Bile acids, receptor key in regenerating livers

HOUSTON (April 14, 2006) Bile must have been the most important thing in medicine for the physicians of ancient Greece and Rome. Yellow bile and black bile are half of the four humors that they believed made up the body, along with blood and phlegm. In their view, restoring health required correcting imbalances in these four components.

Studies by researchers from Baylor College of Medicine in a report that appears in today's issue of the journal Science suggest that they may have been on the right track.

In fact, regenerating liver tissue may depend on signals sent out when there is an imbalance in bile, said Dr. David Moore, BCM professor of molecular and cellular biology. He and colleagues at BCM identified an imbalance of bile, specifically bile acids, as a major signal for this process.

Liver is an unusual organ because it can regrow when injured.

Understanding how this happens could help physicians seeking to treat liver disease.

Bile acids are made in the liver and are the "detergents" of fat metabolism, said Moore. However, they are also signaling molecules that provide the body with key information about the state of the liver.

"They are released into the gut as part of digestion, reabsorbed and then back to the liver. More than 90 percent are cycled," he said. "You do not get rid of the bile acids when you lose a piece of liver," said Moore "Instead, you expose the remaining portion to a higher relative amount of bile acids, sending a signal through a specific receptor called FXR to activate liver regeneration."

Animals bred to lack FXR have difficulty regenerating liver, he said. And when he and his colleagues fed animals a diet that contains bile acids, the liver regenerated faster.

Those who receive drugs that sequester bile acids (such as drugs used to lower cholesterol) cannot regenerate liver.

Drugs could be developed to take advantage of this finding, promot

Contact: Kimberlee Barbour
Baylor College of Medicine

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