Role of cholic acid in the dietary induction of cholesterol gall-bladder stones in mice

The diet of male Swiss mice was supplemented with cholesterol and different bile acids, or the plant sterol diosgenin, to determine the effect on cholesterol metabolism and gallstone formation. Cholic acid enhanced intestinal cholesterol absorption and markedly increased cholesterol levels in serum, liver and bile. In contrast, chenodeoxycholic acid, ursodeoxycholic acid and hyodeoxycholic acid inhibited the increase in cholesterol absorption and liver cholesterol content produced by a cholesterol-supplemented diet. Biliary cholesterol reached saturated levels in mice fed cholesterol and cholic acid or diosgenin, but gallstones were observed only in association with the cholic acid-containing diet. This diet also induced marked gall-bladder enlargement with mucus glycoprotein hypersecretion. These results indicate that both supersaturated bile and gall-bladder mucus production may be necessary for the development of gallstones in mice.