Consumption of a high-iron diet disrupts homeostatic regulation of intestinal copper absorption in adolescent mice
Consumption of a high-iron diet disrupts homeostatic regulation of intestinal copper absorption in adolescent mice
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DOI：
10.1152/ajpgi.00169.2017
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发表时间：
2017-10-01
影响因子：
4.5
通讯作者：
Collins, James F.
中科院分区：
文献类型：
--
作者：
Ha, Jung-Heun;Doguer, Caglar;Collins, James F.
啮齿类动物的高铁喂养通常被用来模拟人类铁超载障碍。我们最近注意到，高铁摄入量会损害生长发育，并导致发育期大鼠严重的全身性铜缺乏，但由于技术限制，这种情况发生的机制无法确定。因此，在目前的研究中，我们使用了小鼠；首先，我们确定相同的现象是否发生在其他哺乳动物物种中，其次，因为我们可以评估小鼠体内对铜的吸收。我们假设饮食中过量的铁会损害肠道铜的吸收。因此，在断奶后的雄性小鼠中，饲喂以AIN-93G为基础的日粮，其中高铁(HFe)(类似于8,800 ppm)或适量(AdFe)(类似于80 ppm)与低(类似于0.9 ppm)、充足(类似于9 ppm)或高(类似于180 ppm)铜相结合。随后对铁和铜的动态平衡进行了评估。食用HFE饲料的小鼠生长较慢，贫血，肝脏铜水平和血清铜蓝蛋白活性较低。这些生理干扰都被较高的饮食铜阻止，这表明铜耗竭是潜在的原因。此外，在食用AdFe饲料的小鼠中注意到铜吸收的动态平衡调节，随着饮食中铜的减少，吸收增加。喂食HFE的小鼠没有铜吸收受损(推翻了我们的假设)，但吸收的动态平衡控制被破坏。在喂食HFE的小鼠中，铜的组织分布也出现了明显的扰动，这表明改变了储存方式，从而导致了明显的铜缺乏。膳食铁负荷从而对抗铜的动态平衡，导致严重的铜缺乏的病理症状。新的和值得注意的高铁喂养是一种常见的实验方法，在啮齿动物体内建立人类铁超载障碍的模型。在这里，我们表明，膳食铁负荷导致严重的铜缺乏，这是由于扰乱了肠道铜吸收和组织分布的动态平衡调节，这可能会降低用于铜酶合成的铜的生物利用率。人体内大剂量补铁是否会对抗铜的动态平衡是值得考虑的。
High-iron feeding of rodents has been commonly used to model human iron-overload disorders. We recently noted that high-iron consumption impaired growth and caused severe systemic copper deficiency in growing rats, but the mechanism by which this occurred could not be determined due to technical limitations. In the current investigation, we thus utilized mice; first to determine if the same phenomenon occurred in another mammalian species, and second since we could assess in vivo copper absorption in mice. We hypothesized that excessive dietary iron impaired intestinal copper absorption. Weanling, male mice were thus fed AIN-93G-based diets containing high (HFe) (similar to 8,800 ppm) or adequate (AdFe) (similar to 80 ppm) iron in combination with low (similar to 0.9 ppm), adequate (similar to 9 ppm), or high (similar to 180 ppm) copper for several weeks. Iron and copper homeostasis was subsequently assessed. Mice consuming the HFe diets grew slower, were anemic, and had lower hepatic copper levels and serum ceruloplasmin activity. These physiological perturbations were all prevented by higher dietary copper, demonstrating that copper depletion was the underlying cause. Furthermore, homeostatic regulation of copper absorption was noted in the mice consuming the AdFe diets, with absorption increasing as dietary copper decreased. HFe-fed mice did not have impaired copper absorption (disproving our hypothesis), but homeostatic control of absorption was disrupted. There were also noted perturbations in the tissue distribution of copper in the HFe-fed mice, suggesting that altered storage and thus bioavailability contributed to the noted copper deficiency. Dietary iron loading thus antagonizes copper homeostasis leading to pathological symptoms of severe copper depletion.NEW & NOTEWORTHY High-iron feeding is a common experimental method to model human iron-overload disorders in rodents. Here, we show that dietary iron loading causes severe copper deficiency due to perturbations in the homeostatic regulation of intestinal copper absorption and tissue distribution, which may decrease the bioavailability of copper for use in cuproenzyme synthesis. Whether high-dose iron supplementation in humans antagonizes copper homeostasis is worthy of consideration.