Mouse breast cancer model-dependent changes in metabolic syndrome-associated phenotypes caused by maternal dioxin exposure and dietary fat
Mouse breast cancer model-dependent changes in metabolic syndrome-associated phenotypes caused by maternal dioxin exposure and dietary fat
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DOI：
10.1152/ajpendo.90368.2008
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发表时间：
2009-01-01
影响因子：
5.1
通讯作者：
Threadgill, David W.
中科院分区：
文献类型：
--
作者：
La Merrill, Michele;Baston, David S.;Threadgill, David W.
La Merrill M, Baston DS, Denison MS, Birnbaum LS, Pomp D, Threadgill DW。小鼠乳腺癌模型依赖于母体二恶英暴露和饮食脂肪引起的代谢综合征相关表型的变化。[J] .中国生物医学工程学报，2009,31(6):563 - 567。首次发表于2008年10月7日；doi: 10.1152 / ajpendo.90368.2008。-高脂肪饮食与肥胖和代谢综合征的易感性增加有关。高脂肪饮食（HFD）引起的脂肪组织增加导致亲脂毒物如2,3,7,8-四氯二苯并-对二恶英（TCDD）的储存改变，这可能进一步增加对代谢综合征的易感性。由于TCDD和HFD都与乳腺癌风险增加有关，我们在三种乳腺癌小鼠模型中检测了它们对代谢综合征相关表型的影响：7,12-二甲基苯[a]蒽（DMBA）， Tg(MMTV-Neu)202Mul/J （HER2）和TgN(MMTV-PyMT)634Mul/J (PyMT)，均具有FVB/N遗传背景。孕鼠在妊娠第12.5天给予1 μ g/kg TCDD或对照物，在分娩时给予高脂或低脂饮食。纵向测量体重、体脂百分比和空腹血糖，并在研究结束时测量甘油三酯。在高热量饮食组，所有的癌症模型都比FVB控制组提前达到青春期生长高峰。在喂食HFD的小鼠中，与PyMT和DMBA模型相比，HER2模型从青春期到成年期的体重和脂肪组织增加更大。然而，DMBA模型的空腹血糖水平始终高于PyMT和HER2模型。在HFD维持的PyMT模型中，TCDD仅影响血清甘油三酯。由于HFD的雌激素活性比LFD低三倍，不同的饮食雌激素活性并没有驱动观察到的表型差异。相反，hfd依赖性的变化是癌症模型依赖性的。这些结果表明，即使在癌症出现之前，癌症模型也可以对代谢综合征相关表型产生不同的影响。
La Merrill M, Baston DS, Denison MS, Birnbaum LS, Pomp D, Threadgill DW. Mouse breast cancer model-dependent changes in metabolic syndrome-associated phenotypes caused by maternal dioxin exposure and dietary fat. Am J Physiol Endocrinol Metab 296: E203-E210, 2009. First published October 7, 2008; doi: 10.1152/ajpendo.90368.2008.-Diets high in fat are associated with increased susceptibility to obesity and metabolic syndrome. Increased adipose tissue that is caused by high-fat diets (HFD) results in altered storage of lipophilic toxicants like 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD), which may further increase susceptibility to metabolic syndrome. Because both TCDD and HFD are associated with increased breast cancer risk, we examined their effects on metabolic syndrome-associated phenotypes in three mouse models of breast cancer: 7,12-dimethylbenz[a]anthracene ( DMBA), Tg(MMTV-Neu)202Mul/J (HER2), and TgN(MMTV-PyMT)634Mul/J (PyMT), all on an FVB/N genetic background. Pregnant mice dosed with 1 mu g/kg of TCDD or vehicle on gestational day 12.5 were placed on a HFD or low-fat diet (LFD) at parturition. Body weights, percent body fat, and fasting blood glucose were measured longitudinally, and triglycerides were measured at study termination. On HFD, all cancer models reached the pubertal growth spurt ahead of FVB controls. Among mice fed HFD, the HER2 model had a greater increase in body weight and adipose tissue from puberty through adulthood compared with the PyMT and DMBA models. However, the DMBA model consistently had higher fasting blood glucose levels than the PyMT and HER2 models. TCDD only impacted serum triglycerides in the PyMT model maintained on HFD. Because the estrogenic activity of the HFD was three times lower than that of the LFD, differential dietary estrogenic activities did not drive the observed phenotypic differences. Rather, the HFD-dependent changes were cancer model dependent. These results show that cancer models can have differential effects on metabolic syndrome-associated phenotypes even before cancers arise.