title: Duodenal absorption and tissue utilization of dietary heme and nonheme iron differ in rats.
abstract: BACKGROUND
  Dietary heme contributes to iron intake, yet regulation of heme absorption and tissue utilization of absorbed heme remains undefined.
  
  
  OBJECTIVE
  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.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY;
authors.forename: Chang
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT; and.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Thomas
authors.affiliation: Department of Internal Medicine, Yale University, New Haven, CT.
authors.forename: Karl L
authors.initials: KL
authors.lastname: Insogna
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY; koo4@cornell.edu.
authors.forename: Kimberly O
authors.initials: KO
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D004386:Duodenum / Q000378:metabolism; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D006454:Hemoglobins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000378:metabolism / Q000493:pharmacokinetics*; D019266:Iron, Dietary / Q000493:pharmacokinetics; D007505:Iron-Dextran Complex / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005296:Ferrous Compounds; D006454:Hemoglobins; D064451:Hepcidins; D019266:Iron, Dietary; C020748:ferrous sulfate; D007505:Iron-Dextran Complex; D007501:Iron