β-Catenin Regulates Cardiac Energy Metabolism in Sedentary and Trained Mice

The role of canonical Wnt signaling in metabolic regulation and development of physiological cardiac hypertrophy remains largely unknown. To explore the function of beta-catenin in the regulation of cardiac metabolism and physiological cardiac hypertrophy development, we used mice heterozygous for cardiac-specific beta-catenin knockout that were subjected to a swimming training model. beta-Catenin haploinsufficient mice subjected to endurance training displayed a decreased beta-catenin transcriptional activity, attenuated cardiomyocytes hypertrophic growth, and enhanced activation of AMP-activated protein kinase (AMPK), phosphoinositide-3-kinase-Akt (Pi3K-Akt), and mitogen-activated protein kinase/extracellular signal-regulated kinases 1/2 (MAPK/Erk1/2) signaling pathways compared to trained wild type mice. We further observed an increased level of proteins involved in glucose aerobic metabolism and beta-oxidation along with perturbed activity of mitochondrial oxidative phosphorylation complexes (OXPHOS) in trained beta-catenin haploinsufficient mice. Taken together, Wnt/beta-catenin signaling appears to govern metabolic regulatory programs, sustaining metabolic plasticity in adult hearts during the adaptation to endurance training.