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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Detalles Bibliográficos
Autores: Santamans, Ayelén M., Montalvo-Romeral, Valle, Mora, Alfonso, Lopez, Juan Antonio, Gonzalez-Romero, Francisco, Jimenez-Blasco, Daniel, Rodríguez, Elena, Pintor-Chocano, Aránzazu, Casanueva-Benítez, Cristina, Acín-Pérez, Rebeca, Leiva-Vega, Luis, Duran, Joan, Guinovart, Joan J., Jiménez-Borreguero, Jesús, Enríquez, José Antonio, Villlalba-Orero, María, Bolaños, Juan P., Aspichueta, Patricia, Vázquez, Jesús, González-Terán, Bárbara, Sabio, Guadalupe
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/262713
Acceso en línea:http://hdl.handle.net/10261/262713
Access Level:acceso abierto
Descripción
Sumario: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.

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