Cell, May 21, 2015, Vol.161(5), p.999(13)
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2015.05.011 Byline: Junli Liu, Jaemin Lee, Mario Andres Salazar Hernandez, Ralph Mazitschek, Umut Ozcan 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. Author Affiliation: (1) Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02130, USA (2) Massachusetts General Hospital, Center for Systems Biology, Boston, MA 02114, USA (3) The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA Article History: Received 26 November 2014; Revised 5 January 2015; Accepted 16 April 2015 Article Note: (miscellaneous) Published: May 21, 2015
Leptin – Analysis ; Obesity – Drug Therapy ; Obesity – Analysis
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