Treatment of obesity with celastrol.

Cell
Authors
Keywords
Abstract

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.

Year of Publication
2015
Journal
Cell
Volume
161
Issue
5
Pages
999-1011
Date Published
2015 May 21
ISSN
1097-4172
DOI
10.1016/j.cell.2015.05.011
PubMed ID
26000480
PubMed Central ID
PMC4768733
Links
Grant list
R01 DK098496 / DK / NIDDK NIH HHS / United States
R01DK098496 / DK / NIDDK NIH HHS / United States