Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor.
Level 5 - mechanism / opinion, no new human data
Preclinical laboratory study using cell culture and mouse models with no human data.
PubMed 23223453 · doi:10.1126/science.1227166
What was done
The authors investigated whether the ketone body d-β-hydroxybutyrate (βOHB) acts as an endogenous inhibitor of class I histone deacetylases (HDACs). They evaluated global histone acetylation in mouse tissues following exogenous βOHB administration, fasting, or calorie restriction. In cellular models, they tested promoter-specific histone acetylation (Foxo3a and Mt2) and gene activation following βOHB treatment or selective HDAC1/HDAC2 depletion. Finally, they assessed oxidative stress protection in mice treated with βOHB.
What was found
The abstract reports no numerical values, effect sizes, or p-values. Qualitatively, exogenous βOHB, fasting, and calorie restriction each increased global histone acetylation in mouse tissues. In cell culture, βOHB treatment increased histone acetylation at the Foxo3a and Mt2 promoters, and selective depletion of HDAC1 and HDAC2 activated both genes. βOHB treatment conferred protection against oxidative stress in mice.
Why it matters
This paper identifies an epigenetic mechanism for ketone bodies, linking fasting and calorie restriction to HDAC inhibition and the transcriptional activation of oxidative stress resistance pathways.
Limits
All results are from in vitro cellular assays and mouse models, without human clinical verification. Sample sizes, effect sizes, doses, and specific oxidative stress assays are not reported in the abstract.
Cited by
- supports Ketone bodies function as histone deacetylase (HDAC) inhibitors.