Portal de investigación
p38 gamma and p38 delta regulate postnatal cardiac metabolism through glycogen synthase 1
Fecha de publicación:
Autores de IBSAL
Autores ajenos a IBSAL
- Santamans, AM
- Montalvo-Romeral, V
- Mora, A
- Lopez, JA
- Gonzalez-Romero, F
- Rodriguez, E
- Pintor-Chocano, A
- Casanueva-Benitez, C
- Acin-Perez, R
- Leiva-Vega, L
- Duran, J
- Guinovart, JJ
- Jimenez-Borreguero, J
- Enriquez, JA
- Villlalba-Orero, M
- Aspichueta, P
- Vazquez, J
- Gonzalez-Teran, B
- Sabio, G
Grupos
Abstract
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 p38 gamma and p38 delta stress-activated protein kinases in the heart. We demonstrate that p38 gamma/delta contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38 gamma/delta 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 p38 gamma/delta 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.
Datos de la publicación
- ISSN/ISSNe:
- 1544-9173, 1545-7885
- Tipo:
- Article
- Páginas:
- -
PLOS BIOLOGY PUBLIC LIBRARY SCIENCE
Citas Recibidas en Web of Science: 5
Documentos
- No hay documentos
Filiaciones
Financiación
Proyectos asociados
3. Frailty and Aging. 3.1. Healthy aging biological mechanisms oriented to the maintenance of functional autonomy and mechanisms leading to frailty and disability. CICERFES
Investigador Principal: Juan Pedro Bolaños Hernández
CB16/10/00282 . Instituto de Salud Carlos III . 2017
Cita
Santamans AM,Montalvo V,Mora A,Lopez JA,Gonzalez F,Jimenez D,Rodriguez E,Pintor A,Casanueva C,Acin R,Leiva L,Duran J,Guinovart JJ,Jimenez J,Enriquez JA,Villlalba M,Bolanos JP,Aspichueta P,Vazquez J,Gonzalez B,Sabio G. p38 gamma and p38 delta regulate postnatal cardiac metabolism through glycogen synthase 1. PLoS Biol. 2021. 19. (11):e3001447. IF:9,593. (1).