Silencing of OB-RGRP in mouse hypothalamic arcuate nucleus increases leptin receptor signaling and prevents diet-induced obesity
| Autor: | Laetitia Corset, Ralf Jockers, Virginie Vauthier, Aude Lenain, Philippe Froguel, Julie Dam, Yves Rouillé, Patty Chen, Jacques Mallet, Cyril Couturier, Chamsy Sarkis, Sandrine Belouzard, Karin Séron, A Dubart |
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| Přispěvatelé: | Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Department of Genomic Medicine, Imperial College London-Hammersmith Hospital, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs ( LGMNPN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Garcia, Marie |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Leptin
Male MESH: Signal Transduction [SDV.BIO]Life Sciences [q-bio]/Biotechnology MESH : Receptors Leptin MESH : Green Fluorescent Proteins Mice 0302 clinical medicine MESH: Oligonucleotides Antisense Genes Reporter MESH: Obesity MESH: Animals [INFO.INFO-BT]Computer Science [cs]/Biotechnology Receptor MESH: Lentivirus 2. Zero hunger 0303 health sciences Multidisciplinary Arc (protein) Intracellular Signaling Peptides and Proteins Biological Sciences MESH : Genes Reporter 3. Good health MESH : Lentivirus Hypothalamus MESH: Dietary Fats MESH : Leptin Receptors Leptin MESH : Obesity MESH : Carrier Proteins [ INFO.INFO-BT ] Computer Science [cs]/Biotechnology Signal Transduction medicine.medical_specialty MESH : Hypothalamus MESH : Male Green Fluorescent Proteins MESH: Arcuate Nucleus MESH: Carrier Proteins MESH : Mice Inbred C57BL MESH: Receptors Leptin Biology MESH : Arcuate Nucleus MESH : Diet 03 medical and health sciences MESH: Green Fluorescent Proteins MESH: Diet MESH: Mice Inbred C57BL Internal medicine MESH : Mice medicine Gene silencing Animals Obesity MESH: Mice 030304 developmental biology MESH : Signal Transduction Leptin receptor Lentivirus MESH : Oligonucleotides Antisense MESH: Genes Reporter Arcuate Nucleus of Hypothalamus [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology MESH: Leptin Oligonucleotides Antisense medicine.disease Dietary Fats MESH: Hypothalamus MESH: Male Diet [SDV.BIO] Life Sciences [q-bio]/Biotechnology Mice Inbred C57BL Endocrinology [INFO.INFO-BT] Computer Science [cs]/Biotechnology MESH : Animals Metabolic syndrome Carrier Proteins 030217 neurology & neurosurgery MESH : Dietary Fats |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 (49), pp.19476-81. ⟨10.1073/pnas.0706671104⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2007, 104 (49), pp.19476-81. ⟨10.1073/pnas.0706671104⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2007, 104 (49), pp.19476-81. 〈10.1073/pnas.0706671104〉 |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.0706671104⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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