Cardiac-specific β-catenin deletion dysregulates energetic metabolism and mitochondrial function in perinatal cardiomyocytes

beta-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 beta-catenin and neonatal rat ventricular myocytes treated with beta-catenin inhibitor to investigate the role of beta-catenin metabolism regulation in perinatal cardiomyocytes. Transcriptomics of perinatal beta-cateninablated 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 beta-catenin deficiency leads to mitochondria dysfunction via the downregulation of Sirt1/PGC-1 alpha pathway. We conclude that cardiac-specific beta-catenin ablation disrupts the energy substrate shift that is essential for postnatal heart maturation, leading to perinatal lethality of homozygous beta-catenin knockout mice.

Automated summary

The beta-Catenin signaling pathway plays a crucial role in regulating metabolic processes in cardiomyocytes. Disruption of this pathway leads to disturbances in energy substrate utilization, hindering postnatal heart maturation and causing perinatal lethality in homozygous beta-catenin knockout mice.