Artículo del mes
diciembre 2021

p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1

Referencia artículo:
Santamans AM*, Montalvo-Romeral V*, Mora A, Lopez JA, González-Romero F, Jimenez-Blasco D, Rodríguez E, Pintor-Chocano A, Casanueva-Benítez C, Acín-Pérez R, Leiva-Vega L, Duran J, Guinovart JJ, Jiménez-Borreguero J, Enríquez JA, Villlalba-Orero M, Bolaños JP, Aspichueta P, Vázquez J, González-Terán B*, Sabio G*. p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1. PLoS Biol. 2021 Nov 10;19(11):e3001447. doi: 10.1371/journal.pbio.3001447. PMID: 34758018; PMCID: PMC8612745.
Las proteínas p38γ y p38δ se activan en el corazón al poco de nacer y reducen la actividad de la enzima Glucógeno Sintasa 1, desencadenando un cambio metabólico en el corazón que deja de usar gucógeno como fuente de energía para comenzar a utilizar ácidos grasos. La expresión prematura de p38γ/δ genera una alteración del metabolismo cardíaco con consecuencias metabólicas globales y daño cardíaco irreversible. Sin embargo, la administración de una dieta alta en grasa a las madres, revierte las consecuencias negativas en las crías tanto a nivel cardíaco como metabólico
Resumen
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
Sobre el grupo investigador