Ciliary Neurotrophic Factor: a novel theraputic agent for the prevention of muscle insulin resistance

1995年，瘦素被发现，全世界的科学家都希望这是治疗肥胖相关疾病的灵丹妙药。然而，从1995年到1997年，发现了一种新的细胞因子诱导化合物，称为细胞因子信号抑制因子（SOCS），它负调控瘦素信号传导并导致瘦素抵抗，使开发一种可行的抗肥胖药物的希望落空。然而，最近，我们小组的工作已经证明，神经生成性细胞因子，纤毛神经营养因子（CNTF），可以以类似瘦素的方式发挥抗肥胖作用。然而，与瘦素不同的是，当我们将啮齿动物置于高脂肪饮食中时，CNTF的影响持续存在并覆盖诱导SOCS蛋白。该项目将研究允许CNTF在饮食引起的肥胖中持续作用的生化途径。这是重要的意义，因为在完成这项工作后，开发治疗肥胖相关疾病的外周组织药物靶点的潜力是切实和现实的。

In 1995 leptin was discovered and scientists world-wide hoped that this was the great panacea in the treatment of obesity related disorders. Alas, from 1995-1997 the identification of a novel cytokine inducible compound termed suppressor of cytokine signaling (SOCS) that negatively regulated leptin signalling and lead to leptin resistance, quashing hopes for a viable anti-obesogenic drug. Recently, however, work from our group has demonstrated that the neuropoietic cytokine, ciliary neurotrophic factor (CNTF), can act in an anti-obesogenic fashion in a manner similar to leptin. However, unlike leptin, when we place rodents on a high fat diet, the effects of CNTF persist and override induction SOCS proteins. This project will examine the biochemical pathways that allow the actions of CNTF to persist in the presence of diet-induced obesity. This is of major significance because in completing this work, the potential for the development of peripheral tissue drug targets for the treatment of obesity related diseases are both tangible and realistic.