The Regulation of ZIP8 by Dietary Manganese in Mice.
The Regulation of ZIP8 by Dietary Manganese in Mice.
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DOI：
10.3390/ijms24065962
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发表时间：
2023-03-22
影响因子：
5.6
通讯作者：
Zhao, Ningning
中科院分区：
文献类型：
--
作者：
Yu, Suetmui;Zhao, Ningning
ZIP8是一种新发现的锰转运蛋白。ZIP8功能缺失导致人和小鼠严重缺锰，表明ZIP8在维持体内锰稳态中起着至关重要的作用。尽管众所周知，ZIP8与锰代谢之间存在联系，但ZIP8在高锰条件下是如何调控的仍不清楚。本研究的主要目的是研究高锰摄入对ZIP8的调节作用。我们使用了新生和成年小鼠模型，在这些模型中，小鼠被提供含有正常或高水平锰的饮食来源。我们发现，高锰摄入导致幼鼠肝脏ZIP8蛋白减少。由于肝脏中ZIP8的减少会导致胆汁中锰的重吸收减少，我们的研究发现了一个在高锰条件下调节锰稳态的新机制：高饮食中的锰摄入量会导致肝脏中ZIP8的减少，进而减少胆汁中锰的重吸收，以防止肝脏中的锰超载。有趣的是，我们发现高锰饮食并没有导致成年动物肝脏中ZIP8的减少。为了确定这种年龄相关变异的潜在原因，我们比较了3周龄和12周龄小鼠肝脏ZIP8的表达。我们发现，在正常情况下，12周龄小鼠的肝脏ZIP8蛋白含量与3周龄小鼠相比有所下降。总之，本研究的结果为理解ZIP8的S调控锰代谢的功能提供了新的见解。
ZIP8 is a newly identified manganese transporter. A lack of functional ZIP8 results in severe manganese deficiency in both humans and mice, indicating that ZIP8 plays a crucial role in maintaining body manganese homeostasis. Despite a well-acknowledged connection between ZIP8 and manganese metabolism, how ZIP8 is regulated under high-manganese conditions remains unclear. The primary goal of this study was to examine the regulation of ZIP8 by high-manganese intake. We used both neonatal and adult mouse models in which mice were supplied with dietary sources containing either a normal or a high level of manganese. We discovered that high-manganese intake caused a reduction in liver ZIP8 protein in young mice. Since a decrease in hepatic ZIP8 leads to reduced manganese reabsorption from the bile, our study identified a novel mechanism for the regulation of manganese homeostasis under high-manganese conditions: high dietary manganese intake results in a decrease in ZIP8 in the liver, which in turn decreases the reabsorption of manganese from the bile to prevent manganese overload in the liver. Interestingly, we found that a high-manganese diet did not cause a decrease in hepatic ZIP8 in adult animals. To determine the potential reason for this age-dependent variation, we compared the expressions of liver ZIP8 in 3-week-old and 12-week-old mice. We found that liver ZIP8 protein content in 12-week-old mice decreases when compared with that of 3-week-old mice under normal conditions. Overall, results from this study provide novel insights to facilitate the understanding of ZIP8’s function in regulating manganese metabolism.
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