Breaking new ground | Action Medical Research

Touching Lives - June 2005

Breaking new ground

We all remember being told to ‘eat our greens’ and understand that the iron in leafy vegetables is essential for our health and wellbeing. In fact healthy eating has been big news in recent months with Jamie Oliver’s plans to start a revolution in school dining halls up and down the country; and where would Popeye have been without his spinach?!

However, it may surprise you to know that we are not quite what we eat…what we eat does not provide the full picture about how healthy we are.

Why is it that someone eating an apparently healthy diet, rich in iron, can suffer from anaemia (low levels of iron in the blood) whilst another eating a similar diet suffers from iron-overload? Health professionals understand that as well as consciously making a choice to eat all the right foods, it is our body’s ability to absorb the nutrients from our diet that is an important factor in providing us with all the energy and nourishment we need to go about our daily lives.

It is part of this absorption process that Professor Jonathan Powell and his team from St Thomas’ Hospital and King’s College London has investigated, with the help of an Action Medical Research grant of £101,154. Professor Powell has used groundbreaking technology to look at the way in which iron is absorbed by the body to learn more about why some people absorb too little and others too much. He has discovered that the answer could lie in the blood itself…

Regulation of iron in the body

^Iron is vital for many body processes and its deficiency is one of the biggest nutritional disorders in the developing world.^ It is used to form haemoglobin in the blood, which then transports oxygen to the body’s tissues and organs.

Too little iron, which affects up to one in three people worldwide, can lead to anaemia, fatigue and in the worst circumstances hospitalisation. Too much iron, on the other hand, can lead to diabetes, heart disease and liver cirrhosis. Those with the inherited disorder primary haemochromatosis, which allows continual over absorption of iron, are at risk of these diseases because our bodies have no natural means to rid themselves of excess iron; instead more and more iron is added to the reserves held within the liver.

Previous studies have concluded that if the body does not have the means to get rid of excess amounts of iron consumed, the key to ensuring a healthy balance within the blood must depend on the amount that is actually absorbed from the food we eat by cells within the intestine.

Researchers have discovered that there are tiny cells called ‘enterocytes’ that line the upper part of the intestine, which is known as the duodenum. These enterocytes absorb iron from digested food with the help of special proteins. A further set of proteins then allow the iron to be released from the enterocytes into the rich blood supply that serves the intestinal area.

Therefore the essential balance of iron within our bodies is reliant upon the two groups of proteins working together to determine firstly, the amount of iron that can be absorbed from food and secondly, its transferral into the bloodstream.

Dcytb — what’s that?

Professor Powell’s study looked specifically at one protein essential for iron absorption, named Dcytb, which converts dietary iron into a form that is readily absorbed by the enterocytes in the duodenum.

^The results of his study have important ramifications across medicine, both in terms of the method of his work and its findings.^ He believes that the team is the first to use an electron microscope to show that the Dcytb protein is attached to the very outer surface of the enterocyte cells on tiny hair-like structures called microvilli.

This discovery goes some way to confirming that the Dcytb proteins act as tiny microscopic doorways on the upper surface of the cells allowing, specifically, the passage of iron into the body of the cells. Interestingly, iron-deficient patients have more Dcytb doorways than those with excess iron, as the body attempts to compensate for low iron levels by creating more opportunities for the absorption of iron.

However, the study found that there was little connection between the levels of Dcytb and the amount of the iron storage protein (ferritin) in the enterocytes or in the rest of the body. Since ferritin is used to allow the storage of iron within cells, its presence is a good indicator of the amount of iron that is stored in the cell.

This suggested to the team that the number of Dcytb doorways present on the upper surfaces of the enterocytes is not determined by the levels of iron stored within the cells.

This led to the team’s second breakthrough — the discovery that the levels of stored iron released into the blood stream is related to the amount of iron already in the bloodstream.

Huge strides forward

Professor Powell said, “For the first time we have been able to demonstrate something that has been speculated about for some time — that it is iron in the bloodstream that regulates the absorption of dietary iron in the gut.

“Up until now it had not been clear as to what determines protein levels on the surface of the cells in the gut and therefore how much iron is absorbed. Initially it was thought to be the amount of iron in the cells lining the duodenum, but our study found that was not the case.

“A second school of thought believed it to be the levels of iron in the body’s stores, for example in the liver, but again we have found this not to be the case.

“Our study has confirmed the third theory, that it is the iron circulating in the blood that sets the absorption levels. And this supports exciting data from other groups showing the presence of a special iron-controlling hormone, called hepcidin, that is likely to co-ordinate all of these processes.”

Professor Powell added, ^”A really significant bonus in all of this work was that during the study, the team used the highest powered electron microscope in the country to look at liver ferritin.^ This was a great step forward because it allowed part of the ferritin molecule to be imaged in sections of human liver at the atomic level.

“For the first time we were able to look at the iron atoms whilst they were actually stored in the ferritin within the cells inside the liver. It’s a huge technical breakthrough.”

It’s a zoo out there

Professor Powell continued, “Previous studies trying to achieve these clear images have had to isolate molecules away from their natural environment, so you were never sure if what you saw was real or a result of the unnatural environment.

“It’s a little like studying the behaviour of animals in the wild versus the way they act in the zoo. ^Hopefully our work can now be used as a platform, not only in helping our understanding of iron absorption and storage, to help those suffering with anaemia or iron overload, but also other areas of medical research.^

“We are using similar techniques in the study of inflammatory diseases, especially Crohn’s disease, and other research teams are using this for bone disease.”

Thanks to Action Medical Research funding, this tremendous breakthrough in knowledge about the way the body regulates iron levels through absorption could lead to life-saving treatments, not only for those suffering iron related disorders, but for many other conditions too.

Our thanks go to Garfield Weston for supporting this project.

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