CHOLATE INHIBITS HIGH-FAT DIET-INDUCED HYPERGLYCEMIA AND OBESITY WITHACYL-COA SYNTHETASE MESSENGER-RNA DECREASE

The effects of sodium cholate on high-fat diet-induced hyperglycemia a nd obesity were investigated. Insulin resistance was estimated by meas uring 2-deoxyglucose uptake in epitrochlearis muscles incubated in vit ro. Addition of 0.5% cholate to high-safflower oil diet completely pre vented high fat-induced hyperglycemia and obesity in C57BL/6J mice wit h a slight decrease of energy intake but with no inhibition of fat abs orption. Furthermore, the addition of cholate decreased blood insulin levels and prevented high-fat diet-induced decrease of glucose uptake in epitrochlearis. However, there was no change in the unsaturation in dex of fatty acids in skeletal muscles and in GLUT-4 levels by cholate . In liver, cholate addition resulted in cholesterol accumulation and completely prevented high-fat diet-induced triglyceride accumulation. The changes of triglyceride level in the liver were paralleled to the changes of acyl-CoA synthetase (ACS) mRNA. ACS catalyzes the formation of acyl-CoA from fatty acid, and acyl-CoA is utilized for triglycerid e formation in liver. ACS has a sterol-responsive element 1 in its pro moter region. These data indicate that the favorable effects of cholat e could be partly the result of downregulation of ACS mRNA.