Hydroxycarboxylic acid receptor 3 (HCA3)

Hydroxycarboxylic acid receptor 3 (HCA3) is a class A G protein-coupled receptor primarily expressed in adipose tissue and immune cells[1][9]. Encoded by the HCAR3 gene in humans, it mediates anti-lipolytic signals, inhibiting the breakdown of fats in adipocytes in response to increased fatty acid oxidation[1][3][5]. HCA3 acts as a receptor for endogenous metabolites such as 3-hydroxyoctanoic acid and kynurenic acid, and as a low-affinity target for the drug niacin (nicotinic acid); pharmacological doses of niacin are required for significant HCA3 activation[1][5]. HCA3, along with related receptors HCA1 and HCA2, is under investigation as a therapeutic target in metabolic disorders (e.g., anti-dyslipidemic therapy), inflammation, and possibly cancer[2][3][6]. Little is currently known about its safety profile in humans due to the absence of selective clinical HCA3-directed drugs[2]. Research continues into the exact roles of HCA3 in disease and therapy[2][7][8].

Other names

Niacin receptor 2GPR109BG-protein coupled receptor 109BNicotinic acid receptor 2NIACR2HM74BG-protein coupled receptor HM74G-protein coupled receptor HM74B

Activation by agonists (e.g., 3-hydroxyoctanoic acid, kynurenic acid, niacin) leads to inhibition of adipocyte lipolysis through Gi/o-mediated anti-lipolytic signaling - Negative feedback on fat cell lipolysis to counteract increases in beta-oxidation