Metabolism Meets Epigenetics: β-Hydroxybutyrate-Driven Lysine β-Hydroxybutyrylation Bridging Energy Metabolism With Transcription and Protein Functional Remodeling

This review covers beta-hydroxybutyrate (BHB) and lysine beta-hydroxybutyrylation (Kbhb), a modification that links ketone metabolism to gene regulation. It describes how BHB production is raised by medium-chain fatty acids, fasting, ketogenic diets, moderate exercise and exogenous ketone supplements, and how Kbhb affects chromatin accessibility, gene transcription and cellular metabolism on both histone and non-histone proteins. It notes that HDACs and sirtuins act as erasers and p300/CBP act as writers of Kbhb, and that the precise regulatory mechanisms remain incompletely understood.