Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes

Abstract

Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes. Am J Physiol Endocrinol Metab 310: E550 -E564, 2016. First published January 26, 2016 doi:10.1152/ajpendo.00384.2015.-Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [14 C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P ϭ 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P Ͻ 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.

Optical and structural properties of biological tissues under diabetes mellitus

“…The aging of organism is accompanied by structural and functional modifications of macromolecules [70]. The changes that occur in the tissues of the organism under the development of diabetes mellitus are investigated both in laboratory animals using experimental models [9][10][11]17, 39, 40, 42, 45-47, [71][72][73][74][75][76][77] and directly in patients in the course of clinical examination [12,35,[78][79][80][81][82][83][84][85][86][87].…”

“…Diabetes mellitus considerably enhances the risk of vascular diseases that finally result in the cerebral stroke [13,19,60,63]. The hyperglycemia accelerates the atherosclerotic processes [13, 61,63], the atherosclerosis and the corresponding loss of elasticity of coronary artery walls cause stenosis and, therefore, reduce the blood supply to the cardiac muscle, which finally leads to angina pectoris, cardiomyopathy, and increased risk of myocardial infarction [12,13,63,64]. These serious complications are due to the glycation of proteins in vascular walls permanently washed by blood in the presence of increased free glucose content in blood [41,129,135,138].…”

“…Since heart is the main organ of the cardiovascular system, through which the process of blood circulation is implemented in the entire organism, it directly experiences the negative effect of the disease with numerous complications [12,13,63,64]. In Ref.…”

“…The insufficient insulin production by the pancreas, or the abnormal reaction of the organism cells to the produced insulin, leads to the excess glucose content in the blood. Long-term increase of the glucose content in blood (above 11 mmol/l (200 mg/dl)) (hyperglycemia) leads to excess glucose content in the interstitial fluid, which violates the metabolism in the organism, causing the development of diabetes mellitus [2,[5][6][7][8][9][10][11][12].…”

“…Since the glucose level in blood is related to its level in the interstitial fluid, the hyperglycemia facilitates the metabolic disbalance and disturbance of the organs functioning [12,[17][18][19]. In this connection, many papers are aimed at determining the concentration of free glucose in blood, interstitial fluid, and other fluids of the body [20][21][22][23][24][25][26][27][28][29][30], revealing the morphological changes in vital organs [10, 12, One third of all patients with diabetes mellitus have complications in the form of skin lesions, the most severe of them being the chronic ulcers that recover very slowly, thus increasing the risk of infection [19,[57][58][59].…”