The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms

Timo D. Müller, Anne Müller, Chun-Xia Yi, Kirk M Habegger, Carola W. Meyer, Bruce D. Gaylinn, Brian Finan, Kristy Heppner, Chitrang Trivedi, Maximilian Bielohuby, William Abplanalp, Franziska Meyer, Carolin L. Piechowski, Juliane Pratzka, Kerstin Stemmer, Jenna Holland, Jazzmin Hembree, Nakul Bhardwaj, Christine Raver, Nickki Ottaway, Radha Krishna, Renu Sah, Floyd R. Sallee, Stephen C. Woods, Diego Perez-Tilve, Martin Bidlingmaier, Michael O. Thorner, Heiko Krude, David Smiley, Richard DiMarchi, Susanna Hofmann, Paul T. Pfluger, Gunnar Kleinau, Heike Biebermann and Matthias H. Tschöp ()
Additional contact information
Timo D. Müller: Institute for Diabetes and Obesity, Technical University
Anne Müller: Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin
Chun-Xia Yi: Institute for Diabetes and Obesity, Technical University
Kirk M Habegger: Metabolic Diseases Institute, University of Cincinnati
Carola W. Meyer: Institute for Diabetes and Obesity, Technical University
Bruce D. Gaylinn: University of Virginia
Brian Finan: Institute for Diabetes and Obesity, Technical University
Kristy Heppner: Metabolic Diseases Institute, University of Cincinnati
Chitrang Trivedi: Metabolic Diseases Institute, University of Cincinnati
Maximilian Bielohuby: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der LMU
William Abplanalp: Metabolic Diseases Institute, University of Cincinnati
Franziska Meyer: Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin
Carolin L. Piechowski: Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin
Juliane Pratzka: Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin
Kerstin Stemmer: Institute for Diabetes and Obesity, Technical University
Jenna Holland: Metabolic Diseases Institute, University of Cincinnati
Jazzmin Hembree: Metabolic Diseases Institute, University of Cincinnati
Nakul Bhardwaj: Metabolic Diseases Institute, University of Cincinnati
Christine Raver: Metabolic Diseases Institute, University of Cincinnati
Nickki Ottaway: Metabolic Diseases Institute, University of Cincinnati
Radha Krishna: Metabolic Diseases Institute, University of Cincinnati
Renu Sah: School of Medicine
Floyd R. Sallee: School of Medicine
Stephen C. Woods: University of Cincinnati
Diego Perez-Tilve: Metabolic Diseases Institute, University of Cincinnati
Martin Bidlingmaier: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der LMU
Michael O. Thorner: University of Virginia
Heiko Krude: Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin
David Smiley: Indiana University
Richard DiMarchi: Indiana University
Susanna Hofmann: Institute of Experimental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health
Paul T. Pfluger: Institute for Diabetes and Obesity, Technical University
Gunnar Kleinau: Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin
Heike Biebermann: Institute of Experimental Pediatric Endocrinology, Charité-Universitätsmedizin Berlin
Matthias H. Tschöp: Institute for Diabetes and Obesity, Technical University

Nature Communications, 2013, vol. 4, issue 1, 1-8

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/ncomms2968

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