Effect of bile acids on hepatic cholesterol synthesis in partial ileal bypass in rabbits

The feedback inhibitor of cholesterol synthesis is thought to be cholesterol itself. The exact role of bile acids in cholesterol synthesis is unclear. Bile acids have been advocated as an inhibitor of cholesterol synthesis by both direct and indirect (e.g., effect on cholesterol absorption) mechanisms of action. An attempt was made to elucidate the effect of bile acids on hepatic cholesterol synthesis (HCS), using a rabbit model which provides continual enterohepatic circulation of bile acids with partial interruption of the enterolymphatic circulation of cholesterol. Failure of bile acids to inhibit hepatic cholesterol synthesis in the rat under conditions of total biliary diversion has been reported. However, cholic acid has been shown to depress the activity of 3 hydroxy 3 methylglutaryl coenzyme A reductase, the enzyme which catalyzes the rate limiting step in cholesterol synthesis, in the liver of lymph fistula rats. The findings in this study lead to the conclusion that bile acid infusion into the bypassed bowel of the rabbit with partial ileal bypass results in an increase in HCS to a greater degree than that engendered by intestinal bypass alone. Thus, under conditions of decreased, but not totally interrupted, enterolymphatic circulation of cholesterol, bile acids may act as a stimulant to hepatic cholesterol synthesis.