Fatty acid oxidation restriction triggered by Cpt1b deficiency specific in cardiomyocyte (CM) with Myh6-Cre benefits heart regeneration [RNA-seq I]

In the heart, metabolic profile switches from glycolysis to fatty acid oxidation (FAO) rapidly after birth accompanied by chromatin reconfiguration, cell cycle exit and cardiomyocyte (CM) maturation, suggesting a synergistic rewiring of transcriptional networks regulated by epigenetic mechanisms in accordance with environmental and metabolic signals. To gain a better insight into the interconnection between epigenetic processes and metabolic pathways during cardiac development, maturation and heart regeneration, we induced a metabolic reprogramming by depleting CPT1b, a crucial enzyme for FAO, specifically in CM. Cpt1b inactivation led to cardiomegaly and attenuated cardiac damage in response to myocardial injury primarily attributed to augmented CM proliferation and enhanced resistance to ischemic injury. Transcriptome profiles of adult CM isolated from Ctrl and Cpt1b-deficient mice. CRE-driver was aMHC-Cre.