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J Appl Physiol 104: 1304-1312, 2008. First published January 31, 2008; doi:10.1152/japplphysiol.01231.2007
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Muscle-specific expression of PPAR{gamma} coactivator-1{alpha} improves exercise performance and increases peak oxygen uptake

Jennifer A. Calvo,1 Thomas G. Daniels,1 Xiaomei Wang,1 Angelika Paul,2 Jiandie Lin,3 Bruce M. Spiegelman,3 Susan C. Stevenson,1 and Shamina M. Rangwala1

1Diabetes and Metabolism Disease Area and 2Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Cambridge; and 3Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts

Submitted 19 November 2007 ; accepted in final form 25 January 2008

The induction of peroxisome proliferator-activated receptor-{gamma} coactivator-1{alpha} (PGC-1{alpha}), a key regulator of mitochondriogenesis, is well-established under multiple physical exercise regimens, including, endurance, resistance, and sprint training. We wanted to determine if increased expression of PGC-1{alpha} in muscle is sufficient to improve performance during exercise in vivo. We demonstrate that muscle-specific expression of PGC-1{alpha} improves the performance during voluntary as well as forced exercise challenges. Additionally, PGC-1{alpha} transgenic mice exhibit an enhanced performance during a peak oxygen uptake exercise test, demonstrating an increased peak oxidative capacity, or whole body oxygen uptake. This increased ability to perform in multiple exercise paradigms is supported by enhanced mitochondrial function as suggested by increased mitochondrial gene expression, mitochondrial DNA, and mitochondrial enzyme activity. Thus this study demonstrates that upregulation of PGC-1{alpha} in muscle in vivo is sufficient to greatly improve exercise performance under various exercise paradigms as well as increase peak oxygen uptake.

exercise capacity; peak oxygen uptake; peroxisome proliferator-activated receptor {gamma}-coactivator-1{alpha}


Address for reprint requests and other correspondence: S. M. Rangwala, Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, MA 02139 (e-mail: shamina.rangwala{at}novartis.com)




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