Determination of
iron accumulation is crucial in diagnosing the occurrence and progression of many liver- and
iron-related diseases. Thus far, little is known about the profiles of
iron deposition in different liver zones, particularly under conditions with disordered
iron homeostasis. Here, uneven
iron distribution in livers of patients with hereditary
hemochromatosis (HH) is uncovered, showing the region with the highest
iron concentration near the entrance site of the portal vein and hepatic artery in contrast to the sites with the lowest
iron concentration close to the distal edge. Distinct
iron distribution profiles are also found throughout liver zones in wild-type mice and various mouse models with
iron metabolism disorders, including
hemochromatosis (Hfe-/- ),
iron deficiency, and
inflammation. Of note, similar findings observed in HH patients are further demonstrated in Hfe-/- mice. Moreover, the zones with greater
iron accumulation appear to be more sensitive to
iron changes, e.g., there is
iron increase upon
iron overload and
iron loss in response to
iron deficiency. Mechanistic investigation manifests that these differential
iron changes in liver zones are subjected to the regulation by the
hepcidin-
ferroportin axis. Additionally, the data corroborate the reliability of magnetic resonance imaging (MRI) in recognizing the differential
iron deposition profiles among liver zones.