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dc.contributor.authorLam, Brian
dc.contributor.authorWilliamson, Alice
dc.contributor.authorFiner, S
dc.contributor.authorDay, Felix
dc.contributor.authorTadross, John A
dc.contributor.authorGonçalves Soares, A
dc.contributor.authorWade, K
dc.contributor.authorSweeney, P
dc.contributor.authorBedenbaugh, MN
dc.contributor.authorPorter, DT
dc.contributor.authorMelvin, A
dc.contributor.authorEllacott, KLJ
dc.contributor.authorLippert, RN
dc.contributor.authorBuller, S
dc.contributor.authorRosmaninho-Salgado, J
dc.contributor.authorDowsett, GKC
dc.contributor.authorRidley, KE
dc.contributor.authorXu, Z
dc.contributor.authorCimino, Irene
dc.contributor.authorRimmington, D
dc.contributor.authorRainbow, K
dc.contributor.authorDuckett, K
dc.contributor.authorHolmqvist, S
dc.contributor.authorKhan, A
dc.contributor.authorDai, X
dc.contributor.authorBochukova, EG
dc.contributor.authorGenes & Health Research Team
dc.contributor.authorTrembath, RC
dc.contributor.authorMartin, HC
dc.contributor.authorColl, Anthony
dc.contributor.authorRowitch, David
dc.contributor.authorWareham, Nicholas
dc.contributor.authorvan Heel, DA
dc.contributor.authorTimpson, N
dc.contributor.authorSimerly, RB
dc.contributor.authorOng, Kenneth
dc.contributor.authorCone, RD
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorPerry, John
dc.contributor.authorYeo, Giles
dc.contributor.authorO'Rahilly, Stephen
dc.date.accessioned2021-10-25T23:31:16Z
dc.date.available2021-10-25T23:31:16Z
dc.date.issued2021-11
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329880
dc.description.abstractThe state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleMC3R links nutritional state to childhood growth and the timing of puberty.
dc.typeArticle
prism.endingPage441
prism.issueIdentifier7885
prism.publicationDate2021
prism.publicationNameNature
prism.startingPage436
prism.volume599
dc.identifier.doi10.17863/CAM.77325
dcterms.dateAccepted2021-10-01
rioxxterms.versionofrecord10.1038/s41586-021-04088-9
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-11
dc.contributor.orcidLam, Brian [0000-0002-3638-9025]
dc.contributor.orcidWilliamson, Alice [0000-0002-7599-9301]
dc.contributor.orcidFiner, S [0000-0002-2684-4653]
dc.contributor.orcidDay, Felix [0000-0003-3789-7651]
dc.contributor.orcidTadross, John A [0000-0002-8424-1252]
dc.contributor.orcidWade, K [0000-0003-3362-6280]
dc.contributor.orcidPorter, DT [0000-0002-8042-3251]
dc.contributor.orcidCimino, Irene [0000-0003-1397-5408]
dc.contributor.orcidHolmqvist, S [0000-0001-6709-6666]
dc.contributor.orcidKhan, A [0000-0002-5189-6906]
dc.contributor.orcidMartin, HC [0000-0002-4454-9084]
dc.contributor.orcidColl, Anthony [0000-0003-2594-7463]
dc.contributor.orcidRowitch, David [0000-0002-0079-0060]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidvan Heel, DA [0000-0002-0637-2265]
dc.contributor.orcidTimpson, N [0000-0002-7141-9189]
dc.contributor.orcidSimerly, RB [0000-0001-5840-0152]
dc.contributor.orcidOng, Kenneth [0000-0003-4689-7530]
dc.contributor.orcidCone, RD [0000-0003-3333-5651]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidPerry, John [0000-0001-6483-3771]
dc.contributor.orcidYeo, Giles [0000-0001-8823-3615]
dc.contributor.orcidO'Rahilly, Stephen [0000-0003-2199-4449]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UU_12015/1)
pubs.funder-project-idMedical Research Council (MR/N003284/1)
pubs.funder-project-idWellcome Trust (208363/Z/17/Z)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/S017593/1)
pubs.funder-project-idMRC (MC_UU_00014/1)
pubs.funder-project-idMRC (MC_UU_00014/5)
pubs.funder-project-idMedical Research Council (MC_UU_12015/2)
pubs.funder-project-idMRC (MC_UU_00006/2)
pubs.funder-project-idMedical Research Council (MC_UU_12012/1)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5)
pubs.funder-project-idEuropean Research Council (789054)
pubs.funder-project-idMRC (MC_UU_00006/1)
pubs.funder-project-idNational Institute for Health Research (IS-BRC-1215-20014)
cam.issuedOnline2021-11-03
cam.orpheus.successMon Nov 08 07:30:23 GMT 2021 - Embargo updated
cam.orpheus.counter1
rioxxterms.freetoread.startdate2022-05-03


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