High-Density Lipoprotein

Abstract

For >30 years it has been known that elevated high-density lipoprotein (HDL) cholesterol is preventative against the development of atherosclerosis.1 Besides its role in cholesterol removal, HDL is also an antioxidant,2,3 it inhibits inflammation4 and thrombosis,5 and also stimulates endothelial nitric oxide6 and prostacyclin7 release. In addition to these cardiovascular protective actions, recent research findings have elucidated the important role of HDL and its constitutive apoprotein components for glucose metabolism. HDL can lower blood glucose levels by mechanisms that include stimulation of insulin secretion from pancreatic β-cells8,9 and activation of the AMPK signaling pathway in skeletal muscle.8,10 These findings have opened up for an important area of investigation, especially given the increasing prevalence of metabolic disorders such as type 2 diabetes mellitus. Article see p 2364 The recent work by Lehti and colleagues11 appearing in this issue of Circulation uses a mouse model of apolipoprotein A-I (ApoA-I; the major protein component of HDL) knockout and overexpression (ApoA-I tg) to examine loss and gain of function effects on fasting plasma cholesterol, lipoprotein profile, glucose homeostasis, body composition, and exercise performance in vivo. From tissue extracts they examine liver and muscle glycogen, muscle AKT phosphorylation, mitochondrial function, and protein expression of mitochondrial ATP …