β-hydroxybutyrate: Much more than a metabolite

The ketone body beta-hydroxybutyrate (beta OHB) is a convenient carrier of energy from adipocytes to peripheral tissues during fasting or exercise. However, beta OHB is more than just a metabolite, having important cellular signaling roles as well. beta OHB is an endogenous inhibitor of histone deacetylases (HDACs) and a ligand for at least two cell surface receptors. In addition, the downstream products of beta OHB metabolism including acetyl-CoA, succinylCoA, and NAD+ (nicotinamide adenine dinucleotide) themselves have signaling activities. These regulatory functions of beta OHB serve to link the outside environment to cellular function and gene expression, and have important implications for the pathogenesis and treatment of metabolic diseases including type 2 diabetes. (C) 2014 Elsevier Ireland Ltd. All rights reserved.