Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA.
Molecular Pharmacology Program and Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
J Nutr. 2020 Jul 1;150(7):1982-1988. doi: 10.1093/jn/nxaa098.
Iron deficiency can result in hyporetinolemia and hepatic vitamin A (VA) sequestration.
We used model-based compartmental analysis to determine the impact of iron repletion on VA metabolism and kinetics in iron-deficient rats.
At weaning, Sprague-Dawley rats were assigned to either a VA-marginal diet (0.35 mg retinol equivalent/kg) with adequate iron (35 ppm, control group [CN]) or reduced iron (3 ppm, iron-deficient group [ID-]), with an equivalent average body weight for each group. After 5 wk, n = 4 rats from each group were euthanized for baseline measurements of VA and iron indices, and the remaining rats (n = 6 CN, n = 10 ID-) received an intravenous injection 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 to initiate iron repletion, referred to as the iron-repletion group (ID+). From the time of dosing, 34 serial blood samples were collected from each rat over a 92-d time course. Plasma tracer and tissue tracee data were fitted to 6- and 4-compartment models, respectively, to analyze the kinetic behavior of VA in all groups.
Our mathematical model indicated that ID- rats exhibited a nearly 6-fold decrease in liver VA secretion and >4-fold reduction in whole-body VA utilization, compared with CN rats, whereas these perturbed kinetic behaviors were notably corrected in ID+ rats, close to those from the CN group.
Iron repletion can remove the inhibitory effect that iron deficiency exerts on hepatic mobilization of VA and restore retinol kinetic parameters to values similar to that of never-deficient CN rats. Together with improvements in iron and VA indices, our results suggest that restoration of an iron-adequate diet is sufficient to improve VA kinetics after a previous state of iron deficiency.
铁缺乏可导致低视黄醇血症和肝脏维生素 A（VA）蓄积。
我们使用基于模型的房室分析来确定铁补充对缺铁大鼠 VA 代谢和动力学的影响。
在断奶时，将 Sprague-Dawley 大鼠分配到铁充足（35ppm，对照组[CN]）或铁缺乏（3ppm，缺铁组[ID-]）的 VA 边缘饮食中，每组的平均体重相当。5 周后，每组处死 4 只大鼠进行 VA 和铁指标的基线测量，其余大鼠（n=6 CN，n=10 ID-）接受静脉注射 3H 标记的视黄醇乳液作为示踪剂以启动动力学研究。给药后第 21 天，一半的 ID-大鼠切换到 CN 饮食以开始铁补充，称为铁补充组（ID+）。从给药时开始，在 92 天的时间过程中，从每只大鼠收集 34 个连续的血样。用 6 室和 4 室模型分别拟合血浆示踪剂和组织示踪剂数据，以分析所有组中 VA 的动力学行为。
我们的数学模型表明，与 CN 大鼠相比，ID-大鼠的肝脏 VA 分泌减少近 6 倍，全身 VA 利用率降低 4 倍以上，而这些被扰乱的动力学行为在 ID+大鼠中明显得到纠正，接近于 CN 组的水平。
铁补充可以消除铁缺乏对肝脏 VA 动员的抑制作用，并将视黄醇动力学参数恢复到类似于从未缺乏的 CN 大鼠的值。伴随着铁和 VA 指标的改善，我们的结果表明，在之前的铁缺乏状态后，恢复铁充足的饮食足以改善 VA 动力学。
