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dc.contributor.authorMaugham, Michelle L
dc.contributor.authorThomas, Patrick B
dc.contributor.authorCrisp, Gabrielle J
dc.contributor.authorPhilp, Lisa K
dc.contributor.authorShah, Esha T
dc.contributor.authorHerington, Adrian C
dc.contributor.authorChen, Chen
dc.contributor.authorGregory, Laura S
dc.contributor.authorNelson, Colleen C
dc.contributor.authorSeim, Inge
dc.contributor.authorJeffery, Penny L
dc.contributor.authorChopin, Lisa K
dc.date.accessioned2020-02-24T04:56:07Z
dc.date.available2020-02-24T04:56:07Z
dc.date.issued2017
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/s41598-017-00443-x
dc.identifier.urihttp://hdl.handle.net/10072/391840
dc.description.abstractHyperinsulinaemia, obesity and dyslipidaemia are independent and collective risk factors for many cancers. Here, the long-term effects of a 23% Western high-fat diet (HFD) in two immunodeficient mouse strains (NOD/SCID and Rag1 −/−) suitable for engraftment with human-derived tissue xenografts, and the effect of diet-induced hyperinsulinaemia on human prostate cancer cell line xenograft growth, were investigated. Rag1 −/−and NOD/SCID HFD-fed mice demonstrated diet-induced impairments in glucose tolerance at 16 and 23 weeks post weaning. Rag1 −/− mice developed significantly higher fasting insulin levels (2.16 ± 1.01 ng/ml, P = 0.01) and increased insulin resistance (6.70 ± 1.68 HOMA-IR, P = 0.01) compared to low-fat chow-fed mice (0.71 ± 0.12 ng/ml and 2.91 ± 0.42 HOMA-IR). This was not observed in the NOD/SCID strain. Hepatic steatosis was more extensive in Rag1 −/− HFD-fed mice compared to NOD/SCID mice. Intramyocellular lipid storage was increased in Rag1 −/− HFD-fed mice, but not in NOD/SCID mice. In Rag1 −/− HFD-fed mice, LNCaP xenograft tumours grew more rapidly compared to low-fat chow-fed mice. This is the first characterisation of the metabolic effects of long-term Western HFD in two mouse strains suitable for xenograft studies. We conclude that Rag1 −/− mice are an appropriate and novel xenograft model for studying the relationship between cancer and hyperinsulinaemia.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofissue1
dc.relation.ispartofjournalScientific Reports
dc.relation.ispartofvolume7
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchOther Physical Sciences
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode0299
dc.subject.keywordsScience & Technology
dc.subject.keywordsMultidisciplinary Sciences
dc.subject.keywordsScience & Technology - Other Topics
dc.subject.keywordsHIGH-FAT-DIET
dc.subject.keywordsADIPOSE-TISSUE
dc.titleInsights from engraftable immunodeficient mouse models of hyperinsulinaemia
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationMaugham, ML; Thomas, PB; Crisp, GJ; Philp, LK; Shah, ET; Herington, AC; Chen, C; Gregory, LS; Nelson, CC; Seim, I; Jeffery, PL; Chopin, LK, Insights from engraftable immunodeficient mouse models of hyperinsulinaemia, Scientific Reports, 2017, 7 (1)
dcterms.dateAccepted2017-02-27
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-02-24T04:53:43Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2017 The Authors. 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.
gro.hasfulltextFull Text
gro.griffith.authorChen, Chen


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