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 xenogra...

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Autores principales:	Michelle L. Maugham, Patrick B. Thomas, Gabrielle J. Crisp, Lisa K. Philp, Esha T. Shah, Adrian C. Herington, Chen Chen, Laura S. Gregory, Colleen C. Nelson, Inge Seim, Penny L. Jeffery, Lisa K. Chopin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c2713d5fce7f4465a1a7d3cfce80dd7e
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spelling	oai:doaj.org-article:c2713d5fce7f4465a1a7d3cfce80dd7e2021-12-02T11:41:01ZInsights from engraftable immunodeficient mouse models of hyperinsulinaemia10.1038/s41598-017-00443-x2045-2322https://doaj.org/article/c2713d5fce7f4465a1a7d3cfce80dd7e2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00443-xhttps://doaj.org/toc/2045-2322Abstract 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.Michelle L. MaughamPatrick B. ThomasGabrielle J. CrispLisa K. PhilpEsha T. ShahAdrian C. HeringtonChen ChenLaura S. GregoryColleen C. NelsonInge SeimPenny L. JefferyLisa K. ChopinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michelle L. Maugham Patrick B. Thomas Gabrielle J. Crisp Lisa K. Philp Esha T. Shah Adrian C. Herington Chen Chen Laura S. Gregory Colleen C. Nelson Inge Seim Penny L. Jeffery Lisa K. Chopin Insights from engraftable immunodeficient mouse models of hyperinsulinaemia
description	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.
format	article
author	Michelle L. Maugham Patrick B. Thomas Gabrielle J. Crisp Lisa K. Philp Esha T. Shah Adrian C. Herington Chen Chen Laura S. Gregory Colleen C. Nelson Inge Seim Penny L. Jeffery Lisa K. Chopin
author_facet	Michelle L. Maugham Patrick B. Thomas Gabrielle J. Crisp Lisa K. Philp Esha T. Shah Adrian C. Herington Chen Chen Laura S. Gregory Colleen C. Nelson Inge Seim Penny L. Jeffery Lisa K. Chopin
author_sort	Michelle L. Maugham
title	Insights from engraftable immunodeficient mouse models of hyperinsulinaemia
title_short	Insights from engraftable immunodeficient mouse models of hyperinsulinaemia
title_full	Insights from engraftable immunodeficient mouse models of hyperinsulinaemia
title_fullStr	Insights from engraftable immunodeficient mouse models of hyperinsulinaemia
title_full_unstemmed	Insights from engraftable immunodeficient mouse models of hyperinsulinaemia
title_sort	insights from engraftable immunodeficient mouse models of hyperinsulinaemia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c2713d5fce7f4465a1a7d3cfce80dd7e
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_version_	1718395483419836416

Insights from engraftable immunodeficient mouse models of hyperinsulinaemia

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