Aims

To investigate the influence of the dose in the FITC-Dextran 4kDa (FD-4) permeability test in an obese mouse model, we tested the bodyweight dose regimen and a lean body mass-based dose regimen in high fat diet (HFD) mice and low fat diet (LFD) mice. We hypothesized that the FD-4 permeation result would be dose-dependent.

Methods

The two dose regimens were compared in HFD and LFD mice. Furthermore, we conducted a dose-response study to test the effect of a low or high dose of FD-4 in weight-stratified lean mice. Gene analysis of tight junctions was also carried out.

Results

The FD-4 intestinal permeability test was dose-dependent as we found a significant increase in plasma levels of FD-4 in obese mice with the bodyweight dose regimen. However, this difference was not detectable with the lean body mass dose regimen, even with variability-adjusted group sizes. However, the qPCR analysis revealed a decrease in tight junction gene expression in obese mice. Furthermore, we found a dose-dependent significant increase in FD-4 measured in plasma samples in lean mice. No significant difference in intestinal weight was observed between lean and obese mice.

Conclusion

Evaluation of the intestinal permeability by FD-4 with the typical bodyweight dose regimen in obese mice will be confounded by the significant difference in dose given when compared to a lean control group. If the test dose is based on lean body mass, no significant difference in intestinal permeability is observed, even with large group sizes. Furthermore, we showed a dose-dependent difference in plasma FD-4 levels in lean mice. Therefore, we conclude that the dose should be based on lean body mass for the FD-4 permeability test if mice with considerable obesity differences are to be compared or to use another test with fixed doses.

中文翻译：

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肠道通透性标志物 FITC-葡聚糖 4kDa 应根据肥胖小鼠的瘦体重给药

宗旨

为了研究剂量对肥胖小鼠模型中 FITC-葡聚糖 4kDa (FD-4) 渗透性测试的影响，我们在高脂肪饮食 (HFD) 小鼠中测试了体重剂量方案和基于瘦体重的剂量方案，并且低脂饮食 (LFD) 小鼠。我们假设 FD-4 渗透结果是剂量依赖性的。

方法

在 HFD 和 LFD 小鼠中比较了两种剂量方案。此外，我们进行了一项剂量反应研究，以测试低剂量或高剂量 FD-4 对体重分层瘦小鼠的影响。还进行了紧密连接的基因分析。

结果

FD-4 肠道通透性测试是剂量依赖性的，因为我们发现体重剂量方案的肥胖小鼠血浆 FD-4 水平显着增加。然而，这种差异在瘦体重剂量方案中是检测不到的，即使是经过变异性调整的组大小也是如此。然而，qPCR 分析显示肥胖小鼠的紧密连接基因表达下降。此外，我们发现在瘦小鼠的血浆样本中测得的 FD-4 呈剂量依赖性显着增加。在瘦小鼠和肥胖小鼠之间没有观察到肠道重量的显着差异。

结论

FD-4 对肥胖小鼠的典型体重剂量方案的肠道通透性的评估将因与瘦对照组相比所给剂量的显着差异而混淆。如果测试剂量基于去脂体重，则观察到肠道通透性没有显着差异，即使是大群体。此外，我们还发现瘦小鼠血浆 FD-4 水平存在剂量依赖性差异。因此，我们得出结论，如果要比较具有相当大肥胖差异的小鼠或使用固定剂量的另一测试，则剂量应基于 FD-4 渗透性测试的瘦体重。