Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G).
Phenolic acids are found in abundance throughout the plant kingdom. Consumption of wine or other rich sources of phenolic acids, such as the "Mediterranean diet," has been associated with a lower risk of cardiovascular disease. The underlying mechanism(s), however, has remained unclear. Here, we show that many phenolic acids, including those from the hydroxybenzoic and hydroxycinnamic acid classes, can bind and activate GPR109A (HM74a/PUMA-G), the receptor for the antidyslipidemic agent nicotinic acid. In keeping with this activity, treatment with a number of phenolic acids, including cinnamic acid, reduces lipolysis in cultured human adipocytes and in fat pats isolated from wild-type mice but not from mice deficient of GPR109A. Oral administration of cinnamic acid significantly reduces plasma levels of FFA in the wild type but not in mice deficient of GPR109A. Activation of GPR109A by phenolic acids may thus contribute to a cardiovascular benefit of these plant-derived products.
Ren
Ning
N
Department of Cardiovascular Diseases, Merck Research Laboratories, Rahway, NJ 07065, USA.
Kaplan
Rebecca
R
Hernandez
Melba
M
Cheng
Kang
K
Jin
Lan
L
Taggart
Andrew K P
AK
Zhu
Amber Y
AY
Gan
Xiaodong
X
Wright
Samuel D
SD
Cai
Tian-Quan
TQ
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002934:Cinnamates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
D002934:Cinnamates; C530636:HCAR2 protein, human; C473652:Hcar2 protein, mouse; D062385:Hydroxybenzoates; D010936:Plant Extracts; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; C029010:cinnamic acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C017616:phenolic acid