Mitchell Knutson

GAINESVILLE, Fla. — A University of Florida Institute of Food and Agricultural Sciences researcher has identified the protein that the liver uses to load iron, thereby opening the door to potential strategies to treat “iron overload” disorders.

One form of these genetic disorders is hereditary hemochromatosis. Not everyone who inherits the gene will get the disease, but those who do so inherit the defective gene from both parents. Hereditary hemochromatosis is found most often in people of Northern European descent.

Over several years, those with the disorder will see excess iron get into the liver, heart, pancreas, joints and pituitary gland, leading to health problems such as cirrhosis of the liver, liver cancer, diabetes, heart disease and joint disease. People with the disease can get their blood drawn routinely to get rid of the excess iron.

“For 150 years, we did not know how iron got taken up by the liver — how it got in there,” said Mitchell Knutson, a UF associate professor in food science and human nutrition. “We knew there was a protein that took it up into to the liver. But nobody knew what that protein was. It’s such a fundamental question, and people just didn’t know the answer.”

Now scientists know that this protein is ZIP14.

In a new study published online May 28 in the journal Cell Metabolism, Knutson and colleagues found that mice lacking ZIP14 — when mated with mice with hemochromatosis — did not load iron in the liver.

With the new finding, scientists can design medications targeting ZIP14 to prevent iron from loading in the liver. Such medications, however, would need to be used in combination with current drugs that bind and remove iron from the body, Knutson said.

Although the finding advances scientists’ understanding of hemochromatosis, that disorder already has a relatively simple treatment: phlebotomy. But Knutson does see this finding as more relevant for possibly treating other incurable iron overload disorders such as thalassemia. Patients with thalassemia can’t make healthy red blood cells and therefore need regular blood transfusions to stay alive.

Transfusions introduce into the bloodstream a lot of iron, which rapidly goes to the liver. If liver iron loading could be prevented—through methods such as blocking ZIP14—the extra iron in the blood would be more accessible to drugs that remove it from the body.

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By: Brad Buck, 352-294-3303, bradbuck@ufl.edu

Source: Mitchell Knutson, 352-359-3507, mknutson@ufl.edu

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