Small intestine controls bile output

The discovery that the small intestine communicates with the liver to control the production of bile acids is a finding that has great medical implications in treating people at risk for certain types of liver disease, declare researchers at the University of Texas Southwestern Medical Center, Dallas.

"We've discovered a new hormone, and new hormones are always exciting," announces Steven Kliewer. The findings eventually may 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 gallbladder, where they are stored until food is digested. The presence of food stimulates the gallbladder into releasing the bile acids to the small intestine, where they do their work. Finally, they are absorbed into the bloodstream and returned to the liver.

Scientists previously have 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 block the gene for CYP7A1, and production stops. For this study, researchers looked at a protein in mice called fibroblast growth factor 15 (FGF15), which is part of a cascade of chemical reactions that also dialed down production of CYP7A1 and reduced the production of bile acids. Surprisingly, they found that FGF15 was made in the small intestine, not the liver, suggesting a new role for the small intestine in regulating bile acid levels.

The findings may be relevant to diseases that involve a condition called chorestatis, in which the bile ducts are blocked. When that happens, bile acids accumulate in the liver and severe liver disease may follow. Cholestatis also can occur in patients who are getting all their nutrition through intravenous feeding, because the gallbladder never receives the signal from the small intestine to release bile acids.

Kliewer indicates that giving cholestatis patients FGF19--the human equivalent of FGF15--may turn off the overproduction of harmful bile acids in these cases. "So, now we have a hormone that's not going to damage the liver, that we could perhaps administer and turn off the production of bile acids, and that could alleviate one of the important causes of cholestatis," he concludes.

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