Hypertrophy and Insulin Resistance of Epicardial Adipose Tissue Adipocytes: Association with the Coronary Artery Disease Severity

Abstract

Changes in the structural and functional characteristics of the epicardial adipose tissue (EAT) are recognized as one of the factors in the development of cardiometabolic diseases. However, the generally accepted quantitative assessment of the accumulation of EAT does not reflect the size of adipocyte and presence of adipocyte hypertrophy in this fat depot. Overall contribution of adipocyte hypertrophy to the development and progression of coronary atherosclerosis remains unexplored. Objective: To compare the morphological characteristics of EAT adipocyte and its sensitivity to insulin with the CAD severity, as well as to identify potential factors involved in the realization of this relationship. The present study involved 24 patients (m/f 16/8) aged 53–72 years with stable CAD, who underwent coronary artery bypass graft surgery. Adipocytes were isolated enzymatically from EAT explants obtained during the operation. The severity of CAD was assessed by calculating the Gensini score according to selective coronary angiography. Insulin resistance of EAT adipocytes was evaluated by reactivity to insulin. In patients with an average size of EAT adipocytes equal to or exceeding the median (87 μm) the percentage of hypertrophic adipocytes was twice as high as in patients in whom the average size of adipocytes was less than 87 μm. This group of patients was also characterized by the higher rate of the Gensini score, lower adiponectin levels, and more severe violation of carbohydrate metabolism. We have revealed direct nonparametric correlation between the size of EAT adipocytes and the Gensini score (rs = 0.56, p = 0.00047). The number of hypertrophic EAT adipocytes showed a direct nonparametric correlation with the Gensini score (rs = 0.6, p = 0.002). Inverse nonparametric correlations were found between the serum adiponectin level and size (rs = −0.60, p = 0.001), hypertrophy of adipocytes (rs = −0.67, p = 0.00), and Gensini score (rs = −0.81, p = 0.00007). An inverse nonparametric correlation was found between the Gensini score and sensitivity of EAT adipocytes to insulin, estimated by the intracellular redox response (rs = −0.90, p = 0.037) and decrease in lipolysis rate upon insulin addition (rs = −0.40, p = 0.05). The intracellular redox response of adipocytes to insulin was directly correlated with fasting insulin and inversely with postprandial insulin. Our data indicate that the size and degree of hypertrophy of the epicardial adipocytes are related to the CAD severity. According to our results, insulin resistance of adipocytes may be considered as one of the factors mediating this relationship.

Association of High Serum Adiponectin Level With Adverse Cardiovascular Outcomes and Progression of Coronary Artery Calcification in Patients With Pre-dialysis Chronic Kidney Disease

“…Meanwhile, impaired kidney function may facilitate the accumulation of epicardial adipose tissue (EAT) ( 25 , 26 ). Although EAT is a source of adiponectin ( 27 ), it also secrets detrimental adipokines, such as leptin, to promote inflammation in adjacent coronary vascular beds, the accumulation of EAT has been associated with CAD severities ( 6 , 27 ). Therefore, based on the current understanding of adiponectin biology, it seems likely that the association of high serum adiponectin level with adverse CV outcomes indicates deteriorating kidney function in the natural course of CKD.…”

Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review

“…Finally, attention should be paid to the current tendency to study the relationship of CAD not only with the thickness and volume of EAT, but also with its structure and size of adipocytes [50,51]. One study has found that the size and degree of hypertrophy of the epicardial adipocytes are related to CAD severity [51].…”

PPARγ—A Factor Linking Metabolically Unhealthy Obesity with Placental Pathologies

“…Enlarged adipocytes have been shown to be the main cause of insulin resistance [ 54 , 55 ]. Small adipocytes counteract the metabolic disorders associated with obesity [ 56 , 57 , 58 ]. Expansion in size exposes adipocytes to mechanical stress due to increased contact with neighboring fat cells thus leading to hypoxia, while their further expansion makes them exceed the limits of oxygen diffusion.…”