Skeletal Muscle PGC-1β Signaling is Sufficient to Drive an Endurance Exercise Phenotype and to Counteract Components of Detraining in Mice

Authors

Samuel Lee, Sanford Burnham Prebys Medical Discovery Institute
Teresa C. Leone, Sanford Burnham Prebys Medical Discovery Institute
Lisa Rogosa, Sanford Burnham Prebys Medical Discovery Institute
John Rumsey, Sanford Burnham Prebys Medical Discovery Institute
Julio Ayala, Sanford Burnham Prebys Medical Discovery Institute
Paul M. Coen, Sanford Burnham Prebys Medical Discovery Institute
Robert H. Fitts, Marquette UniversityFollow
Rick B. Vega, Sanford Burnham Prebys Medical Discovery Institute
Daniel P. Kelly, Sanford Burnham Prebys Medical Discovery Institute

Document Type

Article

Language

eng

Publication Date

5-2017

Publisher

American Physiological Society

Source Publication

American Journal of Physiology: Endocrinology and Metabolism

Source ISSN

1522-1555

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 O₂ uptake (V̇_o2) did not change from baseline with increasing treadmill speed [peak V̇_o2 (ΔV̇_o2max)] 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.

Comments

Accepted version. American Journal of Physiology: Endocrinology and Metabolism, Vol. 312, No. 5 (May 2017): E394-E406. DOI. © 2017 the American Physiological Society. Used with permission.

Recommended Citation

Lee, Samuel; Leone, Teresa C.; Rogosa, Lisa; Rumsey, John; Ayala, Julio; Coen, Paul M.; Fitts, Robert H.; Vega, Rick B.; and Kelly, Daniel P., "Skeletal Muscle PGC-1β Signaling is Sufficient to Drive an Endurance Exercise Phenotype and to Counteract Components of Detraining in Mice" (2017). Biological Sciences Faculty Research and Publications. 592.
https://epublications.marquette.edu/bio_fac/592