Dietary oxidized linoleic acid enhances liver cholesterol biosynthesis andsecretion in rats

Based on studies showing that excretion of cholesterol is elevated in rats fed oxidized linoleic acid, we hypothesized that cholesterol metabolism is enhanced under such oxidative stress. Liver cholesterol biosynthesis and se cretion and fecal choltesterol excretion were studied in mts fed for 4 week s diets containing 10% oxidized linoleic acid. Iacubation of liver slices w ith 1-C-14 acetate and intraperitoneal injection of 5-H-3-mevalonate showed the occurrence of enhanced hepatic cholesterol biosynthesis and elevated l iver cholesterol secretion in animals subjected to oxidative stress. In add ition, impaired liver cholesterol uptake was suggested Higher levels of exc reted cholesterol observed in the experimental animals were accompanied by augmented levels of liver phospholipids, primarily phosphatidylcholine, whi ch most likely increased to enable the excessive cholesterol excretion. Thi s study thus demonstrates that ingestion of oxidized lipids causes profound alterations in cholesterol metabolism. (C) Elsevier Science Inc., 2000. Al l rights reserved.