2026-06-07T11:31:14Zhttps://docta.ucm.es/rest/oai/requestoai:docta.ucm.es:20.500.14352/979952025-03-31T23:53:48Zcom_20.500.14352_14col_20.500.14352_15
p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1
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.
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.
2024-02-01T19:12:06Z
2024-02-01T19:12:06Z
2021
journal article
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
eng
CLU-2017-03
info:eu-repo/grantAgreement/MINECO//SEV-2015-0505/ES/CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III/
2018-PN188
PGC2018- 097019-B-I00
SAF2016-81975-REDT
IT971-16
818798
info:eu-repo/grantAgreement/MINECO//BES-2014-069332/ES/BES-2014-069332/
BES-2016-077635
B2017/BMD-3733
IMMUNOTHERCAN-CM S2010/BMD-2326
info:eu-repo/grantAgreement/MINECO//SVP-2013-067639/ES/SVP-2013-067639/
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105699RB-I00/ES/IMPACTO DE LA REPROGRAMACION METABOLICA DE LOS ASTROCITOS SOBRE LA FUNCION NEURONAL IN VIVO EN SALUD Y ENFERMEDAD/
RED2018-102576-T
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104399RB-I00/ES/ROLE OF MUSCLE STRESS KINASES IN OBESITY RELATED DISEASES/
RTI2018-095134-B-100
SAF2016-79126-R
SAF2016-81975-REDTand2018-PN188
RTI2018-095134-B-100
http://creativecommons.org/licenses/by/4.0/
open access
Attribution 4.0 International
PLOS