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

Nat Med. 2003 Mar;9(3):352-5. doi: 10.1038/nm824. Epub 2003 Feb 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Cell Line
  • Cloning, Molecular
  • Fatty Acids, Nonesterified / metabolism
  • GTP-Binding Proteins / metabolism*
  • Genes, Reporter
  • Humans
  • Hypolipidemic Agents / metabolism*
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Niacin / metabolism*
  • Radioligand Assay
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Tissue Distribution
  • Triglycerides / metabolism


  • Fatty Acids, Nonesterified
  • HCAR2 protein, human
  • HCAR3 protein, human
  • Hcar2 protein, mouse
  • Hypolipidemic Agents
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • Triglycerides
  • Niacin
  • GTP-Binding Proteins

Associated data

  • GENBANK/AJ300199