Comparison of the effects of cholic acid and chenic acid feeding on rates of cholesterol synthesis in the liver of the rat

To compare the ability of cholic acid and chenic acid to suppress cholesterol synthesis in the liver, these two bile acids were fed in varying amounts to rats for either 66 hr or 6 weeks. In both instances there were significant changes in the bile acid pool in the small intestine and suppression of the rate of cholesterol synthesis in the liver. The administration of cholic acid, however, consistently produced greater suppression of the rate of cholesterol synthesis from octanoate or of microsomal HMG CoA reductase activity than did the administration of a similar amount of chenic acid. Furthermore, this difference was present whether the rates of cholesterogenesis were measured at high-substrate concentrations, ie, under conditions where V_max was apparently achieved, or under circumstances where there was essentially no extracellular substrate present. These findings do not support the view that the superiority of chenic acid for dissolution of gallstones is secondary to its greater effect as an inhibitor of hepatic cholesterol synthesis.