The mechanisms of and the interrelationship between bile acid and chylomicron-mediated regulation of hepatic cholesterol synthesis in the liver of the rat

trolled both by the size of the bile acid pool in the enterohepatic circulation and by the amount of choles-terol reaching the liver carried in chylomicron rem-nants. These studies were undertaken to examine how these two control mechanisms are interrelated. When the size of the pool was systematically varied, the loga-rithm of the rate of hepatic cholesterol synthesis varied in an inverse linear fashion with the size of the tauro-cholate pool between the limits of 0 and 60 mg of bile acid per 100 g of body weight. The slope of this rela-tionship gave the fractional inhibition of cholesterol synthesis associated with expansion of the taurocholate pool and was critically dependent upon the amount of cholesterol available for absorption from the gastroin-testinal tract. Furthermore, the degree of inhibition of cholesterol synthesis in the liver seen with taurocho-late feeding was reduced by partially blocking choles-terol absorption with,3-sitosterol even though the bile acid pool was still markedly expanded. In rats with diversion of the intestinal lymph from the blood, a five-fold expansion of the taurocholate pool resulted in only slight suppression of the rate of hepatic cholesterol synthesis, and even this inhibition was shown to be attributable to small amounts of cholesterol absorbed through collateral lymphatic vessels and (or) to a fasting effect. Similarly, the infusion of either taurocholate or a combination of taurocholate and taurochenate into rats with no biliary or dietary cholesterol available for absorption caused no suppression of hepatic choles-terol synthesis. Finally, the effect ofchanges in the rate of bile acid synthesis on hepatic cholesterol synthesis At the time of these studies Dr. Nervi was a postdoctoral fellow partially supported by a grant from the Catholi