OBJECTIVETo investigate differences between hepatic and biliary lipid metabolism and secretion of genetically gallstone-susceptible (C57L) and resistant (AKR) mice and the mechanism of cholesterol gallstone formation.

METHODSThe inbred C57L and AKR mice were fed a lithogenic diet containing 15% fat, 1.25% cholesterol and 0.5% cholic acid for four weeks. Hepatic cholesterol content and secretion rates of biliary lipids, as well as phenotypes of the liver and gallbladder were determined and examined before and after the feeding of the lithogenic diet.

RESULTSBoth before and after ingestion of the lithogenic diet, hepatic secretion rates of all biliary lipids in C57L mice were markedly higher than that of AKR mice (P < 0.05, P < 0.01, respectively), whereas hepatic cholesterol contents of C57L mice were significantly lower than that of AKR mice (P < 0.05). Furthermore, after consumption of the lithogenic diet, the increase in hepatic secretion rate of biliary cholesterol in C57L mice was significantly higher than that in AKR mice (P < 0.01). Cholesterol gallstones formed in C57L mice and fatty livers developed in AKR mice.

CONCLUSIONSBiliary cholesterol hypersecretion is the key pathophysiological defect of gallstone formation, lith genes have effects on biliary cholesterol hypersecretion and susceptibility to cholesterol gallstone formation in C57L mice. Lithogenic bile is formed at the canalicular membrane and precedes the development of cholesterol gallstones. It is most likely that cholesterol and bile acid hyposecretion make the AKR strain susceptible to the development of fatty livers and resistant to gallstone formation.