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

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.-Ren, N

Urinary Biomarkers of Whole Grain Wheat Intake Identified by Non-targeted and Targeted Metabolomics Approaches

“…In addition to the direct radical scavenging activity8384, simple phenolic acids, such as ferulic acid, caffeic acid, gallic acid, and cinnamic acid, possess antidiabetic properties85. Consumption of products rich in phenolic acids correlates with a reduced risk of CVD86. Thus, the health-promoting effects of WG wheat consumption observed in epidemiological studies may be attributed in part to the unique phytochemical contents of ARs, BXs, and phenolic acids in this whole grain.…”

International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B)

“…Despite the high (Ͼ95%) homology between the two receptors, nicotinic acid is in fact very selective for the HCA 2 receptor. Acifran, however, is not very selective for the two receptors, with slightly lower micromolar affinity for the HCA 3 receptor (for example, Mahboubi et al, 2006;Ren et al, 2009). The most extensive structure-activity study with acifran analogs showed that an ethyl rather than a methyl substituent at the chiral center in acifran (see Fig.…”

“…3 H]nicotinic acid radioligand displacement assay, somewhat lower K i values were obtained: for MMF, 0.98 M; for MEF, 1.3 M. A number of "simple" acids were tested by Ren et al (2009) (Fig. 8) can be regarded as derivatives of nicotinamide (Fig.…”

“…3) provided some (5-fold) selectivity for the HCA 3 receptor, whereas all other compounds were slightly selective for the HCA 2 receptor. Ren et al (2009) identified ortho-coumaric acid (Fig. 5) as ϳ20-fold selective for the HCA 3 receptor in a […”

Artificial Sweeteners Stimulate Adipogenesis and Suppress Lipolysis Independently of Sweet Taste Receptors

“…In adipocytes, energy availability is communicated indirectly through insulin concentrations and sympathetic tone (4) but is also sensed directly through G protein-coupled receptors. In adipose tissue, G protein-coupled receptors respond to short chain fatty acids, lactate, ␤-hydroxybutyrate, ␤-hydroxyoctanoate, and succinate to mediate effects on lipolysis (5)(6)(7)(8)(9). A hypothesis explored in this study is whether nutritive signals regulating adipocyte differentiation and metabolism are also mediated in part by sweet taste receptors.…”