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

Author

Listed:
  • 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
    Metabolic Diseases Institute, University of Cincinnati)

  • 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
    Metabolic Diseases Institute, University of Cincinnati)

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.

Suggested Citation

  • 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 & Franzis, 2013. "The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms," Nature Communications, Nature, vol. 4(1), pages 1-8, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2968
    DOI: 10.1038/ncomms2968
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