Duodenal absorption and tissue utilization of dietary heme and nonheme iron differ in rats

Chang Cao, Carrie E Thomas, Karl L Insogna, Kimberly O O'Brien, Chang Cao, Carrie E Thomas, Karl L Insogna, Kimberly O O'Brien

Abstract

Background: Dietary heme contributes to iron intake, yet regulation of heme absorption and tissue utilization of absorbed heme remains undefined.

Objectives: In a rat model of iron overload, we used stable iron isotopes to examine heme- and nonheme-iron absorption in relation to liver hepcidin and to compare relative utilization of absorbed heme and nonheme iron by erythroid (RBC) and iron storage tissues (liver and spleen).

Methods: Twelve male Sprague-Dawley rats were randomly assigned to groups for injections of either saline or iron dextran (16 or 48 mg Fe over 2 wk). After iron loading, rats were administered oral stable iron in the forms of (57)Fe-ferrous sulfate and (58)Fe-labeled hemoglobin. Expression of liver hepcidin and duodenal iron transporters and tissue stable iron enrichment was determined 10 d postdosing.

Results: High iron loading increased hepatic hepcidin by 3-fold and reduced duodenal expression of divalent metal transporter 1 (DMT1) by 76%. Nonheme-iron absorption was 2.5 times higher than heme-iron absorption (P = 0.0008). Absorption of both forms of iron was inversely correlated with hepatic hepcidin expression (heme-iron absorption: r = -0.77, P = 0.003; nonheme-iron absorption: r = -0.80, P = 0.002), but hepcidin had a stronger impact on nonheme-iron absorption (P = 0.04). Significantly more (57)Fe was recovered in RBCs (P = 0.02), and more (58)Fe was recovered in the spleen (P = 0.01).

Conclusions: Elevated hepcidin significantly decreased heme- and nonheme-iron absorption but had a greater impact on nonheme-iron absorption. Differential tissue utilization of heme vs. nonheme iron was evident between erythroid and iron storage tissues, suggesting that some heme may be exported into the circulation in a form different from that of nonheme iron.

Conflict of interest statement

Author disclosures: C. Cao, C. E. Thomas, K. L. Insogna, and K. O. O'Brien, no conflicts of interest.

© 2014 American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Effect of iron dextran injections on hepcidin, serum ferritin, and liver iron transporter expression in rats. Liver hepcidin mRNA in H-Fe, M-Fe, and control groups (A). Serum ferritin concentrations in the H-Fe and M-Fe groups combined (n = 8) and the control group (n = 4) (B). Liver expression of FPN and TFR1 in rats (C). Values are means ± SEMs; n = 4/group. Means without a common letter differ, P < 0.05. *Different from control, P < 0.05. FPN, ferroportin; HO-1, heme oxygenase 1; H-Fe, high iron loading; M-Fe, moderate iron loading; TFR1, transferrin receptor 1.
FIGURE 2
FIGURE 2
Iron absorption and duodenal iron transporter expression in rats after iron overload treatment. Heme- and nonheme-iron absorption in H-Fe, M-Fe, and control rats; n = 4/group (A). Duodenal mRNA expression of genes involved in iron transport (B). Western blotting of proteins involved in duodenal iron transport; n = 2/group (C). Panels A and B: Values are means ± SEMs. Means without a common letter differ, P < 0.05. Dcytb, duodenal cytochrome b; Dmt1, divalent metal transporter 1; FPN, ferroportin; HO-1, heme oxygenase 1; H-Fe, high iron loading; M-Fe, moderate iron loading; PCFT, proton coupled folate transporter.
FIGURE 3
FIGURE 3
Correlations of liver hepcidin mRNA with heme- and nonheme-iron absorption in rats; n = 12.

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