HDAC11 is a novel regulator of fatty acid oxidative metabolism in skeletal muscle
| العنوان: | HDAC11 is a novel regulator of fatty acid oxidative metabolism in skeletal muscle |
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| المؤلفون: | Miguel A. Peinado, Yaiza Núñez-Álvarez, Alberto M. Pendás, Mar Muñoz, Erica Hurtado, Josefina Casas, Mònica Suelves, Cristina Gutiérrez-Caballero |
| المساهمون: | Ministerio de Ciencia e Innovación (España) |
| المصدر: | FEBS Journal r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname Digital.CSIC. Repositorio Institucional del CSIC |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Muscle Fibers, Skeletal, Skeletal muscle, Oxidative phosphorylation, fatigue resistance, Mitochondrion, AMP-Activated Protein Kinases, Biochemistry, Histone Deacetylases, 03 medical and health sciences, 0302 clinical medicine, Lipid oxidation, acylcarnitines, oxidative metabolism, Carnitine, HDAC11, medicine, Animals, skeletal muscle, Muscle, Skeletal, Molecular Biology, Beta oxidation, fatty acid oxidation, chemistry.chemical_classification, Mice, Knockout, Fatty Acids, Fatty acid, Cell Biology, fiber type, Cell biology, Fatigue resistance, Mitochondria, Mitochondria, Muscle, mitochondria, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, chemistry, Gene Expression Regulation, 030220 oncology & carcinogenesis, Fatty acid oxidation, Basal metabolic rate, Energy Metabolism, Glycolysis, Oxidation-Reduction, Acylcarnitines |
| الوصف: | Skeletal muscle is the largest tissue in mammalian organisms and is a key determinant of basal metabolic rate and whole‐body energy metabolism. Histone deacetylase 11 (HDAC11) is the only member of the class IV subfamily of HDACs, and it is highly expressed in skeletal muscle, but its role in skeletal muscle physiology has never been investigated. Here, we describe for the first time the consequences of HDAC11 genetic deficiency in skeletal muscle, which results in the improvement of muscle function enhancing fatigue resistance and muscle strength. Loss of HDAC11 had no obvious impact on skeletal muscle structure but increased the number of oxidative myofibers by promoting a glycolytic‐to‐oxidative muscle fiber switch. Unexpectedly, HDAC11 was localized in muscle mitochondria and its deficiency enhanced mitochondrial content. In particular, we showed that HDAC11 depletion increased mitochondrial fatty acid β‐oxidation through activating the AMP‐activated protein kinase‐acetyl‐CoA carboxylase pathway and reducing acylcarnitine levels in vivo, thus providing a mechanistic explanation for the improved muscle strength and fatigue resistance. Overall, our data reveal a unique role of HDAC11 in the maintenance of muscle fiber‐type balance and the mitochondrial lipid oxidation. These findings shed light on the mechanisms governing muscle metabolism and may have implications for chronic muscle metabolic disease management. We thank Rosa Mª Ampudia and Dr. Sara Capdevila for excellent technical assistance with mice. We also thank Dr. Pilar Armengol for its technological support with the confocal microscopy. We thank Drs. Dolors Serra and Coral Sanfeliu for kindly providing ACC/pACC and TOM20, and COXIV antibodies, respectively. We thank Drs. Mercè Jardí and Monserrat Batlle for sharing with us the grip strength and treadmill equipments, respectively. Finally, we are also very grateful to Drs. Dolors Serra for her advice and helpful discussions. This work was supported by Ministerio de Economía y Competitividad (BFU2016‐80748 to MS and BFU2017‐89408‐R to AMP) and Ministerio de Ciencia, Innovación y Universidades (RTI2018‐094009‐B‐I00 to MAP), Feder funds, Generalitat de Catalunya (2017 SGR969 and 2017 SGR206), and Junta de Castilla y Leon (CSI239P18). EH was supported in part by BFU2016‐80748, and YNA was supported by Ministerio de Educación, Cultura y Deport (FPU12/05668). |
| تدمد: | 1742-4658 1432-1033 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2fc1ef04ac905c2237b309d0b93b9f9 https://pubmed.ncbi.nlm.nih.gov/32563202 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f2fc1ef04ac905c2237b309d0b93b9f9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17424658 14321033 |
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