The transcriptional coactivator PGC-1α is dispensable for chronic overload-induced skeletal muscle hypertrophy and metabolic remodeling

Skeletal muscle mass loss and dysfunction have been linked to many diseases. Conversely, resistance exercise, mainly by activating mammalian target of rapamycin complex 1 (mTORC1), promotes skeletal muscle hypertrophy and exerts several therapeutic effects. Moreover, mTORC1, along with peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha), regulates skeletal muscle metabolism. However, it is unclear whether PGC-1 alpha is required for skeletal muscle adaptations after overload. Here we show that although chronic overload of skeletal muscle via synergist ablation (SA) strongly induces hypertrophy and a switch toward a slow-contractile phenotype, these effects were independent of PGC-1 alpha. In fact, SA down-regulated PGC-1 alpha expression and led to a repression of energy metabolism. Interestingly, however, PGC-1 alpha deletion preserved peak force after SA. Taken together, our data suggest that PGC-1 alpha is not involved in skeletal muscle remodeling induced by SA.