Liver Cholesterol Concentration in Relation to Hepatic Cholesterogenesis and Activity of Certain Liver Enzymes in Rats

The study was conducted to determine 1 ) the interrelationship between liver cholesterol concentration and rate of hepatic cholesterol synthesis, and 2) the effect of cholesterol or cholestyramine feeding on the activity of liver glucose-6-phosphate dehydrogenase and the rate of hepatic fatty acid synthesis. Either cholesterol (1%)- cholic acid (0.33%) or cholestyramine (3%) was added to a basal 20% fat diet to elevate or deplete rat liver cholesterol concentration. The results indicate that cholesterol feeding elevated liver cholesterol concentration, inhibited liver cholesterol synthesis, and depressed the activity of liver glucose-6-phosphate dehydrogenase. Cholestyramine feed ing did not change the level of liver cholesterol but elevated the rate of in vitro liver cholesterol synthesis. Cholestyramine also elevated the activity of liver glucose-6-phos- phate dehydrogenase and the rate of in vitro liver fatty acid synthesis. Rats, prefed a cholesterol diet for 12 days, then fed a cholestyramine (3%) diet, had a reduction in liver cholesterol, and an elevation in liver cholesterol synthesis. These rates approached control levels more rapidly than when a basal diet was refed. Rats with accumulated liver cholesterol had much lower hepatic cholesterol synthesis than rats with "normal" liver cholesterol levels fed the same basal diet. The same was true when the diet was supplemented with cholestyramine. These data suggest that the concentration of liver cholesterol or a related factor(s) may play a role in the control of liver cholesterogenesis. J. Nutr. Â?03:1119-1125, 1973.