Effect of niacin on lipoproteins and atherosclerosis

Niacin has been in use for the past 50 years to treat lipid disorders and atherosclerotic cardiovascular disease. We have recently demonstrated that niacin, by selective inhibition of liver diacylglycerol acyltransferae (DGAT)2, a rate-limiting enzyme in triglyceride synthesis, inhibits triglyceride synthesis thereby decreasing the secretion of apolipoprotein (Apo)B-containing very low-density lipoprotein and low-density lipoprotein particles. We have demonstrated that niacin increases ApoAl-high-density lipoprotein (HDL), mainly through the selective inhibition of hepatic uptake and removal of ApoAl-HDL (but not HDL-cholesterol ester). Emerging data from our laboratory provide evidence for the nonlipid-related effects of niacin on vascular oxidative and inflammatory processes involved in atherosclerosis. Although decreased free fatty acid mobilization from adipose tissue via a newly described niacin receptor (HM74A) is reported as a mechanism by which niacin decreases triglycerides, both physiologically and clinically this pathway may only have a minor role in the lipid effects of niacin. Thus, niacin, through its effects on liver DGAT2 and lipid/lipoprotein metabolism, and pleotropically via vascular oxidation-inflammatory processes, decreases atherosclerotic cardiovascular disease.