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Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice.

ABSTRACT: The ferritin core is composed of fine nanoparticulate Fe(3+) oxohydroxide, and we have developed a synthetic mimetic, nanoparticulate Fe(3+) polyoxohydroxide (nanoFe(3+)). The aim of this study was to determine how dietary iron derived in this fashion is absorbed in the duodenum. Following a 4 wk run-in on an Fe-deficient diet, mice with intestinal-specific disruption of the Fpn-1 gene (Fpn-KO), or littermate wild-type (WT) controls, were supplemented with Fe(2+) sulfate (FeSO4), nanoFe(3+), or no added Fe for a further 4 wk. A control group was Fe sufficient throughout. Direct intestinal absorption of nanoFe(3+) was investigated using isolated duodenal loops. Our data show that FeSO4 and nanoFe(3+) are equally bioavailable in WT mice, and at wk 8 the mean ± SEM hemoglobin increase was 18 ± 7 g/L in the FeSO4 group and 30 ± 5 g/L in the nanoFe(3+) group. Oral iron failed to be utilized by Fpn-KO mice and was retained in enterocytes, irrespective of the iron source. In summary, although nanoFe(3+) is taken up directly by the duodenum its homeostasis is under the normal regulatory control of dietary iron absorption, namely via ferroportin-dependent efflux from enterocytes, and thus offers potential as a novel oral iron supplement.

SUBMITTER: Aslam MF

PROVIDER: S-EPMC4101650 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice.

Aslam Mohamad F MF Frazer David M DM Faria Nuno N Bruggraber Sylvaine F A SF Wilkins Sarah J SJ Mirciov Cornel C Powell Jonathan J JJ Anderson Greg J GJ Pereira Dora I A DI

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20140428 8

The ferritin core is composed of fine nanoparticulate Fe(3+) oxohydroxide, and we have developed a synthetic mimetic, nanoparticulate Fe(3+) polyoxohydroxide (nanoFe(3+)). The aim of this study was to determine how dietary iron derived in this fashion is absorbed in the duodenum. Following a 4 wk run-in on an Fe-deficient diet, mice with intestinal-specific disruption of the Fpn-1 gene (Fpn-KO), or littermate wild-type (WT) controls, were supplemented with Fe(2+) sulfate (FeSO4), nanoFe(3+), or ...[more]

PMID: 24776745

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Project description:BackgroundAlcohol consumption is associated with increased iron stores. In sub-Saharan Africa, high dietary ionic iron and the ferroportin Q248H allele have also been implicated in iron accumulation. We examined the associations of ferroportin Q248H, alcohol and dietary iron with serum ferritin, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) concentrations in African-Americans.MethodsInner-city African-Americans (103 men, 40 women) were recruited from the community according to reported ingestion of >4 alcoholic drinks/d or <2/wk. Typical daily heme iron, nonheme iron and alcohol were estimated using University of Hawaii's multiethnic dietary questionnaire. Based on dietary questionnaire estimates we established categories of < versus > or =56 g alcohol/d, equivalent to 4 alcoholic drinks/d assuming 14 g alcohol per drink.ResultsAmong 143 participants, 77% drank <56 g alcohol/d and 23%> or =56 g/d as estimated by the questionnaire. The prevalence of ferroportin Q248H was 23.3% with alcohol >56 g/d versus 7.5% with lower amounts (p = 0.014). Among subjects with no history of HIV disease, serum ferritin concentration had positive relationships with male gender (p = 0.041), alcohol consumption (p = 0.021) and ALT concentration (p = 0.0001) but not with dietary iron intake or ferroportin Q248H. Serum AST and ALT concentrations had significant positive associations with male gender and hepatitis C seropositivity but not with alcohol or dietary iron intake or ferroportin Q248H.ConclusionsOur findings suggest a higher prevalence of ferroportin Q248H with greater alcohol consumption, and this higher prevalence raises the possibility that the allele might ameliorate the toxicity of alcohol. Our results suggest that alcohol but not dietary iron contributes to higher body iron stores in African-Americans. Studies with larger numbers of participants are needed to further clarify the relationship of ferroportin Q248H with the toxicity of alcohol consumption.

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Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice.

Publications

Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice.

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