Induction of gallstone formation by hepatic insulin resistance

Abstract

Objective To observe the induction effect of hepatic insulin resistance on gallstone formation.Methods Liver insulin receptor knockout mice were employed as research subjects (mouse model),and the incidence of gallstones caused by hthogenic diet was measured.Secretion of bile acids and the expression of related enzymes such as cholesterol 7-hydroxylase (Cyp7a1),cholesterol 12 alpha hydroxylase (Cyp8b1),cholesterol 7 alpha hydroxylase (Cyp7b1) and cholesterol 27 alpha hydroxylase (Cyp27a1),the expression of the farnesoid derivative X receptor (farnesoid-X-receptor,FXR),liver cholesterol content and the cholesterol transporter ATP binding cassette transporter G5 (Abcg5) and Abcg8 expression were assayed.Results The incidence of gallstones in model group was 100％,about 8 times higher than normal mice after lithogenic diet administration.Bile acid level in model mice was 9.2 μmol/g and less than the value of 14.9 μmol/g in normal group significantly.The FXR and Cyp7a1,Cyp8b1,Cyp7bl and Cyp27a1 expression levels were all decreased,and cholesterol content was 2.2 mg/g liver tissue in model mice,and that was 1.2 mg/g liver tissue in normal mice (P ＜ 0.05).The expression of Abcg5 and Abcg8 was also increased in model mice.Conclusion The hepatic insulin resistance in mice inhibits FXR,Cyp7a1,Cyp8b1,Cyp7b1 and Cyp27a1 expression,and increases Abcg5 and Abcg8 expression,resulting in the decreased bile acid levels and increased cholesterol ratio,finally inducing formation of gallstones. Key words: Liver; Insulin resistance; Gallstones