Exploring the role of histone deacetylases and histone deacetylase inhibitors in obesity and emerging evidence from Anorexia Nervosa.

Authors

Emanuela Micioni Di Bonaventura, Luca Botticelli, Mariangela Pucci, Giacomo Einaudi, Elena Conte, Maurizio Crestani, Annamaria De Luca, Francesco Alessandro Palermo, Carlo Cifani, Maria Vittoria Micioni Di Bonaventura

Published in

Pharmacological research. Pages 109694. Oct 16, 2026. Epub Oct 16, 2026.

Abstract

Histone deacetylases (HDACs) are key epigenetic regulators that modulate chromatin accessibility and transcriptional programs controlling metabolism, energy balance, and reward-related behaviors. Aberrant HDACs activity contributes to metabolic dysfunction by altering adipogenesis, thermogenic capacity, lipid profile, and hypothalamic circuits governing appetite. In obesity, specific HDAC isoforms promote adipocyte hypertrophy, impair browning of white adipose tissue, disrupt mitochondrial function, and exacerbate inflammation and insulin resistance. HDAC inhibitors (HDACi) counteract these effects by enhancing oxidative metabolism, stimulating thermogenesis, reducing adipocyte size, and improving systemic glucose and lipid homeostasis in preclinical models. Beyond peripheral metabolism, HDACi can also modulate neural pathways implicated in food intake, highlighting their potential influence in eating disorders, an area of research currently largely limited to anorexia nervosa. Research on HDACs, HDACi, and eating disorders is relatively recent; therefore, the characterization of potential molecular alterations and the identification of specific HDAC targets remain areas of ongoing development. Collectively, current evidence suggests that selective targeting of HDACs may offer a promising therapeutic strategy to correct epigenetic dysfunctions underlying both obesity and maladaptive feeding behaviors; however, translating these findings into clinical practice will require overcoming key challenges, including achieving isoform-specific selectivity, minimizing central nervous system-related side effects, and establishing efficacy and safety in human studies.

PMID:
42887616
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.

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