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dc.contributor.authorVan de Pette, Mathew
dc.contributor.authorTunster, Simon J
dc.contributor.authorJohn, Rosalind M
dc.date.accessioned2019-05-13T14:51:42Z
dc.date.available2019-05-13T14:51:42Z
dc.date.issued2018-09-12
dc.identifier.issn1422-0067
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/292715
dc.description.abstractCyclin dependent kinase inhibitor 1c (Cdkn1c) is a maternally expressed imprinted gene with roles in embryonic development, post-natal metabolism and behaviour. Using mouse models with altered dosages of Cdkn1c, we have previously identified a role for the gene in promoting brown adipose tissue formation. Here, we use these transgenic mouse lines to model the loss of imprinting of Cdkn1c in adulthood. We demonstrate that only a two-fold increase in the expression of Cdkn1c during development is sufficient to protect against age-related weight gain in addition to glucose and insulin intolerance. Further to this, we show that the loss of imprinting of Cdkn1c protects against diet-induced obesity. Bisulphite sequencing was performed to test the stability of the two differentially methylated regions that regulate Cdkn1c imprinting, and both were found to be unaltered in aged or diet-challenged adipose tissue, despite drastic reductions in Cdkn1c expression. These data demonstrate a critical role for Cdkn1c in regulating adult adipose tissue, with modest changes in expression capable of protecting against both age and diet-induced obesity and metabolic syndrome, with a natural decline in Cdkn1c expression observed that may contribute to less healthy metabolic aging. Finally, we have observed a post-natal insensitivity of the imprint to environmental factors, in contrast to recent observations of an in utero sensitivity.
dc.description.sponsorshipM.V.d.P. was supported by a BBSRC DTG studentship BB/F016557. S.J.T. was supported by BBSRC project grant BB/J015156 awarded to R.M.J.
dc.languageeng
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBACs
dc.subjectCdkn1c
dc.subjectadipose
dc.subjectaging
dc.subjecthigh fat diet
dc.subjectimprinting
dc.subjectmethylation
dc.subjectAging
dc.subjectAnimals
dc.subjectChromosomes, Artificial, Bacterial
dc.subjectCyclin-Dependent Kinase Inhibitor p57
dc.subjectDiet, High-Fat
dc.subjectFemale
dc.subjectGenomic Imprinting
dc.subjectMale
dc.subjectMice
dc.subjectObesity
dc.titleLoss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity.
dc.typeArticle
prism.issueIdentifier9
prism.publicationDate2018
prism.publicationNameInternational Journal of Molecular Sciences
prism.volume19
dc.identifier.doi10.17863/CAM.39869
dcterms.dateAccepted2018-09-10
rioxxterms.versionofrecord10.3390/ijms19092734
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2018-09-12
dc.contributor.orcidVan De Pette, Mathew [0000-0002-1423-5957]
dc.contributor.orcidTunster, Simon [0000-0002-2242-9452]
dc.identifier.eissn1422-0067
rioxxterms.typeJournal Article/Review
cam.issuedOnline2018-09-12


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International