A computer study of the risk of cholesterol gallstone associated with obesity and normal weight

Abstract

Obese people differ from the people of normal weight in gall bladder motility and have a higher risk of cholesterol stone formation. In this study, using a mathematical model of cholesterol homeostasis, which also considers the enterohepatic circulation of bile as well as cholesterol, we investigated the risk of cholesterol stone formation in obese and normal-weight groups who had normal blood cholesterol levels. We associated the risk of stone formation with the amount of cholesterol released into bile and the amount of de novo-synthesized cholic acid. For both groups, we determined the conditions of low and high risk. In addition, we analyzed the potential effects of changes in gall bladder motility with increased weight. The results showed that the obese group exhibited increased kinetics of enterohepatic circulation, leading to a significant increase in blood cholesterol levels, which can be reduced by increasing the amount of cholesterol in bile. Based on this finding, we suggest that for obese people, it is beneficial to reduce the amount and change the composition of circulating bile through the inhibition of cholic acid synthesis along with cholesterol synthesis. Furthermore, obese people should maintain a triglyceride-lowering diet and consume small meals containing fat, preferably in combination with agents that can reduce bile output from the gall bladder.