Development of rat and mouse models of heme-iron absorption

Heme iron (HI), derived principally from hemoglobin (Hb) in animal foods, is a highly bioavailable source of dietary iron for humans. Despite several decades of focused research, however, molecular mechanisms governing HI absorption remain undefined. Previous studies in mice and rats have not produced a consensus, definitive model of efficient HI absorption/utilization. We hypothesized that a nutritional approach, using semipurified, HI-containing diets, could be utilized to establish a tractable rodent model of HI absorption that could ultimately be employed to test the roles of receptors, transporters, and enzymes using genetic engineering technology. Experiments were designed to assess HI utilization by feeding animals AIN-93G-based, HI-enriched experimental diets formulated with lyophilized porcine RBCs, containing approximately 85% HI and 15% nonheme iron (NHI). Total iron was within the physiological range (50-75 ppm) and precisely matched NHI control diets containing ferrous sulfate were utilized as comparators. Notably, in Sprague-Dawley (S-D) rats and C57BL/6 (B6) mice, dietary HI effectively (a) resolved iron-deficiency anemia; (b) supported normal pregnancy, lactation, and neonatal development; and (c) contributed to iron loading in Hamp-KO mice and rats (modeling hereditary hemochromatosis). A nutritional paradigm has thus been established that facilitates investigation into mechanisms of HI absorption by S-D rats and B6 mice.