title: Effects of nicotinic acid on gene expression: potential mechanisms and implications for wanted and unwanted effects of the lipid-lowering drug.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We reviewed articles reporting NA effects on gene expression, identified by searching PubMed, focusing on potential underlying mechanisms and implications for unexplained NA effects.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyung Hee University School of Medicine, Seoul 1130-701, Korea.
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
authors.forename: Jang H
authors.initials: JH
authors.lastname: Youn
mesh_terms: D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D006728:Hormones / Q000502:physiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D007333:Insulin Resistance; D008066:Lipolysis / Q000187:drug effects; D009525:Niacin / Q000009:adverse effects* / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism
chemical_list: C085126:FOXO1 protein, human; D005230:Fatty Acids, Nonesterified; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006728:Hormones; D000960:Hypolipidemic Agents; D011978:Receptors, Nicotinic; D009525:Niacin