Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor

TLDR

During prolonged fasting, fatty‑acid oxidation raises β‑hydroxybutyrate levels, which inhibit class I histone deacetylases and thereby alter histone acetylation and transcriptional activity. High β‑hydroxybutyrate levels upregulate genes involved in oxidative‑stress responses, and pre‑treatment with β‑hydroxybutyrate protects mice from paraquat‑induced oxidative toxicity. Citation: Shimazu et al.

Abstract

Stress Protector During prolonged fasting, the oxidation of fatty acids leads to increased accumulation of d -β-hydroxybutyrate (βOHB) in the bloodstream. Such increased concentrations of βOHB inhibit class I histone deacetylases. Histone acetylation in turn influences transcriptional activity at various genes. Shimazu et al. (p. 211 , published online 6 December; see the Perspective by Sassone-Corsi ) found that among the genes showing increased transcription in animals treated with high concentrations of βOHB were two genes implicated in cellular responses to oxidative stress. When treated ahead of time with βOHB, mice were protected from the toxic effects of the oxidative stress causing poison paraquat.