Matthews Vance B, Febbraio Mark A
Division of Diabetes and Metabolism, Cellular and Molecular Metabolism Laboratory, Baker Heart Research Institute, P.O. Box 6492, St Kilda Road Central, VIC 8008, Australia.
J Mol Med (Berl). 2008 Apr;86(4):353-61. doi: 10.1007/s00109-007-0286-y. Epub 2008 Jan 22.
Obesity and type 2 diabetes are the most prevalent metabolic diseases in the western world. Alarmingly, the cluster of pathologies characteristic of obesity-induced disease have started to emerge in children, a phenomenon that up until a decade ago was inconceivable. Hence, the development of new strategies to treat 'metabolic disease' is most warranted. Growing evidence suggests that during type 2 diabetes, a state of chronic low-grade inflammation exists in metabolically active tissues such as the liver, adipose tissue and skeletal muscle. This inflammation is often secondary to lipid accumulation in insulin-responsive tissues. Recent studies have focused on the therapeutic potential of ciliary neurotrophic factor (CNTF). CNTF is a pluripotent neurocytokine and, has shown promise as a potential anti-obesogenic therapy. CNTF acts both centrally and peripherally, mimics the biological actions of leptin while overcoming "leptin resistance", remains effective even after termination of therapy if administered centrally, and appears to reduce inflammatory signaling cascades associated with lipid accumulation in liver and skeletal muscle. The advantages and disadvantages of CNTF as a therapeutic strategy to alleviate obesity-associated diseases will be highlighted in this review.
肥胖症和2型糖尿病是西方世界最普遍的代谢性疾病。令人担忧的是,肥胖诱发疾病所特有的一系列病理特征已开始在儿童中出现,而这一现象在十年前是不可想象的。因此,开发治疗“代谢性疾病”的新策略非常必要。越来越多的证据表明,在2型糖尿病期间,肝脏、脂肪组织和骨骼肌等代谢活跃组织中存在慢性低度炎症状态。这种炎症通常继发于胰岛素反应性组织中的脂质积累。最近的研究集中在睫状神经营养因子(CNTF)的治疗潜力上。CNTF是一种多能神经营养因子,已显示出作为一种潜在的抗肥胖疗法的前景。CNTF在中枢和外周均有作用,模拟瘦素的生物学作用,同时克服“瘦素抵抗”,如果通过中枢给药,即使在治疗终止后仍保持有效,并且似乎能减少与肝脏和骨骼肌脂质积累相关的炎症信号级联反应。本文将重点介绍CNTF作为缓解肥胖相关疾病治疗策略的优缺点。