DOI: 10.1126/science.1227166 ISSN:

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

Tadahiro Shimazu, Matthew D. Hirschey, John Newman, Wenjuan He, Kotaro Shirakawa, Natacha Le Moan, Carrie A. Grueter, Hyungwook Lim, Laura R. Saunders, Robert D. Stevens, Christopher B. Newgard, Robert V. Farese, Rafael de Cabo, Scott Ulrich, Katerina Akassoglou, Eric Verdin
  • Multidisciplinary

Stress Protector

During prolonged fasting, the oxidation of fatty acids leads to increased accumulation of

-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.

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