HCAR3 (GPR109B) is activated by 3-hydroxyoctanoic acid (3HO) (Ahmed et al. 2009) and nicotinic acid (niacin) (Wise et al. 2003). 3HO is an intermediate of fatty acid beta-oxidation. Under conditions of increased beta-oxidation flux, such as during starvation, under a ketogenic diet, or in patients with diabetic ketoacidosis, 3HO plasma concentrations are sufficient to activate the HCAR3 receptor (Costa et al. 1998, Jones et al. 2002, Ahmed et al. 2009).