Estrogen-related receptor-γ: conductor of muscle angiogenesis through conversion of fast- to slow-twitch fibers?

Tissue vascularization is tightly coupled to its oxidative capacity. This phenomenon is especially well characterized in skeletal muscle, which can be enriched in either oxidative slow-twitch or glycolytic fast-twitch myofibers.1,2 Slow-twitch muscles are characterized by high-oxidativecapacity fatigue-resistant (type I) fibers and dense vascularity. Conversely, fast-twitch (type II) muscles have lower oxidative capacity, with a less developed vascular network, and are fatigue sensitive.3 Different studies have well demonstrated that nuclear receptors including peroxisome proliferator–activated receptor-[alpha) (PPAR), PPAR, and estrogen-related receptor(ERR), along with coregulators PPARcoactivator-1 (PGC-1 ), PGC-1 , and nuclear receptor-interacting protein 1 (RIP140), control fatty acid oxidation, oxidative phosphorylation, and mitochondrial biogenesis in skeletal muscle4–10; however, the mechanisms linking the oxidative profile of the muscle to its vasculature remain a matter of major interest.