Effects of High-Fructose Diet vs. Teklad Diet in the MNU-Induced Rat Mammary Cancer Model: Altered Tumorigenesis, Metabolomics and Tumor RNA Expression

Amit Kumar, R. Lubet, Jennifer T Fox, W. Nelson, H. Seifried, C. Grubbs, M. S. Miller
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引用次数: 3

Abstract

Epidemiology, clinical and experimental animal studies suggest high fructose diets are detrimental to metabolic status and may contribute to tumor development. This due to increased obesity and metabolic syndrome, known risk factors for many types of cancer. We compared tumor development in N-methyl-N-nitrosourea (MNU)-treated rats fed either a high (60%)-fructose diet (HFD) or a standard diet (SD). Female Sprague-Dawley rats at 43 days of age (DOA) were fed a SD or HFD followed by administration of MNU at 50 DOA. Rats were palpated weekly and sacrificed at 190 DOA. MNU-treated rats on HFD exhibited decreased tumor latency and roughly a two-fold increase in tumor multiplicity. RNA-Seq on frozen tumors (SD vs. HFD rats) showed altered expression of approximately 10% of genes (P < 0.05). When examined by Ingenuity Pathway Analysis, multiple highly significant pathways were identified including A) mechanisms of cancer, B) Wnt pathway, C) immune response (e.g., “Th1 and Th2 activation” and “antigen presentation”) and D) LXR/RXR nuclear receptor. These generalized pathways were indirectly confirmed by alterations of various interrelated disease pathways (epithelial cancers, T cell numbers and apoptosis). In a second study, serum was collected from rats on the HFD or SD pre-MNU and at the time of sacrifice. Metabolomics revealed that the HFD yielded: A) increased levels of fructose, B) increases of various monoglycerols, C) reduced levels of various diacylglycerols and oxygenated inflammatory lipids (9 and 13 HODE and 12,13 DHOME) and D) increased levels of secondary bile acids (hyodeoxycholate and 6-oxolithocholate), which may reflect microbiome changes. These metabolomic changes, which are distinct from those on a high-fat diet, may prove relevant when examining individuals who consume higher levels of fructose.
高果糖饮食与Teklad饮食对mnu诱导的大鼠乳腺癌模型的影响:改变肿瘤发生、代谢组学和肿瘤RNA表达
流行病学、临床和实验动物研究表明,高果糖饮食对代谢状态有害,并可能导致肿瘤的发展。这是由于肥胖和代谢综合征的增加,这是许多类型癌症的已知危险因素。我们比较了n -甲基-n -亚硝基脲(MNU)处理的大鼠在高(60%)果糖饮食(HFD)和标准饮食(SD)中的肿瘤发展情况。雌性SD - dawley大鼠于43日龄(DOA)饲喂SD或HFD, 50日龄时给予MNU。每周触诊大鼠,并于190doa处死。mnu处理的大鼠在HFD上表现出肿瘤潜伏期减少,肿瘤多样性增加大约两倍。冷冻肿瘤(SD大鼠与HFD大鼠)的RNA-Seq显示约10%的基因表达改变(P < 0.05)。通过独创性途径分析,确定了多个高度重要的途径,包括A)癌症机制,B) Wnt途径,C)免疫反应(例如“Th1和Th2激活”和“抗原呈递”)和D) LXR/RXR核受体。各种相关疾病通路(上皮细胞癌、T细胞数量和细胞凋亡)的改变间接证实了这些广义通路。在第二项研究中,收集了HFD或SD大鼠在mnu前和牺牲时的血清。代谢组学显示,HFD产生:A)果糖水平升高,B)各种单甘油增加,C)各种二酰基甘油和氧化炎性脂质(9和13 HODE和12,13 DHOME)水平降低,D)次级胆汁酸(羟脱氧胆酸和6-氧胆酸)水平升高,这可能反映了微生物组的变化。这些代谢组学变化不同于高脂肪饮食的人,在检查果糖摄入量较高的个体时,可能被证明是相关的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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