An increase in murine skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mRNA in response to exercise is mediated by β-adrenergic receptor activation
An increase in murine skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mRNA in response to exercise is mediated by β-adrenergic receptor activation
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DOI：
10.1210/en.2006-1646
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发表时间：
2007-07-01
期刊：
影响因子：
4.8
通讯作者：
Ezaki, Osamu
中科院分区：
文献类型：
--
作者：
Miura, Shinji;Kawanaka, Kentaro;Ezaki, Osamu
单次运动增加过氧化物酶体增殖物激活受体-γ共激活因子（PGC）-1 α mRNA的表达，这可能促进骨骼肌中的线粒体生物合成。在棕色脂肪组织中，冷暴露通过肾上腺素能受体（AR）激活上调PGC-1 α表达。由于运动也激活交感神经系统，我们研究了运动诱导的骨骼肌中PGC-1 α mRNA表达的增加是否通过AR激活介导。在C57 BL/6 J小鼠中，注射β 2-AR激动剂克仑特罗，而不是α-，β 1-或β 3-AR激动剂，增加骨骼肌中PGC-1 α mRNA表达超过30倍。用β-AR拮抗剂普萘洛尔预处理可抑制克伦特罗诱导的小鼠PGC-1 α mRNA表达增加。在离体实验中，大鼠上滑车直接暴露于β 2-AR激动剂，而不是α-、β 1-和β 3-AR激动剂，导致PGC-1 α mRNA水平增加。注射β 2-AR激动剂不会增加β 1-、β 2-和β 3-AR敲除小鼠（无β小鼠）中PGC-1 α mRNA的表达。腓肠肌中的PGC-1 α mRNA在跑步机上跑步45分钟后增加3.5倍。运动诱导的PGC-1 α mRNA增加被普萘洛尔或β 2-AR特异性抑制剂ICI 118，551抑制约70%。运动诱导的PGC-1 α mRNA在β-less小鼠中的增加也比野生型小鼠低36%。这些数据表明，运动引起的骨骼肌中PGC-1 α表达的上调至少部分由β-AR激活介导。在AR中，β 2-AR可能通过运动介导PGC-1 α的增加。
A single bout of exercise increases expression of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1 alpha mRNA, which may promote mitochondrial biogenesis in skeletal muscle. In brown adipose tissue, cold exposure up-regulates PGC-1 alpha expression via adrenergic receptor (AR) activation. Because exercise also activates the sympathetic nervous system, we examined whether exercise-induced increase in PGC-1 alpha mRNA expression in skeletal muscle was mediated via AR activation. In C57BL/6J mice, injection of the beta 2-AR agonist clenbuterol, but not alpha-, beta 1-, or beta 3-AR agonists, increased PGC-1 alpha mRNA expression more than 30-fold in skeletal muscle. The clenbuterol-induced increase in PGC-1 alpha mRNA expression in mice was inhibited by pretreatment with the beta-AR antagonist propranolol. In ex vivo experiments, direct exposure of rat epitrochlearis to beta 2-AR agonist, but not alpha-, beta 1-, and beta 3-AR agonist, led to an increase in levels of PGC-1 alpha mRNA. Injection of beta 2-AR agonist did not increase PGC-1 alpha mRNA expression in beta 1-, beta 2-, and beta 3-AR knockout mice (beta-less mice). PGC-1 alpha 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 alpha mRNA was inhibited by approximately 70% by propranolol or the beta 2-AR-specific inhibitor ICI 118,551. The exercise-induced increase in PGC-1 alpha mRNA in beta-less mice was also 36% lower than that in wild-type mice. These data indicate that up-regulation of PGC-1 alpha expression in skeletal muscle by exercise is mediated, at least in part, by beta-ARs activation. Among ARs, beta 2-AR may mediate an increase in PGC-1 alpha by exercise.