Echocardiographic abnormalities in normotensive obese patients: Relationship with visceral fat

Objective: To evaluate the relationship of echocardiographic characteristics and visceral adipose tissue (VAT) distribution in normotensive obese patients. Research Methods and Procedures: Echocardiographic parameters were assessed in 28 normotensive obese patients [7 men, 21 women, mean age, 43.2 years; mean body mass index (BMI), 37.2 kg/m2; 10 with impaired glucose tolerance (IGT); 6 with type 2 diabetes] and 18 sex-and age-matched healthy, normal-weight controls (4 men, 14 women; mean age, 45.8 years; mean BMI, 22.4 kg/m2) by an M-mode, color-doppler videofluoroscope. VAT in the obese patients was assessed by computed tomography (at L4 level). Results: The obese patients had a significantly larger internal diastolic left ventricular (LV) diameter (p < 0.05), a thicker end-diastolic septum (p < 0.001) and posterior wall (p < 0.001), a greater indexed (g/m2.7) LV mass (p < 0.001), a higher atrial diastolic filling wave velocity (p < 0.001), a lower ratio between early and atrial diastolic filling wave velocities (p < 0.01), and a prolonged isovolumic relaxation time (p < 0.05). End-diastolic septum and posterior wall thickness and the LV mass were significantly greater in patients with a VAT area > 130 cm2 than with <130 cm2. In the multivariate regression analysis, only VAT (p < 0.0001), waist-to-hip ratio (p < 0.001), and sex (p < 0.001) were associated with the most important echocardiographic alterations. Discussion: The morphological and functional echocardiographic alterations usually found in normotensive obese patients closely correlate with the amount of intra-abdominal fat deposition, even in the presence of diabetes or IGT

Amino acids contribute to adaptive thermogenesis. New insights into the mechanisms of action of recent drugs for metabolic disorders are emerging

Adaptive thermogenesis is the heat production by muscle contractions (shivering thermogenesis) or brown adipose tissue (BAT) and beige fat (non-shivering thermogenesis) in response to external stimuli, including cold exposure. BAT and beige fat communicate with peripheral organs and the brain through a variegate secretory and absorption processes − controlling adipokines, microRNAs, extracellular vesicles, and metabolites − and have received much attention as potential therapeutic targets for managing obesity-related disorders. The sympathetic nervous system and norepinephrine-releasing adipose tissue macrophages (ATM) activate uncoupling protein 1 (UCP1), expressed explicitly in brown and beige adipocytes, dissolving the electrochemical gradient and uncoupling tricarboxylic acid cycle and the electron transport chain from ATP production. Mounting evidence has attracted attention to the multiple effects of dietary and endogenously synthesised amino acids in BAT thermogenesis and metabolic phenotype in animals and humans. However, the mechanisms implicated in these processes have yet to be conclusively characterized. In the present review article, we aim to define the principal investigation areas in this context, including intestinal microbiota constitution, adipose autophagy modulation, and secretome and metabolic fluxes control, which lead to increased brown/beige thermogenesis. Finally, also based on our recent epicardial adipose tissue results, we summarise the evidence supporting the notion that the new dual and triple agonists of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG) receptor − with never before seen weight loss and insulin-sensitizing efficacy − promote thermogenic-like amino acid profiles in BAT with robust heat production and likely trigger sympathetic activation and adaptive thermogenesis by controlling amino acid metabolism and ATM expansion in BAT and beige fat

Subcutaneous, Paracardiac, and Epicardial Fat CT Density Before/After Contrast Injection: Any Correlation with CAD?

Adipose tissue, in particular epicardial adipose tissue, has been identified as a potential biomarker of cardiovascular pathologies such as coronary artery disease (CAD) in the light of its metabolic activity and close anatomic and pathophysiologic relationship to the heart. Our purpose was to evaluate epicardial adipose tissue density at both unenhanced and contrast-enhanced computed tomography (CT), along with CT densities of paracardiac and subcutaneous adipose tissue, as well as the relations of such densities with CAD. We retrospectively reviewed patients who underwent cardiac CT at our institution for CAD assessment. We segmented regions of interest on epicardial, paracardiac, and subcutaneous adipose tissue on unenhanced and contrast-enhanced scans. A total of 480 patients were included, 164 of them presenting with CAD. Median epicardial adipose tissue density measured on contrast-enhanced scans (-81.5 HU; interquartile range -84.9 to -78.0) was higher than that measured on unenhanced scans (-73.4 HU; -76.9 to -69.4) (p < 0.001), whereas paracardiac and subcutaneous adipose tissue densities were not (p >= 0.055). Patients with or without CAD, did not show significant differences in density of epicardial, paracardiac, and subcutaneous adipose tissue either on unenhanced or contrast-enhanced scans (p >= 0.092). CAD patients may experience different phenomena (inflammation, fibrosis, increase in adipose depots) leading to rises or drops in epicardial adipose tissue density, resulting in variations that are difficult to detect

Relationship between soluble receptor for advanced glycation end products (sRAGE), body composition and fat distribution in healthy women

Purpose: Soluble receptor for advanced glycation end products (sRAGE) is a decoy receptor which sequesters RAGE ligands and acts as a cytoprotective agent. To date, it is unclear whether the lower sRAGE levels observed in obesity are a marker of increased overall adiposity or reflect increases in particular fat depots. Therefore, we evaluated in healthy women the relationship among sRAGE and indicators of adiposity, including abdominal visceral (VAT) and epicardial visceral (EAT) adipose tissues, to explore the potential role of sRAGE as an earlier biomarker of cardiometabolic risk. Methods: Plasma sRAGE levels were quantified by an enzyme-linked immunosorbent assay in 47 healthy women. Total fat mass (FM) and fat-free mass were estimated with bioimpedance analysis. Anthropometric measures and biochemical data were recorded. Subcutaneous adipose tissue, VAT and EAT volumes were measured by magnetic resonance imaging. Results: Obese women had lower sRAGE levels compared to normal-weight women. sRAGE levels were also lower in women with a waist circumference (WC) larger than 80 cm. Correlation analyses indicated an inverse association of sRAGE with body mass index and FM. Concerning adipose tissue distribution, sRAGE inversely correlated with WC, EAT and VAT depots. In a multiple stepwise regression analysis, performed to emphasize the role of fat distribution, EAT volume was the only predictor of sRAGE. Conclusions: Lower sRAGE levels reflect accumulation of visceral fat mainly at the epicardial level and are present in advance of metabolic complications in adult women. sRAGE quantification might be an early marker of cardiometabolic risk

MicroRNA dysregulation in diabetic ischemic heart failure patients

Increased morbidity and mortality associated with ischemic heart failure (HF) in type 2 diabetic patients requires a deeper understanding of the underpinning pathogenetic mechanisms. Given the implication of microRNAs (miRNAs) in HF, we investigated their regulation and potential role. miRNA expression profiles were measured in left ventricle biopsies from 10 diabetic HF (D-HF) and 19 nondiabetic HF (ND-HF) patients affected by non- end stage dilated ischemic cardiomyopathy. The HF groups were compared with each other and with 16 matched nondiabetic, non- HF control subjects. A total of 17 miRNAs were modulated in D-HF and/or ND-HF patients when compared with control subjects. miR-216a, strongly increased in both D-HF and ND-HF patients, negatively correlated with left ventricular ejection fraction. Six miRNAs were differently expressed when comparing D-HF and ND-HF patients: miR-34b, miR-34c, miR-199b, miR- 210, miR-650, and miR-223. Bioinformatic analysis of their modulated targets showed the enrichment of cardiac dysfunctions and HF categories. Moreover, the hypoxia-inducible factor pathway was activated in the noninfarcted, vital myocardium of D-HF compared with ND-HF patients, indicating a dysregulation of the hypoxia response mechanisms. Accordingly, miR-199a, miR-199b, and miR-210 were modulated by hypoxia and high glucose in cardiomyocytes and endothelial cells cultured in vitro. In conclusion, these findings show a dysregulation of miRNAs in HF, shedding light on the specific disease mechanisms differentiating diabetic patients