Treatment of obesity with celastrol.
Treatment of obesity with celastrol.
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DOI：
10.1016/j.cell.2015.05.011
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发表时间：
2015-05-21
期刊：
影响因子：
64.5
通讯作者：
Ozcan U
中科院分区：
文献类型：
--
作者：
Liu J;Lee J;Salazar Hernandez MA;Mazitschek R;Ozcan U
尽管现代医学取得了很大的进步，但迄今为止还没有发现一种有效的治疗肥胖的药物。二十年前瘦素的发现为治疗肥胖带来了希望。然而，瘦素抵抗的发展一直是一个很大的障碍，减轻了以瘦素为中心的肥胖治疗。本研究通过计算机药物筛选方法，发现从雷公藤（雷公藤）根部提取的一种五环三萜Celastrol是一种有效的抗肥胖药物。Celastrol抑制食物摄入，阻断能量消耗的减少，并通过增加瘦素敏感性导致高瘦素血症饮食诱导肥胖（DIO）小鼠体重减轻45%，但在瘦素缺乏（ob/ob）或瘦素受体缺乏（db/db）小鼠模型中无效。这些结果表明，雷公藤红素是一种瘦素增敏剂，是一种很有前景的药物治疗肥胖。
Despite all modern advances in medicine, an effective drug treatment of obesity has not been found yet. Discovery of leptin two decades ago created hopes for treatment of obesity. However, development of leptin resistance has been a big obstacle, mitigating a leptin-centric treatment of obesity. Here, by using in silico drug screening methods we discovered that Celastrol, a pentacyclic triterpene extracted from the roots of Tripterygium Wilfordi (Thunder of God Vine) plant, is a powerful anti-obesity agent. Celastrol suppresses food intake, blocks reduction of energy expenditure and leads up to 45% weight loss in hyperleptinemic diet-induced obese (DIO) mice by increasing leptin sensitivity, but is ineffective in leptin-deficient (ob/ob) or leptin receptor-deficient (db/db) mouse models. These results indicate that Celastrol is a leptin sensitizer and a promising agent for the pharmacological treatment of obesity.