The Regulation of ZIP8 by Dietary Manganese in Mice

Suetmui Yu, Ningning Zhao

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Article number5962
JournalInternational journal of molecular sciences
Issue number6
StatePublished - Mar 2023


  • liver
  • manganese
  • nutrient metabolism
  • SLC39A8
  • ZIP8

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


Dive into the research topics of 'The Regulation of ZIP8 by Dietary Manganese in Mice'. Together they form a unique fingerprint.

Cite this