title: Treatment of obesity with celastrol.
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.
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02130, USA.
authors.forename: Junli
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02130, USA.
authors.forename: Jaemin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02130, USA.
authors.forename: Mario Andres
authors.initials: MA
authors.lastname: Salazar Hernandez
authors.affiliation: 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.
authors.forename: Ralph
authors.initials: R
authors.lastname: Mazitschek
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02130, USA. Electronic address: umut.ozcan@childrens.harvard.edu.
authors.forename: Umut
authors.initials: U
authors.lastname: Ozcan
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage* / Q000378:metabolism; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts / Q000008:administration & dosage; D029757:Tripterygium / Q000737:chemistry; D014315:Triterpenes / Q000008:administration & dosage
chemical_list: D019440:Anti-Obesity Agents; D020738:Leptin; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; D005947:Glucose; C050414:celastrol