Figure 1.

Under conditions of normal iron metabolism, iron is absorbed by enterocytes and exits enterocytes via ferroportin, which is regulated by the hormone hepcidin. The liver secretes hepcidin, whose main role is to keep iron levels balanced. Hepcidin is regulated by HFE. With iron overload, there is decreased expression of the HFE gene. As a result, HFE is unable to regulate hepcidin, which leads to a decrease in hepcidin levels. This in turn activates the ferroportin channel, allowing an efflux of iron into the blood and tissues and leading to a state of iron overload.