Intestinal iron absorption in the neonatal rat is refractory to systemic stimuli due to reduced ferroportin expression

Abstract

Background and Aims High iron absorption in neonatal mammals helpsto ensure an adequate supply of iron to the growing infant, but the mechanismof iron absorption during suckling is poorly understood. The goal ofthis study was to determine whether systemic stimuli (high body iron andinfl ammation) that reduce iron absorption in adult rats have similar effectsin neonates and to examine the molecular basis of their effects.Methods Sprague-Dawley rats maintained with their mothers duringsuckling and were weaned at 21 days. Body iron was increased using irondextran (0.3 mg/g i.p.) and infl ammation was induced with bacterial lipopolysaccharide (LPS; 100 ng/g i.p.). Duodenum and liver were collectedfor measurement of gene expression by qPCR and protein levels bywestern blotting. Intestinal iron absorption was determined by whole bodycounting by measuring the retention of an oral dose of 59Fe.Results Suckling (15-day-old) rats absorbed 93.1 ± 2.0% of an oral irontest dose compared to 39.1 ± 2.6% in adult (7 week) animals. In responseto iron dextran and LPS, iron absorption in adults declined by 53% and72% respectively, but by only 14% and 9% in suckling animals.Nevertheless, hepatic hepcidin mRNA (a negative regulator of ironabsorption) was strongly induced by both iron dextran (neonates—120-fold; adults—10-fold) and LPS (neonates—380-fold; adults—threefold) atboth ages. Baseline levels were much lower in neonates. To investigatewhy iron absorption was not refl ecting the high hepcidin levels in neonates,we examined the expression of the hepcidin target, ferroportin(Fpn), in the duodenum. In suckling animals up to approximately 17 daysold, Fpn mRNA was expressed but Fpn protein was undetectable.Expression of Fpn protein was robust in adults. Further analysis showedthat the Fpn1A splice variant, which is under iron-dependent translationalcontrol, predominates in neonates.Conclusions Our data suggest that iron absorption in the neonate islargely refractory to the action of the systemic iron regulator hepcidin, andthat this refl ects the limited expression of Fpn protein in the small intestine.How neonates maintain high iron absorption in the absence of Fpn remainsto be determined.