Abstract
Iron and zinc are essential micronutrients required for growth and health. Deficiencies of these nutrients are highly prevalent among populations, but can be alleviated by supplementation and food fortification. Cross-sectional studies in humans showed positive association of serum zinc levels with hemoglobin and markers of iron status. Dietary restriction of zinc or intestinal specific conditional knock out of ZIP4 (SLC39A4), an intestinal zinc transporter, in experimental animals demonstrated iron deficiency anemia and tissue iron accumulation. Similarly, increased iron accumulation has been observed in cultured cells exposed to zinc deficient media. These results together suggest a potential role of zinc in modulating intestinal iron absorption and mobilization from tissues. Studies in intestinal cell culture models demonstrate that zinc induces iron uptake and transcellular transport via induction of divalent metal iron transporter-1 (DMT1) and ferroportin (FPN1) expression, respectively. It is interesting to note that intestinal cells are exposed to very high levels of zinc through pancreatic secretions, which is a major route of zinc excretion from the body. Therefore, zinc appears to be modulating the iron metabolism possibly via regulating the DMT1 and FPN1 levels. Herein we critically reviewed the available evidence to hypothesize novel mechanism of Zinc-DMT1/FPN1 axis in regulating intestinal iron absorption and tissue iron accumulation to facilitate future research aimed at understanding the yet elusive mechanisms of iron and zinc interactions.
Highlights
Iron and zinc are essential micronutrients required for growth and sustained health
The available evidence from experimental animals, cross-sectional studies in human subjects, and genetic studies clearly point to an association of whole-body zinc status with iron homeostasis
The in vitro studies in intestinal cell culture models and studies in animals point to a role for zinc in modulating divalent metal iron transporter-1 (DMT1) and FPN1 expression, respectively
Summary
Iron and zinc are essential micronutrients required for growth and sustained health. Physiologically, iron is defined as type 1 nutrient, while zinc is a type 2 nutrient [1]. Cellular iron accumulation in humans reveal a positivein association of serum with hemoglobin zinc induces iron uptake and transcellular transport intestinal cells zinc via levels induction of DMT1 and FPN1 and markers of iron status [12,13,14,15]. Zinc appears to be a key modulator of intestinal iron absorption and have demonstrated modulation of iron transporter expression and iron regulatory proteins by tissue iron distribution possibly viathat regulating the DMT1. Here,that we have reviewed the mechanism of airon and zinc homeostasis and interactions both at the level of intestinal absorption and tissue mobilization in theof context zinczinc status. 2. Iron the available evidence, it appears that zinc-DMT1/FPN1 axis is a critical determinant of zinc-deficiency-induced changes in iron homeostasis and helps understand the mechanism of iron. Iron is highly conserved and there are no obligatory pathways for its excretion
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