DIETARY OXIDIZED CHOLESTEROL MODULATES CHOLESTEROL-METABOLISM AND LINOLEIC-ACID DESATURATION IN RATS FED HIGH-CHOLESTEROL DIETS

The interactive effect of high dietary levels of oxidized cholesterol on exogenous cholesterol and linoleic acid metabolism was examined in male 4-wk-old Sprague-Dawley rats given high-cholesterol diets. The ra ts were pair-fed purified diets free of or containing either 0.5% chol esterol alone or both 0.5% cholesterol and 0.5% oxidized cholesterol m ixture (containing 93% oxidized cholesterol) for 3 wk. Hepatic 3-hydro xy-3-methyl-glutaryl CoA reductase activity was reduced in rats given cholesterol alone or both cholesterol and oxidized cholesterol. Howeve r, hepatic cholesterol 7 alpha-hydroxylase activity was lowered only w hen rats were given both cholesterol and oxidized cholesterol, althoug h dietary cholesterol increased this activity. Reflecting this effect, acidic steroid excretion was lowest among the groups of rats given ch olesterol and oxidized cholesterol. On the other hand, the activity of hepatic Delta desaturase, a key enzyme in the metabolism of linoleic acid to arachidonic acid, was increased in rats given both cholesterol and oxidized cholesterol, although dietary cholesterol alone lowered its activity. As a result, the Delta 6 desaturation index, 20:3n-6 + 2 0:4n-6/18:2n-6, in liver and serum phospholipids tended to be higher i n the group fed both cholesterol and oxidized cholesterol than in the one fed cholesterol alone. Thus, dietary oxidized cholesterol signific antly modulated exogenous cholesterol metabolism and promoted linoleic acid desaturation even when it was given at high levels together with a high cholesterol diet.