Treatment with a synthetic agent that stimulates activity of receptors that latch on to bile acid prevents cholesterol gallstone disease in mice, new research shows.

The results suggest that the bile acid receptor (known as FXR) may be a useful target for drugs designed to prevent or treat gallstone disease.

Precipitation of cholesterol in bile, when the composition of bile is favorable, has been implicated in the production of cholesterol gallstones.

In their experiments, Dr. David J. Mangelsdorf, and colleagues from the University of Texas Southwestern Medical Center in Dallas, show that FXR plays a key role in this process, at least in mice.

Genetically engineered mice that lack FXR displayed all of the features commonly seen with cholesterol gallstone disease, the team reports in the science journal Nature Medicine.

The researchers then treated normal mice and mice lacking FXR with a synthetic FXR-stimulating drug while all of the animals were fed a diet intended to promote gallstone formation.

Treatment with the experimental drug prevented gallstone disease in the normal mice, but not in those without FXR. This confirms that the effects of this agent were FXR-dependent, the investigators note.

Further analysis showed that the drug altered the composition of bile so that cholesterol remained dissolved, and was not precipitated.

“Given the identical physical-chemical behavior of biliary lipids in mice and humans ... there is strong evidence to believe that the protective effects of FXR (stimulating drugs) can translated from the mouse to the human cholesterol gallstone model,” the authors conclude.

SOURCE: Nature Medicine, November 21, 2004.