Proceedings of The Physiological Society

University of Cambridge (2008) Proc Physiol Soc 11, C88

Oral Communications

Mouse duodenal iron transport is decreased following chronic exposure to hepcidin.

T. Chaston1, J. Marks2, E. Debnam2, S. K. Srai3, P. Sharp1

1. Nutritional Sciences, King's College London, London, United Kingdom. 2. Department of Physiology, University College London, London, United Kingdom. 3. Department of Structural & Molecular Biology, University College London, London, United Kingdom.


  • Table 1. In vivo duodenal iron transport (n = 4-6 mice in each group)
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Hepcidin, the main circulating iron regulatory hormone exerts its actions by binding to the iron efflux protein ferroportin, inducing transporter degradation and thereby inhibiting iron release from cells [1]. We have shown previously that injection of hepcidin into mice results in a rapid (within 4h) decrease in serum iron and a concomitant decrease in ferroportin expression in splenic macrophages [2]. Interestingly, duodenal ferroportin expression in the same animals was not altered within this time frame [2]. The aim of this study was to examine the effects of longer-term exposure to hepcidin on duodenal iron transport. Male C57BL/6 mice (aged 4 weeks) were given injections of hepcidin (10µg/mouse, i.p.) or an equivalent volume of saline at 24h intervals. A final injection of hepcidin was administered 4h prior to experimentation. In anaesthetised animals (sodium pentobarbitone, 60 mg/kg, i.p.), tied-off duodenal segments were washed with saline, followed by air, filled with Hepes-buffered saline (pH6.5) containing 0.2mM 59Fe, complexed with 4mM ascorbate and incubated for 10 min. At the end of the exposure period, the amount of 59Fe in the duodenal mucosa and the animal carcass were determined by gamma counting. Data are presented as mean ± SEM, and were analysed using one-way ANOVA and Tukey’s post hoc test with differences considered significant at P<0.05. Iron transfer from the duodenal mucosa to the animal was significantly decreased in both 24h and 72h hepcidin treated mice compared with the control group (Table 1). Interestingly, iron retention within the mucosal tissue was significantly elevated in 24h hepcidin treated mice compared with the other two experimental groups, suggesting that enterocytes were still able to take up iron despite the inhibition of the efflux pathway. Taken together with our previous data [2], we propose that duodenal enterocytes are less sensitive than splenic macrophages to a hepcidin challenge, and that this is consistent with the relative importance of these two cell types in maintaining body iron homeostasis.

Where applicable, experiments conform with Society ethical requirements