2026-06-14T03:43:00Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/189182024-09-27T08:52:03Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Santamans, Ayelén M author Montalvo-Romeral, Valle author Mora, Alfonso author Lopez, Juan Antonio author González-Romero, Francisco author Jimenez-Blasco, Daniel author Rodríguez, Elena author Pintor-Chocano, Aránzazu author Casanueva-Benítez, Cristina author Acin-Perez, Rebeca author Leiva-Vega, Luis author Duran, Jordi author Guinovart, Joan J author Jiménez-Borreguero, Jesús author Enriquez, Jose Antonio author Villlalba-Orero, María author Bolaños, Juan P author Aspichueta, Patricia author Vázquez, Jesús author González-Terán, Bárbara author Sabio, Guadalupe author 2021-11 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. PLoS Biol. 2021 Nov 10;19(11):e3001447. 10.1371/journal.pbio.3001447 1545-7885 PLoS biology 34758018 http://hdl.handle.net/20.500.12105/18918 p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.