β-Catenin signaling pathway regulates cardiomyocytes proliferation and differentiation, though its involvement in metabolic regulation of cardiomyocytes remains unknown. We used one-day-old mice with cardiac-specific knockout of β-catenin and neonatal rat ventricular myocytes treated with β-catenin inhibitor to investigate the role of β-catenin metabolism regulation in perinatal cardiomyocytes. Transcriptomics of perinatal β-catenin-ablated hearts revealed a dramatic shift in the expression of genes involved in metabolic processes. Further analysis indicated an inhibition of lipolysis and glycolysis in both in vitro and in vivo models. Finally, we showed that β-catenin deficiency leads to mitochondria dysfunction via the downregulation of Sirt1/PGC-1α pathway. We conclude that cardiac-specific β-catenin ablation disrupts the energy substrate shift that is essential for postnatal heart maturation, leading to perinatal lethality of homozygous β-catenin knockout mice.

β-Catenin信号通路调节心肌细胞增殖和分化，但其参与心肌细胞代谢调节的作用仍不清楚。我们使用心脏特异性敲除β-连环蛋白的一日龄小鼠和用β-连环蛋白抑制剂处理的新生大鼠心室肌细胞来研究β-连环蛋白代谢调节在围生期心肌细胞中的作用。围产期 β-连环蛋白消除心脏的转录组学揭示了参与代谢过程的基因表达的巨大变化。进一步的分析表明在体外和体内模型中均抑制脂肪分解和糖酵解。最后，我们发现β-连环蛋白缺乏通过下调Sirt1/PGC-1α途径导致线粒体功能障碍。我们得出的结论是，心脏特异性β-连环蛋白消融破坏了对出生后心脏成熟至关重要的能量底物转移，导致纯合子-连环蛋白敲除小鼠的围产期死亡。