Human G Protein Coupled Receptor 109B (GPR109B) Protein

Background

HCAR3, also known as GPR109B, is a G protein-coupled receptor closely related to HCAR2 and activated by nicotinic acid and specific long-chain fatty acid derivatives. It is primarily expressed in adipose tissue, immune cells, and skin, where it regulates lipid metabolism, inflammation, and immune responses. Similar to HCAR2, HCAR3 activation inhibits cAMP production through Gi/o proteins, leading to the suppression of lipolysis and decreased free fatty acid release. HCAR3 has been linked to lipid and energy homeostasis, particularly in regulating triglyceride levels and promoting energy storage. In immune cells, HCAR3 signaling mediates anti-inflammatory effects, contributing to the resolution of inflammation and tissue repair. While its physiological roles are less characterized compared to HCAR2, HCAR3 is emerging as a potential target for metabolic and inflammatory diseases. HCAR3 expression in the skin has also been associated with niacin-induced flushing, a side effect relevant to lipid-lowering therapies. Its involvement in lipid regulation and immune modulation makes HCAR3 a candidate for therapeutic interventions targeting metabolic and inflammatory disorders.