Hydroxycarboxylic acid receptor 2 (HCA2 (also known as GPR109A))

Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin or nicotinic acid receptor and previously called GPR109A, is a G protein-coupled receptor highly expressed in adipose tissue and immune cells. It mediates many therapeutic effects of nicotinic acid on lipid metabolism. Upon activation by niacin or related agonists, HCA2 inhibits adenylate cyclase activity through Gi proteins, leading to reduced cAMP levels. This suppresses hormone-sensitive lipase activity and decreases the release of free fatty acids from adipose tissue into circulation. The resulting reduction in circulating free fatty acids limits their availability for hepatic VLDL-triglyceride synthesis—thereby lowering plasma VLDL and LDL cholesterol concentrations while raising HDL cholesterol levels. Additionally, direct inhibition by niacin at the level of hepatocyte DGAT2 further reduces triglyceride production independent from its antilipolytic effect. These mechanisms underlie the clinical use of niacin for dyslipidemia management but are also associated with side effects such as flushing due to prostaglandin-mediated vasodilation[1][2][3][4].

Other names

Niacin receptorG protein-coupled receptor 109A (GPR109A)HM74APUMA-GHydroxycarboxylic acid receptor 2

Activation by nicotinic acid leads to inhibition of adenylate cyclase via Gi proteins, reducing cAMP levels in adipocytes and suppressing the release of free fatty acids from fat stores[2][3][4]. - Reduced free fatty acids decrease hepatic VLDL synthesis and secretion[1][3]. - Direct inhibition by niacin of diacylglycerol O-acyltransferase 2 (DGAT2), a key enzyme for triglyceride synthesis in hepatocytes[2][3].