Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2

• Published in: Metabolism, clinical and experimental Vol. 65; no. 2; pp. 102 - 113
• Main Authors: Graff, Emily C, Fang, Han, Wanders, Desiree, Judd, Robert L
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2016
• Subjects: Animals; Atherosclerosis - prevention & control; Beta-Hydroxybutyrate; Colitis - prevention & control; Diabetic Retinopathy - prevention & control; Endocrinology & Metabolism; GPR109a; HCA2; Humans; Inflammation; Inflammation - prevention & control; Mice; Neoplasms - prevention & control; Neurodegenerative Diseases - prevention & control; Niacin; Niacin - therapeutic use; Obesity - prevention & control; Receptors, G-Protein-Coupled - analysis; Receptors, G-Protein-Coupled - physiology; Receptors, Nicotinic - analysis; Receptors, Nicotinic - physiology; high-density lipoprotein; GPR; hormone sensitive lipase; TNF; very late antigen; NF-κB; G-protein coupled receptor; NEFA; iNOS; nuclear factor kappa-light-chain-enhancer of activated B cells; Toll-like receptor; HSL; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; IL; HCA; MMF; PKA; cyclooxygenase; non-esterified fatty acid; ATP-binding cassette sub-family G member 1; SCFA; Niacin; HCA 2; IκBα; EC 50; beta-hydroxybutyrate; fumaric acid esters; monocyte chemoattractant protein one; lipopolysaccharide; Prostaglandin D 2; ABCG1; monomethyl fumarate; vascular cell adhesion molecule one; short-chain fatty acid; T2DM; MCP-1; β-OHB; transforming growth factor β; PGE 2; GPR109a; VLA; cAMP; LPS; inducible nitric oxide synthase; silencing ribonucleic acid; G i; HDL; G-inhibitory; LDL; type 2 diabetes mellitus; NLRP3; TLR; interleukin; protein kinase A; half maximal effective concentration; ICAM; NOD-like receptor family, pyrin domain containing 3; siRNA; Inflammation; FAE; hydroxycarboxylic acid; COX; low-density lipoprotein; VCAM-1; cyclic adenosine monophosphate; tumor necrosis factor; PGD 2; TGFβ; intracellular adhesion molecule; Prostaglandin E 2; PGD2; Beta-Hydroxybutyrate; Gi; EC50; PGE2; HCA2
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2015.10.001

Abstract The hydroxycarboxylic acid receptors (HCA1–3 ) 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, HCA2 is highly expressed on immune cells, including macrophages, monocytes, neutrophils and dermal dendritic cells, among other cell types. The endogenous ligand for HCA2 is beta-hydroxybutyrate (β-OHB), a ketone body produced by the liver through β-oxidation when an individual is in a negative energy balance. Recent studies demonstrate that HCA2 mediates profound anti-inflammatory effects in a variety of tissues, indicating that HCA2 may be an important therapeutic target for treating inflammatory disease processes. This review summarizes the roles of HCA2 on inflammation in a number of tissues and clinical states.