Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2

The hydroxycarboxylic acid receptors (HCA(1-3)) are a family of G-protein-coupled receptors that are critical for sensing endogenous intermediates of metabolism. All three receptors are predominantly expressed on adipocytes and mediate anti-lipolytic effects. In addition to adipocytes, HCA(2) is highly expressed on immune cells, including macrophages, monocytes, neutrophils and dermal dendritic cells, among other cell types. The endogenous ligand for HCA(2) is beta-hydroxybutyrate (beta-OHB), a ketone body produced by the liver through beta-oxidation when an individual is in a negative energy balance. Recent studies demonstrate that HCA(2) mediates profound anti-inflammatory effects in a variety of tissues, indicating that HCA(2) may be an important therapeutic target for treating inflammatory disease processes. This review summarizes the roles of HCA(2) on inflammation in a number of tissues and clinical states. (C) 2015 Elsevier Inc. All rights reserved.