scholarly journals Managing Genetic Hemochromatosis: An Overview of Dietary Measures, Which May Reduce Intestinal Iron Absorption in Persons With Iron Overload

2021 ◽  
Vol 14 (2) ◽  
pp. 66-80
Author(s):  
Nils Thorm Milman
Keyword(s):  
Iron Overload ◽  
Iron Absorption ◽  
Intestinal Iron Absorption ◽  
Genetic Hemochromatosis

Dietary Supplementation with Genistein Increases Hepcidin Expression in Wild Type Mice

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3208-3208
Author(s):  
Aileen W. Zhen ◽  
Josephine Volovetz ◽  
Paula G. Fraenkel
Keyword(s):  
Iron Overload ◽  
Iron Content ◽  
Iron Absorption ◽  
Small Scale ◽  
Iron Release ◽  
Liver Iron ◽  
Transcript Levels ◽  
Intestinal Iron Absorption ◽  
Hepcidin Expression ◽  
Liver Iron Content

Abstract Abstract 3208 Iron overload is an important cause of morbidity and death in patients with hemoglobinopathies, transfusion-dependent anemias, and hereditary hemochromatosis. As humans have no means of excreting iron, regulation of iron homeostasis depends on limiting intestinal iron absorption and optimizing iron release from macrophages to developing erythrocytes. Hepcidin, a peptide hormone produced in the liver, modulates intestinal iron absorption and macrophage iron release via effects on ferroportin. Hepcidin is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. We conducted a small-scale chemical screen and found that the isoflavone genistein, a major dietary component of soybeans, enhanced Hepcidin transcript levels in zebrafish embryos. Furthermore genistein treatment increased Hepcidin transcript levels and Hepcidin promoter activity in human hepatocytes (HepG2 cells) in a Stat3 and Smad4-dependent manner. To evaluate genistein's effect in a mammalian model, we placed groups of 4 four-week old male C57BL/6 mice on an iron-sufficient, low soy diet (AIN93G containing 35 mg of iron/kg) supplemented with 0, 250, or 500 mg of genistein per kg of food for 7 weeks, and then sacrificed the animals for analysis. Plasma genistein levels (mean±SE) at the time of sacrifice were 0.015±0.015, 0.52±0.173, and 2.07±0.65 micromolar, respectively. Compared to mice not treated with genistein, the 250 mg/kg dose produced a significant increase in hepatic Hepcidin (HAMP1) transcript levels (1.49±0.10 vs 0.93±0.10, p=0.01), while the 500 mg/kg dose did not. Although liver iron content, spleen iron content, and weight gain were not significantly different among the groups, the ratio of Hepcidin expression to liver iron content was significantly increased in the animals treated with genistein 250 mg/kg compared to controls (0.013±0.0009 vs 0.0074±0.00068, p=0.0068). In conclusion, genistein is the first orally administered small molecule experimental drug shown to increase Hepcidin transcript levels in vivo. Future experiments will evaluate the effects of genistein on genetic models of iron overload syndromes. Disclosures: No relevant conflicts of interest to declare.

Modulation of the HIF2-NCOA4 axis in enterocytes attenuates iron loading in a mouse model of hemochromatosis

Blood ◽  
2022 ◽  
Author(s):  
Nupur K Das ◽  
Chesta Jain ◽  
Amanda D. Sankar ◽  
Andrew J Schwartz ◽  
Naiara Santana-Codina ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Mouse Model ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Hypoxia Inducible Factor ◽  
Whole Body ◽  
Deficiency Anemia ◽  
Null Mouse ◽  
Intestinal Iron Absorption

Intestinal iron absorption is activated during increased systemic iron demand. The best-studied example is iron-deficiency anemia, which increases intestinal iron absorption. Interestingly, the intestinal response to anemia is very similar to that of iron overload disorders, as both the conditions activate a transcriptional program that leads to a hyperabsorption of iron via the transcription factor hypoxia-inducible factor (HIF)2a. However, pathways to selectively target intestinal-mediated iron overload remain unknown. Nuclear receptor co-activator 4 (NCOA4) is a critical cargo receptor for autophagic breakdown of ferritin (FTN) and subsequent release of iron, in a process termed ferritinophagy. Our work demonstrates that NCOA4-mediated intestinal ferritinophagy is integrated to systemic iron demand via HIF2a. To demonstrate the importance of intestinal HIF2a/ferritinophagy axis in systemic iron homeostasis, whole body and intestine-specific NCOA4-null mouse lines were generated and assessed. These analyses revealed that the intestinal and systemic response to iron deficiency was not altered following disruption of intestinal NCOA4. However, in a mouse model of hemochromatosis, ablation of intestinal NCOA4 was protective against iron overload. Therefore, NCOA4 can be selectively targeted for the management of iron overload disorders without disrupting the physiological processes involved in the response to systemic iron deficiency.

Intestinal iron absorption studies in mouse models of iron-overload

1994 ◽  
Vol 86 (1) ◽  
pp. 156-162 ◽  
Author(s):  
K. B. Raja ◽  
R. J. Simpson ◽  
T. J. Peters
Keyword(s):  
Iron Overload ◽  
Mouse Models ◽  
Iron Absorption ◽  
Intestinal Iron Absorption ◽  
Absorption Studies

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

scholarly journals Molecular mechanisms involved in intestinal iron absorption

2007 ◽  
Vol 13 (35) ◽  
pp. 4716 ◽  
Author(s):  
Paul Sharp
Keyword(s):  
Molecular Mechanisms ◽  
Iron Absorption ◽  
Intestinal Iron Absorption

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

P117 Preliminary report of a study on the the role of H63D mutation on iron overload in genetic hemochromatosis in Italy

2003 ◽  
Vol 14 ◽  
pp. S65
Author(s):  
C. Velati ◽  
L. Fomiatti ◽  
V. Sancassani ◽  
G. Garozzo ◽  
P. Delbini ◽  
...  
Keyword(s):  
Iron Overload ◽  
Preliminary Report ◽  
H63d Mutation ◽  
Genetic Hemochromatosis

Compartmental analysis of intestinal iron absorption and mucosal iron kinetics

2020 ◽  
pp. 187-204
Author(s):  
Gordon D. McLaren ◽  
Michael H. Nathanson ◽  
Gerald M. Saidel
Keyword(s):  
Iron Absorption ◽  
Compartmental Analysis ◽  
Intestinal Iron Absorption ◽  
Iron Kinetics

Studies on intestinal iron absorption —a comparative histologic study on rats treated with CCL4 and DL-ethionine

1969 ◽  
Vol 4 (2) ◽  
pp. 158-159
Author(s):  
I. Urushizaki ◽  
M. Fukuda ◽  
T. Kodama ◽  
T. Takazawa
Keyword(s):  
Iron Absorption ◽  
Histologic Study ◽  
Intestinal Iron Absorption
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