In addition to controlling muscle mass, myostatin may support oxidative metabolism and endurance. Loss of function through gene knockout or post-natal blockade generally lowers muscle oxidative capacity and increases fatigability. These observations imply that myostatin activation could promote a more oxidative and less fatigable muscle phenotype. Gain-of-function approaches that activate myostatin in vivo, however, are largely absent. To test whether myostatin promotes oxidative metabolism in muscle, we constructed transgenic (TG) mice with myostatin (Mstn) gene overexpression restricted to skeletal muscle by inserting an Mstn cDNA construct under the MCK promoter to drive muscle-specific expression of recombinant myostatin protein. On standard diet, TG had greater oxidative fibre expression, greater coupled maximal mitochondrial oxidative phosphorylation (OXPHOS), and increased in situ muscle fatigue resistance. Untargeted metabolomics identified greater stored carbohydrate...