RT Journal Article
T1 p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1
A1 Santamans, Ayelén M.
A1 Montalvo-Romeral, Valle
A1 Mora, Alfonso
A1 Lopez, Juan Antonio
A1 González-Romero, Francisco
A1 Jimenez-Blasco, Daniel
A1 Rodríguez, Elena
A1 Pintor-Chocano, Aránzazu
A1 Casanueva-Benítez, Cristina
A1 Acín-Pérez, Rebeca
A1 Leiva-Vega, Luis
A1 Duran, Jordi
A1 Guinovart, Joan J.
A1 Jiménez-Borreguero, Jesús
A1 Aspichueta, Patricia
A1 Vázquez, Jesús
A1 González-Terán, Bárbara
A1 Sabio, Guadalupe
A1 Enríquez González, José Antonio
A1 Villalba Orero, María
A1 Bolaños, Juan P.
AB 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.
PB PLOS
SN 1545-7885
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/97995
UL https://hdl.handle.net/20.500.14352/97995
LA eng
NO Santamans AM, Montalvo-Romeral V, Mora A, Lopez JA, González-Romero F, Jimenez-Blasco D, et al. (2021) p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1. PLoS Biol 19(11): e3001447
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III
NO Comunidad de Madrid
NO European Commission 
DS Docta Complutense
RD 23 ene 2026