Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program

Classic physiological studies have documented the endurance-promoting effects of glucocorticoid (GC) hormones on skeletal muscle. Pharmacologic GC therapy also improves muscle function in patients with Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. Despite these well-established physiological and clinical observations, the molecular basis underlying the beneficial effects of GCs in skeletal muscle remains obscure. This study shows that physiological effects of GCs on muscle endurance and their therapeutic effect in DMD are mediated, in part, via activation of a potent metabolic gene called Kruppel-like factor 15 (KLF15). Importantly, KLF15 does not drive GC-mediated muscle wasting. These data shed light on the poorly understood ergogenic properties of GCs, findings that may inform steroid-sparing therapies for DMD and other muscle diseases.