play a key role in the metabolic syndrome. Plasma adiponectin concentrations were studied in 36 typical nonalcoholic fatty liver (NAFL) women which is commonly associated with the metabolic syndrome. They were diagnosed as NAFL by ultrasound brightness, slightly elevated serum ALT levels and the exclusion of history of alcohol abuse and other known liver diseases. Compared with 64 control women, NAFL had a significant increase in the variables of the metabolic syndrome, other hepatic enzymes and leptin levels, while a reduction in AST/ALT ratio and adiponectin before (mean +/- SE: 7.2 +/- 0.5 vs 9.0 +/- 0.4 microg/ml, p < 0.005) and after adjustment for body fat mass (0.24 +/- 0.02 vs 0.34 +/- 0.02, p < 0.0001), atherogenic Index [(total cholesterol - HDLC)/HDLC: 3.2 +/- 0.3 vs 4.6 +/- 0.3, p < 0.005] or calculated insulin resistance (HOMA-R) (6.6 +/- 1.9 vs 8.6 +/- 0.9, p < 0.005). BMI and amylase were positive, and adiponectin/BMI was negative significant independent determinants of ALT value in multiple regression model. In conclusion, while hypoadiponectinemia was observed in NAFL, hypoadiponectinemia provides the possibility of fat accumulation in the liver.

Topics: Adiponectin; Adipose Tissue; Adult; Aged; Alanine Transaminase; Amylases; Aspartate Aminotransferases; Body Composition; Cholesterol; Fatty Liver; Female; Humans; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Middle Aged; Regression Analysis

The objectives of this study were to evaluate the relationships of leptin with the metabolic syndrome and to examine leptin's role in clustering of the metabolic components among Korean adolescents.. A cross sectional study was carried out in 68 male and 80 female adolescents aged 13-18 years in an urban area of South Korea. Anthropometric variables were measured and blood pressure, fasting plasma glucose, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, and serum leptin were obtained.. As more metabolic components were clustered, body mass index, body fat, waist circumference, and serum leptin levels were significantly increased. Principal components factor analysis revealed three factors in males and females that explained 70% and 65%, respectively, of the observed variance of the 10 measured variables. These were obesity-leptin-lipid factor, blood pressure factor, and glucose-cholesterol factor in males and obesity-leptin-glucose factor, blood pressure factor, and cholesterol factor in females. Leptin loaded on only one factor in both genders.. Leptin did not appear to have a major role linking various components of the metabolic syndrome, even though it was strongly associated with obesity indices. Gender difference of linking of leptin with glucose or lipid was observed. There seems to be more than one pathophysiological mechanism which might underlie full expression of the metabolic syndrome among Korean adolescents.

Topics: Adolescent; Age Distribution; Anthropometry; Cross-Sectional Studies; Factor Analysis, Statistical; Female; Humans; Incidence; Korea; Leptin; Male; Metabolic Syndrome; Probability; Risk Assessment; Severity of Illness Index; Sex Distribution

To evaluate the relationship between serum leptin levels and metabolic syndrome, fasting insulin level and anthropometric index in obese pre-pubertal children.. A cross-sectional study was carried out on obese children.. A study was made of 41 obese children (aged 6-9 y) and the same number of non-obese children (control group), matched by age and sex.. Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined in each child. Serum leptin, glucose, insulin, lipid profile, sex hormone binding globulin (SHBG), plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator (t-PA) and fibrinogen were all measured.. The serum leptin level was significantly higher in obese children (15.47 vs 4.73 ng/ml). In the obese group, leptin showed a positive correlation with BMI (P<0.001), insulin (P<0.001), triglycerides (P<0.05), PAI-1 (P<0.05) and t-PA (P<0.05), and correlated negatively with SHBG (P<0.01), apolipoprotein A-I (P<0.05) and high-density lipoproteins cholesterol (HDL-C) (P<0.05). Corrected for BMI and WHR, leptin (P partial=0.002) is only an independent predictive factor for basal insulin. Using multivariant regression analysis, only insulin (P partial=0.003) and BMI (P partial=0.018) were independent predictive factors for leptin.. For this age group, high leptin resistance may be another component of metabolic syndrome, and may be involved in its etiopathogenesis. The involvement of leptin in this syndrome may be indirect, modulating the insulin's action.

Topics: Body Mass Index; Child; Cross-Sectional Studies; Female; Fibrinogen; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Obesity; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator

To evaluate the effect of plasma leptin, nonsterified fatty acids (NEFAs), and tumor necrosis factor-receptor 1 (TNFR1) on plasma insulin and insulin-resistance status in children.. One thousand thirty-two children (521 boys and 511 girls) were included in this study. We measured plasma insulin and leptin levels by radioimmunoassay, plasma NEFA levels by enzymatic acyl-coenzyme A synthase-acyl-coenzyme A oxidase spectrophotometric methods, and TNFR1 levels by enzyme-linked immunosorbent assay. We calculated insulin resistance index (IRI) using homeostasis model assessment and calculated insulin-resistance syndrome summary score (IRS) by adding the quartile ranks from the distribution of systolic blood pressure (BP), serum triglyceride, high-density lipoprotein-cholesterol (inverse), and insulin levels.. Overweight children had higher BP, plasma leptin, and insulin levels and higher IRI and IRS than normal-weight children. Plasma leptin and TNFR1 were positively correlated with insulin levels, IRI, and IRS. The correlation coefficients of leptin and TNFR1 in IRI were 0.53 and 0.12, respectively, for boys and 0.25 and 0.18, respectively, for girls. In multivariate regression analyses, TNFR1 was positively associated with insulin level and IRI in girls; NEFA was positively associated only with IRS. Plasma leptin levels were significantly positively associated with insulin levels, IRI, and IRS, even after adjusting for BMI and other potential confounders.. Overweight children had higher BP, plasma insulin, and leptin levels and adverse insulin-resistance status than normal-weight children. Plasma leptin levels, rather than NEFA and TNFR1, may play a significant role in the development of hyperinsulinemia and insulin resistance in children.

Topics: Adolescent; Antigens, CD; Blood Pressure; Body Mass Index; Child; Cholesterol, HDL; Cross-Sectional Studies; Fatty Acids, Nonesterified; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Regression Analysis; Triglycerides

The authors investigated the interrelationships between the components of the metabolic syndrome in severe obesity.. In non-diabetic, severely obese women, the degree of obesity (BMI), the insulin sensitivity (from the Homeostatic Model of Assessment, HOMA), the serum leptin concentration and the presence of dyslipidemia and arterial hypertension were evaluated.. In insulin-resistant patients, an overall impaired metabolic status and a greater cardiovascular risk were observed, while serum leptin concentration was higher than in the insulin-sensitive ones. Leptin levels and HOMA data correlated independent of BMI findings, while the presence of dyslipidemia and hypertension was unrelated to the other metabolic syndrome factors.. In severely obese women, although other factors independently intervene, serum leptin has a role in developing the metabolic syndrome.

Topics: Female; Humans; Insulin; Leptin; Metabolic Syndrome; Obesity, Morbid

To investigate the effect of the K121Q plasma cell membrane glycoprotein (PC-1) polymorphism on the components of the insulin resistance syndrome in a population-based nationwide multicenter study in Spain.. The subjects of the study were 293 nonrelated adults (44.7% men and 55.3% women) ages 35 to 64 years randomly chosen from a nationwide population-based survey on obesity and related conditions, including insulin resistance and cardiovascular risk factors. Obesity-related anthropometric measurements included blood pressure, oral glucose tolerance test, lipid profile (total cholesterol, high-density lipoprotein- and low-density lipoprotein-cholesterol, and triglycerides), plasma leptin, insulin levels by radioimmunoassay, and insulin resistance (homeostasis model assessment). K121Q PC-1 genotypes were determined by restriction fragment-length polymorphism-polymerase chain reaction.. Overall Q allele frequency was 0.14, with no differences between obese and nonobese individuals (0.15 vs. 0.13). After adjustment for sex, age, BMI, and degree of glucose tolerance, the Q allele was associated with high plasma leptin and triglyceride levels, but not with insulin resistance.. The results showed that the K121Q PC-1 polymorphism in the Spanish population has no significant impact on insulin sensitivity.

Topics: Anthropometry; Cross-Sectional Studies; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Phosphoric Diester Hydrolases; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Pyrophosphatases; Spain

Inflammation has been suggested as a risk factor for the development of atherosclerosis, while some components of metabolic syndrome X have been related to inflammatory markers. We hypothesized that adipocyte secreting protein, adiponectin and leptin, for which have been demonstrated an association with metabolic syndrome X and coronary artery disease, may be associated with inflammatory markers in nondiabetic humans.. We measured high-sensitivity C-reactive protein (hs-CRP), as an inflammatory marker, and adiponectin and leptin concentrations in 384 nondiabetic Japanese women (mean+/-s.e.m. age 53.6+/-0.8 Years, body mass index (BMI) 23.0+/-0.2 kg/m(2)) undergoing measurement of markers of metabolic syndrome X.. The women who had a low-grade hs-CRP elevation (>2.0 mg/l) were significantly older and had higher BMI, body fat mass (BFM), total cholesterol (TC), triglyceride (TG), atherogenic index (AI=(TC-HDLC)/HDLC), where HDLC is high-density lipoproten-cholesterol), fasting blood glucose and leptin concentrations before and after adjustment for BMI or BFM, while lower HDLC and adiponectin concentrations before and after adjustment compared with women with normal CRP levels (<0.5 mg/l). BMI, BFM, TG, AI and leptin before and after adjustment were found to be correlated with hs-CRP levels, while HDLC and adiponectin before and after adjustment were inversely correlated (all P<0.0001). hs-CRP was independently associated with white blood cell count, blood urea nitrogen and AI and inversely with adiponectin/BFM in the stepwise regression analysis model.. These data demonstrate a significant decrease in plasma adiponectin in low-grade chronic inflammation, and suggest that there is an important linkage between inflammation/adipose tIssue/atherosclerosis.

Topics: Adiponectin; Adolescent; Adult; Aged; Aged, 80 and over; Arteriosclerosis; Biomarkers; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Leukocyte Count; Metabolic Syndrome; Middle Aged; Proteins; Sensitivity and Specificity; Triglycerides; Uric Acid

In obesity, plasma leptin is high and soluble leptin receptor (sOb-R) levels are low, resulting in a low fraction of bound leptin. The aim of this study was to investigate the influence of insulin resistance (IR) and the metabolic syndrome (MS) on sOb-R concentration and the bound-free ratio of leptin.. sOb-R, leptin levels, and homeostasis model assessment (HOMA) index for IR were determined in 76 middle-aged obese or overweight men.. Concentration of sOb-R and soluble receptor-bound fraction of leptin were lowest in the highest tertile of HOMA-IR. sOb-R and the bound-free ratio of leptin correlated with HOMA-IR, leptin concentration, and waist-to-hip ratio independently of age, BMI, and fat mass. Leptin and waist-to-hip ratio were the sole independent determinants of sOb-R concentration, and BMI, HOMA-IR, and visceral adipose tissue were independent determinants of the bound fractin of leptin. sOb-R concentration and the bound fraction of leptin decreased with increasing numbers of components of the MS, resulting in lower sOb-R concentration and a lower fraction of bound leptin in men with the MS.. IR and abdominal obesity are associated with low sOb-R concentration and low bound-free ratio of leptin independent of fat mass. Low sOb-R concentration and low bound-free ratio of leptin segregate with components of the MS. We suggest that low sOb-R levels and a low fraction of specifically bound leptin are markers of leptin resistance, which is independently associated with IR and abdominal obesity and may constitute an additional component of the MS.

Topics: Adipose Tissue; Adult; Blood Pressure; Body Composition; Body Constitution; Body Mass Index; Fasting; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Protein Binding; Receptors, Cell Surface; Receptors, Leptin

To examine the relation of leptin to insulin resistance, as measured by euglycemic insulin clamp, and insulin resistance syndrome factors in thin and heavy children.. Anthropometrics, insulin, blood pressure, and leptin were measured in 342 11- to 14-year-old children (189 boys, 153 girls, 272 white, 70 black). Insulin sensitivity (M) was determined by milligrams glucose uptake per kilogram per minute and expressed as M/lean body mass (Mlbm). Children were divided by median BMI (boys = 20.5 kg/m(2); girls = 21.4 kg/m(2)) into below-median (thin) and above-median (heavy) groups. Correlation coefficients between log-leptin and components of insulin resistance syndrome were adjusted for Tanner stage, gender, and race.. BMI was related to leptin in boys (r = 0.70, p < 0.001) and girls (r = 0.75, p < 0.001). Leptin was higher in girls than boys (32.6 vs. 12.3 ng/mL, p = 0.0001). Leptin levels increased in girls and decreased in boys during puberty, paralleling the changes in body fat. Leptin was significantly correlated with insulin, Mlbm, triglycerides, and blood pressure in heavy children and only with insulin in thin children. After adjustment for body fat, the correlations remained significant for insulin and Mlbm in heavy children and with insulin in thin children.. Significant associations were found between leptin and insulin resistance in children, and these associations were attenuated by adjustment for adiposity. These findings at age 13 likely have long-term consequences in the development of the obesity-insulin resistance-related cardiovascular risk profile.

Topics: Adolescent; Aging; Anthropometry; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Clamp Technique; Humans; Leptin; Male; Metabolic Syndrome; Obesity; Puberty; Risk Factors; Sex Characteristics

To compare plasma leptin in Saudi subjects with Type 2 diabetes and coronary heart disease (CHD) with non-diabetic control subjects and to examine the relationship of plasma leptin to other CHD risk factors.. Serum leptin concentrations were measured in 144 Saudi men. Subjects studied included 59 with Type 2 diabetes mellitus [BMI 27.5 (3.7) kg/m2 mean (sd)], 34 with coronary heart disease [BMI 29.6 (1.8) kg/m2], and 51 non-diabetic controls [BMI 28.0 (3.5) kg/m2]. There was no significant difference in BMI between the groups. Fasting serum leptin, lipids, insulin, apolipoproteins and glucose were measured. BMI, blood pressure; smoking habit and age were also recorded. Insulin resistance was assessed using the HOMA model.. Leptin concentrations were significantly higher in diabetic and CHD patients than in controls (P = 0.024 and 0.016, respectively). Multiple regression analysis showed that body weight (P < 0.0006), serum triglyceride concentration (P = 0.046) and systolic blood pressure (P = 0.013) were all significantly related to the logarithm of the serum leptin concentration (R2 = 0.549) in CHD patients. A subgroup analysis, comparing those patients who had the metabolic syndrome, as defined by WHO, with controls, showed higher serum leptin in those with metabolic syndrome (P = 0.05).. Serum leptin is increased in Saudi subjects with diabetes mellitus, metabolic syndrome and CHD. Leptin may be a marker of risk of CHD, at least in men, and contribute to the CHD risk profile in subjects with insulin resistance. Further studies are needed to evaluate this relationship prospectively.

Topics: Adult; Apolipoprotein A-I; Blood Glucose; Blood Pressure; Body Mass Index; Case-Control Studies; Cholesterol; Coronary Disease; Diabetes Mellitus, Type 2; Diastole; Humans; Insulin; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Saudi Arabia; Triglycerides

Topics: Animals; C-Reactive Protein; Coronary Disease; Diabetes Mellitus; Glucose Intolerance; Humans; Hypertension; Inflammation; Leptin; Lipoproteins, HDL; Matrix Metalloproteinase 9; Metabolic Syndrome; Mice; Mice, Knockout; Obesity; Oxidative Stress; Phosphatidylcholine-Sterol O-Acyltransferase; Receptors, LDL; Risk Factors; Smoking

Syndrome X, typified by obesity, insulin resistance (IR), dyslipidemia, and other metabolic abnormalities, is responsive to antidiabetic thiazolidinediones (TZDs). Peroxisome proliferator-activated receptor (PPAR) gamma, a target of TZDs, is expressed abundantly in adipocytes, suggesting an important role for this tissue in the etiology and treatment of IR. Targeted deletion of PPARgamma in adipose tissue resulted in marked adipocyte hypocellularity and hypertrophy, elevated levels of plasma free fatty acids and triglyceride, and decreased levels of plasma leptin and ACRP30. In addition, increased hepatic glucogenesis and IR were observed. Despite these defects, blood glucose, glucose and insulin tolerance, and insulin-stimulated muscle glucose uptake were all comparable to those of control mice. However, targeted mice were significantly more susceptible to high-fat diet-induced steatosis, hyperinsulinemia, and IR. Surprisingly, TZD treatment effectively reversed liver IR, whereas it failed to lower plasma free fatty acids. These results suggest that syndrome X may be comprised of separable PPARgamma-dependent components whose origins and therapeutic sites may reside in distinct tissues.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Hypoglycemic Agents; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Lipodystrophy; Liver; Liver Function Tests; Metabolic Syndrome; Mice; Mice, Knockout; Muscle, Skeletal; Organ Specificity; Proteins; Receptors, Cytoplasmic and Nuclear; Rosiglitazone; Thiazolidinediones; Transcription Factors

Ghrelin, leptin and adiponectin are three hormones which are frequently associated with metabolism, obesity and appetite. Recently, it has been shown that they may possess other physiologic roles, specially in connection with the circulation. Ghrelin infusion increases forearm blood-flow in a dose-dependent manner. Leptin has been shown to be involved not only in thermogenesis but angiogenesis as well. Adiponectin, apart from its insulin-sensitizing action, appears to modulate inflammation by inhibiting monocyte adhesion to endothelial cells. Six monkeys, which had been classified as being in the pre-diabetic state, where administered a triglyceride lowering regimen. Microvascular function was assessed using a laser Doppler flow-meter during a temperature provocation test. Percent change in flow from baseline following temperature elevation, as well as percent change in flow/degree rise in temperature were used to evaluate microvascular reserve and reactivity. Using univariate analysis, it appears that increased perfusion is significantly correlated with adiponectin, followed by leptin. Flow was also positively correlated with ghrelin, but the relationship did not attain significance. As expected, flow was also negatively and significantly correlated with fibrinogen. Trends show that flow was also negatively correlated to circulating triglyceride levels (p=0.08). The data indicate that the three hormones appear to possess microvascular actions that may impact on their other physiologic functions.

Topics: Adiponectin; Animals; Blood Glucose; Fibrinogen; Ghrelin; Hyperglycemia; Hyperinsulinism; Hypertriglyceridemia; Hypolipidemic Agents; Intercellular Signaling Peptides and Proteins; Leptin; Macaca mulatta; Metabolic Syndrome; Microcirculation; Obesity; Peptide Hormones; Prediabetic State; Proteins

Metabolic syndrome is characterized by a clustering of metabolic abnormalities: insulin resistance - hyperinsulinemia, dyslipidemia (high triglycerides and low HDL - cholesterol serum concentrations), impaired glucose tolerance and/or type 2 diabetes, and hypertension. The aim of this study was to analyse the role of different variables of metabolic syndrome, including leptin, in 74 non-obese children and 68 children with non-syndromal obesity. As metabolic syndrome variables, we have included body mass index, waist circumference, trunk-to-total skinfolds (%), systolic blood pressure, diastolic blood pressure, glucose, uric acid, fasting insulin, triglycerides and high-density lipoprotein-cholesterol (HDL-C). Factor analysis showed 4 factors in each group. In non-obese children, waist circumference, BMI, fasting insulin, triglycerides, trunk-to-total skinfolds (%), leptin and uric acid loaded positively on factor 1, and HDL-C loaded negatively on this factor; systolic and diastolic blood pressure had high positive loadings in factor 2; HDL-C and leptin showed positive loadings and triglycerides and uric acid, negative loadings in factor 3; and, finally, glucose and insulin showed positive loadings in factor 4. These four factors explained 72.16 % of the total variance in the non-obese group. In obese children, BMI, waist circumference, leptin, diastolic blood pressure and systolic blood pressure loaded positively on factor 1; diastolic blood pressure, trunk-to-total skinfolds (%), uric acid and systolic blood pressure showed high positive loadings in factor 2; fasting insulin, glucose and triglycerides showed positive loadings in factor 3; and, finally, triglycerides showed positive loadings and HDL-C negative loadings in factor 4. These four factors explained 74.18 % of the total variance in the obese group. Our results point to a different homeostatic control of metabolic syndrome characteristics in obese and non-obese children. Leptin seems to play a key underlying role in metabolic syndrome, especially in the obese group.

Topics: Blood Glucose; Blood Pressure; Body Height; Body Weight; Child; Cholesterol, HDL; Factor Analysis, Statistical; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Obesity; Triglycerides; Uric Acid

Topics: Body Constitution; Humans; Leptin; Metabolic Syndrome; Obesity; Polysomnography; Risk Factors; Sleep Apnea, Obstructive

The serum uric acid level has been said to be an independent predictor of cardiovascular disease death, mainly for women, and to be linked with the metabolic Syndrome X of insulin resistance, obesity, hypertension, and dyslipidemia. Recently, it has been suggested that the elevation of serum leptin, the ob gene product, may have a role in metabolic Syndrome X. Therefore, we studied the relationship of uric acid to leptin in 822 Japanese women in a cross-sectional manner. To estimate the effect of uric acid on the variables of metabolic Syndrome X, we calculated mean values of various components of the syndrome according to tertiles of uric acid (UA < 4.0 mg/dl, 4.0 < or = UA < 5.5, 5.5 < or = UA). Age, systolic and diastolic blood pressure (BP), body mass index (BMI), percent body fat mass (BFM), serum total cholesterol, triglyceride, atherogenic index, leptin, fasting immunoreactive insulin and homeostasis model assessment-ratio (HOMA-R: calculated insulin resistance) were significantly different across the uric acid tertiles with higher levels in the highest tertile in comparison to the first (ANOVA, p < 0.001, 0.001, 0.002, 0.001, 0.001, 0.025, 0.001, 0.001, 0.001, 0.001, 0.001, respectively), while high density lipoprotein cholesterol showed lower levels (p < 0.001). Serum leptin concentrations were also elevated in hyperuricemic women after adjusting for BMI or BFM (both p < 0.001), and were weakly correlated with serum uric acid concentrations (r = 0.22, p < 0.0001). BMI, HOMA-R, serum triglyceride, diastolic BP and age-adjusted serum leptin concentrations were calculated for each tertile of serum uric acid. Compared with the lowest tertile of uric acid level, BMI, HOMA-R, serum triglyceride, diastolic BP and age-adjusted leptin concentrations were higher in the highest tertile. In the stepwise regression analysis, serum leptin was the significant independent variable for uric acid values. These results indicate an independent relationship between leptin and uric acid, further supporting the involvement of leptin in metabolic Syndrome X.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arteriosclerosis; Blood Glucose; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Hyperuricemia; Insulin; Leptin; Metabolic Syndrome; Middle Aged; Triglycerides; Uric Acid

The aim of the present study was to investigate the association between the serum lipid profile and components of the metabolic syndrome, such as central obesity (anthropometric, computed tomography and fat cell data), insulin, sex-hormone-binding-globulin (SHBG) and different hormones influencing this important syndrome, e.g. sex steroids, leptin and tumor necrosis factor-alpha (TNF-alpha). The sample consisted of 85 obese patients (30 men and 55 women) who had undergone abdominal surgery. Fasting serum lipids were analysed, as well as anthropometric and computed tomography data, perivisceral and subcutaneous fat cell size and serum glucose and hormones. Abdominal fat revealed itself as an important correlator of the adverse changes in plasma lipoprotein levels, the waist-to-hip-ratio and waist-to-thigh-ratio being the best morphological correlators in men and women, respectively. Intra-abdominal fat (VA) correlated significantly and positively to perivisceral fat cell size in women, while no correlation was found between subcutaneous fat accumulation (SA) and adipocyte size in both genders. Perivisceral fat cell size showed the greatest number of correlations with the adverse plasma lipid profile compared to that in the subcutaneous depot. SHBG and sex steroids showed a negative correlation with serum lipids considered a cardiovascular risk. In contrast, TNF-alpha and C-peptide were inversely correlated with potential protector lipids. In conclusion, abdominal obesity, adipocyte hypertrophy from visceral fat, serum TNF-alpha and C-peptide seem to be the best correlators of the lipoprotein disturbance characteristic of the metabolic syndrome, whereas SHBG and sex steroids could play a protective role regarding the lipid profile associated to this syndrome.

Topics: Adipocytes; Adipose Tissue; Adult; Aged; Body Constitution; Body Mass Index; C-Peptide; Cell Size; Female; Hormones; Humans; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Postmenopause; Risk Factors; Sex Factors; Sex Hormone-Binding Globulin; Steroids; Tumor Necrosis Factor-alpha; Viscera

Growth hormone (GH) possesses multiple metabolic effects, in particular with regard to glucose and lipid homeostasis. Studies on the effects of GH on body weight and food and water intake are scarce and have yielded controversial results. We investigated the effects of different modes of GH administration on the parameters of body weight and food intake as well as on insulin and leptin concentrations in fa/fa Zucker rats. In control experiments, aqua pro injection was given. GH was administered over a time period of 11 days at a daily dose of 250 microg intraperitoneally (i.p.) and 25 microg intracerebroventricularly (i.c.v.). While both food intake and body weight were found to be unaltered in the four groups after this observation period, there was an enhanced food intake and consecutively an increase in body weight over the day period when compared to the night period in the groups of rats that received GH i.c.v. or i.p. This tendency was also shown for water intake. Insulin and leptin concentrations were similar in all groups. Thus, injection of GH appears to modify food intake-related behavior, since the periods of enhanced food and water intake were shifted from night- to daytime. Thus, while in general the metabolic parameters remained unchanged, the activity pattern was clearly modified.

Topics: Animals; Body Weight; Carrier Proteins; Disease Models, Animal; Eating; Feeding Behavior; Growth Hormone; Homozygote; Injections, Intraperitoneal; Injections, Intraventricular; Insulin; Leptin; Male; Metabolic Syndrome; Mutation; Rats; Rats, Zucker; Receptors, Cell Surface; Receptors, Leptin; Time Factors

Comparative studies have shown that Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) develop a nearly complete metabolic syndrome with obesity, moderate hypertension, dyslipidemia, hyperinsulinemia, and impaired glucose tolerance up to an age of 28 weeks. Because metabolic data thereafter are missing, WOKW and disease-resistant DA rats were studied for 12 months beginning at an age of 5 months.. Eighteen male inbred WOKW and DA rats were studied monthly from the 5th to the 17th month of life for traits of the metabolic syndrome such as body weight, body mass index (BMI), serum triglycerides, total cholesterol, leptin, insulin as well as glucose tolerance, 24 h excretion of urine total protein and creatinine including telemetric measurement of blood pressure in six males per each group.. Except for serum total cholesterol, the measured values for most traits studied were significantly higher in WOKW than in DA rats at an age of 5 months. At an age of 17 months all traits were significantly elevated in WOKW compared with DA rats. WOKW rats were hypertensive, dyslipidemic, obese, glucose intolerant, hyperinsulinemic and proteinuric.. Considering the phenotype of the WOKW rat described until now and the fact that the metabolic syndrome in this rat is polygenetically determined, the WOKW rat is the most suitable animal model to study the pathophysiology of the facets of the syndrome.

Topics: Aging; Animals; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Creatinine; Glucose Tolerance Test; Insulin; Leptin; Male; Metabolic Syndrome; Proteinuria; Rats; Triglycerides

To use factor analysis to examine the putative role of leptin in the Metabolic Syndrome, and to define better the associations among observed variables and the identified factors.. Factor analysis of cross-sectional data from a 1987 survey.. Non-diabetic residents of Mauritius who participated in population-based surveys in 1987 and 1992 (1414 men and 1654 women).. Fasting and 2 h plasma glucose and insulin following a 75 g oral glucose load; seated blood pressure; body mass index (BMI); waist-to-hip ratio (WHR); and fasting serum triglycerides, HDL-cholesterol, leptin and uric acid concentrations.. Principal components factor analysis revealed three factors for men and women that explained between 54 and 55% of the observed variance of the 12 measured variables. General features of these factors were as follows: factor 1, WHR, BMI, leptin, fasting and 2 h insulin, triglycerides, and HDL-cholesterol; factor 2, systolic and diastolic blood pressure, uric acid (men only), and fasting glucose (women only); and factor 3, fasting and 2 h glucose and insulin. Only three variables loaded on more than one factor with a loading > or = 0.4 (fasting and 2 h insulin, fasting glucose in women only). Leptin loaded on one factor only in both men and women.. Since multiple factors underlie the Metabolic Syndrome, and since no observed variable loads on all three factors, more than one mechanism might account for the observed clustering of risk characteristics. Leptin does not unite features of this syndrome due to its loading on one factor only. Uric acid is related to a different factor in men and women. The absence of gender differences in factor loadings argues for similar mechanisms for the Metabolic Syndrome in men and women in Mauritius. International Journal of Obesity (2001) 25, 126-131

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Cluster Analysis; Cross-Sectional Studies; Data Collection; Factor Analysis, Statistical; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Mauritius; Metabolic Syndrome; Middle Aged

The adverse metabolic consequences of obesity are best predicted by the quantity of visceral fat. Excess glucocorticoids produce visceral obesity and diabetes, but circulating glucocorticoid levels are normal in typical obesity. Glucocorticoids can be produced locally from inactive 11-keto forms through the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11beta HSD-1). We created transgenic mice overexpressing 11beta HSD-1 selectively in adipose tissue to an extent similar to that found in adipose tissue from obese humans. These mice had increased adipose levels of corticosterone and developed visceral obesity that was exaggerated by a high-fat diet. The mice also exhibited pronounced insulin-resistant diabetes, hyperlipidemia, and, surprisingly, hyperphagia despite hyperleptinemia. Increased adipocyte 11beta HSD-1 activity may be a common molecular etiology for visceral obesity and the metabolic syndrome.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Abdomen; Adipocytes; Adipose Tissue; Animals; Body Composition; Cell Size; Corticosterone; Dietary Fats; Disease Models, Animal; Eating; Gene Targeting; Humans; Hydroxysteroid Dehydrogenases; Hyperglycemia; Hyperinsulinism; Insulin Resistance; Leptin; Lipid Metabolism; Lipids; Lipoprotein Lipase; Male; Metabolic Syndrome; Mice; Mice, Transgenic; Obesity; Receptors, Glucocorticoid; Viscera; Weight Gain

Topics: Antipsychotic Agents; Benzodiazepines; Body Weight; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Obesity; Olanzapine; Pirenzepine; Psychotic Disorders

While multiple growth factor, cytokines, and immune cells are identified in atherosclerotic lesions, as well as an essential nonneuronal function of neurotrophins implicated in cardiovascular tissue development and in lipid and glucose metabolism, the role of the neurotrophins NGF and BDNF and also the adipokine leptin in human coronary atherosclerosis and related disorders, such as metabolic syndrome, remains unclear. Here we report that (i) both the amount and the immunoreactivity of NGF was reduced and the expression of p75NGF receptor and the number of mast cell increased in human atherosclerotic coronary arteries (n = 12) compared with control specimens (n = 9) obtained from autopsy cases, and (ii) NGF and BDNF plasma levels were reduced in patients with metabolic syndrome (n = 23) compared with control subjects (n = 10). Also, in metabolic syndrome patients, a positive correlation between the plasma leptin levels and the number of adipose tissue mast cells was found, suggesting that leptin may be a novel adipoimmune mediator. Altogether, the results provide the first correlative evidence for the potential involvement of NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome, implying neuroimmune and adipoimmune pathways in the pathobiology of these cardiovascular disorders.

Topics: Brain-Derived Neurotrophic Factor; Coronary Artery Disease; Coronary Circulation; Female; Humans; Leptin; Male; Mast Cells; Metabolic Syndrome; Middle Aged; Nerve Growth Factor