The level of reactive oxygen species production by adipocytes of epicardial adipose tissue is associated with an increase in postprandial glycemia in patients with severe coronary atherosclerosis

Abstract

The mechanisms of oxidative stress in adipocytes of local fat depots in patients with cardiometabolic diseases have been studied insufficiently.Purpose. To study the levels of reactive oxygen species (ROS) production in adipocytes of epicardial (EAT) and subcutaneous adipose tissue (SAT) in patients with stable coronary artery disease (CAD) and severe coronary atherosclerosis who underwent coronary artery bypass grafting; to investigate the potential relationships between the levels of ROS production by EAT and SAT adipocytes and obesity parameters, EAT accumulation, basal and postprandial glycemia, and blood lipid transport function.Material and Methods. The study included 19 patients (12 men and 7 women including 6 patients (31.5%) with type 2 diabetes mellitus) aged 53–72 years with stable CAD and severe coronary atherosclerosis. The material for the study was EAT and SAT adipocytes obtained by the enzymatic method from intraoperative explants. The ROS level in adipocytes was determined using the fluorimetry with 2,3-dihydrodichlorofluorescein diacetate. Anthropometric parameters of obesity and EAT thickness were studied using echocardiography. The blood lipid transport function and the levels of basal and postprandial glucose were assessed.Results. The levels of ROS production by EAT and SAT adipocytes in the overall group of patients did not differ significantly and amounted to 1710 (1608; 2079) and 1876 (1374; 2215) arbitrary units, respectively. The level of ROS production by SAT adipocytes did not correlate with the parameters of obesity, EAT thickness, or biomarker levels. The level of ROS production by EAT adipocytes directly correlated with the level of postprandial glycemia (rs = 0.62, p < 0.05), but did not correlate with measures of general and abdominal obesity, EAT thickness, and dyslipidemia. The level of ROS production by EAT adipocytes in patients with postprandial glycemia ≥ 7.7 mmol/L (n = 9) exceeded the corresponding value in patients with lower level of postprandial glycemia (n = 10): 2079 (1710; 2458) against 1625.5 (1332; 1699) arbitrary units (p = 0.015), respectively.Conclusion. We showed for the first time that the level of ROS production by EAT adipocytes in CAD patients with severe coronary atherosclerosis was directly associated with the level of postprandial glycemia. The highest level of ROS production in EAT adipocytes occurred in these patients when the level of postprandial glycemia exceeds 7.7 mmol/L.

Production of Reactive Oxygen Species by Epicardial Adipocytes Is Associated with an Increase in Postprandial Glycemia, Postprandial Insulin, and a Decrease in Serum Adiponectin in Patients with Severe Coronary Atherosclerosis

“…Our earlier data evidenced the insulin-mediated dysregulation of EAT adipocytes. The relationships between serum insulin levels (both postprandial and basal) and insulin resistance of EAT adipocytes were demonstrated in patients with coronary heart disease [ 28 ]. In the same study, we demonstrated that insulin resistance of the EAT adipocyte in this category of patients was closely associated with the severity of coronary atherosclerosis [ 28 ].…”

“…The relationships between serum insulin levels (both postprandial and basal) and insulin resistance of EAT adipocytes were demonstrated in patients with coronary heart disease [ 28 ]. In the same study, we demonstrated that insulin resistance of the EAT adipocyte in this category of patients was closely associated with the severity of coronary atherosclerosis [ 28 ]. These data support the current view that, in contrast to the physiological role of ROS in insulin signaling, ROS overproduction promotes insulin resistance and impairs glucose uptake in adipocytes [ 36 , 37 ].…”

“…To date, the mechanisms of adipogenic oxidative stress in patients with cardiometabolic diseases have not been fully established; the data on the ability of epicardial adipocytes to produce reactive oxygen species in patients with coronary heart disease are extremely limited [ 20 ]. Recently, in our pilot study, we have demonstrated that the production of ROS by EAT adipocytes in CAD patients with severe coronary atherosclerosis is directly related to the level of postprandial glycemia [ 28 ]. It has been demonstrated that EAT has a greater potential for ROS production compared to subcutaneous adipose tissue, due to a higher expression of the NADPH components gp91phox and p47phox [ 29 ].…”