PGC-1α in the myofibers regulates the balance between myogenic and adipogenic progenitors affecting muscle regeneration

ABSTRACT Skeletal muscle repair is accomplished by satellite cells (MuSC) in cooperation with interstitial stromal cells (ISCs). So far, the relationship between the function of these cells and the metabolic state of myofibers remains unclear. The present study reports alterations in the proportion of both MuSCs and adipogenesis regulators (Aregs) induced by overexpression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the myofibers (MCK-PGC-1α mice). Although PGC-1α–driven increase of MuSCs does not accelerate muscle regeneration, myogenic progenitors isolated from MCK-PGC-1α mice and transplanted into intact and regenerating muscles are more prone to fuse with recipient myofibers than those derived from WT donors. Moreover, both young and aged MCK-PGC-1α animals show reduced perilipin-positive areas when challenged with an adipogenic stimulus, demonstrating low propensity to accumulate adipocytes within the muscle. These results provide new insights on the role played by PGC-1α in promoting myogenesis and hindering adipogenesis in the skeletal muscle.