CHANGES IN DUODENAL IRON TRANSPORT GENE EXPRESSION IN RATS FOLLOWING A SWITCH TO AN IRON DEFICIENT DIET OCCUR BEFORE ALTERATIONS IN BODY IRON STORES

Abstract

Introduction and aims The level of body iron stores is an important factor controlling the rate of intestinal iron absorption but how storage iron influences intestinal iron transport is unclear. A switch from a control diet to an iron deficient diet results in an increase in iron absorption within 5 days; long before any changes in body iron stores or haematological parameters. To investigate the mechanism by which this occurs, we have studied the adaptation in expression of iron transport genes in rat duodenum following the change to an iron deficient diet.Methods Adult Sprague–Dawley rats on a control diet were switched to an iron deficient diet and duodenal tissue was taken after 0, 2, 4, 6, 10 and 14 days. RNA was extracted and the expression of iron transport genes was determined by ribonuclease protection assay. Intestinal iron absorption was determined by measuring the retention of an oral dose of 59Fe.Results Intestinal iron absorption in rats on a control diet was approximately 10%, but by 6 days following a change to an iron deficient diet it had increased to near maximal levels of approximately 60%. No change in haematological status or hepatic iron stores was evident over this time period. Analysis of duodenal gene expression revealed a large increase in the expression of the brush border ferric reductase DcytB and iron transporter DMT1 (IRE form) within the first 6 days on a deficient diet. The expression of DMT1 (non‐IRE) and the basolateral transporter Ireg1 increased to a lesser extent, but the expression of hephaestin, which is also involved in basolateral iron transport, remained unchanged. The changes in intestinal iron transporter expression parallel the observed increase in iron absorption.Conclusions These results demonstrate that the expression of duodenal iron transport genes can be influenced by the amount of iron in the diet before body iron stores and red blood cell production are affected. Further studies will be required to determine whether the mechanism involves local changes in intestinal iron status or involves a systemic signal that is responsive to dietary iron content.