ArticleJournal of molecular cell biology2019
The HDAC3 enzymatic activity regulates skeletal muscle fuel metabolism.
Article in Journal of molecular cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Time trajectories in the transcriptomic response to exercise - a meta-analysis.Nature communications · 2021Pooled it
- Histone deacetylases: Function in tumor development and therapeutic prospects (Review).Oncology letters · 2026Review
- The role and mechanism of histone deacetylase in COPD.Molecular and cellular biochemistry · 2026Review
- Integrative Multi-omics Analysis of the Human Skeletal Muscle Response to Endurance or Resistance Exercise: Findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC).bioRxiv : the preprint server for biology · 2026Article
- Intermittent AP-1 activation in muscles contributes to exercise-induced health benefits.bioRxiv : the preprint server for biology · 2026Article
- HDAC3-driven immunometabolic reprogramming in type 2 diabetes and its complications: from enzymatic deacetylation to non-enzymatic scaffolding.Frontiers in immunology · 2026Review
- Catalytic-independent roles of chromatin modifiers in mammalian development and the implications for treating human disease.Biochemical Society transactions · 2025Review
- Article
- Enzyme-independent functions of HDAC3 in the adult heart.Acta pharmaceutica Sinica. B · 2025Article
- Muscle Rev-erb controls time-dependent adaptations to chronic exercise in mice.Nature communications · 2025Article
- De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder.American journal of human genetics · 2024Article
- HDAC inhibitors as pharmacological treatment for Duchenne muscular dystrophy: a discovery journey from bench to patients.Trends in molecular medicine · 2024Review
- Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use.Nature communications · 2024Article
- Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies.International journal of molecular sciences · 2023Review
- Histone deacetylase functions and therapeutic implications for adult skeletal muscle metabolism.Frontiers in molecular biosciences · 2023Review
- Male histone deacetylase 6 (HDAC6) knockout mice have enhanced ventilatory responses to hypoxic challenge.Frontiers in physiology · 2023Article
- Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases.Frontiers in molecular biosciences · 2023Review
- First Fluorescent Acetylspermidine Deacetylation Assay for HDAC10 Identifies Selective Inhibitors with Cellular Target Engagement.Chembiochem : a European journal of chemical biology · 2022Article
- Post-translational Modifications: The Signals at the Intersection of Exercise, Glucose Uptake, and Insulin Sensitivity.Endocrine reviews · 2022Review
- Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway.Circulation research · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Histone deacetylase 3 (HDAC3) is a major HDAC, whose enzymatic activity is targeted by small molecule inhibitors for treating a variety of conditions. However, its enzymatic activity is largely dispensable for its function in embryonic development and hepatic lipid metabolism. HDAC3 plays a pivotal role in regulating muscle fuel metabolism and contractile function. Here, we address whether these muscular functions of HDAC3 require its enzymatic activity. By mutating the NCoR/SMRT corepressors in a knock-in mouse model named NS-DADm, we ablated the enzymatic activity of HDAC3 without affecting its protein levels. Compared to the control mice, skeletal muscles from NS-DADm mice showed lower force generation, enhanced fatigue resistance, enhanced fatty acid oxidation, reduced glucose uptake during exercise, upregulated expression of metabolic genes involved in branched-chain amino acids catabolism, and reduced muscle mass during aging, without changes in the muscle fiber-type composition or mitochondrial protein content. These muscular phenotypes are similar to those observed in the HDAC3-depleted skeletal muscles, which demonstrates that, unlike that in the liver or embryonic development, the metabolic function of HDAC3 in skeletal muscles requires its enzymatic activity. These results suggest that drugs specifically targeting HDAC3 enzyme activity could be developed and tested to modulate muscle energy metabolism and exercise performance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.