Perturbed Whole-body Vitamin a Kinetics Induced by Iron Deficiency Is Corrected by Dietary Iron Repletion in Rats (OR05-03-19)

Abstract

ObjectivesWe investigated the impact of iron repletion on vitamin A (VA) metabolism and kinetics in iron-deficient rats, hypothesizing that iron repletion can remove the inhibitory effect of iron deficiency on hepatic mobilization of VA and improve the hyporetinolemia of iron deficiency. MethodsAt weaning, rats were divided into two groups and fed either a VA-marginal diet (control group, CN) with normal levels of iron (37 ppm) or the same diet with reduced iron (5 ppm, iron deficient group, ID-). After 5 weeks, n = 4 rats from each group were euthanized for baseline measurements, and the remaining rats (n = 6 CN, n = 10 ID-) received an i.v. dose of 3H-labeled retinol in an emulsion as tracer to initiate the kinetic study. On day 21 after dosing, half of the ID- rats were switched to the CN diet, thus creating an iron repletion group (ID+). Serial blood samples were collected from each rat at 34 preselected time points after dosing. On day 92, all rats were euthanized. Iron and VA status were determined, and model-based compartmental analysis was applied to the plasma tracer data to develop VA kinetic models for rats from all groups. ResultsRats fed the iron-deficient diet developed iron deficiency, and exhibited reduced plasma retinol (0.67 vs. 1.19 μmol/L), with higher liver VA (265 vs. 187 nmol) at the start of the kinetic study, suggesting impaired hepatic VA mobilization. At the study conclusion, ID+ rats had recovered from iron deficiency, as indicated by hematological indices including hemoglobin, hematocrit, and serum iron. While liver VA storage was more than doubled in ID- rats (456 nmol) vs. CN rats (190 nmol), hyporetinolemia was maintained in ID- rats. In contrast, VA in the liver of ID+ rats was mobilized, reflected by the reduced liver VA mass (276 nmol) and increased hepatic output of VA into plasma based on predictions of the compartmental model, and plasma retinol in ID + rats returned to normal. ConclusionsIron repletion restored plasma retinol concentrations and increased liver vitamin A mobilization in iron deficient rats. Funding SourcesNational Institutes of Health.