%0 Journal Article
%A Santamans, Ayelén M.
%A Montalvo-Romeral, Valle
%A Mora, Alfonso
%A Lopez, Juan Antonio
%A González-Romero, Francisco
%A Jimenez-Blasco, Daniel
%A Rodríguez, Elena
%A Pintor-Chocano, Aránzazu
%A Casanueva-Benítez, Cristina
%A Acín-Pérez, Rebeca
%A Leiva-Vega, Luis
%A Duran, Jordi
%A Guinovart, Joan J.
%A Jiménez-Borreguero, Jesús
%A Aspichueta, Patricia
%A Vázquez, Jesús
%A González-Terán, Bárbara
%A Sabio, Guadalupe
%A Enríquez González, José Antonio
%A Villalba Orero, María
%A Bolaños, Juan P.
%T p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1
%D 2021
%@ 1545-7885
%U https://hdl.handle.net/20.500.14352/97995
%X 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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