Influence of Bile Salts on Cholesterol Synthesis in the Isolated Perfused Rat Liver

Abstract

The effect of taurocholate and cholate on hepatic cholesterol synthesis has been studied with the isolated perfused rat liver. By the infusion of bile salts at a constant rate to the portal vein, conditions in the enterohepatic circulation of taurocholate and cholate in vivo were simulated. A 1‐h infusion of sodium taurocholate, at a rate of 10mg × (100g body wt) −1 × h −1 , did not inhibit cholesterol synthesis, as measured by 3 H 2 O incorporation. The same results were obtained, when livers with enhanced cholesterol synthesis were studied or when bile salt infusions were extended to 2 h before starting incorporation measurements. Stimulation was achieved by feeding a 2% cholestyramine diet during 7 days to the donor animals. A 3‐h infusion of taurocholate, at the above rate, exerted no toxic effect on liver metabolism, as judged from hepatic enzyme leakage to the perfusion medium, from the rate of ketone body production and the 3‐hydroxybutyrate/acetoacetate ratio. Cholic acid in amounts equivalent to those of taurocholate did not influence cholesterol synthesis under these conditions. It is concluded, that inhibition of cholesterol synthesis by bile salts in vivo is not mediated by a short‐acting ( e.g. allosteric) mechanism at the enzymatic level, but rather by a change of enzyme content.