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: Santamans, Ayelén M., Montalvo-Romeral, Valle, Mora, Alfonso, Lopez, Juan Antonio, González-Romero, Francisco, Jimenez-Blasco, Daniel, Rodríguez, Elena, Pintor-Chocano, Aránzazu, Casanueva-Benítez, Cristina, Acín-Pérez, Rebeca, Leiva-Vega, Luis, Duran, Jordi, Guinovart, Joan J., Jiménez-Borreguero, Jesús, Aspichueta, Patricia, Vázquez, Jesús, González-Terán, Bárbara, Sabio, Guadalupe, Enríquez González, José Antonio, Villalba Orero, María, Bolaños, Juan P.
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/97995
Acesso em linha:https://hdl.handle.net/20.500.14352/97995
Access Level:acceso abierto
Palavra-chave:61
Medicina
2407 Biología Celular
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oai_identifier_str oai:docta.ucm.es:20.500.14352/97995
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spelling p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1Santamans, Ayelén M.Montalvo-Romeral, ValleMora, AlfonsoLopez, Juan AntonioGonzález-Romero, FranciscoJimenez-Blasco, DanielRodríguez, ElenaPintor-Chocano, AránzazuCasanueva-Benítez, CristinaAcín-Pérez, RebecaLeiva-Vega, LuisDuran, JordiGuinovart, Joan J.Jiménez-Borreguero, JesúsAspichueta, PatriciaVázquez, JesúsGonzález-Terán, BárbaraSabio, GuadalupeEnríquez González, José AntonioVillalba Orero, MaríaBolaños, Juan P.61Medicina2407 Biología CelularDuring 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.PLOSUniversidad Complutense de Madrid20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/97995reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/979952026-06-02T12:44:21Z
dc.title.none.fl_str_mv p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1
title p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1
spellingShingle p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1
Santamans, Ayelén M.
61
Medicina
2407 Biología Celular
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
dc.creator.none.fl_str_mv Santamans, Ayelén M.
Montalvo-Romeral, Valle
Mora, Alfonso
Lopez, Juan Antonio
González-Romero, Francisco
Jimenez-Blasco, Daniel
Rodríguez, Elena
Pintor-Chocano, Aránzazu
Casanueva-Benítez, Cristina
Acín-Pérez, Rebeca
Leiva-Vega, Luis
Duran, Jordi
Guinovart, Joan J.
Jiménez-Borreguero, Jesús
Aspichueta, Patricia
Vázquez, Jesús
González-Terán, Bárbara
Sabio, Guadalupe
Enríquez González, José Antonio
Villalba Orero, María
Bolaños, Juan P.
author Santamans, Ayelén M.
author_facet Santamans, Ayelén M.
Montalvo-Romeral, Valle
Mora, Alfonso
Lopez, Juan Antonio
González-Romero, Francisco
Jimenez-Blasco, Daniel
Rodríguez, Elena
Pintor-Chocano, Aránzazu
Casanueva-Benítez, Cristina
Acín-Pérez, Rebeca
Leiva-Vega, Luis
Duran, Jordi
Guinovart, Joan J.
Jiménez-Borreguero, Jesús
Aspichueta, Patricia
Vázquez, Jesús
González-Terán, Bárbara
Sabio, Guadalupe
Enríquez González, José Antonio
Villalba Orero, María
Bolaños, Juan P.
author_role author
author2 Montalvo-Romeral, Valle
Mora, Alfonso
Lopez, Juan Antonio
González-Romero, Francisco
Jimenez-Blasco, Daniel
Rodríguez, Elena
Pintor-Chocano, Aránzazu
Casanueva-Benítez, Cristina
Acín-Pérez, Rebeca
Leiva-Vega, Luis
Duran, Jordi
Guinovart, Joan J.
Jiménez-Borreguero, Jesús
Aspichueta, Patricia
Vázquez, Jesús
González-Terán, Bárbara
Sabio, Guadalupe
Enríquez González, José Antonio
Villalba Orero, María
Bolaños, Juan P.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 61
Medicina
2407 Biología Celular
topic 61
Medicina
2407 Biología Celular
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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/97995
url https://hdl.handle.net/20.500.14352/97995
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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