The G-protein-coupled receptors Hydroxy-carboxylic acid receptor 1 (HCAR1, GPR81), HCAR2 (GPR109A), and HCAR3 (GPR109B) have significant sequence homology and are encoded by clustered genes. Their endogenous ligands are hydroxy-carboxylic acid metabolites. HCAR1 is activated by lactate (2-hydroxy-propanoic acid). HCAR2 is a receptor for 3-hydroxy-butyric acid. HCAR3 is activated by 3-hydroxy-octanoic acid. HCAR1 and HCAR2 are found in most mammalian species; HCA3 is found only in higher primates. All three receptors are expressed in adipocytes and are coupled to Gi-type G-proteins, mediating antilipolytic effects in fat cells. HCAR2 and HCAR3 are also expressed in a variety of immune cells. HCAR2 is a receptor for the antidyslipidemic drug nicotinic acid (niacin) and related natural and synthetic compounds.