The authors found that when nicotinic acid activates GPR109A expressed on the surface of fat cells it induces a lowering of lipid levels. However nicotinic acid–induced activation of GPR109A expressed on immune cells in the skin prompts the conversion of arachidonic acid to prostaglandins that cause blood vessels near the skin surface to dilate, resulting in the characteristic flushing response. In an accompanying commentary Nicholas Pike writes, "this elegant study…supports the hypothesis that immune cells in the skin are the most likely source of arachidonic acid and prostaglandins." Furthermore, this study should help researchers develop therapeutics that can achieve the same beneficial cholesterol-lowering effects of nicotinic acid, but without the marked flushing response.
TITLE: GPR109A (PUMA-G/HM74A) mediates nicotinic acid–induced flushing
AUTHOR CONTACT:
Stefan Offermanns
University of Heidelberg, Heidelberg, Germany
Phone: +49-6221-548246; Fax: +49-6221-548549; E-mail: stefan.offermanns@urz.uni-heidelberg.de
View the PDF of this article at: https://www.the-jci.org/article.php?id=23626
ACCOMPANYING COMMENTARY:
TITLE: Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid
Nicholas B. Pike
GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom
Phone: 44-01438-764178; Fax: 44-01438-763232; E-mail: Nick.B.Pike@gsk.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=27160
Journal of Clinical Investigation