Treatment of Obesity with Celastrol

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 god vine) plant, is a powerful anti-obesity agent. Celastrol suppresses food intake, blocks reduction of energy expenditure, and leads to up to 45% weight loss in hyperleptinemic diet-induced obese (DIO) mice by increasing leptin sensitivity, but it is ineffective in leptin-deficient (ob/ob) and 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. [Display omitted] •Celastrol is a natural compound extracted from thunder god vine•Celastrol creates similar expression profile to those of reduced ER stress conditions•Celastrol is a powerful leptin sensitizer•Celastrol has potential as an anti-obesity therapeutic agent Celastrol, a natural compound found in the roots of the thunder god vine, increases leptin sensitivity to suppress food intake and dramatically reduce body weight of obese mice.