Stimulation of hepatic cholesterol biosynthesis by oleic acid

Livers from normal fed male rats were perfused $\text{in vitro}$ with an erythrocyte-free, bloodless medium containing serum albumin (3%), and glucose (100 mg %). Oleic acid (663 μmoles) bound to albumin, or albumin alone, was infused at a constant rate. Biosynthesis of cholesterol was evaluated by incorporation of radioactivity from ³H₂O. Oleic acid stimulated output of cholesterol (1.60 ± 0.08 SEM vs 1.18 ± 0.04 μmoles/g) but did not change the concentration of cholesterol in the liver or hepatic microsomes. Incorporation of ³H into cholesterol was stimulated by oleate; dpm per μmole cholesterol/dpm per μg atom H was 3.94 ± 0.33, 3.46 ± 0.32, and 4.46 ± 0.37 in the total cholesterol of liver, perfusate, and microsomes, respectively, when oleate was infused. Corresponding values when oleate was not infused were 1.71 ± 0.23, 1.62 ± 0.20, and 2.09 ± 0.26, respectively (P<0.001 in all cases). It is suggested that the stimulation of biosynthesis of cholesterol by oleate results from the obligatory requirement of cholesterol, as a moiety of the very low density lipoprotein, for the secretion of triglyceride by the liver.