Apolipoprotein CIII

Apolipoprotein CIII (apoCIII) was first identified more than 40 years ago as a component of very-low-density lipoprotein (VLDL)1 and shortly thereafter as an inhibitor of lipoprotein lipase.2 More than a decade later, apoCIII was found to inhibit lipoprotein remnant uptake by the liver.3 Its relevance to human lipid metabolism was made clear by its absence, along with apolipoprotein AI, in 2 sisters with essentially no plasma high-density lipoprotein and very low triglyceride levels.4 These individuals had marked increases in the fractional removal of TG from VLDL (increased lipoprotein lipase activity) and increased conversion of VLDL to low-density lipoprotein (LDL) (less remnant removal).5 These findings spurred investigations at a molecular level, including demonstrations of hypertriglyceridemia in apoCIII transgenic mice6 and decreased TG levels in apoCIII knockout mice.7 In humans, apoCIII levels are associated with hypertriglyceridemia and increases in VLDL and inversely related to the size of LDL particles.8,9 ApoCIII was the first lipid-associated gene to be linked by a common polymorphism to hypertriglyceridemia.10See accompanying article on page 513Studies of the regulation of apoCIII gene expression have identified responsiveness to insulin,11,12 peroxisome proliferator-activated receptor-α (PPAR-α),13 farnesoid X receptor,14 and Rev-erbα.15 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Caron et al16 demonstrate responsiveness of the apoCIII promoter to glucose. In a series of well-designed and well-conducted studies, these investigators provide …