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This metabolic change is contemporaneous to the up-regulation and activation of the p38\u03b3 and p38\u03b4 stress-activated protein kinases in the heart. We demonstrate that p38\u03b3\/\u03b4 contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38\u03b3\/\u03b4 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\u03b3\/\u03b4 activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. 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