Hydroxycarboxylic Acid Receptor Family

Hydroxy-carboxylic acid (HCA) receptor family consists of three members, HCA1, HCA2, and HCA3, also known as GPR81, GPR109A, andGPR109B, respectively, which are encoded by closely related genes located next to each other on human chromosome 12 and mouse chromosome 5. HCA1 is the phylogeneticallyearliest receptor found in fish.

Regulation of Adipocyte Function through HCA Receptors. Fig.1 Regulation of Adipocyte Function through HCA Receptors. (Offermanns, 2017)

The physiological ligands of HCA receptors are key metabolic intermediates whose local and systemic levels reflect specific metabolic states. All three HCA receptors are highly expressed in white and brown adipocytes. It has been shown that the expression of HCA1 and HCA2 increases during differentiation of adipocytes from preadipocytes and after activation of peroxisome proliferator-activated receptor-gamma. Lactic acid activates HCA1 on adipocytes in an autocrine manner. It inhibits lipolysis and thus promotes anabolic effects. Blocking HCA1 can prevent and treat obesity. HCA2 and HCA3 regulate adipocyte lipolysis and immune function under conditions that increase FFA formation by lipolysis. HCA2 agonists that act primarily through immune cell receptors exert antiatherogenic and anti-inflammatory effects. HCA2 is a butyrate receptor and mediates some of the beneficial effects of short-chain fatty acids produced by the intestinal flora. HCA is also important for controlling the metabolism and proliferation of breast cancer cells.

Human HCA Receptor Members

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  1. Offermanns S, et al. (2017). Hydroxy-Carboxylic Acid Receptor Actions in Metabolism. Trends EndocrinolMetab. 28(3): 227-236.

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