Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism

Abstract 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 bala...

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Autores principales:	Silvia Giannattasio, Giacomo Giacovazzo, Agnese Bonato, Carla Caruso, Siro Luvisetto, Roberto Coccurello, Maurizia Caruso
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/adf1b3c9b11f492ea0cdab5e5ffaa16c
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spelling	oai:doaj.org-article:adf1b3c9b11f492ea0cdab5e5ffaa16c2021-12-02T11:41:02ZLack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism10.1038/s41598-018-31090-52045-2322https://doaj.org/article/adf1b3c9b11f492ea0cdab5e5ffaa16c2018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31090-5https://doaj.org/toc/2045-2322Abstract 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.Silvia GiannattasioGiacomo GiacovazzoAgnese BonatoCarla CarusoSiro LuvisettoRoberto CoccurelloMaurizia CarusoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-18 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Silvia Giannattasio Giacomo Giacovazzo Agnese Bonato Carla Caruso Siro Luvisetto Roberto Coccurello Maurizia Caruso Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism
description	Abstract 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	article
author	Silvia Giannattasio Giacomo Giacovazzo Agnese Bonato Carla Caruso Siro Luvisetto Roberto Coccurello Maurizia Caruso
author_facet	Silvia Giannattasio Giacomo Giacovazzo Agnese Bonato Carla Caruso Siro Luvisetto Roberto Coccurello Maurizia Caruso
author_sort	Silvia Giannattasio
title	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_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_sort	lack of cyclin d3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/adf1b3c9b11f492ea0cdab5e5ffaa16c
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Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism

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