Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes
Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes
复制标题
脱氢表雄酮激活 AMP 激酶并调节 C2C12 肌管中 GLUT4 和 PGC-1α 的表达
DOI：
10.1016/j.bbrc.2015.05.013
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发表时间：
2015
影响因子：
3.1
通讯作者：
Hashimoto T
中科院分区：
文献类型：
--
作者：
Yokokawa T;Sato K;Iwanaka N;Honda H;Higashida K;Iemitsu M;Hayashi T;Hashimoto T
据报道，运动和热量限制（CR）具有抗衰老、抗肥胖和促进健康的作用。这两种干预措施都会增加肌肉和血液中脱氢表雄酮 (DHEA) 的水平，表明 DHEA 可能部分介导这些作用。此外，人们认为 5'-单磷酸腺苷激活蛋白激酶 (AMPK) 或过氧化物酶体增殖物激活受体-γ 辅激活因子-1α (PGC-1α) 介导运动和 CR 的有益效果。然而，DHEA 对 AMPK 活性和 PGC-1α 表达的影响仍不清楚。因此，我们探讨了肌管中的 DHEA 是否充当 AMPK 激活剂并增加 PGC-1α。DHEA 暴露会增加葡萄糖摄取，但不会增加 C2C12 肌管中 Akt 和 PKCz/λ 的磷酸化水平。相反，暴露 DHEA 后 AMPK 的磷酸化水平升高。最后，我们发现DHEA诱导PGC-1α和GLUT4基因的表达。我们目前的结果可能揭示了DHEA以前未被认识到的生理作用； DHEA 激活 AMPK 和诱导 PGC-1α 可能会介导其在生物体中的抗肥胖和促进健康的作用。
Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5′-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α.DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4.Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms.