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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Corset, Laetitia Mallet, Jacques Belouzard, Sandrine Sarkis, Chamsy Jockers, Ralf Lenain, Aude Séron, Karin Couturier, Cyril Chen, Patty Vauthier, Virginie Rouillé, Yves Dubart, Anne Dam, Julie Froguel, Philippe |
| Description | Author Affiliation: Couturier C ( Departments of Cell Biology and Hematology, Institut Cochin, Unité Mixte de Recherche 8104, Centre National de la Recherche Scientifique, Université Paris Descartes, 75014 Paris, France.); |
| Abstract | Obesity is a major public health problem and is often associated with type 2 diabetes mellitus, cardiovascular disease, and metabolic syndrome. Leptin is the crucial adipostatic hormone that controls food intake and body weight through the activation of specific leptin receptors (OB-R) in the hypothalamic arcuate nucleus (ARC). However, in most obese patients, high circulating levels of leptin fail to bring about weight loss. The prevention of this 'leptin resistance' is a major goal for obesity research. We report here a successful prevention of diet-induced obesity (DIO) by silencing a negative regulator of OB-R function, the OB-R gene-related protein (OB-RGRP), whose transcript is genetically linked to the OB-R transcript. We provide in vitro evidence that OB-RGRP controls OB-R function by negatively regulating its cell surface expression. In the DIO mouse model, obesity was prevented by silencing OB-RGRP through stereotactic injection of a lentiviral vector encoding a shRNA directed against OB-RGRP in the ARC. This work demonstrates that OB-RGRP is a potential target for obesity treatment. Indeed, regulators of the receptor could be more appropriate targets than the receptor itself. This finding could serve as the basis for an approach to identifying potential new therapeutic targets for a variety of diseases, including obesity. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 49 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Arcuate Nucleus Of Hypothalamus Metabolism Carrier Proteins Antagonists & Inhibitors Leptin Obesity Prevention & Control Receptors, Leptin Animals Genetics Diet Dietary Fats Administration & Dosage Genes, Reporter Green Fluorescent Proteins Hypothalamus Lentivirus Mice Mice, Inbred C57BL Oligonucleotides, Antisense Signal Transduction Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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