Peroxisome proliferator-activated receptor NS (PPAR beta/delta) regulates postnatal myogenesis by alleviating myostatin activity, but the molecular mechanisms by which it regulates myogenesis are not fully understood. In this study, we investigate molecular mechanisms of PPAR beta/delta in myoblast differentiation. C2C12 myoblasts treated with a PPAR beta/delta agonist, GW0742 exhibit enhanced myotube formation and muscle-specific gene expression. GW0742 treatment dramatically activates promyogenic kinases, p38MAPK and Akt, in a dose-dependent manner. GW0742-stimulated myoblast differentiation is mediated by p38MAPK and Akt, since it failed to restore myoblast differentiation repressed by inhibition of p38MAPK and Akt. In addition, GW0742 treatment enhances MyoD-reporter activities. Consistently, overexpression of PPAR beta/delta enhances myoblast differentiation accompanied by elevated activation of p38MAPK and Akt. Collectively, these results suggest that PPAR beta/delta enhances myoblast differentiation through activation of promyogenic signaling pathways. (C) 2016 Elsevier Inc. All rights reserved.