Abstract

Peroxisome proliferator-activated receptor (PPAR) gamma co-activator 1alpha (PGC-1alpha) up-regulation induces FNDC5 expression in muscle and consequently causes browning of white adipose tissue (WAT). In addition to skeletal muscle, FNDC5 is mainly expressed in heart and brain tissues. Here, we demonstrate that FNDC5 expression increased during the process of cardiac differentiation of mouse embryonic stem cells (mESCs) similar to PGC-1alpha and PPARalpha. To testify the correlation between PGC-1alpha and FNDC5 in cardiac cell differentiation of mESCs, we utilized specific PPARgamma agonist and antagonist in two stages of cardiac differentiation, during and post-cardiac precursor cells (CPCs) formation. Our results indicated that a reduction in PGC-1alpha expression, via treatment with GW9662 during CPCs formation stage, down-regulated FNDC5 transcript levels as well as mitochondrial markers which negatively influenced on the whole process of cardiac differentiation efficiency. On the other hand, increase PGC-1alpha expression during CPCs formation stage via rosiglitazone treatment increase FNDC5 and mitochondrial markers transcript levels which enhanced cardiac differentiation efficiency. Importantly, such alteration in PGC-1alpha expression at post-CPCs formation stage did not affect overall cardiac differentiation rate as expression of FNDC5 and mitochondrial markers were not significantly changed. We concluded that PPARgamma agonist and antagonist induced up and down-regulation of PGC-1alpha and subsequently modulated the process of CPCs formation through an alteration in FNDC5 and mitochondrial markers expression.