Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats.
OBJECTIVE
Hepcidin is an antimicrobial peptide thought to be involved in the regulation of intestinal iron absorption. To further investigate its role in this process, we examined hepatic and duodenal gene expression in rats after the switch from a control diet to an iron-deficient diet.


METHODS
Adult rats on an iron-replete diet were switched to an iron-deficient diet and the expression of iron homeostasis molecules in duodenal and liver tissue was studied over 14 days. Intestinal iron absorption was determined at these same time-points by measuring the retention of an oral dose of (59)Fe.


RESULTS
Iron absorption increased 2.7-fold within 6 days of switching to an iron-deficient diet and was accompanied by an increase in the duodenal expression of Dcytb, divalent metal transporter 1, and Ireg1. These changes precisely correlated with decreases in hepatic hepcidin expression and transferrin saturation. No change in iron stores or hematologic parameters was detected.


CONCLUSIONS
This study showed a close relationship between the expression of hepcidin, duodenal iron transporters, and iron absorption. Both hepcidin expression and iron absorption can be regulated before iron stores and erythropoiesis are affected, and transferrin saturation may signal such changes.
Joint Clinical Sciences Program, The Queensland Institute of Medical Research and The University of Queensland, Royal Brisbane Hospital, Brisbane, Queensland, Australia.
David M
DM
Frazer
Sarah J
SJ
Wilkins
Erika M
EM
Becker
Christopher D
CD
Vulpe
Andrew T
AT
McKie
Deborah
D
Trinder
Gregory J
GJ
Anderson
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D004032:Diet; D004386:Duodenum / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D064451:Hepcidins; D007408:Intestinal Absorption / Q000502:physiology*; D007501:Iron / Q000378:metabolism / Q000493:pharmacokinetics*; D000090463:Iron Deficiencies; D033862:Iron-Binding Proteins; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003573:Cytochrome b Group; D064451:Hepcidins; D007501:Iron; D033862:Iron-Binding Proteins; D010088:Oxidoreductases; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C000598701:Cybrd1 protein, rat; C578703:Hamp protein, rat