Journal article
MRAP2 regulates ghrelin receptor signaling and hunger sensing
Nature Communications, Vol.8(1), 713
09/28/2017
DOI: 10.1038/s41467-017-00747-6
PMCID: PMC5620068
PMID: 28959025
Abstract
Ghrelin is the only known circulating orexigenic hormone. It is primarily secreted by the stomach and acts at its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), in the hypothalamus to signal hunger and promote food intake. The melanocortin receptor accessory protein 2 (MRAP2) was previously shown to regulate energy homeostasis through the modulation of the activity of the melanocortin-4 receptor and prokineticin receptors. In this study we identify MRAP2 as a partner of ghrelin-GHSR1a signaling. We show that MRAP2 interacts with GHSR1a and potentiates ghrelin-stimulated signaling both in vitro and in vivo. We demonstrate that in the absence of MRAP2, fasting fails to activate agouti-related protein neurons. In addition, we show that the orexigenic effect of ghrelin is lost in mice lacking MRAP2. Our results suggest that MRAP2 is an important modulator of the energy homeostasis machinery that operates through the regulation of multiple GPCRs throughout the hypothalamus.
Details
- Title: Subtitle
- MRAP2 regulates ghrelin receptor signaling and hunger sensing
- Creators
- Dollada SrisaiTerry C YinAbigail A LeeAlix A J RouaultNicole A Pearson - University of Iowa, Neuroscience and PharmacologyJustin L GrobeJulien A Sebag - University of Iowa, Molecular Physiology and Biophysics
- Resource Type
- Journal article
- Publication Details
- Nature Communications, Vol.8(1), 713
- Publisher
- Nature Publishing Group; London
- DOI
- 10.1038/s41467-017-00747-6
- PMID
- 28959025
- PMCID
- PMC5620068
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Copyright
- © 2017, Springer Nature
- Grant note
- Funding: This work was supported by J.A.S. startup funds provided by the Department of Molecular Physiology and Biophysics and the F.O.E.D.R.C at the University of Iowa. Competing Interests: The authors declare that they have no competing interests.
- Language
- English
- Date published
- 09/28/2017
- Academic Unit
- Molecular Physiology and Biophysics; Neuroscience and Pharmacology
- Record Identifier
- 9983763598902771
Metrics
18 File views/ downloads
25 Record Views