p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1

[EN]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 p38gamma and p38delta stress-activated pro...

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Detalles Bibliográficos
Autores: Santamans, Ayelén M., Montalvo Romeral, Valle, Moro Corral, Alfonso, López del Olmo, Juan Antonio, González Romero, Francisco, Jiménez Blasco, Daniel, Rodriguez, Elena, Pintor Chocano, Aránzazu, Casanueva Benítez, Cristina, Acín Pérez, Rebeca, Leiva Vega, Luis, Durán, Jordi, Guinovart Cirera, Joan Josep, Jiménez Borreguero, Jesús, Enríquez Domínguez, José Antonio, Villalba Orero, María, Bolaños Hernández, Juan Pedro, Aspichueta Celaá, Patricia, Vázquez Cobos, Jesús María, González Terán, Bárbara, Sabio, Guadalupe
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/54617
Acceso en línea:http://hdl.handle.net/10810/54617
Access Level:acceso abierto
Descripción
Sumario:[EN]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 p38gamma and p38delta stress-activated protein kinases in the heart. We demonstrate that p38gamma/delta contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38gamma/delta 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 p38gamma/delta 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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