| First Author | Santamans AM | Year | 2021 |
| Journal | PLoS Biol | Volume | 19 |
| Issue | 11 | Pages | e3001447 |
| PubMed ID | 34758018 | Mgi Jnum | J:322240 |
| Mgi Id | MGI:6828351 | Doi | 10.1371/journal.pbio.3001447 |
| Citation | Santamans AM, et al. (2021) p38gamma and p38delta regulate postnatal cardiac metabolism through glycogen synthase 1. PLoS Biol 19(11):e3001447 |
| abstractText | 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 p38gamma and p38delta stress-activated protein kinases in the heart. We demonstrate that p38gamma/delta contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38gamma/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 p38gamma/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. |
