The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms
| Autor: | Michael O. Thorner, Kirk M. Habegger, Gunnar Kleinau, Chun-Xia Yi, Carola W. Meyer, Jenna Holland, Franziska Meyer, Heiko Krude, Anne Müller, Floyd R. Sallee, Jazzmin Hembree, Paul T. Pfluger, Christine Raver, Kristy M. Heppner, Bruce D. Gaylinn, Martin Bidlingmaier, Heike Biebermann, Diego Perez-Tilve, Juliane Pratzka, Renu Sah, William Abplanalp, Stephen C. Woods, Timo D. Müller, Nickki Ottaway, David L. Smiley, Nakul Bhardwaj, Richard D. DiMarchi, Susanna M. Hofmann, Brian Finan, Kerstin Stemmer, Chitrang Trivedi, Radha Krishna, Carolin L. Piechowski, Matthias H. Tschöp, Maximilian Bielohuby |
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| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty General Physics and Astronomy Biology Diet High-Fat Article General Biochemistry Genetics and Molecular Biology Receptors G-Protein-Coupled Mice Internal medicine Orexigenic medicine Animals Humans Agouti-Related Protein Obesity ddc:610 Receptors Ghrelin Receptor Mice Knockout Orphan receptor Multidisciplinary Gene Expression Profiling Body Weight digestive oral and skin physiology Arcuate Nucleus of Hypothalamus Feeding Behavior General Chemistry Metabolism Ghrelin ddc Rats Mice Inbred C57BL Protein Transport Phenotype Endocrinology Adipogenesis Body Composition Protein Multimerization Signal transduction Melanocortin Energy Metabolism hormones hormone substitutes and hormone antagonists Receptor Melanocortin Type 3 Signal Transduction medicine.drug |
| Zdroj: | Nature communications, 4. Nature Publishing Group Nature Communications Nat. Commun. 4:1968 (2013) |
| DOI: | 10.1038/ncomms2968 |
| Popis: | The G protein-coupled receptor 83 (Gpr83) is widely expressed in brain regions regulating energy metabolism. Here we report that hypothalamic expression of Gpr83 is regulated in response to nutrient availability and is decreased in obese mice compared with lean mice. In the arcuate nucleus, Gpr83 colocalizes with the ghrelin receptor (Ghsr1a) and the agouti-related protein. In vitro analyses show heterodimerization of Gpr83 with Ghsr1a diminishes activation of Ghsr1a by acyl-ghrelin. The orexigenic and adipogenic effect of ghrelin is accordingly potentiated in Gpr83-deficient mice. Interestingly, Gpr83 knock-out mice have normal body weight and glucose tolerance when fed a regular chow diet, but are protected from obesity and glucose intolerance when challenged with a high-fat diet, despite hyperphagia and increased hypothalamic expression of agouti-related protein, Npy, Hcrt and Ghsr1a. Together, our data suggest that Gpr83 modulates ghrelin action but also indicate that Gpr83 regulates systemic metabolism through other ghrelin-independent pathways. The murine G protein-coupled receptor 83 (Gpr83) is expressed widely in the brain, but its physiological role is largely unknown. Here Müller et al. show that Gpr83 regulates systemic energy metabolism in part by modulating ghrelin signalling in the arcuate nucleus of the hypothalamus. |
| Databáze: | OpenAIRE |
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