Liver-gut Axis in the Regulation of Iron Homeostasis

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2007 Aug 31

PMID 17729395

Citations 7

Authors

Deepak Darshan

Gregory-J Anderson

Affiliations

Soon will be listed here.

Abstract

The human body requires about 1-2 mg of iron per day for its normal functioning, and dietary iron is the only source for this essential metal. Since humans do not possess a mechanism for the active excretion of iron, the amount of iron in the body is determined by the amount absorbed across the proximal small intestine and, consequently, intestinal iron absorption is a highly regulated process. In recent years, the liver has emerged as a central regulator of both iron absorption and iron release from other tissues. It achieves this by secreting a peptide hormone called hepcidin that acts on the small intestinal epithelium and other cells to limit iron delivery to the plasma. Hepcidin itself is regulated in response to various systemic stimuli including variations in body iron stores, the rate of erythropoiesis, inflammation and hypoxia, the same stimuli that have been known for many years to modulate iron absorption. This review will summarize recent findings on the role played by the liver and hepcidin in the regulation of body iron absorption.

Citing Articles

Expression and Functional Analysis of Hepcidin from Mandarin Fish ().

Shen Y, Zhao Z, Zhao J, Chen X, Cao M, Wu M Int J Mol Sci. 2019; 20(22).

PMID: 31717495 PMC: 6887715. DOI: 10.3390/ijms20225602.

Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D-HFE Polymorphism Carriers.

Meadowcroft M, Wang J, Purnell C, Eslinger P, Neely E, Yang Q J Neuroimaging. 2017; 28(1):126-133.

PMID: 28771940 PMC: 5760459. DOI: 10.1111/jon.12461.

The effect of feeding a low iron diet prior to and during gestation on fetal and maternal iron homeostasis in two strains of rat.

Cornock R, Gambling L, Langley-Evans S, McArdle H, McMullen S Reprod Biol Endocrinol. 2013; 11:32.

PMID: 23635304 PMC: 3654972. DOI: 10.1186/1477-7827-11-32.

Ferroportin is a manganese-responsive protein that decreases manganese cytotoxicity and accumulation.

Yin Z, Jiang H, Lee E, Ni M, Erikson K, Milatovic D J Neurochem. 2009; 112(5):1190-8.

PMID: 20002294 PMC: 2819584. DOI: 10.1111/j.1471-4159.2009.06534.x.

A ferroportin transcript that lacks an iron-responsive element enables duodenal and erythroid precursor cells to evade translational repression.

Zhang D, Hughes R, Ollivierre-Wilson H, Ghosh M, Rouault T Cell Metab. 2009; 9(5):461-73.

PMID: 19416716 PMC: 2685206. DOI: 10.1016/j.cmet.2009.03.006.

References

Nicolas G, Chauvet C, Viatte L, Danan J, Bigard X, Devaux I . The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002; 110(7):1037-44. PMC: 151151. DOI: 10.1172/JCI15686. View

Papanikolaou G, Tzilianos M, Christakis J, Bogdanos D, Tsimirika K, MacFarlane J . Hepcidin in iron overload disorders. Blood. 2005; 105(10):4103-5. PMC: 1895089. DOI: 10.1182/blood-2004-12-4844. View

Lebron J, West Jr A, Bjorkman P . The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor. J Mol Biol. 1999; 294(1):239-45. DOI: 10.1006/jmbi.1999.3252. View

Lee P, Peng H, Gelbart T, Wang L, Beutler E . Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci U S A. 2005; 102(6):1906-10. PMC: 548537. DOI: 10.1073/pnas.0409808102. View

Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J . Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet. 2002; 33(1):21-2. DOI: 10.1038/ng1053. View

Frazer D, Anderson G . The orchestration of body iron intake: how and where do enterocytes receive their cues?. Blood Cells Mol Dis. 2003; 30(3):288-97. DOI: 10.1016/s1079-9796(03)00039-1. View

Gehrke S, Herrmann T, Kulaksiz H, Merle U, Bents K, Kaiser I . Iron stores modulate hepatic hepcidin expression by an HFE-independent pathway. Digestion. 2005; 72(1):25-32. DOI: 10.1159/000087400. View

Nemeth E, Roetto A, Garozzo G, Ganz T, Camaschella C . Hepcidin is decreased in TFR2 hemochromatosis. Blood. 2004; 105(4):1803-6. DOI: 10.1182/blood-2004-08-3042. View

Shi Y, Massague J . Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003; 113(6):685-700. DOI: 10.1016/s0092-8674(03)00432-x. View

10.

Pietrangelo A . Hereditary hemochromatosis. Biochim Biophys Acta. 2006; 1763(7):700-10. DOI: 10.1016/j.bbamcr.2006.05.013. View

11.

Robb A, Wessling-Resnick M . Regulation of transferrin receptor 2 protein levels by transferrin. Blood. 2004; 104(13):4294-9. DOI: 10.1182/blood-2004-06-2481. View

12.

Means R . Hepcidin and cytokines in anaemia. Hematology. 2005; 9(5-6):357-62. DOI: 10.1080/10245330400018540. View

13.

West Jr A, Bennett M, Sellers V, Andrews N, Enns C, Bjorkman P . Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem. 2000; 275(49):38135-8. DOI: 10.1074/jbc.C000664200. View

14.

Nemeth E, Valore E, Territo M, Schiller G, Lichtenstein A, Ganz T . Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2002; 101(7):2461-3. DOI: 10.1182/blood-2002-10-3235. View

15.

Herrmann T, Muckenthaler M, van der Hoeven F, Brennan K, Gehrke S, Hubert N . Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin. J Mol Med (Berl). 2003; 82(1):39-48. DOI: 10.1007/s00109-003-0508-x. View

16.

Shayeghi M, Latunde-Dada G, Oakhill J, Laftah A, Takeuchi K, Halliday N . Identification of an intestinal heme transporter. Cell. 2005; 122(5):789-801. DOI: 10.1016/j.cell.2005.06.025. View

17.

Leung P, Srai S, Mascarenhas M, Churchill L, Debnam E . Increased duodenal iron uptake and transfer in a rat model of chronic hypoxia is accompanied by reduced hepcidin expression. Gut. 2005; 54(10):1391-5. PMC: 1774692. DOI: 10.1136/gut.2004.062083. View

18.

Bridle K, Frazer D, Wilkins S, Dixon J, Purdie D, Crawford D . Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet. 2003; 361(9358):669-73. DOI: 10.1016/S0140-6736(03)12602-5. View

19.

Lin L, Goldberg Y, Ganz T . Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin. Blood. 2005; 106(8):2884-9. DOI: 10.1182/blood-2005-05-1845. View

20.

Babitt J, Huang F, Wrighting D, Xia Y, Sidis Y, Samad T . Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006; 38(5):531-9. DOI: 10.1038/ng1777. View