Insights from engraftable immunodeficient mouse models of hyperinsulinaemia

Michelle Maugham; P B Thomas; G J Crisp; L K Philp; E T Shah; A C Herington; C Chen; L S Gregory; C C Nelson; I Seim; P L Jeffery; L K Chopin

doi:10.1038/s41598-017-00443-x

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Insights from engraftable immunodeficient mouse models of hyperinsulinaemia

Journal article

Open access

Peer reviewed

Insights from engraftable immunodeficient mouse models of hyperinsulinaemia

Michelle Maugham, P B Thomas, G J Crisp, L K Philp, E T Shah, A C Herington, C Chen, L S Gregory, C C Nelson, I Seim, …

Scientific Reports, Vol.7(1), 491

2017

DOI: https://doi.org/10.1038/s41598-017-00443-x

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Abstract

Hyperinsulinaemia, 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 longterm 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.

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Title: Insights from engraftable immunodeficient mouse models of hyperinsulinaemia
Authors: Michelle Maugham (Author) - Queensland University of Technology
P B Thomas (Author)
G J Crisp (Author)
L K Philp (Author)
E T Shah (Author)
A C Herington (Author)
C Chen (Author)
L S Gregory (Author)
C C Nelson (Author)
I Seim (Author)
P L Jeffery (Author)
L K Chopin (Author)
Publication details: Scientific Reports, Vol.7(1), 491
Publisher: Nature Publishing Group
Date published: 2017
DOI: 10.1038/s41598-017-00443-x
ISSN: 2045-2322
Copyright note: Copyright © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99450813602621
Output Type: Journal article

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Web Of Science research areas: Endocrinology & Metabolism

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