Biphasic effect of oleic acid on hepatic cholesterogenesis

Livers isolated from adult male rats were perfused in vitro with oleic acid (0.6 mM) as a complex with bovine serum albumin. Albumin alone was infused in control experiments. Oleic acid exerted a biphasic effect on incorporation of 3H2O into cholesterol, which was inhibitory during the first hour of perfusion, but exhibited a net stimulatory effect over a four hour period. No differences were observed in total activity or apparent phosphorylation state of HMG-CoA reductase after one hour of perfusion, with or without addition of oleic acid, implying that some other step limits the rate of cholesterol synthesis during this interval. After four hours of perfusion, HMG-CoA reductase activity was higher in livers perfused with oleic acid than in those perfused in its absence, in agreement with the observed differences in rates of cholesterol synthesis.