The interaction between vitamin A status and iron homeostasis is mediated by iron regulatory proteins

Vitamin A deficiency anemia is well recognized in both animal and human studies; however, the mechanistic basis by which vitamin A status alters iron homeostasis is not well understood. Iron regulatory proteins (IRPs) control iron homeostasis by regulating the translationof proteins involved in the transport, storage and useof iron. Thus, our study tested the hypothesis that vitamin A status alters hepatic iron homeostasis through modulation of IRP function. Rats were assigned to 1 of 4 treatment groups: control, vitamin A‐deficient (VAD), iron‐deficient (ID) or both deficiencies (BD). Rats were fed either a control or VAD diet for the first 4 wks, after which half the rats in both groups were fed an ID diet for the next 4 wk. In addition, half of the rats in each treatment group were dosed daily with retinoic acid (RA; 30μmol/kg body weight) the final wk of the study. For both the ID and BD groups, IRP RNA binding activity (% of total IRP) was significantly increased compared to control values (p<0.05). However, RA treatment decreased these IRP activities to levels that were not statistically different from control values. Liver ferritin abundance in the ID and BD groups was decreased to ≤ 5% of the control. RA treatment appeared to increase ferritin abundance in some samples while decreasing transferrin receptor abundance in all groups. Taken together, the results indicate that vitamin A restores hepatic intracellular iron levels, as indicated by the decrease in IRP RNA‐binding activity and subsequent modulation of ferritin and transferrin receptor abundance. Thus, IRP function may be a useful index for the evaluation of retinoid and/or carotenoid compounds with respect to their ability to maintain iron homeostasis. (Support: CPRF)