HCAR2

Hydroxycarboxylic Acid Receptor 2 (HCAR2), also known as GPR109A, is a G-protein coupled receptor (GPCR) expressed in adipocytes, immune cells, and intestinal epithelium. Its ligands include niacin (vitamin B3) and short-chain fatty acids like butyrate. Activation triggers Gi/o signaling, inhibiting adenylate cyclase to reduce cyclic AMP levels, regulating lipid metabolism and anti-inflammatory responses.
HCAR2 is linked to dyslipidemia, obesity, inflammatory bowel disease, and psoriasis. Niacin, a classic agonist, lowers LDL and raises HDL but causes flushing. Novel agonists (e.g., niacin-laropiprant combinations) mitigate this side effect. Its role in gut microbiota-mediated SCFA signaling also makes it a target for microbiota-related inflammatory disorders.