Niacin (Vitamin B3, Nicotinic Acid) Decreases Apolipoprotein B (ApoB) and VLDL Secretion from Mouse Hepatocytes

Abstract

Niacin reduces plasma atherogenic apolipoprotein B (apoB)‐containing lipoproteins. To further understand if part of the mechanism of the VLDL‐lowering effect is on secretion of apoB‐containing lipoproteins, we isolated primary hepatocytes from Apobec1−/ − mice, which, like human liver, express apoB100 only. Niacin was well tolerated by hepatocytes showing no hepatotoxicity up to 100 mM. Metabolic labeling and pulse‐chase studies showed that niacin increased intracellular apoB100 degradation by 30%, decreased VLDL secretion from hepatocytes by 40%. These effects were found depend on medium supplementation of nicotinamide, the amide of niacin, which supplies sufficient NAD biosynthesis. The nicotinamide supplementation resulted in a dose‐dependent increase of apoB100 secretion and recovery, suggesting that adequate cellular NAD level is important for maximum VLDL secretion and a critical condition for niacin‐induced apoB100 degradation. Intraperitoneal niacin administration to Apobec1−/− mice caused a 40% decrease in the hepatic VLDL‐triglyceride production rate in vivo. Taken together, these data suggest that niacin decreases apoB100 and VLDL secretion from hepatocytes. The molecular mechanism responsible for these effects of niacin on the assembly and secretion steps of apoB100‐containing lipoprotein is under further investigation. Supported by grants from the NIH (HL58541) and Merck & Co., Inc.