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The Regulation of ZIP8 by Dietary Manganese in Mice

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 metabolis...

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Autores principales: Yu, Suetmui, Zhao, Ningning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056016/
https://www.ncbi.nlm.nih.gov/pubmed/36983036
http://dx.doi.org/10.3390/ijms24065962
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author Yu, Suetmui
Zhao, Ningning
author_facet Yu, Suetmui
Zhao, Ningning
author_sort Yu, Suetmui
collection PubMed
description 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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spelling pubmed-100560162023-03-30 The Regulation of ZIP8 by Dietary Manganese in Mice Yu, Suetmui Zhao, Ningning Int J Mol Sci Article 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. MDPI 2023-03-22 /pmc/articles/PMC10056016/ /pubmed/36983036 http://dx.doi.org/10.3390/ijms24065962 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yu, Suetmui
Zhao, Ningning
The Regulation of ZIP8 by Dietary Manganese in Mice
title The Regulation of ZIP8 by Dietary Manganese in Mice
title_full The Regulation of ZIP8 by Dietary Manganese in Mice
title_fullStr The Regulation of ZIP8 by Dietary Manganese in Mice
title_full_unstemmed The Regulation of ZIP8 by Dietary Manganese in Mice
title_short The Regulation of ZIP8 by Dietary Manganese in Mice
title_sort regulation of zip8 by dietary manganese in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056016/
https://www.ncbi.nlm.nih.gov/pubmed/36983036
http://dx.doi.org/10.3390/ijms24065962
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