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      Treatment of obesity with celastrol.

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          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.

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          Author and article information

          Journal
          Cell
          Cell
          1097-4172
          0092-8674
          May 21 2015
          : 161
          : 5
          Affiliations
          [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; The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
          [3 ] Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02130, USA. Electronic address: umut.ozcan@childrens.harvard.edu.
          Article
          S0092-8674(15)00559-0 NIHMS689103
          10.1016/j.cell.2015.05.011
          26000480
          Copyright © 2015 Elsevier Inc. All rights reserved.

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