Rethinking iron regulation and assessment in iron deficiency, anemia of chronic disease, and obesity: introducing hepcidin.
Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed.
US Department of Agriculture/Agricultural Research Service (USDA/ARS), Baton Rouge, LA 70803, USA. lisa.tussing@ars.usda.gov
Lisa
L
Tussing-Humphreys
Cenk
C
Pusatcioglu
Cenk
C
Pustacioglu
Elizabeta
E
Nemeth
Carol
C
Braunschweig
D018798:Anemia, Iron-Deficiency / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000502:physiology*; D001682:Biological Availability; D002908:Chronic Disease; D005786:Gene Expression Regulation; D064451:Hepcidins; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D009753:Nutritive Value; D009765:Obesity / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D007501:Iron