PGC-1β prevents statin-associated myotoxicity in oxidative skeletal muscle

Statins are generally well-tolerated, but can induce myopathy. Statins are associated with impaired expression of PGC-1{beta} in human and rat skeletal muscle. The current study was performed to investigate the relation between PGC-1{beta} expression and function and statin-associated myopathy. In WT mice, atorvastatin impaired mitochondrial function in glycolytic, but not in oxidative muscle. In PGC-1{beta} KO mice, atorvastatin induced a shift from oxidative type IIA to glycolytic type IIB myofibers mainly in oxidative muscle and mitochondrial dysfunction was observed in both muscle types. In glycolytic muscle of WT and KO mice and in oxidative muscle of KO mice, atorvastatin suppressed mitochondrial proliferation and oxidative defense, leading to apoptosis. In contrast, mitochondrial function was maintained or improved and apoptosis decreased by atorvastatin in oxidative muscle of WT mice. In conclusion, PGC-1{beta} has an important role in preventing damage to oxidative muscle in the presence of a mitochondrial toxicant such as atorvastatin.