p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1

Santamans, Ayelén M.Montalvo-Romeral, ValleMora, AlfonsoLopez, Juan AntonioGonzález-Romero, FranciscoJimenez-Blasco, DanielRodríguez, ElenaPintor-Chocano, AránzazuCasanueva-Benítez, CristinaAcín-Pérez, RebecaLeiva-Vega, LuisDuran, JordiGuinovart, Joan J.Jiménez-Borreguero, JesúsAspichueta, PatriciaVázquez, JesúsGonzález-Terán, BárbaraSabio, GuadalupeEnríquez González, José AntonioVillalba Orero, MaríaBolaños, Juan P.2024-02-012024-02-012021Santamans 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): e30014471545-788510.1371/journal.pbio.3001447https://hdl.handle.net/20.500.14352/97995During 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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1journal articlehttps://doi.org/10.1371/journal.pbio.300144734758018https://pubmed.ncbi.nlm.nih.gov/34758018/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612745/https://digital.csic.es/bitstream/10261/262713/1/p38%ce%b3_and_%20p8%ce%b4.pdfopen access61Medicina2407 Biología Celular