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

1 Diabetes and Metabolism Disease Area and 2 Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Cambridge; and 3 Dana 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- coactivator-1 (PGC-1 ), 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 in muscle is sufficient to improve performance during exercise in vivo. We demonstrate that muscle-specific expression of PGC-1 improves the performance during voluntary as well as forced exercise challenges. Additionally, PGC-1 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 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 -coactivator-1 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 )