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dc.contributor.authorPatel, Satish
dc.contributor.authorAlvarez-Guaita, Anna
dc.contributor.authorMelvin, Audrey
dc.contributor.authorRimmington, Debra
dc.contributor.authorDattilo, Alessia
dc.contributor.authorMiedzybrodzka, Emily L
dc.contributor.authorCimino, Irene
dc.contributor.authorMaurin, Anne-Catherine
dc.contributor.authorRoberts, Geoffrey P
dc.contributor.authorMeek, Claire L
dc.contributor.authorVirtue, Samuel
dc.contributor.authorSparks, Lauren M
dc.contributor.authorParsons, Stephanie A
dc.contributor.authorRedman, Leanne M
dc.contributor.authorBray, George A
dc.contributor.authorLiou, Alice P
dc.contributor.authorWoods, Rachel M
dc.contributor.authorParry, Sion A
dc.contributor.authorJeppesen, Per B
dc.contributor.authorKolnes, Anders J
dc.contributor.authorHarding, Heather P
dc.contributor.authorRon, David
dc.contributor.authorVidal-Puig, Antonio
dc.contributor.authorReimann, Frank
dc.contributor.authorGribble, Fiona M
dc.contributor.authorHulston, Carl J
dc.contributor.authorFarooqi, I Sadaf
dc.contributor.authorFafournoux, Pierre
dc.contributor.authorSmith, Steven R
dc.contributor.authorJensen, Jorgen
dc.contributor.authorBreen, Danna
dc.contributor.authorWu, Zhidan
dc.contributor.authorZhang, Bei B
dc.contributor.authorColl, Anthony P
dc.contributor.authorSavage, David B
dc.contributor.authorO'Rahilly, Stephen
dc.date.accessioned2018-12-22T00:32:31Z
dc.date.available2018-12-22T00:32:31Z
dc.date.issued2019-03-05
dc.identifier.issn1550-4131
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287446
dc.description.abstractGDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress.
dc.description.sponsorshipThis work and authors were funded by the NIHR Cambridge Biomedical Research Centre; NIHR Rare Disease Translational Research Collaboration; Medical Research Council [MC_UU_12012/2 and MRC_MC_UU_12012/3]; MRC Metabolic Diseases Unit [MRC_MC_UU_12012/5 and MRC_MC_UU_12012.1]; Wellcome Trust Strategic Award [100574/Z/12/Z and 100140]; Wellcome Trust [107064 , 095515/Z/11/Z , 098497/Z/12/Z, 106262/Z/14/Z and 106263/Z/14/Z]; British Heart Foundation [RG/12/13/29853]; Addenbrooke’s Charitable Trust / Evelyn Trust Cambridge Clinical Research Fellowship [16-69] US Department of Agriculture: 2010-34323-21052; EFSD project grant and a Royal College of Surgeons Research Fellowship, Diabetes UK Harry Keen intermediate clinical fellowship (17/0005712). European Research Council, Bernard Wolfe Health Neuroscience Endowment, Experimental Medicine Training Initiative/AstraZeneca and Medimmune.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.subjectCell Line
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectHumans
dc.subjectMice
dc.subjectEnergy Intake
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectGrowth Differentiation Factor 15
dc.subjectYoung Adult
dc.subjectDiet, High-Fat
dc.titleGDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.
dc.typeArticle
prism.endingPage718.e8
prism.issueIdentifier3
prism.publicationDate2019
prism.publicationNameCell Metab
prism.startingPage707
prism.volume29
dc.identifier.doi10.17863/CAM.34749
dcterms.dateAccepted2018-12-17
rioxxterms.versionofrecord10.1016/j.cmet.2018.12.016
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-03
dc.contributor.orcidPatel, Satish [0000-0002-5345-8942]
dc.contributor.orcidCimino, Irene [0000-0003-1397-5408]
dc.contributor.orcidMeek, Claire [0000-0002-4176-8329]
dc.contributor.orcidHarding, Heather [0000-0002-7359-7974]
dc.contributor.orcidRon, David [0000-0002-3014-5636]
dc.contributor.orcidVidal-Puig, Antonio [0000-0003-4220-9577]
dc.contributor.orcidReimann, Frank [0000-0001-9399-6377]
dc.contributor.orcidGribble, Fiona [0000-0002-4232-2898]
dc.contributor.orcidFarooqi, Ismaa [0000-0001-7609-3504]
dc.contributor.orcidColl, Anthony [0000-0003-2594-7463]
dc.contributor.orcidSavage, David [0000-0002-7857-7032]
dc.contributor.orcidO'Rahilly, Stephen [0000-0003-2199-4449]
dc.identifier.eissn1932-7420
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Institute for Health Research (NIHR) (unknown)
pubs.funder-project-idEuropean Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (1153372)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idMRC (Unknown)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5)
pubs.funder-project-idWellcome Trust (106262/Z/14/Z)
pubs.funder-project-idWellcome Trust (107064/Z/15/Z)
pubs.funder-project-idWellcome Trust (200848/Z/16/Z)
pubs.funder-project-idWellcome Trust (100574/Z/12/Z)
pubs.funder-project-idWellcome Trust (207462/Z/17/Z)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idDiabetes UK (17/0005712)
pubs.funder-project-idWellcome Trust (084812/Z/08/Z)
pubs.funder-project-idMedical Research Council (G0900554)
pubs.funder-project-idMedical Research Council (MC_UU_12012/1)
pubs.funder-project-idMedical Research Council (MC_UU_12012/2)
pubs.funder-project-idMedical Research Council (MC_UU_12012/3)
pubs.funder-project-idWellcome Trust (095515/Z/11/Z)
pubs.funder-project-idWellcome Trust (098497/Z/12/Z)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idMedical Research Council (G9824984)
pubs.funder-project-idMedical Research Council (G0600717)
pubs.funder-project-idMedical Research Council (G0802051)
pubs.funder-project-idMedical Research Council (G0400192)
pubs.funder-project-idMRC (MC_UU_00014/1)
pubs.funder-project-idMRC (MC_UU_00014/2)
pubs.funder-project-idMRC (MC_UU_00014/3)
pubs.funder-project-idMRC (MC_UU_00014/5)
cam.issuedOnline2019-01-10
cam.orpheus.successThu Jan 30 10:52:51 GMT 2020 - Embargo updated
rioxxterms.freetoread.startdate2020-03-31


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