• PPARα;
  • PGC-1α;
  • Embryonic stem cells;
  • Cardiomyocytes;
  • Differentiation


Peroxisome proliferator-activated receptor α (PPARα) plays a key role in the transcriptional regulation of genes involved in cellular lipid and energy metabolism, which is abundantly expressed in tissues with high energy demand, including the mammalian heart. Although multiple roles for PPARα in adult cardiomyocytes have been proposed, little is known about the significance of PPARα in early differentiation of cardiomyocytes. To address this issue, murine embryonic stem (ES) cells were adopted in this study since they would differentiate in vitro into cardiomyocytes that faithfully recapitulated cardiomyocyte differentiation in vivo. As determined by semi-quantitative RT-PCR and Western-blot, both PPARα and its coactivatior PGC-1α were increased during cardiomyocyte differentiation. A positive correlation between PPARα and Troponin-T expression was also observed by immunofluorescence in early differentiation. Application of PPARα antagonist GW6471 prevented cardiomyocyte differentiation as indicated by reduced expression of cardiac specific genes (α-MHC, MLC2v) and cardiac sarcomeric proteins (α-Actinin, Troponin-T). However, gene expression of cardiac specific transcription factors (GATA4, Nkx2.5, and MEF2C) remained unchanged. Moreover, cardiomyocyte differentiation of EBs could be efficiently stimulated by WY14643 treatment, the specific agonist of PPARα. Taken together, these results suggested a facilitating role of PPARα in cardiomyocyte differentiation of murine ES cells in vitro.