Muscle-specific expression of PPARgamma coactivator-1alpha improves exercise performance and increases peak oxygen uptake.
The induction of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), 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-1alpha in muscle is sufficient to improve performance during exercise in vivo. We demonstrate that muscle-specific expression of PGC-1alpha improves the performance during voluntary as well as forced exercise challenges. Additionally, PGC-1alpha 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-1alpha in muscle in vivo is sufficient to greatly improve exercise performance under various exercise paradigms as well as increase peak oxygen uptake.
Calvo
Jennifer A
JA
Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, MA 02139, USA.
Daniels
Thomas G
TG
Wang
Xiaomei
X
Paul
Angelika
A
Lin
Jiandie
J
Spiegelman
Bruce M
BM
Stevenson
Susan C
SC
Rangwala
Shamina M
SM
D015308:Anaerobic Threshold / Q000502:physiology*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000096:biosynthesis; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000235:genetics; D018149:Glucose Intolerance / Q000503:physiopathology; D006003:Glycogen / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology*; D047495:PPAR gamma / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011659:Pulmonary Gas Exchange / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012420:Running / Q000502:physiology; D015534:Trans-Activators / Q000096:biosynthesis* / Q000502:physiology*; D014157:Transcription Factors
D004272:DNA, Mitochondrial; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D006003:Glycogen; D002950:Citrate (si)-Synthase