Hydroxy-Carboxylic Acid Receptor Actions in Metabolism

Lactic acid, the ketone body 3-hydroxy-butyric acid, also known as β-hydroxybutyrate, and the β-oxidation intermediate 3-hydroxy-octanoic acid are hydroxy-carboxylic acids (HCAs) that serve as intermediates of energy metabolism. However, they also regulate cellular functions, in part by directly activating the G protein-coupled receptors HCA1/GPR81, HCA2/GPR109A, and HCA3/GPR109B. During the past decade, it has become clear that HCA receptors help to maintain homeostasis under changing metabolic and dietary conditions, by controlling metabolic, immune, and other body functions. Work based on genetic mouse models and synthetic ligands of HCA receptors has, in addition, shown that members of this receptor family can serve as targets for the prevention and therapy of diseases such as metabolic and inflammatory disorders.