Advances in understanding the molecular basis for the regulation of dietary iron absorption

The number of newly identified genes participating in the regulation of iron homeostasis has continued to expand at a remarkable pace. The roles for many have begun to be elucidated and there is an increasing indication that hepatocytes play a central role in determining the level of intestinal iron absorption. Total body iron homeostasis is dependent upon carefully regulated absorption of dietary iron, thus these genes are of fundamental importance in understanding of pathophysiology of such common disorders as hereditary hemochromatosis (HH) and the anaemia of chronic diseases.

The hepatic peptide hepcidin plays a key role as a circulating hormone that regulates the absorption of dietary iron from the duodenum. Hepcidin expression is inappropriately decreased in hereditary hemochromatosis and is abnormally increased in the anaemia of chronic diseases. Other hepatic proteins essential for normal iron homeostasis, including HFE, transferrin receptor 2 (TfR2), and hemojuvelin, function at least in part, by modulating the expression of hepcidin.

New insights into the pathophysiology of hereditary hemochromatosis and the anaemia of chronic diseases have been achieved with the recognition of the central role for hepcidin as an iron regulatory hormone. Investigations into the biologic control of this hormone and its mechanism of action offer the possibility of new therapeutic approaches to disorders of iron metabolism.