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Ketone body β-hydroxybutyrate-mediated histone β-hydroxybutyrylation upregulates lipolysis and attenuates metabolic syndrome

Sachin Aryal, Blair Mell, Ishan Manandhar, Beng San Yeoh, Xue Mei, Oluwatosin Mautin Akinola, Wisdom Ahlidja, Bina Joe

2025American Journal of Physiology-Cell Physiology7 citationsDOIOpen Access PDF

Abstract

This is the first study to demonstrate that exogenous β-hydroxybutyrate supplementation attenuates metabolic syndrome (MetS) and identifies histone β-hydroxybutyrylation-mediated chromatin remodeling as one of the mechanisms to upregulate the transcription of the lipid catabolic genes, Hmgcs2, Cyp2d4, Cyp2e1, and Acaa1b. Our work constitutes a strong foundation for the use of 1,3-butanediol as an alternative epigenetic therapeutic for individuals who are physically unable to achieve the MetS lowering benefits of lifestyle modifications such as exercise and intermittent fasting.

Topics & Concepts

LipolysisHistoneEpigeneticsEndocrinologyDownregulation and upregulationInternal medicineMetabolic syndromeBiologyBiochemistryAdipose tissueMedicineGeneObesityDiet and metabolism studiesMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism
Ketone body β-hydroxybutyrate-mediated histone β-hydroxybutyrylation upregulates lipolysis and attenuates metabolic syndrome | Litcius