Exercise and PGC1α-independent Synchronization of Type I Muscle Metabolism and Vasculature by ERRγ

• Published in: Cell metabolism Vol. 13; no. 3; pp. 283 - 293
• Main Authors: Narkar, Vihang A., Fan, Weiwei, Downes, Michael, Yu, Ruth T., Jonker, Johan W., Alaynick, William A., Banayo, Ester, Karunasiri, Malith S., Lorca, Sabina, Evans, Ronald M.
• Format: Journal Article
• Language: English
• Published: 02-03-2011
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2011.01.019

How type I skeletal muscle inherently maintains high oxidative and vascular capacity in absence of exercise in unclear. We show that nuclear receptor ERRγ is highly expressed in type I muscle and when transgenically expressed in anaerobic type II muscles (ERRGO mice), dually induces metabolic and vascular transformation in absence of exercise. ERRGO mice show increased expression of genes promoting fat metabolism, mitochondrial respiration and type I fiber specification. Muscles in ERRGO mice also display an activated angiogenic program marked by myofibrillar induction and secretion of pro-angiogenic factors, neo-vascularization and a 100% increase in running endurance. Surprisingly, the induction of type I muscle properties by ERRγ does not involve PGC1α. Instead, ERRγ genetically activates the energy sensor AMPK, in mediating the metabo-vascular changes in the ERRGO mice. Therefore, ERRγ represents a previously unrecognized determinant that specifies intrinsic vascular and oxidative metabolic features that distinguish type I from type II muscle.