PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect.

Sorin Tunaru, Jukka Kero, Annette Schaub, Christian Wufka, Andree Blaukat, Klaus Pfeffer, Stefan Offermanns

Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany.

Nature medicine 2003 Mar

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Nicotinic acid (niacin), a vitamin of the B complex, has been used for almost 50 years as a lipid-lowering drug. The pharmacological effect of nicotinic acid requires doses that are much higher than those provided by a normal diet. Its primary action is to decrease lipolysis in adipose tissue by inhibiting hormone-sensitive triglyceride lipase. This anti-lipolytic effect of nicotinic acid involves the inhibition of cyclic adenosine monophosphate (cAMP) accumulation in adipose tissue through a G(i)-protein-mediated inhibition of adenylyl cyclase. A G-protein-coupled receptor for nicotinic acid has been proposed in adipocytes. Here, we show that the orphan G-protein-coupled receptor, 'protein upregulated in macrophages by interferon-gamma' (mouse PUMA-G, human HM74), is highly expressed in adipose tissue and is a nicotinic acid receptor. Binding of nicotinic acid to PUMA-G or HM74 results in a G(i)-mediated decrease in cAMP levels. In mice lacking PUMA-G, the nicotinic acid-induced decrease in free fatty acid (FFA) and triglyceride plasma levels was abrogated, indicating that PUMA-G mediates the anti-lipolytic and lipid-lowering effects of nicotinic acid in vivo. The identification of the nicotinic acid receptor may be useful in the development of new drugs to treat dyslipidemia.

Citation

Sorin Tunaru, Jukka Kero, Annette Schaub, Christian Wufka, Andree Blaukat, Klaus Pfeffer, Stefan Offermanns. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nature medicine. 2003 Mar;9(3):352-5