Insights from engraftable immunodeficient mouse models of hyperinsulinaemia

15Citations
Citations of this article
53Readers
Mendeley users who have this article in their library.

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 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.

Cite

CITATION STYLE

APA

Maugham, M. L., Thomas, P. B., Crisp, G. J., Philp, L. K., Shah, E. T., Herington, A. C., … Chopin, L. K. (2017). Insights from engraftable immunodeficient mouse models of hyperinsulinaemia. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-00443-x

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free