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Iron and Zinc Homeostasis and Interactions: Does Enteric Zinc Excretion Cross-Talk with Intestinal Iron Absorption?

1
Biochemistry Division, National Institute of Nutrition, ICMR, Hyderabad 500 007, India
2
Department of Nutritional Sciences, Kings College London, London SE1 9NH, UK
*
Authors to whom correspondence should be addressed.
Nutrients 2019, 11(8), 1885; https://doi.org/10.3390/nu11081885
Received: 8 July 2019 / Revised: 6 August 2019 / Accepted: 8 August 2019 / Published: 13 August 2019
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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. View Full-Text
Keywords: iron; zinc; interactions; DMT1; ZIP4; pancreas; metabolism; homeostasis; intestine; Caco-2 cells iron; zinc; interactions; DMT1; ZIP4; pancreas; metabolism; homeostasis; intestine; Caco-2 cells
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Kondaiah, P.; Yaduvanshi, P.S.; Sharp, P.A.; Pullakhandam, R. Iron and Zinc Homeostasis and Interactions: Does Enteric Zinc Excretion Cross-Talk with Intestinal Iron Absorption? Nutrients 2019, 11, 1885.

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