What makes the body absorb too much iron? - ping doe



J

Jim Carter

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Public release date: 25-Apr-2003

Contact: Russ Hodge [email protected] 49-622-138-7252 European Molecular Biology Laboratory

What makes the body absorb too much iron?

Researchers at EMBL and Harvard gain new insights into the most common inherited disease in the
Western world Like most nutrients, iron is good for people in the right doses. When the body has
enough iron, our cells stop absorbing it from food; if there is too little, they absorb more. This
system breaks down in the most common inherited disease in the Western world: hemochromatosis, which
affects about one in every 250 people and is often fatal if it is not recognized and treated. Now
researchers at the European Molecular Biology Laboratory in Heidelberg (EMBL) and Harvard Medical
School (U.S.) have linked the response of a gene in the liver to the disease. The study, which
appears in the current issue of Nature Genetics, is changing our understanding of how
hemochromatosis develops. "Untreated iron overload can result in liver cancer, heart disease, or
other fatal conditions," says Martina Muckenthaler, a staff scientist at EMBL in the research group
of Matthias Hentze. "The mutation that causes the disease was thought to have its major effects in
the intestine, where cells absorb iron from food. Our current study has changed that picture."

Sufferers of hemochromatosis have inherited a defective copy of a gene called Hfe from each parent.
The mutation can be traced back several centuries into Celtic history, where it originated in a
single person who passed it down to his or her children. It has now spread throughout Europe and the
Western world.

The defect leads a person's intestine to absorb too much iron from his or her diet. Over the course
of many years, this builds up, and by middle age, the overload may be very serious. Hentze and his
group at EMBL have been trying to trace these effects back to their molecular causes.

Until now, most researchers have thought that the problem stems from a faulty intestinal signal that
there is too little iron, leading cells in the intestines to produce more transport proteins that
draw iron inside.

By combining two approaches, the EMBL and Harvard teams have now rewritten this model. Their study
shows that the link between Hfe and iron is probably in the liver, rather than the intestine.

The EMBL group was investigating iron absorption with a technology called DNA chips. The method
allows scientists to monitor how a cell's genes respond to changes such as a raise in levels of
iron. Working with the research team of Wilhelm Ansorge, Muckenthaler put together a set of probes
that could watch for changes in 300 genes known to have some connection to iron.

Simultaneously, Nancy Andrews' group at Harvard was working on hemochromatosis in mice which are
often used to create models of human disease. The Harvard scientists had developed strains of mice
without Hfe, or with the mutant version found in hemochromatosis. Both strains absorbed too much
iron and exhibited the symptoms of the disease.

The DNA chips were used to compare cells taken from these mice and their healthy cousins. In
the former model, cells with defective Hfe were expected to behave like healthy mice with an
iron deficiency they ought to produce more iron-absorbing proteins in the intestine. That
wasn't the case.

So the researchers started to look farther afield for other effects of mutant Hfe. They discovered
something intriguing in the liver. A molecule called hepcidin wasn't being activated properly.

When iron levels rise in a healthy mouse, its liver produces more hepcidin, and hepcidin acts like a
hormone to reduce iron absorption by the intestine. This didn't happen in mice with mutant or
missing Hfe even when the researchers directly injected them with iron. This was proof that Hfe is
necessary to make a connection between iron and hepcidin, and that shakes up the old model. The
importance of low hepcidin production in Hemochromatosis is further underlined by the co-published
work of the team of Sophie Vaulont at the Cochin Institute in Paris. They were able to show that the
liver does not load iron when hepcidin is added to mice lacking the hemochromatosis gene. It means
that focus should change from the intestine to the liver where the lack of Hfe seems to be doing the
most damage.

How can hepcidin expression by the liver change iron absorption among intestinal cells? A lot of
questions remain, Muckenthaler says, but data from the DNA chips suggest how this might be
happening. Without hepcidin, the body can't seem to put the brakes on intestinal molecule,
called Cybrd1.

Normally iron atoms carry three positive charges; in that form they can't be brought into cells.
Cybrd1's job is to reduce the number of charges to two, making iron transportable. If it were active
all the time, a lot more of the body's iron would be absorbable. When it isn't active, there is very
little to be absorbed. Hepcidin's normal function might be to lock down Cybrd1, thereby shutting
down the supply of available iron. This would make activating hepcidin – which can't happen with a
mutant form of Hfe – essential to stopping the flow of iron into the body.

This spells an important shift in hemochromatosis research: scientists will now turn their attention
to the liver, in hopes of working out the details of the circuit that connects iron, Hfe and
hepcidin. It also hints strongly at a link between the body's uptake of iron and the immune system,
where hepcidin also has a role to play.
 
Once upon a time, our fellow Jim Carter rambled on about "What makes the body absorb too much iron?
- ping doe." Our champion De-Medicalizing in sci.med.nutrition retorts, thusly ...

>What makes the body absorb too much iron?

That has got to be either the stomach or the intestines.

Ha, ... Hah, Ha!
 
>Subject: Re: What makes the body absorb too much iron? - ping doe

http://herbivore.7h.com/hemeiron.html

Heme iron found in meat is able to and does bind to other iron ingested at the same meal and THAT
iron TOO is absorbed at a high rate at ALL 'times of iron status'.

This means even though the body is downregulating the absorption of iron this heme iron is able to
barge past the defensive {downregulation of absorption] mechanism and is absorbed at a high rate.

Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
 
[email protected] (doe) wrote in message news:<[email protected]>...
> >Subject: Re: What makes the body absorb too much iron? - ping doe
>
> http://herbivore.7h.com/hemeiron.html
>
> Heme iron found in meat is able to and does bind to other iron ingested at the same meal and THAT
> iron TOO is absorbed at a high rate at ALL 'times of iron status'.
>
> This means even though the body is downregulating the absorption of iron this heme iron is able to
> barge past the defensive {downregulation of absorption] mechanism and is absorbed at a high rate.
>
> Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore!
> http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING
> http://pages.ivillage.com/ironjustice/deadpeoplewalking

What a choice! Do I listen to a nut case with no credentials or to researchers at Harvard
University?

Hmmm...