Fatty acid oxidation restriction triggered by Cpt1b deficiency specific in adult cardiomyocyte (CM) with aMHC-MCM promotes CM dedifferentiation [RNA-seq II]. Fatty acid oxidation restriction triggered by Cpt1b deficiency specific in adult cardiomyocyte (CM) with aMHC-MCM promotes CM dedifferentiation [RNA-seq II]

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. Overall design: Transcriptome profiles of adult CM isolated from Ctrl and Cpt1b-deficient mice 4 weeks after TAM injection

出生后，心脏的代谢谱会快速由糖酵解切换至脂肪酸氧化（fatty acid oxidation, FAO），同时伴随染色质重构、细胞周期退出与心肌细胞（cardiomyocyte, CM）成熟，这提示由表观遗传机制调控的转录网络发生了协同重编程，以适配环境与代谢信号的变化。为深入解析心脏发育、成熟及心脏再生过程中表观遗传过程与代谢通路的内在关联，我们通过在心肌细胞中特异性敲除脂肪酸氧化关键酶肉碱棕榈酰转移酶1b（CPT1b），诱导了代谢重编程。Cpt1b基因失活可导致心脏肥大，并在心肌损伤应答中减轻心脏损伤，该效应主要源于心肌细胞增殖能力增强以及对缺血损伤的抵抗性提升。整体实验设计：采集他莫昔芬（tamoxifen, TAM）注射4周后，从对照组（Ctrl）与Cpt1b缺陷型小鼠中分离的成年心肌细胞的转录组谱。