Award details

The role of hepcidin in regulating intestinal iron absorption

Reference	BB/D015456/1
Principal Investigator / Supervisor	Professor Paul Sharp
Co-Investigators / Co-Supervisors	Professor Surjit Srai
Institution	King's College London
Department	Nutritional Sciences c
Funding type	Research
Value (£)	351,088
Status	Completed
Type	Research Grant
Start date	02/10/2006
End date	01/10/2009
Duration	36 months

Abstract

Iron deficiency and associated anaemia represent major global health problems - current estimates suggest that up to 2 billion people (mainly in the developing world) are affected. In the UK, while full-blown anaemia is relatively rare it is thought that up to 30% of pre-menopausal women have low iron stores. This places a major burden on the NHS - the cost of treating iron deficiency is estimated to be £25 million per annum. Current treatment involves the use of high dose iron supplements which in a number of cases are poorly tolerated. At present, alternative therapies remain elusive, though one possible target might be the iron regulatory peptide hepcidin. In order to develop this possibility it is essential to gain a better understanding of the cellular mechanisms involved in the hepcidin regulatory pathway. With this aim in mind, the current proposal will explore the interactions between hepcidin and the intestinal epithelium (responsible for regulating dietary iron absorption). The timecourse of events following exposure to hepcidin will be determined and will include measurement of iron transport across the epithelium and changes in the expression of key genes and proteins involved in intestinal iron metabolism. Possible regulatory mechanisms involved in the response to hepcidin at the cellular level will also be explored using genomic technology. Together these studies will give us a better understanding of the mechanisms by which the major regulator of body iron metabolism operates. This information is essential if the hepcidin pathway is to be exploited as an avenue for improved treatment of people with iron deficiency and iron deficiency anaemia.

Summary

Iron deficiency anaemia is the most common nutritional deficiency affecting 2 billion people worldwide. While the majority of those affected live in the developing world, up to 30% of women of childbearing age in the UK are also iron deficient. It is estimated that the treatment of ailments associated with iron deficiency costs the NHS approximately £25 million per year. Conventional treatment for iron deficient patients relies on supplements containing relatively high doses of iron. While these supplements improve iron status in the long term, they can cause gastro-intestinal disturbances and are therefore poorly tolerated by some patients. The development of improved treatment regimes would therefore benefit those on supplementation therapy. Hepcidin, a regulatory peptide that controls iron absorption, might be a target for the development of such alternative therapies. As a first step in exploring this possibility, our study will establish a better understanding of the mechanisms by which hepcidin interacts (i) with intestinal epithelial cells to regulate dietary iron absorption and (ii) with macrophages which recover iron from dead red blood cells so that it can be re-used for the production of erythrocyte haemoglobin . These preliminary studies will highlight important cellular mechanisms that can be explored further as possible targets for therapeutic intervention.

Committee	Closed Committee - Agri-food (AF)
Research Topics	Diet and Health
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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