Pericardial Adipose Tissue, Atherosclerosis, and Cardiovascular Disease Risk Factors: The Jackson Heart Study Comment on Liu et al.

We read the article by Liu et al. (1) with great interest. The investigators carefully stated that because it is difficult to distinguish pericardial from epicardial fat with computed tomography (CT), they measured pericardial adipose tissue by the combination of pericardial fat and epicardial fat. While they recognized this important misclassification, we also noted that they not only technically but conceptually discussed pericardial and epicardial fat as identical to adipose tissue. This appears to be incorrect and misleading. Epicardial and pericardial adipose tissue are clearly different anatomically, embriologically, physiologically, biomolecularly, and clinically (2,3). Epicardial adipose tissue is the fat located between

Factors associated with body weight gain and insulin-resistance: a longitudinal study

Background: Obesity is the result of energy intake (EI) chronically exceeding energy expenditure. However, the potential metabolic factors, including insulin resistance, remain unclear. This study longitudinally investigated factors associated with changes in body weight. Subjects: A cohort of 707 adults without diabetes were investigated at the 4-year follow-up visit. The habitual intake of energy and macronutrients during the past 12 months was assessed using a validated Food Frequency Questionnaire for the local population. Homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR) was used as a surrogate measure of insulin resistance. Additionally, PNPLA3 was genotyped. Results: Eighty-seven participants were weight gainers (G; cutoff value = 5 kg), and 620 were non-gainers (NG). Initial anthropometric (G vs. NG: age, 44 ± 13 vs 51 ± 13 years, P < 0.001; body mass index, 27.8 ± 6.5 vs 28.1 ± 5.1 kg/m2, P = ns; body weight, 76.7 ± 22.1 vs 74.2 ± 14.7 kg, P = ns; final body weight, 86.3 ± 23.7 vs 72.9 ± 14.2 kg, P < 0.001) and diet characteristics, as well as insulin concentrations and HOMA-IR values, were similar in both groups. Four years later, G showed significantly increased EI, insulin concentrations, and HOMA-IR values. G had a higher prevalence of the PNPLA3 CG and GG alleles than NG (P < 0.05). The presence of G was independently associated with age (OR = 1.031), EI change (OR = 2.257), and unfavorable alleles of PNPLA3 gene (OR = 1.700). Final body mass index, waist circumference, and EI were independently associated with final HOMA-IR (P < 0.001). Conclusions: EI is associated with body weight gain, and genetic factors may influence the energy balance. Insulin resistance is a consequence of weight gain, suggesting a possible intracellular protective mechanism against substrate overflow. Clinical trial registration: ISRCTN15840340

COVID‐19 Rise in Younger Adults with Obesity: Visceral Adiposity Can Predict the Risk

A concerning rise in coronavirus disease 2019 (COVID‐19) cases has been recently reported, particularly in the USA. The causes of this increase are likely multifactorial and the object of an ongoing health and socio‐economic debate. However, preliminary data indicate that the new COVID‐19 cases are increasing among younger and obese adults. Considering this recent spike, the timing of the paper by Deng et al is of particular importance (1). Deng et al not only confirmed that obesity is a major and independent risk factor for COVID‐19 complications in young adults (2), they pointed out ectopic and visceral fat depots as new markers of that risk. The authors found that computed tomography (CT) imaging of fatty liver and epicardial adipose tissue (EAT) were significantly higher in severely and critically ill COVID‐19 patients under 40 years old as compared to those with milder disease

Targeting Epicardial Fat in Obesity and Diabetes Pharmacotherapy

Epicardial adipose tissue surrounds and infiltrates the heart. Epicardial fat displays unique anatomic, genetic, and biomolecular properties. People with obesity and in particular, those with abdominal obesity and associated type 2 diabetes mellitus, have an increased amount of epicardial adipose tissue (EAT). Epicardial fat works well as therapeutic target due to its fast-responding metabolism, organ fat specificity, and easy measurability. Epicardial fat responds to thiazolidinediones (TZD), glucagon-like peptide 1-receptor agonists (GLP1A), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), and statins. Modulating epicardial fat morphology and genetic profile with targeted pharmacological agents suggests novel strategies in the pharmacotherapy of diabetes and obesity

Response to Cardiotrophin-1 in Adolescents: Impact of Obesity and Blood Pressure

n/

The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

“Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P=0.006 and P=0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose

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

GLP‐1 Receptor Is Associated with Genes Involved in Fatty Acids Oxidation and White‐to‐Brown Fat Differentiation in Epicardial Adipose Tissue (EAT)

Epicardial adipose tissue (EAT) is an important risk factor for cardiovascular diseases (CVD). Recent clinical evidence suggested that the potential beneficial effects of glucagon‐like peptide 1 (GLP‐1) analogs on CVD may deal with the reduction of EAT amount, possibly by targeting EAT GLP‐1 receptor (GLP‐1R), as recently discovered. Nevertheless, the role of EAT GLP‐1R and its interplay with EAT genes involved in adipogenesis and fatty acids metabolism are presently unknown. EAT was collected from 17 patients with coronary artery disease (CAD) undergoing elective coronary artery bypass graft for microarray analysis of GLP‐1R and genes involved in fatty acid metabolism and adipogenesis. GLP‐1 plasma levels were measured by enzyme‐linked immunosorbent assay. EAT thickness was measured by echocardiography. The study has been performed in accordance with the Principles of Declaration of Helsinki. EAT GLP‐1R was directly correlated with genes promoting beta‐oxidation and white‐to‐brown adipocyte differentiation, and inversely with pro‐adipogenic genes. Circulating GLP‐1 levels were higher in CAD than healthy subjects and in patients with greater ultrasound‐measured EAT thickness. GLP‐1 and its analogs may target EAT GLP‐1R and therefore reduce local adipogenesis, improve fat utilization and induce brown fat differentiation. The increase in circulating GLP‐1 levels may be a compensatory mechanism to improve metabolic dysfunctions. As EAT lies in direct contiguity to the myocardium and coronary arteries, the beneficial effects of GLP‐1 activation may extent to the heart. Support or Funding Information The study was supported by funding from Fondazione E. A. Fiera Internazionale di Milano to Università degli Studi di Milano and Ricerca Corrente funding from Italian Ministry of Health to IRCCS Policlinico San Donato. This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal