Abstract
A single bout of exercise increases expression of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha mRNA, which may promote mitochondrial biogenesis in skeletal muscle. In brown adipose tissue, cold exposure up-regulates PGC-1alpha expression via adrenergic receptor (AR) activation. Because exercise also activates the sympathetic nervous system, we examined whether exercise-induced increase in PGC-1alpha mRNA expression in skeletal muscle was mediated via AR activation. In C57BL/6J mice, injection of the beta2-AR agonist clenbuterol, but not alpha-, beta1-, or beta3-AR agonists, increased PGC-1alpha mRNA expression more than 30-fold in skeletal muscle. The clenbuterol-induced increase in PGC-1alpha mRNA expression in mice was inhibited by pretreatment with the beta-AR antagonist propranolol. In ex vivo experiments, direct exposure of rat epitrochlearis to beta2-AR agonist, but not alpha-, beta1-, and beta3-AR agonist, led to an increase in levels of PGC-1alpha mRNA. Injection of beta2-AR agonist did not increase PGC-1alpha mRNA expression in beta1-, beta2-, and beta3-AR knockout mice (beta-less mice). PGC-1alpha mRNA in gastrocnemius was increased 3.5-fold in response to running on a treadmill for 45 min. The exercise-induced increase in PGC-1alpha mRNA was inhibited by approximately 70% by propranolol or the beta2-AR-specific inhibitor ICI 118,551. The exercise-induced increase in PGC-1alpha mRNA in beta-less mice was also 36% lower than that in wild-type mice. These data indicate that up-regulation of PGC-1alpha expression in skeletal muscle by exercise is mediated, at least in part, by beta-ARs activation. Among ARs, beta2-AR may mediate an increase in PGC-1alpha by exercise.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-Agonists / pharmacology
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Adrenergic beta-1 Receptor Agonists
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Adrenergic beta-2 Receptor Agonists
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Adrenergic beta-3 Receptor Agonists
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Adrenergic beta-Agonists / pharmacology
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Animals
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Blotting, Northern
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Clenbuterol / pharmacology
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Dioxoles / pharmacology
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Dobutamine / pharmacology
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Gene Expression Regulation / drug effects
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / metabolism*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Phenylephrine / pharmacology
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Physical Conditioning, Animal / physiology*
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Propranolol / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism*
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Receptors, Adrenergic, alpha / metabolism
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Receptors, Adrenergic, beta / genetics
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Receptors, Adrenergic, beta / metabolism*
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Receptors, Adrenergic, beta-1 / genetics
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Receptors, Adrenergic, beta-1 / metabolism
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Receptors, Adrenergic, beta-2 / genetics
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Receptors, Adrenergic, beta-2 / metabolism
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Receptors, Adrenergic, beta-3 / genetics
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Receptors, Adrenergic, beta-3 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Trans-Activators / genetics*
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Transcription Factors
Substances
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Adrenergic alpha-Agonists
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Adrenergic beta-1 Receptor Agonists
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Adrenergic beta-2 Receptor Agonists
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Adrenergic beta-3 Receptor Agonists
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Adrenergic beta-Agonists
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Dioxoles
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Ppargc1a protein, mouse
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RNA, Messenger
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Receptors, Adrenergic, alpha
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Receptors, Adrenergic, beta
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Receptors, Adrenergic, beta-1
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Receptors, Adrenergic, beta-2
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Receptors, Adrenergic, beta-3
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Trans-Activators
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Transcription Factors
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disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
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Phenylephrine
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Dobutamine
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Propranolol
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Clenbuterol