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

Santamans, Ayelén M. Montalvo-Romeral, Valle Mora, Alfonso Lopez, Juan Antonio González-Romero, Francisco Jimenez-Blasco, Daniel Rodríguez, Elena Pintor-Chocano, Aránzazu Casanueva-Benítez, Cristina Acín-Pérez, Rebeca Leiva-Vega, Luis Duran, Jordi Guinovart, Joan J. Jiménez-Borreguero, Jesús Aspichueta, Patricia Vázquez, Jesús González-Terán, Bárbara Sabio, Guadalupe Enríquez González, José Antonio Villalba Orero, María Bolaños, Juan P. 2024-02-01T19:12:06Z 2024-02-01T19:12:06Z 2021 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 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. eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1 journal article