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J Appl Physiol (January 31, 2008). doi:10.1152/japplphysiol.01231.2007
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Submitted on November 19, 2007
Accepted on January 25, 2008

Muscle-specific expression of PPAR{gamma}coactivator-1{alpha} improves exercise performance and increases peak oxygen uptake

Jennifer A Calvo1, Thomas G Daniels1, Xiaomei Wang1, Angelika Paul2, Jiandie Lin3, Bruce M. Spiegelman4, Susan C Stevenson1, and Shamina M Rangwala1*

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

* To whom correspondence should be addressed. E-mail: shamina.rangwala{at}novartis.com.

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 VO2 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.




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