@article{3b52d9ac9b6c4ff09f193fb5629fc6b1,
title = "The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms",
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.",
author = "M{\"u}ller, {Timo D.} and Anne Mu{\"l}ler and Yi, {Chun Xia} and Habegger, {Kirk M.} and Meyer, {Carola W.} and Gaylinn, {Bruce D.} and Brian Finan and Kristy Heppner and Chitrang Trivedi and Maximilian Bielohuby and William Abplanalp and Franziska Meyer and Piechowski, {Carolin L.} and Juliane Pratzka and Kerstin Stemmer and Jenna Holland and Jazzmin Hembree and Nakul Bhardwaj and Christine Raver and Nickki Ottaway and Radha Krishna and Renu Sah and Sallee, {Floyd R.} and Woods, {Stephen C.} and Diego Perez-Tilve and Martin Bidlingmaier and Thorner, {Michael O.} and Heiko Krude and David Smiley and Richard DiMarchi and Susanna Hofmann and Pfluger, {Paul T.} and Gunnar Kleinau and Heike Biebermann and Tscḧop, {Matthias H.}",
note = "Funding Information: This work has received grant support from the Hilda & Preston Davis Foundation— Davis Foundation Postdoctoral Fellowship Program in Eating Disorders and by the Deutsche Forschungsgemeinschaft GRK1208, TP1, BI893/2-1, BI893/5-1. We thank Desiree Kunkel (Berlin-Brandenburg Center for Regenerative Therapies, Charit{\'e} Berlin) for her support with the flow cytometry.",
year = "2013",
doi = "10.1038/ncomms2968",
language = "English",
volume = "4",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
}