Secretory products from epicardial adipose tissue from patients with type 2 diabetes impair mitochondrial β-oxidation in cardiomyocytes via activation of the cardiac renin-angiotensin system and induction of miR-208a.

Secretory products from epicardial adipose tissue (EAT) from patients with type 2 diabetes (T2D) impair cardiomyocyte function. These changes associate with alterations in miRNA expression, including the induction of miR-208a. Recent studies suggest that activation of the cardiac-specific renin-angiotensin system (RAS) may affect cardiac energy metabolism via induction of miR-208a.

Determinants of testosterone levels in human male obesity.

Testosterone (T) levels are decreased in obese men, but the underlying causes are incompletely understood. Our objective was to explore the relation between low (free) T levels and male obesity, by evaluating metabolic parameters, subcutaneous adipose tissue (SAT) aromatase expression, and parameters of the hypothalamic-pituitary-gonadal axis. We recruited 57 morbidly obese men [33 had type 2 diabetes (DM2)] and 25 normal-weight men undergoing abdominal surgery.

Activin A is associated with impaired myocardial glucose metabolism and left ventricular remodeling in patients with uncomplicated type 2 diabetes.

Background: Activin A released from epicardial adipose tissue has been linked to contractile dysfunction and insulin resistance in cardiomyocytes. This study investigated the role of activin A in clinical diabetic cardiomyopathy by assessing whether circulating activin A levels associate with cardiometabolic parameters in men with uncomplicated type 2 diabetes (T2D), and the effects of treatment with pioglitazone versus metformin on these associations.

Methods: Seventy-eight men with uncomplicated T2D and fourteen healthy men with comparable age were included, in this randomized, double-blind, active comparator intervention study.

Beneficial and adverse effects of testosterone on the cardiovascular system in men.

Context: The widespread use of T therapy, particularly in aging males, necessitates knowledge of the relationship between T and the cardiovascular system.

Evidence Acquisition: The review is based on a 1970 to 2013 PubMed search with terms related to androgens in combination with cardiovascular disease, including T, dihydrotestosterone, trial, mortality, cardiovascular disease, myocardial infarction, blood pressure, endothelial function, dyslipidemia, thrombosis, ventricular function, and arrhythmia. Original articles, systematic reviews and meta-analyses, and relevant citations were screened.

Activin A impairs insulin action in cardiomyocytes via up-regulation of miR-143.

Aims: Enhanced activin A release from epicardial adipose tissue (EAT) has been linked to the development of cardiac dysfunction in type 2 diabetes (T2D). This study examined whether the inhibition of insulin action induced by epicardial adipokines in cardiomyocytes can be ascribed to alterations in miRNA expression.

Methods And Results: Expression levels of miRNAs were assessed by real-time PCR in primary adult rat cardiomyocytes (ARC) exposed to conditioned media generated from EAT biopsies (CM-EAT) from patients with and without T2D.

Secretory products from epicardial adipose tissue of patients with type 2 diabetes mellitus induce cardiomyocyte dysfunction.

Background: Secreted factors from epicardial adipose tissue (EAT) have been implicated in the development of cardiomyocyte dysfunction. This study aimed to assess whether alterations in the secretory profile of EAT in patients with type 2 diabetes mellitus (DM2) affect contractile function and insulin action in cardiomyocytes.

Methods And Results: Contractile function and insulin action were analyzed in primary adult rat cardiomyocytes incubated with conditioned media (CM) generated from explants of EAT biopsies obtained from patients without and with DM2.

Glucose intolerance and the amount of visceral adipose tissue contribute to an increase in circulating triglyceride concentrations in Caucasian obese females.

Context: Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2), cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG) concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2.

Endogenous oestradiol and cardiovascular disease in healthy men: a systematic review and meta-analysis of prospective studies.

Context: The literature provides no clear answer as to whether total oestradiol (E2) concentrations increase the risk of incident cardiovascular disease (CVD) in healthy men.

Objective: The authors conducted a systematic review and meta-analysis to estimate the predictive value of E2 for CVD, and to identify study features explaining conflicting results.

Data Sources: Articles were identified by a Medline and Embase search and citation tracking.

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

Context: Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men.

Objective: The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines.

Design: Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches.

Chemerin as biomarker for insulin sensitivity in males without typical characteristics of metabolic syndrome.

To allow early detection and prevention of metabolic disorders, circulating levels of adipokines involved in insulin sensitivity were compared with the hyperinsulinemic-euglycemic clamp. Twenty non-obese normo-glycaemic men (age 32.1 ± 6 years) underwent a clamp procedure.

Combined gene and protein expression of hormone-sensitive lipase and adipose triglyceride lipase, mitochondrial content, and adipocyte size in subcutaneous and visceral adipose tissue of morbidly obese men.

Aims: Lipotoxicity in obesity might be a failure of adipocytes to respond sufficiently adequate to persistent energy surplus. To evaluate the role of lipolytic enzymes or mitochondria in lipotoxicity, we studied expression levels of genes and proteins involved in lipolysis and mitochondrial DNA (mtDNA) content.

Methods: As differences in lipid metabolism between men and women are extremely complex, we recruited only men (lean and morbidly obese) and collected subcutaneous and visceral adipose tissue during abdominal surgery for real-time PCR gene expression, protein expression, and microscopic study.

Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis.

Context: The literature provides no clear answer as to whether low endogenous testosterone increases risk of cardiovascular disease (CVD) in healthy men.

Objective: Our purpose was to estimate the predictive value of testosterone for CVD and to identify study features explaining conflicting results.

Data Sources: Articles were identified by a Medline and Embase search and citation tracking.

Does low testosterone affect adaptive properties of adipose tissue in obese men?

Obesity and (pre)diabetes in males is associated with low serum testosterone and increased oestradiol levels. It is unknown whether these changes in sex steroids are part of a vicious circle resulting in an increase of risk for metabolic complications of obesity, or whether it presents merely an epiphenomenon. The risk for metabolic complications in obesity seems to be determined by adaptation and integrity of adipose tissue.

The effects of a pedometer-based behavioral modification program with telephone support on physical activity and sedentary behavior in type 2 diabetes patients.

Objective: Effectiveness of a behavioral modification program on physical activity (PA) and sedentary behavior in diabetes patients.

Methods: Ninety-two patients were randomly assigned to an intervention or control group. The 24-weeks intervention consisted of a face-to-face session, pedometer and seven telephone follow-ups.

Sex steroids affect triglyceride handling, glucose-dependent insulinotropic polypeptide, and insulin sensitivity: a 1-week randomized clinical trial in healthy young men.

Objective: To evaluate metabolic effects of sex steroids in nonfasting and fasting conditions, independent from changes in body composition.

Research Design And Methods: A randomized clinical trial was performed to create contrasting sex steroid levels in healthy young men: by letrozole (aromatase inhibitor) to lower estradiol (E(2)) and increase testosterone (group T, n = 10) versus letrozole plus E(2) patches to lower T and raise E(2) (group E, n = 10). Mixed meals and hyperinsulinemic-euglycemic clamps were performed before and after a 1-week treatment period.

Low fasting triglycerides: hallmark of the healthy large hip?

Body fat distribution modulates risk for type 2 diabetes mellitus. We evaluated potentially involved metabolic risk factors. In a population of 282 male and 157 female healthy subjects (data from the San Antonio and the European Group of Insulin Resistance (EGIR) study cohorts), we evaluated associations between body fat distribution (assessed by waist and hip circumference) and parameters of lipid- and glucose metabolism, including clamp measurements of insulin sensitivity.

Fasting-based estimates of insulin sensitivity in overweight and obesity: a critical appraisal.

Objective: To identify simple methods to estimate the degree of insulin resistance.

Research Methods And Procedures: The performance of a wide range of fasting-based index estimates of insulin sensitivity was compared by receiver operating characteristic analysis (area under curves and their 95% confidence intervals) against the M value from euglycemic insulin clamp studies collected in the San Antonio (non-Hispanic whites and Hispanic residents of San Antonio, TX) and European Group for the Study of Insulin Resistance (non-diabetic white Europeans) databases (n = 638).

Results: Insulin resistance differed substantially between lean (BMI < 25 kg/m2), overweight or obese (BMI > or = 25 kg/m2), and type 2 diabetic individuals.

Inverse relationship between plasminogen activator inhibitor-I activity and adiponectin in overweight and obese women. Interrelationship with visceral adipose tissue, insulin resistance, HDL-chol and inflammation.

Adipose tissue is an active endocrine organ secreting different adipokines such as plasminogen activator inhibitor-1 (PAI-1) and adiponectin, among many others. In this study, we investigated the association between PAI-1 activity and serum adiponectin levels in a group of 444 overweight and obese women and assessed the interrelationship with visceral adipose tissue (VAT; CT-scan L4-L5), insulin resistance (HOMA-IR), HDL cholesterol (HDL-chol) and inflammation (hs-CRP). PAI-1 was inversely related to adiponectin (r = -0.

Opposite effects of insulin-like molecules and leptin in coronary heart disease of type 2 diabetes Preliminary data.

Introduction: Leptin and insulin have been reported to be risk factors for coronary heart disease (CHD) in the general population, but their role in type 2 diabetes still remains unclear.

Materials And Methods: The role of leptin and insulin upon CHD in type 2 diabetes was assessed in 154 patients, aged 31-77 years, who were treated with oral anti-diabetic agents. Multivariate logistic regression analyses were used with CHD (an established history of CHD or an abnormal treadmill test) as dependent, and leptin, insulin and potential confounders as independent variables.

Resting metabolic rate is an important predictor of serum adiponectin concentrations: potential implications for obesity-related disorders.

Background: Little is known about the regulation of adiponectin. Animal studies suggest local regulation by adipocytokines or alterations in energy expenditure, and studies in humans suggest regulation by alcohol intake and ethnicity.

Objective: To identify regulators of adiponectin in humans, we measured resting metabolic rate (RMR), serum adiponectin, glucose, insulin, triacylglycerol, alcohol intake, and anthropometric indexes in 457 white patients with overweight or obesity.