Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis

Abstract

Obesity is the most common nutritional disorder worldwide and is associated with dyslipidemia and atherosclerotic cardiovascular disease. The hallmark of dyslipidemia in obesity is low high density lipoprotein (HDL) cholesterol (HDL-C) levels. Moreover, the quality of HDL is also changed in the obese setting. However, there are still some disputes on the explanations for this phenomenon. There is increasing evidence that adipose tissue, as an energy storage tissue, participates in several metabolism activities, such as hormone secretion and cholesterol efflux. It can influence overall reverse cholesterol transport and plasma HDL-C level. In obesity individuals, the changes in morphology and function of adipose tissue affect plasma HDL-C levels and HDL function, thus, adipose tissue should be the main target for the treatment of HDL metabolism in obesity. In this review, we will summarize the cross-talk between adipocytes and HDL related to cardiovascular disease and focus on the new insights of the potential mechanism underlying obesity and HDL dysfunction.

Keywords: Adipocyte; Cardiovascular disease; Cholesterol; HDL; Obesity.

Fig. 1

Under normal condition, adipocytes regulate HDL-C levels and HDL function in three ways. ①Intracellular cholesterol can efflux to HDL through ABCA1 and SR-BI receptors on the surface of cell membrane to increase HDL-C levels. ② The free fatty acids released by intracellular triglyceride hydrolysis are used for hepatic production of VLDL, which in turn may reduce HDL-C levels by increasing the transfer of triglycerides to HDL. ③ Brown adipocytes mediate HDL-cholesterol clearance and increase macrophage-to-faeces reverse cholesterol transport through intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL by SR-BI. Chronic inflammation, which is the hallmark of obesity, can impair the cholesterol efflux ability of adipocytes, thereby decrease HDL-C levels in plasma. In addition, enhanced lipolysis of adipocytes under the state of obesity releases more free fatty acids into the blood, leading to hypertriglyceridemia and reduced HDL-C levels. FFAs could also induce insulin resistance and alter CETP activity, which have roles in HDL metabolism. The reverse cholesterol transport capacity of HDL might be impaired because of BAT whitening in obesity