Duodenal expression of heme and non‐heme iron transporters and tissue partitioning of dietary heme and non‐heme iron in a rat mode of iron overload (246.8)

Dietary heme is an important Fe source yet the regulation of heme absorption and tissue partitioning of absorbed heme remain undefined. In a rat model of Fe overload, we aimed to 1) examine duodenal heme and non‐heme Fe transporters in relation to hepcidin, and 2) to compare utilization of absorbed heme and non‐heme Fe by erythroid (RBCs) and Fe storage tissues (liver and spleen). Twelve male Sprague Dawley rats were randomized to receive injections of PBS (control) or Fe dextran providing a total of 16 mg (Moderate Fe) or 48 mg Fe (High Fe) over 2 weeks. After Fe loading, rats were gavaged with 57 Fe‐FeSO4 and 58 Fe‐porcine RBC. Duodenal Fe transporter expression and tissue isotopic enrichment were assessed 10‐days post‐dosing. Fe injection in the High Fe group suppressed duodenal transcript expression of divalent metal transporter 1 ( Dmt1 ) and duodenal cytochrome b ( Dcytb ) by 70% but did not impact heme carrier protein 1 ( Hcp1 ) or Ferroportin . Liver hepcidin expression correlated with Dmt1 , Dcytb and Ferroportin but not with Hcp1 . Tissue isotopic analysis found greater non‐heme than heme Fe incorporation into RBC (80.5% vs. 71.3%, p = 0.02) while this relationship was reversed in the spleen (2.7% vs. 7.5%, p = 0.01). Fe status and hepcidin had no impact on duodenal Hcp1 expression. Differential tissue utilization of absorbed heme vs. non‐heme Fe suggests that heme Fe is exported in an alternate form from non‐heme Fe. Grant Funding Source : Supported by USDA 2008‐0857