Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice.
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.
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK;
Mohamad F
MF
Aslam
Iron Metabolism Laboratory, Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia; and.
David M
DM
Frazer
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK;
Nuno
N
Faria
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK;
Sylvaine F A
SF
Bruggraber
Iron Metabolism Laboratory, Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia; and.
Sarah J
SJ
Wilkins
Iron Metabolism Laboratory, Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia; and.
Cornel
C
Mirciov
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK;
Jonathan J
JJ
Powell
Iron Metabolism Laboratory, Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia; and School of Chemistry and Molecular Bioscience and School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Greg J
GJ
Anderson
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK; dora.pereira@mrc-hnr.cam.ac.uk.
Dora I A
DI
Pereira
D000284:Administration, Oral; D018798:Anemia, Iron-Deficiency / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004386:Duodenum / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism*; D005290:Ferric Compounds / Q000493:pharmacokinetics*; D005296:Ferrous Compounds / Q000493:pharmacokinetics; D005786:Gene Expression Regulation; D006454:Hemoglobins / Q000032:analysis; D064451:Hepcidins / Q000096:biosynthesis / Q000235:genetics; D006706:Homeostasis; D007408:Intestinal Absorption / Q000502:physiology*; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000493:pharmacokinetics*; D051379:Mice; D018345:Mice, Knockout; D053758:Nanoparticles; D013154:Spleen / Q000378:metabolism; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D005290:Ferric Compounds; D005296:Ferrous Compounds; D006454:Hemoglobins; D064451:Hepcidins; D019266:Iron, Dietary; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C579599:Hamp protein, mouse; C021024:ferric hydroxide; C020748:ferrous sulfate
basolateral export; hepcidin; iron homeostasis; knockout mice; nanoiron