Clinical Implications of New Insights into Hepcidin-Mediated Regulation of Iron Absorption and Metabolism

Prentice, Andrew M.
December 2017
Annals of Nutrition & Metabolism;Dec2017, Vol. 71, p40
Academic Journal
The fact that humans must balance their need for iron against its potential for causing harm has been known for several centuries, but the molecular mechanisms by which we achieve this feat have only been revealed in the last 2 decades. Chief amongst these is the discovery of the master-regulatory liver-derived hormone hepcidin. By switching off ferroportin in enterocytes and macrophages, hepcidin exerts fine control over both iron absorption and its distribution among tissues. Hepcidin expression is downregulated by low iron status and active erythropoiesis and upregulated by iron overload and infection and/or inflammation. The latter mechanism explains the etiology of the anemia of chronic infection. Pharmaceutical companies are actively developing hepcidin agonists and antagonists to combat iron overload and anemia, respectively. In a global health context the discovery of hepcidin shines a new light on the world's most prevalent micronutrient problem; iron deficiency and its consequent anemia. It is now apparent that humans are not poorly designed to absorb dietary iron, but rather are exerting a tonic downregulation of iron absorption to protect themselves against infection. These new insights suggest that interventions to reduce infections and inflammation will be at least as effective as dietary interventions and that the latter will not succeed without the former.


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