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oai:docta.ucm.es:20.500.14352/979952025-03-31T23:53:48Zcom_20.500.14352_14col_20.500.14352_15

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 Acín-Pérez, Rebeca author Leiva-Vega, Luis author Duran, Jordi author Guinovart, Joan J. author Jiménez-Borreguero, Jesús author Aspichueta, Patricia author Vázquez, Jesús author González-Terán, Bárbara author Sabio, Guadalupe author Enríquez González, José Antonio author Villalba Orero, María author Bolaños, Juan P. author 2021 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. 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 1545-7885 10.1371/journal.pbio.3001447 https://hdl.handle.net/20.500.14352/97995 https://doi.org/10.1371/journal.pbio.3001447 34758018 https://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.pdf p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1