Adipose Modulation of High-Density Lipoprotein Cholesterol Implications for Obesity, High-Density Lipoprotein Metabolism, and Cardiovascular Disease

High-density lipoprotein-cholesterol (HDL-C) levels inversely correlate with atherosclerotic cardiovascular disease (CVD).1 HDL plays a key role in reverse cholesterol transport by promoting cholesterol efflux from peripheral cells, including cholesterol-laden macrophages, and delivering acquired cholesterol to liver for excretion, a process that is believed to be atheroprotective.2 However, whether low HDL-C is merely a bystander or is causal in CVD remains controversial.3 Genetic factors that influence HDL-C levels are not consistently associated with altered CVD risk, and failure of the cholesterol ester transfer protein inhibitor torcetrapib and, more recently, niacin to reduce cardiovascular events, despite their HDL-raising effects, has raised doubts about the therapeutic potential of raising HDL.4,5 We recently demonstrated that measurement of HDL efflux capacity is a stronger predictor of CVD than plasma HDL-C levels,6 strengthening the argument that measures of HDL functionality may be more useful than HDL-C levels as predictors of risk and better targets of novel therapies. In any case, regulation of HDL metabolism and function and their relationship to atherosclerosis remains incompletely understood.