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dc.contributor.authorHarno, Erika
dc.contributor.authorSefton, Charlotte
dc.contributor.authorWray, Jonathan R
dc.contributor.authorAllen, Tiffany-Jayne
dc.contributor.authorDavies, Alison
dc.contributor.authorColl, Anthony
dc.contributor.authorWhite, Anne
dc.date.accessioned2021-06-08T23:30:36Z
dc.date.available2021-06-08T23:30:36Z
dc.date.issued2021-07-02
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/323603
dc.description.abstractGlucocorticoids (GCs) are widely prescribed anti-inflammatory medicines, but their use can lead to metabolic side-effects. These may occur through direct actions of GCs on peripheral organs, but could also be mediated by the hypothalamic AgRP neurons, which can increase food intake and modify peripheral metabolism. Therefore, the aim of this study was to examine the metabolic effects of chronic treatment with the GC corticosterone (Cort, 75 μg/ml in drinking water) in mice lacking the glucocorticoid receptor (GR) on AgRP neurons. Female AgRP-GR KO mice had delayed onset of Cort-induced hyperphagia. However, AgRP-GR KO had little impact on the increased body weight or adiposity seen with 3 weeks Cort treatment. Cort caused hepatic steatosis in control mice, but in Cort treated female AgRP-GR KO mice there was a 25% reduction in liver lipid content and lower plasma triglycerides. Additionally, Cort treatment led to hyperinsulinaemia, but compared to controls, Cort-treated AgRP-GR KO mice had both lower fasting insulin levels and lower insulin levels during a glucose tolerance test. In conclusion, these data indicate that GCs do act through AgRP neurons to contribute, at least in part, to the adverse metabolic consequences of chronic GC treatment.
dc.description.sponsorshipMRC
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.titleChronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2021
prism.publicationNameSci Rep
prism.startingPage13776
prism.volume11
dc.identifier.doi10.17863/CAM.71064
dcterms.dateAccepted2021-06-04
rioxxterms.versionofrecord10.1038/s41598-021-93378-3
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-07-02
dc.contributor.orcidColl, Anthony [0000-0003-2594-7463]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMRC (MC_UU_00014/1)
pubs.funder-project-idMedical Research Council (MC_UU_12012/1)
cam.issuedOnline2021-07-02
cam.orpheus.counter6
rioxxterms.freetoread.startdate2024-06-08


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