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A rare human variant that disrupts GPR10 signalling causes weight gain in mice

dc.contributor.authorTalbot, F
dc.contributor.authorFeetham, CH
dc.contributor.authorMokrosiński, J
dc.contributor.authorLawler, K
dc.contributor.authorKeogh, JM
dc.contributor.authorHenning, E
dc.contributor.authorMendes de Oliveira, E
dc.contributor.authorAyinampudi, V
dc.contributor.authorSaeed, S
dc.contributor.authorBonnefond, A
dc.contributor.authorArslan, M
dc.contributor.authorYeo, GSH
dc.contributor.authorFroguel, F
dc.contributor.authorBechtold, DA
dc.contributor.authorAdamson, A
dc.contributor.authorHumphreys, N
dc.contributor.authorBarroso, I
dc.contributor.authorLuckman, SM
dc.contributor.authorFarooqi, IS
dc.date.accessioned2022-06-16T14:27:03Z
dc.date.issued2023-03-15
dc.date.updated2022-06-16T14:10:13Z
dc.description.abstractDisruption of brain-expressed G-protein-coupled receptor-10 (GPR10) causes obesity in animals. Here, we identified multiple rare variants in GPR10 in people with severe obesity and in normal weight controls. These variants impaired ligand binding and G-protein-dependent signalling in cells. Transgenic mice harbouring a loss of function GPR10 variant found in an obese individual, gained excessive weight due to decreased energy expenditure rather than increased food intake. This evidence supports a role for GPR10 in human energy homeostasis. Therapeutic targeting of GPR10 may represent an effective weight-loss strategy.en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.description.sponsorshipNational Institute for Health Research (NIHR)en_GB
dc.description.sponsorshipBernard Wolfe Health Neuroscience Endowmenten_GB
dc.description.sponsorshipBotnar Fondationen_GB
dc.description.sponsorshipEvelyn Trusten_GB
dc.description.sponsorshipResearch Englanden_GB
dc.description.sponsorshipFrench National Research Agencyen_GB
dc.description.sponsorshipNational Center for Precision Diabetic Medicineen_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.description.sponsorshipBiotechnology and Biological Sciences Research Council (BBSRC)en_GB
dc.identifier.citationVol. 14, article 1450en_GB
dc.identifier.grantnumber207462/Z/17/Zen_GB
dc.identifier.grantnumberWT098051en_GB
dc.identifier.grantnumber203513/Z/16/Zen_GB
dc.identifier.grantnumberANR-10-LABX-46en_GB
dc.identifier.grantnumberANR10-EQPX-07-01en_GB
dc.identifier.grantnumberMR/S026193/1en_GB
dc.identifier.grantnumber208363/Z/17/Zen_GB
dc.identifier.grantnumberBB/M001067/1en_GB
dc.identifier.grantnumberBB/P01867X/1en_GB
dc.identifier.urihttp://hdl.handle.net/10871/129964
dc.identifierORCID: 0000-0001-5800-4520 (Barroso, Ines)
dc.language.isoenen_GB
dc.publisherNature Researchen_GB
dc.rights© The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
dc.titleA rare human variant that disrupts GPR10 signalling causes weight gain in miceen_GB
dc.typeArticleen_GB
dc.date.available2022-06-16T14:27:03Z
dc.identifier.issn2041-1723
dc.descriptionThis is the author accepted manuscript.en_GB
dc.descriptionData availability: Exome sequencing data are accessible from the European Genome Archive under a managed access agreement (EGAS00001000124 and EGAS00001000825). Additional data that support the findings of this study are available upon request from the corresponding authors (ISF and SML).en_GB
dc.identifier.journalNature Communicationsen_GB
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_GB
dcterms.dateAccepted2023-02-23
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2023-02-23
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2022-06-16T14:10:22Z
refterms.versionFCDAM
refterms.dateFOA2023-03-24T15:53:19Z
refterms.panelAen_GB


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© The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
Except where otherwise noted, this item's licence is described as © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.