Morphometric and Functional Changes in Epicardial Adipose Tissue Adipocytes in Coronary Atherosclerosis: Relationship...

Aim    To study the relationship between adipocyte size and reactive oxygen species (ROS) production in epicardial/subcutaneous adipose tissue (EAT/SAT) with metabolic and inflammatory markers in patients with ischemic heart disease (IHD) undergoing coronary artery bypass grafting (CABG).Material and methods    The study included 46 patients (32 men, 14 women) aged 45-72 years with IHD and coronary atherosclerosis, who had indications for CABG. Adipocytes from EAT and SAT obtained intraoperatively served as the material. The average size of adipocytes in EAT and SAT and the degree of their hypertrophy were determined; the level of ROS in adipocytes was assessed in 38 patients. The state of blood lipid transport function, glucose/insulin metabolism, the content of adipokines, and inflammatory biomarkers were studied, and surrogate indices of insulin resistance (IR) were calculated.Results    The average size of EAT adipocytes, in contrast to SAT adipocytes, correlated with serum concentrations of tumor necrosis factor-α (TNF-α) (rs=0.43), basal C-peptide (rs=0.40), triglycerides (TG) (rs=0.36), adiponectin (rs=0.34), interleukin-1β (IL-1β) (rs=0.29) and the TyG index (rs=0.32). ROS production by EAT adipocytes correlated with the concentrations of resistin (rs=0.39), TG (rs=0.35), adiponectin (rs=-0.34), and the TyG index (rs=0.35). The following independent determinants of increased ROS production by EAT adipocytes were identified: blood concentrations of TG, TNF-α, and resistin. A threshold TG level of 1.44 mM was determined, which was associated with ROS production by EAT adipocytes above the first tertile. Increased blood TG concentrations ≥1.44 mM were associated with increased EAT adipocyte hypertrophy, ROS production, a more atherogenic dyslipoproteinemic profile, higher IL-1β levels, IR indices, and lower adiponectin concentration.Conclusion    For the first time it was shown that in patients with coronary atherosclerosis, elevated TG levels and the TyG index are independently associated with abnormal morphometry of EAT adipocytes and their dysfunction is manifested by increased ROS production. Combined blood levels of TG, resistin, and TNF-α serve as independent determinants of ROS production by EAT adipocytes. Blood TG concentrations ≥1.44 mM are associated with activation of oxidative stress in EAT adipocytes, exacerbation of IR, adipokine imbalance, and low-grade inflammation. These findings support the need to identify optimal TG concentrations in patients with IHD and coronary atherosclerosis.