Gene expression analysis on the liver of cholestyramine-treated type 2 diabetic model mice

Recent experimental and clinical studies have indicated that bile acid-binding agents are effective not only for treating hypercholesterolemia, but also for type 2 diabetes. To investigate the molecular mechanism underlying the effect of cholestyramine, a bile acid-binding agent, on type 2 diabetes, we examined gene expression of the livers of cholestyramine-treated type 2 diabetic model mice. Type 2 diabetic NSY/Hos mice were fed a high fat diet supplemented with 1% (w/w) cholestyramine for 8 weeks. Cholestyramine treatment prevented the increase in body weight, plasma cholesterol, triglycerides, glucose, insulin levels, and hepatic steatosis. DNA microarray analysis was performed on the liver, which revealed that the genes related to synthesis of cholesterol and its derivatives were increased and the genes regulated by liver X receptors, such as the sterol regulatory element-binding protein 1 gene, were decreased in the group treated with cholestyramine. Expression of the genes related to carbohydrate metabolism was little changed in the cholestyramine group. Furthermore, we performed real-time RT-PCR analysis, which highly correlated with DNA microarray data (r = 0.957, P < 0.001). This study provides a valuable basis for further research on the biological functions of bile acid-binding agents in models of type 2 diabetes.