CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK
CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK
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DOI：
10.1038/nm1383
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发表时间：
2006-05-01
期刊：
影响因子：
82.9
通讯作者：
Steinberg, Gregory R.
中科院分区：
文献类型：
--
作者：
Watt, Matthew J.;Dzamko, Nicolas;Steinberg, Gregory R.
睫状神经营养因子（CNTF）诱导体重减轻并改善人类和啮齿动物的葡萄糖耐量。CNTF被认为是通过诱导下丘脑神经发生来调节食物摄入的中枢作用和通过改变肝脏基因表达的外周作用，其方式类似于瘦素。在这里，我们表明，CNTF信号通过CNTFR α-IL-6 R-gp 130 β受体复合物，以增加脂肪酸氧化，并通过激活AMP活化蛋白激酶（AMPK），减少骨骼肌胰岛素抵抗，独立于通过大脑的信号。因此，我们的研究结果进一步表明，CNTF在外周的抗肥胖作用是由对骨骼肌的直接作用引起的，并且这些外周作用不受肥胖的饮食诱导或遗传模型的抑制，这是肥胖相关疾病治疗的基本要求。
Ciliary neurotrophic factor (CNTF) induces weight loss and improves glucose tolerance in humans and rodents. CNTF is thought to act centrally by inducing hypothalamic neurogenesis to modulate food intake and peripherally by altering hepatic gene expression, in a manner similar to that of leptin. Here, we show that CNTF signals through the CNTFR alpha-IL-6R-gp130 beta receptor complex to increase fatty-acid oxidation and reduce insulin resistance in skeletal muscle by activating AMP-activated protein kinase (AMPK), independent of signaling through the brain. Thus, our findings further show that the antiobesogenic effects of CNTF in the periphery result from direct effects on skeletal muscle, and that these peripheral effects are not suppressed by diet-induced or genetic models of obesity, an essential requirement for the therapeutic treatment of obesity-related diseases.