ArticleMolecular metabolism2020
Histone deacetylase 5 regulates interleukin 6 secretion and insulin action in skeletal muscle.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses.Frontiers in endocrinology · 2024Pooled it
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Mechanomedicine for Addressing Skeletal Muscle Insulin Resistance.Endocrine reviews · 2025Review
- In vitro muscle contraction: A technical review on electrical pulse stimulation in C2C12 cells.Experimental physiology · 2025Article
- Article
- Skeletal Muscle as Endocrine Organ.Advances in experimental medicine and biology · 2025Review
- Regulatory mechanism of ABCB1 transcriptional repression by HDAC5 in rat hepatocytes under hypoxic environment.Frontiers in physiology · 2025Article
- HDAC inhibitors as pharmacological treatment for Duchenne muscular dystrophy: a discovery journey from bench to patients.Trends in molecular medicine · 2024Review
- Natural Drugs: A New Direction for the Prevention and Treatment of Diabetes.Molecules (Basel, Switzerland) · 2023Review
- Article
- Article
- Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies.International journal of molecular sciences · 2023Review
- The epigenetic regulatory effect of histone acetylation and deacetylation on skeletal muscle metabolism-a review.Frontiers in physiology · 2023Review
- HDAC5 inactivates CYR61-regulated CD31/mTOR axis to prevent the occurrence of preeclampsia.Cell and tissue research · 2022Article
- Impact of Exercise and Aging on Mitochondrial Homeostasis in Skeletal Muscle: Roles of ROS and Epigenetics.Cells · 2022Review
- Histone Deacetylases as Modulators of the Crosstalk Between Skeletal Muscle and Other Organs.Frontiers in physiology · 2022Review
- The role of exercise-induced myokines in promoting angiogenesis.Frontiers in physiology · 2022Review
- Epigenetic regulation of energy metabolism in obesity.Journal of molecular cell biology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePhysical exercise training is associated with increased glucose uptake in skeletal muscle and improved glycemic control. HDAC5, a class IIa histone deacetylase, has been shown to regulate transcription of the insulin-responsive glucose transporter GLUT4 in cultured muscle cells. In this study, we analyzed the contribution of HDAC5 to the transcriptional network in muscle and the beneficial effect of muscle contraction and regular exercise on glucose metabolism.
methodsHDAC5 knockout mice (KO) and wild-type (WT) littermates were trained for 8 weeks on treadmills, metabolically phenotyped, and compared to sedentary controls. Hdac5-deficient skeletal muscle and cultured Hdac5-knockdown (KD) C2C12 myotubes were utilized for studies of gene expression and glucose metabolism. Chromatin immunoprecipitation (ChIP) studies were conducted to analyze Il6 promoter activity using H3K9ac and HDAC5 antibodies.
resultsGlobal transcriptome analysis of Hdac5 KO gastrocnemius muscle demonstrated activation of the IL-6 signaling pathway. Accordingly, knockdown of Hdac5 in C2C12 myotubes led to higher expression and secretion of IL-6 with enhanced insulin-stimulated activation of AKT that was reversed by Il6 knockdown. Moreover, Hdac5-deficient myotubes exhibited enhanced glucose uptake, glycogen synthesis, and elevated expression levels of the glucose transporter GLUT4. Transcription of Il6 was further enhanced by electrical pulse stimulation in Hdac5-deficient C2C12 myotubes. ChIP identified a ∼1 kb fragment of the Il6 promoter that interacts with HDAC5 and demonstrated increased activation-associated histone marker AcH3K9 in Hdac5-deficient muscle cells. Exercise intervention of HDAC5 KO mice resulted in improved systemic glucose tolerance as compared to WT controls.
conclusionsWe identified HDAC5 as a negative epigenetic regulator of IL-6 synthesis and release in skeletal muscle. HDAC5 may exert beneficial effects through two different mechanisms, transcriptional control of genes required for glucose disposal and utilization, and HDAC5-dependent IL-6 signaling cross-talk to improve glucose uptake in muscle in response to exercise.
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