Effects of nicotinic acid on gene expression: potential mechanisms and implications for wanted and unwanted effects of the lipid-lowering drug.

Abstract

Nicotinic acid (NA), or niacin, lowers circulating levels of lipids, including triglycerides, very low-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol. The lipid-lowering effects have been attributed to its effect to inhibit lipolysis in adipocytes and thus lower plasma free fatty acid (FFA) level. However, evidence accumulates that the FFA-lowering effect may account for only a fraction of NA effects on plasma lipids, and other mechanisms may be involved. Recent studies have reported NA effects on gene expression in various tissues in vivo and in cultured cells in vitro. We reviewed articles reporting NA effects on gene expression, identified by searching PubMed, focusing on potential underlying mechanisms and implications for unexplained NA effects. The effects of NA on gene expression may be mediated directly via the NA receptor in the affected cells, indirectly via changes in circulating FFA or hormone levels induced by NA, or by activating the transcription factor FOXO1 in insulin-sensitive tissues. NA effects on gene expression provide new insights into previously unexplained NA effects, such as FFA-independent lipid-lowering effects, FFA rebound, and insulin resistance observed in clinics during NA treatment.