title: Iron absorption in hepcidin1 knockout mice.
abstract: Hepcidin, the Fe-regulatory peptide, has been shown to inhibit Fe absorption and reticuloendothelial Fe recycling. The present study was conducted to explore the mechanism of in vivo Fe regulation through genetic disruption of hepcidin1 and acute effects of hepcidin treatment in hepcidin1 knockout (Hepc1-/-) and heterozygous mice. Hepcidin1 disruption resulted in significantly increased intestinal Fe uptake. Hepcidin injection inhibited Fe absorption in both genotypes, but the effects were more evident in the knockout mice. Hepcidin administration was also associated with decreased membrane localisation of ferroportin in the duodenum, liver and, most significantly, in the spleen of Hepc1-/- mice. Hypoferraemia was induced in heterozygous mice by hepcidin treatment, but not in Hepc1-/- mice, 4 h after injection. Interestingly, Fe absorption and serum Fe levels in Hepc1-/- and heterozygous mice fed a low-Fe diet were not affected by hepcidin injection. The present study demonstrates that hepcidin deficiency causes increased Fe absorption. The effects of hepcidin were abolished by dietary Fe deficiency, indicating that the response to hepcidin may be influenced by dietary Fe level or Fe status.
authors.affiliation: Nutritional Sciences Research Division, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Patarabutr
authors.initials: P
authors.lastname: Masaratana
authors.forename: Abas H
authors.initials: AH
authors.lastname: Laftah
authors.forename: Gladys O
authors.initials: GO
authors.lastname: Latunde-Dada
authors.forename: Sophie
authors.initials: S
authors.lastname: Vaulont
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McKie
mesh_terms: D000042:Absorption; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins; D007501:Iron / Q000097:blood / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019159:Nonheme Iron Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C579599:Hamp protein, mouse; D006454:Hemoglobins; D064451:Hepcidins; D019159:Nonheme Iron Proteins; D000098742:Ferroportin; D007501:Iron