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

Abstract

Nicotinic acid (niacin), a vitamin of the B complex, has been used for almost 50 years as a lipid-lowering drug1,2. The pharmacological effect of nicotinic acid requires doses that are much higher than those provided by a normal diet3,4. Its primary action is to decrease lipolysis in adipose tissue by inhibiting hormone-sensitive triglyceride lipase5. This anti-lipolytic effect of nicotinic acid involves the inhibition of cyclic adenosine monophosphate (cAMP) accumulation in adipose tissue6 through a Gi-protein-mediated inhibition of adenylyl cyclase7,8,9. A G-protein-coupled receptor for nicotinic acid has been proposed in adipocytes10,11. Here, we show that the orphan G-protein-coupled receptor, 'protein upregulated in macrophages by interferon-γ' (mouse PUMA-G, human HM74)12,13, is highly expressed in adipose tissue and is a nicotinic acid receptor. Binding of nicotinic acid to PUMA-G or HM74 results in a Gi-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.

NOTE: In the version of this article initially published online, the statements concerning equal author contribution and corresponding authors were incorrect. This mistake has been corrected for the HTML and print versions of the article.

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Figure 1: PUMA-G and HM74 expression in adipose tissue.
Figure 2: PUMA-G and HM74 are Gi-coupled receptors for nicotinic acid and related compounds.
Figure 3: Generation and analysis of PUMA-G-deficient mice.

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Change history

  • 10 February 2003

    This was incorrect in AOP version but corrected in print. Changed Klaus Pfeffer to be a corresponding author as per note.

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Acknowledgements

The authors wish to thank A. Fütterer, J. Meinecke, K. Meyer, K. Mink, E. Schaller and B. Wallenwein for technical assistance and G. Scholze and W. Fiehn for help with triglyceride determinations. J.K. received a fellowship from the Serono Foundation. This work was supported by the Deutsche Forschungsgemeinschaft.

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Correspondence to Klaus Pfeffer or Stefan Offermanns.

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Tunaru, S., Kero, J., Schaub, A. et al. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med 9, 352–355 (2003). https://doi.org/10.1038/nm824

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