Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G)

Ning Ren,Rebecca Kaplan,Melba Hernandez,Kang Cheng,Lan Jin,Andrew K.P Taggart,Amber Y Zhu,Xiaodong Gan,Samuel D Wright,Tian-Quan Cai

doi:10.1194/jlr.m800625-jlr200

Abstract

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.

Highlights

Phenolic acids are found in abundance throughout the plant kingdom
We observed an EC50 of 1127 6 59 nM for human GPR109A and 7037 6 598 nM for GPR109B. Based on their commercial availability and potential existence in the plant products, we assembled a set of phenolic acids from the hydroxybenzoic and hydroxycinnamic acid classes and studied them in the same assay
Our data clearly show that many of the phenolic acids could act as ligands of the nicotinic acid receptor GPR109A, and activation of GPR109A by the phenolic compounds leads to a reduction of adipocyte lipolysis

Summary

Introduction

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. 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. Activation of GPR109A by phenolic acids may contribute to a cardiovascular benefit of these plant-derived products.— Ren, N., R. Cai. Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G).

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Results

Conclusion