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Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism
The mitogen-induced D-type cyclins (D1, D2 and D3) are regulatory subunits of the cyclin-dependent kinases CDK4 and CDK6 that drive progression through the G1 phase of the cell cycle. In skeletal muscle, cyclin D3 plays a unique function in controlling the proliferation/differentiation balance of my...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109157/ https://www.ncbi.nlm.nih.gov/pubmed/30143714 http://dx.doi.org/10.1038/s41598-018-31090-5 |
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author | Giannattasio, Silvia Giacovazzo, Giacomo Bonato, Agnese Caruso, Carla Luvisetto, Siro Coccurello, Roberto Caruso, Maurizia |
author_facet | Giannattasio, Silvia Giacovazzo, Giacomo Bonato, Agnese Caruso, Carla Luvisetto, Siro Coccurello, Roberto Caruso, Maurizia |
author_sort | Giannattasio, Silvia |
collection | PubMed |
description | The mitogen-induced D-type cyclins (D1, D2 and D3) are regulatory subunits of the cyclin-dependent kinases CDK4 and CDK6 that drive progression through the G1 phase of the cell cycle. In skeletal muscle, cyclin D3 plays a unique function in controlling the proliferation/differentiation balance of myogenic progenitor cells. Here, we show that cyclin D3 also performs a novel function, regulating muscle fiber type-specific gene expression. Mice lacking cyclin D3 display an increased number of myofibers with higher oxidative capacity in fast-twitch muscle groups, primarily composed of myofibers that utilize glycolytic metabolism. The remodeling of myofibers toward a slower, more oxidative phenotype is accompanied by enhanced running endurance and increased energy expenditure and fatty acid oxidation. In addition, gene expression profiling of cyclin D3−/− muscle reveals the upregulation of genes encoding proteins involved in the regulation of contractile function and metabolic markers specifically expressed in slow-twitch and fast-oxidative myofibers, many of which are targets of MEF2 and/or NFAT transcription factors. Furthermore, cyclin D3 can repress the calcineurin- or MEF2-dependent activation of a slow fiber-specific promoter in cultured muscle cells. These data suggest that cyclin D3 regulates muscle fiber type phenotype, and consequently whole body metabolism, by antagonizing the activity of MEF2 and/or NFAT. |
format | Online Article Text |
id | pubmed-6109157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61091572018-08-31 Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism Giannattasio, Silvia Giacovazzo, Giacomo Bonato, Agnese Caruso, Carla Luvisetto, Siro Coccurello, Roberto Caruso, Maurizia Sci Rep Article The mitogen-induced D-type cyclins (D1, D2 and D3) are regulatory subunits of the cyclin-dependent kinases CDK4 and CDK6 that drive progression through the G1 phase of the cell cycle. In skeletal muscle, cyclin D3 plays a unique function in controlling the proliferation/differentiation balance of myogenic progenitor cells. Here, we show that cyclin D3 also performs a novel function, regulating muscle fiber type-specific gene expression. Mice lacking cyclin D3 display an increased number of myofibers with higher oxidative capacity in fast-twitch muscle groups, primarily composed of myofibers that utilize glycolytic metabolism. The remodeling of myofibers toward a slower, more oxidative phenotype is accompanied by enhanced running endurance and increased energy expenditure and fatty acid oxidation. In addition, gene expression profiling of cyclin D3−/− muscle reveals the upregulation of genes encoding proteins involved in the regulation of contractile function and metabolic markers specifically expressed in slow-twitch and fast-oxidative myofibers, many of which are targets of MEF2 and/or NFAT transcription factors. Furthermore, cyclin D3 can repress the calcineurin- or MEF2-dependent activation of a slow fiber-specific promoter in cultured muscle cells. These data suggest that cyclin D3 regulates muscle fiber type phenotype, and consequently whole body metabolism, by antagonizing the activity of MEF2 and/or NFAT. Nature Publishing Group UK 2018-08-24 /pmc/articles/PMC6109157/ /pubmed/30143714 http://dx.doi.org/10.1038/s41598-018-31090-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Giannattasio, Silvia Giacovazzo, Giacomo Bonato, Agnese Caruso, Carla Luvisetto, Siro Coccurello, Roberto Caruso, Maurizia Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism |
title | Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism |
title_full | Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism |
title_fullStr | Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism |
title_full_unstemmed | Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism |
title_short | Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism |
title_sort | lack of cyclin d3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109157/ https://www.ncbi.nlm.nih.gov/pubmed/30143714 http://dx.doi.org/10.1038/s41598-018-31090-5 |
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