Ketone bodies as signaling metabolites

Trends Endocrinol Metab. 2014 Jan;25(1):42-52. doi: 10.1016/j.tem.2013.09.002. Epub 2013 Oct 18.


Traditionally, the ketone body β-hydroxybutyrate (βOHB) has been looked upon as a carrier of energy from liver to peripheral tissues during fasting or exercise. However, βOHB also signals via extracellular receptors and acts as an endogenous inhibitor of histone deacetylases (HDACs). These recent findings support a model in which βOHB functions to link the environment, in this case the diet, and gene expression via chromatin modifications. We review the regulation and functions of ketone bodies, the relationship between ketone bodies and calorie restriction, and the implications of HDAC inhibition by the ketone body βOHB in the modulation of metabolism and in diseases of aging.

Keywords: HDAC; acetylation; calorie restriction; epigenetics; longevity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3-Hydroxybutyric Acid / metabolism*
  • Aging / physiology*
  • Animals
  • Caloric Restriction
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / metabolism
  • Humans
  • Ketone Bodies / metabolism*
  • Monocarboxylic Acid Transporters / metabolism
  • Signal Transduction / physiology*


  • Histone Deacetylase Inhibitors
  • Ketone Bodies
  • Monocarboxylic Acid Transporters
  • Histone Deacetylases
  • 3-Hydroxybutyric Acid