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Insights from engraftable immunodeficient mouse models of hyperinsulinaemia.

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.

SUBMITTER: Maugham ML

PROVIDER: S-EPMC5428450 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Insights from engraftable immunodeficient mouse models of hyperinsulinaemia.

Maugham Michelle L ML Thomas Patrick B PB Crisp Gabrielle J GJ Philp Lisa K LK Shah Esha T ET Herington Adrian C AC Chen Chen C Gregory Laura S LS Nelson Colleen C CC Seim Inge I Jeffery Penny L PL Chopin Lisa K LK

Scientific reports 20170328 1

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 <sup>-/-</sup>) 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 <sup>-/-</sup>and NOD/SCID HFD-fed mice demonstrated diet-induced i ...[more]

PMID: 28352127

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Insights from engraftable immunodeficient mouse models of hyperinsulinaemia.

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Insights from engraftable immunodeficient mouse models of hyperinsulinaemia.

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