Muscle-specific expression of PPARγ coactivator-1α improves exercise performance and increases peak oxygen uptake

被引:299
作者
Calvo, Jennifer A. [1 ]
Daniels, Thomas G. [1 ]
Wang, Xiaomei [1 ]
Paul, Angelika [2 ]
Lin, Jiandie [3 ]
Spiegelman, Bruce M. [3 ]
Stevenson, Susan C. [1 ]
Rangwala, Shamina M. [1 ]
机构
[1] Novartis Inst BioMed Res, Diabet & Metab Dis Area, Cambridge, MA 02139 USA
[2] Novartis Inst BioMed Res, Musculoskeletal Dis Area, Cambridge, MA 02139 USA
[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
关键词
exercise capacity; peak oxygen uptake; peroxisome proliferator-activated receptor gamma-coactivator-1 alpha;
D O I
10.1152/japplphysiol.01231.2007
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:1304 / 1312
页数:9
相关论文
共 46 条
[1]   Exercise stimulates Pgc-1α transcription in skeletal muscle through activation of the p38 MAPK pathway [J].
Akimoto, T ;
Pohnert, SC ;
Li, P ;
Zhang, M ;
Gumbs, C ;
Rosenberg, PB ;
Williams, RS ;
Yan, Z .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (20) :19587-19593
[2]   Transcriptional coactivator PGC-1α controls the energy state and contractile function of cardiac muscle [J].
Arany, Z ;
He, HM ;
Lin, JD ;
Hoyer, K ;
Handschin, C ;
Toka, O ;
Ahmad, F ;
Matsui, T ;
Chin, S ;
Wu, PH ;
Rybkin, II ;
Shelton, JM ;
Manieri, M ;
Cinti, S ;
Schoen, FJ ;
Bassel-Duby, R ;
Rosenzweig, A ;
Ingwall, JS ;
Spiegelman, BM .
CELL METABOLISM, 2005, 1 (04) :259-271
[3]   The transcriptional coactivator PGC-1β drives the formation of oxidative type IIX fibers in skeletal muscle [J].
Arany, Zoltan ;
Lebrasseur, Nathan ;
Morris, Carl ;
Smith, Eric ;
Yang, Wenli ;
Ma, Yanhong ;
Chin, Sherry ;
Spiegelman, Bruce M. .
CELL METABOLISM, 2007, 5 (01) :35-46
[4]   Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1 [J].
Baar, K ;
Wende, AR ;
Jones, TE ;
Marison, M ;
Nolte, LA ;
Chen, M ;
Kelly, DP ;
Holloszy, JO .
FASEB JOURNAL, 2002, 16 (14) :1879-1886
[5]   RESPIRATORY CAPACITY OF WHITE, RED, AND INTERMEDIATE MUSCLE - ADAPTATIVE RESPONSE TO EXERCISE [J].
BALDWIN, KM ;
TERJUNG, RL ;
HOLLOSZY, JO ;
KLINKERFUSS, GH ;
MOLE, PA .
AMERICAN JOURNAL OF PHYSIOLOGY, 1972, 222 (02) :373-+
[6]   EFFECTS OF DETRAINING ON ENZYMES OF ENERGY-METABOLISM IN INDIVIDUAL HUMAN-MUSCLE FIBERS [J].
CHI, MMY ;
HINTZ, CS ;
COYLE, EF ;
MARTIN, WH ;
IVY, JL ;
NEMETH, PM ;
HOLLOSZY, JO ;
LOWRY, OH .
AMERICAN JOURNAL OF PHYSIOLOGY, 1983, 244 (03) :C276-C287
[7]   EFFECT OF PHYSICAL-TRAINING ON INSULIN ACTION IN OBESITY [J].
DEFRONZO, RA ;
SHERWIN, RS ;
KRAEMER, N .
DIABETES, 1987, 36 (12) :1379-1385
[8]   Poor physical fitness, and impaired early insulin response but late hyperinsulinaemia, as predictors of NIDDM in middle-aged Swedish men [J].
Eriksson, KF ;
Lindgarde, F .
DIABETOLOGIA, 1996, 39 (05) :573-579
[9]   Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training [J].
Friedlander, Anne L. ;
Jacobs, Kevin A. ;
Fattor, Jill A. ;
Horning, Michael A. ;
Hagobian, Todd A. ;
Bauer, Timothy A. ;
Wolfel, Eugene E. ;
Brooks, George A. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2007, 292 (01) :E107-E116
[10]   Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity [J].
Goodpaster, BH ;
Katsiaras, A ;
Kelley, DE .
DIABETES, 2003, 52 (09) :2191-2197