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

1995年，瘦素被发现，全世界的科学家希望这是治疗肥胖相关疾病的伟大灵丹妙药。遗憾的是，1995年至1997年发现了一种新的细胞因子诱导化合物，称为细胞因子信号转导抑制因子(SOCS)，它负调控瘦素信号转导并导致瘦素耐药，粉碎了人们对可行的抗肥胖药物的希望。然而，最近我们小组的工作表明，神经生成细胞因子睫状神经营养因子(CNTF)可以以类似于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，并超过诱导SOCS蛋白。该项目将研究使CNTF的作用在饮食诱导的肥胖中持续存在的生化途径。这具有重大意义，因为在完成这项工作的过程中，开发用于治疗肥胖相关疾病的外周组织药物靶点的潜力既是切实的，也是现实的。

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.