title: Skeletal muscle PGC-1β signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice.
abstract: Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2(ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy.
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida.
authors.forename: Samuel
authors.initials: S
authors.lastname: Lee
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida.
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Leone
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rogosa
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida.
authors.forename: John
authors.initials: J
authors.lastname: Rumsey
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida.
authors.forename: Julio
authors.initials: J
authors.lastname: Ayala
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida.|Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida; and.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Coen
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Fitts
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida.
authors.forename: Rick B
authors.initials: RB
authors.lastname: Vega
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida; dkelly@sbpdiscovery.org.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Kelly
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000502:physiology*; D020966:Muscular Disorders, Atrophic / Q000503:physiopathology / Q000517:prevention & control; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D010641:Phenotype; D010805:Physical Conditioning, Animal / Q000379:methods*; D010807:Physical Endurance / Q000502:physiology*; D010809:Physical Fitness / Q000502:physiology*; D012420:Running / Q000502:physiology*
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse
keywords: PGC-1; endurance exercise; muscle detraining; skeletal muscle