p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.

During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases...

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Autores principales:	Ayelén M Santamans, Valle Montalvo-Romeral, Alfonso Mora, Juan Antonio Lopez, Francisco González-Romero, Daniel Jimenez-Blasco, Elena Rodríguez, Aránzazu Pintor-Chocano, Cristina Casanueva-Benítez, Rebeca Acín-Pérez, Luis Leiva-Vega, Jordi Duran, Joan J Guinovart, Jesús Jiménez-Borreguero, José Antonio Enríquez, María Villlalba-Orero, Juan P Bolaños, Patricia Aspichueta, Jesús Vázquez, Bárbara González-Terán, Guadalupe Sabio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c36e9e81543246be91c8817f25d367e5
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spelling	oai:doaj.org-article:c36e9e81543246be91c8817f25d367e52021-12-02T19:54:43Zp38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.1544-91731545-788510.1371/journal.pbio.3001447https://doaj.org/article/c36e9e81543246be91c8817f25d367e52021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001447https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases in the heart. We demonstrate that p38γ/δ contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38γ/δ activation in cardiomyocytes of newborn mice results in an early GYS1 phosphorylation and inhibition of cardiac glycogen production, triggering an early metabolic shift that induces a deficit in cardiomyocyte fuel supply, leading to whole-body metabolic deregulation and maladaptive cardiac pathogenesis. Notably, the adverse effects of forced premature cardiac p38γ/δ activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. These results suggest that diet interventions have a potential for treating human cardiac genetic diseases that affect heart metabolism.Ayelén M SantamansValle Montalvo-RomeralAlfonso MoraJuan Antonio LopezFrancisco González-RomeroDaniel Jimenez-BlascoElena RodríguezAránzazu Pintor-ChocanoCristina Casanueva-BenítezRebeca Acín-PérezLuis Leiva-VegaJordi DuranJoan J GuinovartJesús Jiménez-BorregueroJosé Antonio EnríquezMaría Villlalba-OreroJuan P BolañosPatricia AspichuetaJesús VázquezBárbara González-TeránGuadalupe SabioPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 11, p e3001447 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Ayelén M Santamans Valle Montalvo-Romeral Alfonso Mora Juan Antonio Lopez Francisco González-Romero Daniel Jimenez-Blasco Elena Rodríguez Aránzazu Pintor-Chocano Cristina Casanueva-Benítez Rebeca Acín-Pérez Luis Leiva-Vega Jordi Duran Joan J Guinovart Jesús Jiménez-Borreguero José Antonio Enríquez María Villlalba-Orero Juan P Bolaños Patricia Aspichueta Jesús Vázquez Bárbara González-Terán Guadalupe Sabio p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.
description	During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases in the heart. We demonstrate that p38γ/δ contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38γ/δ activation in cardiomyocytes of newborn mice results in an early GYS1 phosphorylation and inhibition of cardiac glycogen production, triggering an early metabolic shift that induces a deficit in cardiomyocyte fuel supply, leading to whole-body metabolic deregulation and maladaptive cardiac pathogenesis. Notably, the adverse effects of forced premature cardiac p38γ/δ activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. These results suggest that diet interventions have a potential for treating human cardiac genetic diseases that affect heart metabolism.
format	article
author	Ayelén M Santamans Valle Montalvo-Romeral Alfonso Mora Juan Antonio Lopez Francisco González-Romero Daniel Jimenez-Blasco Elena Rodríguez Aránzazu Pintor-Chocano Cristina Casanueva-Benítez Rebeca Acín-Pérez Luis Leiva-Vega Jordi Duran Joan J Guinovart Jesús Jiménez-Borreguero José Antonio Enríquez María Villlalba-Orero Juan P Bolaños Patricia Aspichueta Jesús Vázquez Bárbara González-Terán Guadalupe Sabio
author_facet	Ayelén M Santamans Valle Montalvo-Romeral Alfonso Mora Juan Antonio Lopez Francisco González-Romero Daniel Jimenez-Blasco Elena Rodríguez Aránzazu Pintor-Chocano Cristina Casanueva-Benítez Rebeca Acín-Pérez Luis Leiva-Vega Jordi Duran Joan J Guinovart Jesús Jiménez-Borreguero José Antonio Enríquez María Villlalba-Orero Juan P Bolaños Patricia Aspichueta Jesús Vázquez Bárbara González-Terán Guadalupe Sabio
author_sort	Ayelén M Santamans
title	p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.
title_short	p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.
title_full	p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.
title_fullStr	p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.
title_full_unstemmed	p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.
title_sort	p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c36e9e81543246be91c8817f25d367e5
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p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.

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