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Submitted on December 7, 2006
Accepted on April 6, 2007
mRNA in Response to Exercise is Mediated by 
-Adrenergic Receptor Activation
National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan; Niigata University of Health and Welfare, 1398 Shimami-cho, Niigata 950-3198, Japan; Molecular Medicine Research Labs, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba 305-8585, Japan; National Institute for Physiological Sciences and the Graduate University for Advanced Studies, 38 Nishigonaka, Myodaiji, Okazaki 444-8585, Japan
* To whom correspondence should be addressed. E-mail: shinjim{at}nih.go.jp or ezaki{at}nih.go.jp.
A single bout of exercise increases expression of peroxisome proliferator-activated receptor 
coactivator 1
(PGC-1) mRNA, which may promote mitochondrial biogenesis in skeletal muscle. In brown adipose tissue, cold exposure up-regulates PGC-1 expression via adrenergic receptor (AR) activation. Because exercise also activates the sympathetic nervous system (SNS), we examined whether exercise-induced increase in PGC-1 mRNA expression in skeletal muscle was mediated via AR activation. In C57BL/6J mice, injection of the 
2-AR agonist clenbuterol, but not -, 1-, or 3-AR agonists, increased PGC-1 mRNA expression more than 30-fold in skeletal muscle. The clenbuterol-induced increase in PGC-1 mRNA expression in mice was inhibited by pretreatment with the -AR antagonist propranolol. In ex vivo experiments, direct exposure of rat epitrochlearis to 2-AR agonist, but not -, 1-, and 3-AR agonist, lead to an increase in levels of PGC-1 mRNA. Injection of 2-AR agonist did not increase PGC-1 mRNA expression in 1-, 2-, and 3-ARs knockout mice (-less mice). PGC-1 mRNA in gastrocnemius was increased 3.5-fold in response to running on a treadmill for 45 min. The exercise-induced increase in PGC-1 mRNA was inhibited by approximately 70% by propranolol or the 2-AR-specific inhibitor ICI 118,551. The exercise-induced increase in PGC-1 mRNA in -less mice was also 36% lower that that in wild-type mice. These data indicate that up-regulation of PGC-1 expression in skeletal muscle by exercise is mediated, at least in part, by -ARs activation. Among ARs, 2-AR may mediate an increase in PGC-1 by exercise.
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