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This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/E549    most recent 91004.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Plaisance, E. P. Articles by Judd, R. L. Search for Related Content PubMed PubMed Citation Articles by Plaisance, E. P. Articles by Judd, R. L.

Niacin stimulates adiponectin secretion through the GPR109A receptor

¹Boshell Diabetes and Metabolic Diseases Research Program, Department of Anatomy, Physiology, and Pharmacology, Auburn University, Auburn, Alabama; ²Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany; and ³Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana

Submitted 15 December 2008 ; accepted in final form 7 January 2009

Niacin (nicotinic acid) has recently been shown to increase serum adiponectin concentrations in men with the metabolic syndrome. However, little is known about the mechanism(s) by which niacin regulates the intracellular trafficking and secretion of adiponectin. Since niacin appears to exert its effects on lipolysis through receptor (GPR109A)-dependent and -independent pathways, the purpose of this investigation was to examine the role of the recently identified GPR109A receptor in adiponectin secretion. Initial in vivo studies in rats demonstrated that niacin (30 mg/kg po) acutely increases serum adiponectin concentrations, whereas it decreases NEFAs. Further in vitro studies demonstrated an increase in adiponectin secretion and a decrease in lipolysis in primary adipocytes following treatment with niacin or β-hydroxybutyrate (an endogenous ligand of the GPR109A receptor), but these effects were blocked when adipocytes were pretreated with pertussis toxin. Niacin had no effect on adiponectin secretion or lipolysis in 3T3-L1 adipocytes, which have limited cell surface expression of the GPR109A receptor. To further substantiate these in vitro findings, wild-type and GPR109A receptor knockout mice were administered a single dose of niacin or placebo, and serum was obtained for the determination of adiponectin and NEFA concentrations. Serum adiponectin concentrations increased and serum NEFAs decreased in the wild-type mice within 10 min following niacin administration. However, niacin administration had no effect on adiponectin and NEFA concentrations in the GPR109A receptor knockout mice. These results demonstrate that the GPR109A receptor plays an important role in the dual regulation of adiponectin secretion and lipolysis.

nicotinic acid; PUMA-G; HM74A; nonesterified fatty acids; lipolysis