Effect of zinc depletion/repletion on intestinal iron absorption and iron status in Rats

2021 ◽  
pp. 108800
Author(s):  
Palsa Kondaiah ◽  
Ravindranadh Palika ◽  
Purnachandra Mashurabad ◽  
Puneeta Singh Yaduvanshi ◽  
Paul A. Sharp ◽  
...  
Keyword(s):  
Iron Absorption ◽  
Iron Status ◽  
Intestinal Iron Absorption ◽  
Zinc Depletion

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

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1885 ◽  
Author(s):  
Palsa Kondaiah ◽  
Puneeta Singh Yaduvanshi ◽  
Paul A Sharp ◽  
Raghu Pullakhandam
Keyword(s):  
Iron Absorption ◽  
Iron Status ◽  
The Body ◽  
Zinc Homeostasis ◽  
Iron Accumulation ◽  
Intestinal Cell ◽  
Deficiency Anemia ◽  
Intestinal Iron Absorption ◽  
Tissue Iron ◽  
Iron And Zinc

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.

Iron supply determines apical/basolateral membrane distribution of intestinal iron transporters DMT1 and ferroportin 1

2010 ◽  
Vol 298 (3) ◽  
pp. C477-C485 ◽  
Author(s):  
Marco T. Núñez ◽  
Victoria Tapia ◽  
Alejandro Rojas ◽  
Pabla Aguirre ◽  
Francisco Gómez ◽  
...  
Keyword(s):  
Translational Regulation ◽  
Fluorescent Protein ◽  
Iron Absorption ◽  
Iron Status ◽  
Basolateral Membrane ◽  
Membrane Domains ◽  
Divalent Metal Transporter 1 ◽  
Intestinal Iron Absorption ◽  
Divalent Metal Transporter ◽  
Iron Supply

Intestinal iron absorption comprises the coordinated activity of the influx transporter divalent metal transporter 1 (DMT1) and the efflux transporter ferroportin (FPN). In this work, we studied the movement of DMT1 and FPN between cellular compartments as a function of iron supply. In rat duodenum, iron gavage resulted in the relocation of DMT1 to basal domains and the internalization of basolateral FPN. Considerable FPN was also found in apical domains. In Caco-2 cells, the apical-to-basal movement of cyan fluorescent protein-tagged DMT1 was complete 90 min after the addition of iron. Steady-state membrane localization studies in Caco-2 cells revealed that iron status determined the apical/basolateral membrane distribution of DMT1 and FPN. In agreement with the membrane distribution of the transporters,55Fe flux experiments revealed inward and outward iron fluxes at both membrane domains. Antisense oligonucleotides targeted to DMT1 or FPN inhibited basolateral iron uptake and apical iron efflux, respectively, indicating the participation of DMT1 and FPN in these fluxes. The fluxes were regulated by the iron supply; increased iron reduced apical uptake and basal efflux and increased basal uptake and apical efflux. These findings suggest a novel mechanism of regulation of intestinal iron absorption based on inward and outward fluxes at both membrane domains, and repositioning of DMT1 and FPN between membrane and intracellular compartments as a function of iron supply. This mechanism should be complementary to those based in the transcriptional or translational regulation of iron transport proteins.

Iron Imports. VI. HFE and regulation of intestinal iron absorption

2006 ◽  
Vol 290 (4) ◽  
pp. G590-G594 ◽  
Author(s):  
Robert E. Fleming ◽  
Robert S. Britton
Keyword(s):  
Iron Homeostasis ◽  
Iron Absorption ◽  
Iron Status ◽  
Hfe Gene ◽  
Primary Role ◽  
Intestinal Iron Absorption ◽  
Downstream Effects ◽  
Cell Type Specific ◽  
Intestinal Enterocytes

The majority of clinical cases of iron overload is caused by mutations in the HFE gene. However, the role that HFE plays in the physiology of intestinal iron absorption remains enigmatic. Two major models have been proposed: 1) HFE exerts its effects on iron homeostasis indirectly, by modulating the expression of hepcidin; and 2) HFE exerts its effects directly, by changing the iron status (and therefore the iron absorptive activity) of intestinal enterocytes. The first model places the primary role of HFE in the liver (hepatocytes and/or Kupffer cells). The second model places the primary role in the duodenum (crypt cells or villus enterocytes). These models are not mutually exclusive, and it is possible that HFE influences the iron status in each of these cell populations, leading to cell type-specific downstream effects on intestinal iron absorption and body iron distribution.

scholarly journals Cloning and gastrointestinal expression of rat hephaestin: relationship to other iron transport proteins

2001 ◽  
Vol 281 (4) ◽  
pp. G931-G939 ◽  
Author(s):  
David M. Frazer ◽  
Christopher D. Vulpe ◽  
Andrew T. McKie ◽  
Sarah J. Wilkins ◽  
Deborah Trinder ◽  
...  
Keyword(s):  
Iron Transport ◽  
Iron Absorption ◽  
Iron Status ◽  
Critical Role ◽  
Transport Proteins ◽  
Ribonuclease Protection Assay ◽  
Intestinal Iron Absorption ◽  
Genes Encoding ◽  
Ribonuclease Protection ◽  
Iron Transport Proteins

The membrane-bound ceruloplasmin homolog hephaestin plays a critical role in intestinal iron absorption. The aims of this study were to clone the rat hephaestin gene and to examine its expression in the gastrointestinal tract in relation to other genes encoding iron transport proteins. The rat hephaestin gene was isolated from intestinal mRNA and was found to encode a protein 96% identical to mouse hephaestin. Analysis by ribonuclease protection assay and Western blotting showed that hephaestin was expressed at high levels throughout the small intestine and colon. Immunofluorescence localized the hephaestin protein to the mature villus enterocytes with little or no expression in the crypts. Variations in iron status had a small but nonsignificant effect on hephaestin expression in the duodenum. The high sequence conservation between rat and mouse hephaestin is consistent with this protein playing a central role in intestinal iron absorption, although its precise function remains to be determined.

The relative importance of luminal and systemic signals in the control of intestinal iron absorption

2001 ◽  
Vol 120 (5) ◽  
pp. A678-A679
Author(s):  
G ANDERSON ◽  
S WILKINS ◽  
T MURPHY ◽  
G CLEGHORN ◽  
D FRAZER
Keyword(s):  
Iron Absorption ◽  
Relative Importance ◽  
Intestinal Iron Absorption ◽  
Systemic Signals

984 Suppression of LPS and IL-6 Signaling By Iron Deficiency Alters Expression of the Intestinal Iron Absorption Regulator Hepcidin

2008 ◽  
Vol 134 (4) ◽  
pp. A-147
Author(s):  
Deepak Darshan ◽  
David M. Frazer ◽  
Sarah J. Wilkins ◽  
Gregory J. Anderson
Keyword(s):  
Iron Deficiency ◽  
Iron Absorption ◽  
Intestinal Iron Absorption

scholarly journals An intensified training schedule in recreational male runners is associated with increases in erythropoiesis and inflammation and a net reduction in plasma hepcidin

2018 ◽  
Vol 108 (6) ◽  
pp. 1324-1333 ◽  
Author(s):  
Diego Moretti ◽  
Samuel Mettler ◽  
Christophe Zeder ◽  
Carsten Lundby ◽  
Anneke Geurts-Moetspot ◽  
...  
Keyword(s):  
Exercise Training ◽  
Iron Absorption ◽  
Iron Status ◽  
Geometric Mean ◽  
Iron Bioavailability ◽  
Oral Iron ◽  
Low Grade ◽  
Hemoglobin Mass ◽  
Low Grade Inflammation ◽  
Iron Utilization

ABSTRACT Background Iron status is a determinant of physical performance, but training may induce both low-grade inflammation and erythropoiesis, exerting opposing influences on hepcidin and iron metabolism. To our knowledge, the combined effects on iron absorption and utilization during training have not been examined directly in humans. Objective We hypothesized that 3 wk of exercise training in recreational male runners would decrease oral iron bioavailability by increasing inflammation and hepcidin concentrations. Design In a prospective intervention, nonanemic, iron-sufficient men (n = 10) completed a 34-d study consisting of a 16-d control phase and a 22-d exercise-training phase of 8 km running every second day. We measured oral iron absorption and erythroid iron utilization using oral 57Fe and intravenous 58Fe tracers administered before and during training. We measured hemoglobin mass (mHb) and total red blood cell volume (RCV) by carbon monoxide rebreathing. Iron status, interleukin-6 (IL-6), plasma hepcidin (PHep), erythropoietin (EPO), and erythroferrone were measured before, during, and after training. Results Exercise training induced inflammation, as indicated by an increased mean ± SD IL-6 (0.87 ± 1.1 to 5.17 ± 2.2 pg/mL; P < 0.01), while also enhancing erythropoiesis, as indicated by an increase in mean EPO (0.66 ± 0.42 to 2.06 ± 1.6 IU/L), mHb (10.5 ± 1.6 to 10.8 ± 1.8 g/kg body weight), and mean RCV (30.7 ± 4.3 to 32.7 ± 4.6 mL/kg) (all P < 0.05). Training tended to increase geometric mean iron absorption by 24% (P = 0.083), consistent with a decreased mean ± SD PHep (7.25 ± 2.14 to 5.17 ± 2.24 nM; P < 0.05). The increase in mHb and erythroid iron utilization were associated with the decrease in PHep (P < 0.05). Compartmental modeling indicated that iron for the increase in mHb was obtained predominantly (>80%) from stores mobilization rather than from increased dietary absorption. Conclusions In iron-sufficient men, mild intensification of exercise intensity increases both inflammation and erythropoiesis. The net effect is to decrease hepcidin concentrations and to tend to increase oral iron absorption. This trial was registered at clinicaltrials.gov as NCT01730521.

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