Niacin stimulates adiponectin secretion through the GPR109A receptor
| Autor: | Youyan Zhang, Stefan Offermanns, Martina Lukasova, Guoqing Cao, Eric P. Plaisance, Robert L. Judd |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Physiology Endocrinology Diabetes and Metabolism Lipolysis Adipokine Biology Fatty Acids Nonesterified Receptors Nicotinic Niacin Receptors G-Protein-Coupled Mice Physiology (medical) Internal medicine 3T3-L1 Cells medicine Adipocytes Cyclic AMP Animals Humans Adiponectin secretion Receptor Cells Cultured Hypolipidemic Agents Mice Knockout Adiponectin 3-Hydroxybutyric Acid digestive oral and skin physiology food and beverages nutritional and metabolic diseases Rats B vitamins Endocrinology Nicotinic agonist Pertussis Toxin |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 296(3) |
| ISSN: | 0193-1849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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