From ketogenic metabolism to targeted therapeutics: current advances in β-hydroxybutyrylation.
Level 5 - mechanism / opinion, no new human data
Narrative review of preclinical mechanisms and molecular pathways with no original human trial data.
PubMed 41624834 · doi:10.3389/fimmu.2025.1690224
What was done
This narrative review summarizes research on β-hydroxybutyrylation (Kbhb), a post-translational modification driven by β-hydroxybutyrate. The authors outline inducers (such as the ketogenic diet), modification site prediction methods (KbhbXG, pFunK, SLAM, iBhb-Lys), regulatory enzymes (ENL, SIRT6), histone and non-histone substrates (e.g., Bcl6, P53, STAT1, UvSlt2), and mechanistic involvement in cancer, immune regulation, and cardiovascular/cerebrovascular diseases.
What was found
The abstract describes functional roles and regulatory pathways (such as mTOR and cGAS-STING signaling) mediated by Kbhb across various biological processes. No quantitative findings, sample sizes, or numerical effect sizes are reported in the abstract.
Why it matters
It outlines how ketone body metabolism directly intersects with epigenetic and post-translational regulation, highlighting potential metabolic and molecular targets for cancer and immune therapies.
Limits
The abstract describes a broad narrative synthesis of mechanistic and preclinical research without systematic review methodology, meta-analytic quantification, or clinical trial data in humans.
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- context Beta-hydroxybutyrate directly interacts with histones via beta-hydroxybutyrylation to modify histones and activate anticancer gene programs.