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Feedback loop found that could forestall liver disease

DALLAS Oct. 11, 2005 Researchers at UT Southwestern Medical Center have discovered that the small intestine communicates with the liver to control the production of bile acids a finding that has great medical implications in treating people at risk for certain types of liver disease.

"We've discovered a new hormone, and new hormones are always exciting," said Dr. Steven Kliewer, professor of molecular biology and pharmacology and senior author of a study available online and appearing in the October issue of Cell Metabolism.

The findings may eventually play a role in understanding and preventing liver damage that can occur in biliary cirrhosis, viral hepatitis, alcoholic liver disease and pregnancy.

The central elements in the research are the body's bile acids powerful and essential detergents that help digest fatty foods and fat-soluble vitamins in the small intestine.

The liver makes bile acids out of cholesterol and sends them to the gall bladder, where they're stored until food is digested. The presence of food stimulates the gall bladder into releasing the bile acids to the small intestine, where they do their work. Finally, they're absorbed into the bloodstream and returned to the liver.

Because they're so powerful, bile acids can damage the body if not controlled properly.

"These bile acids are really nasty in terms of being strong detergents," said Dr. Kliewer, holder of the Nancy B. and Jake L. Hamon Distinguished Chair in Basic Cancer Research.

Scientists have previously known about a mechanism within the liver that prevents too much bile acid from being produced. Normally, a protein called CYP7A1 stimulates production of the acids. When enough bile acids are made, they trigger a series of reactions that blocks the gene for CYP7A1, and production stops.

For this study, UT Southwestern researchers looked at a protein in mice called fibroblast growth factor 15 (FGF15), which is part of a cascade of chemical
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
11-Oct-2005


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