Dietary iron deficiency increases Zip14 expression in rats

Abstract

Zip14 (Slc39a14) is a transmembrane protein that can transport iron and zinc. We have found that Zip14 expression is markedly up‐regulated in the liver, spleen, and duodenum of rats made anemic by repeated phlebotomy, suggesting that Zip14 responds to body iron status. The present study aimed to determine how Zip14 expression is affected by iron deficiency and overload. Weanling male Sprague‐Dawley rats (n=18) were randomized to 3 dietary groups: iron deficient (9 ppm Fe), control (215 ppm Fe), or iron‐loaded (2.9% carbonyl Fe). After 3 weeks, mean hemoglobin levels were 7.2, 13.2, and 14.5 g/dL, respectively, and mean liver non‐heme iron levels were 0.27, 1.56, and 93.5 μmol/g. Immunoblot analysis reveals that Zip14 protein levels increased dramatically in iron‐deficient liver, pancreas, and heart, tissues that express abundant Zip14. In iron‐deficient liver, zinc concentrations did not differ from controls, indicating that the marked increase in Zip14 levels did not result from altered zinc status. Zip14 expression also increased in duodenum in response to iron deficiency. The iron transport capacity of Zip14 along with its robust induction by iron deficiency strongly implicates Zip14 in physiologic iron metabolism. Supported by NIH grant DK065064 (MDK).