Watt Matthew J, Dzamko Nicolas, Thomas Walter G, Rose-John Stefan, Ernst Matthias, Carling David, Kemp Bruce E, Febbraio Mark A, Steinberg Gregory R
Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, Royal Melbourne Institute of Technology, PO Box 71, Bundoora, 3083, Australia.
Nat Med. 2006 May;12(5):541-8. doi: 10.1038/nm1383. Epub 2006 Apr 9.
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 CNTFRalpha-IL-6R-gp130beta 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.
睫状神经营养因子（CNTF）可导致人类和啮齿动物体重减轻并改善糖耐量。人们认为CNTF通过诱导下丘脑神经发生来调节食物摄入，从而在中枢发挥作用；同时，它也通过改变肝脏基因表达，以类似于瘦素的方式在周围发挥作用。在此，我们表明CNTF通过CNTFRα-IL-6R-gp130β受体复合物发出信号，通过激活AMP激活的蛋白激酶（AMPK）来增加骨骼肌中的脂肪酸氧化并降低胰岛素抵抗，这一过程不依赖于通过大脑的信号传导。因此，我们的研究结果进一步表明，CNTF在周围组织中的抗肥胖作用源于对骨骼肌的直接作用，并且这些周围组织的作用不会被饮食诱导的肥胖模型或遗传肥胖模型所抑制，这是治疗肥胖相关疾病的一项基本要求。
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