title: Exercise and PGC-1α-independent synchronization of type I muscle metabolism and vasculature by ERRγ.
abstract: How type I skeletal muscle inherently maintains high oxidative and vascular capacity in the absence of exercise is 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 the 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 proangiogenic factors, neovascularization, and a 100% increase in running endurance. Surprisingly, the induction of type I muscle properties by ERRγ does not involve PGC-1α. Instead, ERRγ genetically activates the energy sensor AMPK in mediating the metabovascular changes in 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.
authors.affiliation: Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.
authors.forename: Vihang A
authors.initials: VA
authors.lastname: Narkar
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.forename: Michael
authors.initials: M
authors.lastname: Downes
authors.forename: Ruth T
authors.initials: RT
authors.lastname: Yu
authors.forename: Johan W
authors.initials: JW
authors.lastname: Jonker
authors.forename: William A
authors.initials: WA
authors.lastname: Alaynick
authors.forename: Ester
authors.initials: E
authors.lastname: Banayo
authors.forename: Malith S
authors.initials: MS
authors.lastname: Karunasiri
authors.forename: Sabina
authors.initials: S
authors.lastname: Lorca
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism* / Q000502:physiology; D018919:Neovascularization, Physiologic; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D011494:Protein Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: C490916:Esrrg protein, mouse; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases