Obesity and gallstones often go hand in hand, but not in mice developed at the School of Medicine.
Even when these mice eat high-fat diets, they don’t get fat, but they do develop gallstones. Researchers say the findings offer clues about genetic factors related to gallstones and that better understanding of those factors may one day allow physicians to monitor people at risk and even perhaps to intervene before gallstones can become a serious problem.
Learning more about susceptibility to gallstones is an important public-health issue, particularly in the United States. Between 16 million and 22 million Americans have gallstones, which are deposits of cholesterol or calcium salts that form in the gallbladder or in the bile ducts. In many cases, people require surgery, and more than half a million undergo operations to treat gallstones and remove the gallbladder each year.
“Gallstones form when cholesterol is secreted in bile from the liver at high concentrations, and that typically happens in patients who are obese, who have diabetes, take estrogens or who have lost a lot of weight very rapidly,” said senior investigator Nicholas O. Davidson, M.D., professor of medicine and of developmental biology. “Since these mice don’t become obese, we thought they might be protected against gallstones. But we found that they were dramatically more susceptible.”
The researchers studied a strain of mice without a substance called liver fatty acid binding protein (L-fabp). Davidson’s group compared those genetically engineered mice to their healthy, normal littermates. Both groups of mice ate either a standard chow diet or a more typical “Western” diet that provided about 20 percent of its total calories from fat and cholesterol.
After two weeks on the experimental diet, only one in 17 of the normal mice developed gallstones, but six of the eight mice without L-fabp had gallstones. Davidson’s team reported the findings in the May issue of the Journal of Lipid Research.
Davidson said in addition to risk factors such as diabetes and obesity, these experiments show that genetics play a role in gallstone risk. The L-fabp gene, which both mice and humans have, may be a key to understanding how genes can predispose to cholesterol gallstone formation.
“The L-fabp gene is located in a part of the mouse genome that appears likely to be involved in genetic susceptibility to gallstones,” Davidson said. “We believe it also may be involved in gallstone susceptibility in humans.”
Although minimally invasive gallbladder surgery has made gallstone problems much less serious than in the past, sometimes the symptoms can be severe and dramatic, Davidson said.
“Patients can develop acute pancreatitis or ascending cholangitis, which occurs when gallstones obstruct the pancreatic or bile duct and become infected,” he said. “Even without those problems, gallstones can cause severe, recurrent abdominal pain in a very large number of people. So better understanding who is susceptible and learning how to safely intervene could be very important for people at risk.”