Ghrelin Research Group, Translational Research Institute, Institute of Health and Biomedical Innovation, and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
Sci Rep. 2017 Mar 28;7(1):491. doi: 10.1038/s41598-017-00443-x.
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.
高胰岛素血症、肥胖和血脂异常是许多癌症的独立和共同危险因素。在这里，我们研究了一种 23%的西方高脂肪饮食（HFD）对两种适合植入人源组织异种移植物的免疫缺陷小鼠（NOD/SCID 和 Rag1）的长期影响，以及饮食诱导的高胰岛素血症对人前列腺癌细胞系异种移植物生长的影响。在断奶后 16 周和 23 周时，Rag1 和 NOD/SCID HFD 喂养的小鼠表现出葡萄糖耐量受损。与低脂饲料喂养的小鼠相比，Rag1 小鼠的空腹胰岛素水平（2.16±1.01ng/ml，P=0.01）和胰岛素抵抗（6.70±1.68HOMA-IR，P=0.01）显著升高。在 NOD/SCID 品系中没有观察到这种情况。与 NOD/SCID 小鼠相比，Rag1 HFD 喂养的小鼠肝脂肪变性更为严重。Rag1 HFD 喂养的小鼠肌内脂质储存增加，但 NOD/SCID 小鼠没有。在 Rag1 HFD 喂养的小鼠中，LNCaP 异种移植瘤的生长速度比低脂饲料喂养的小鼠更快。这是首次对两种适合异种移植研究的小鼠品系进行长期西方 HFD 代谢影响的特征描述。我们得出结论，Rag1 小鼠是研究癌症与高胰岛素血症之间关系的合适且新颖的异种移植模型。
