Oxidized cholesterol modulates age-related change in lipid metabolism in rats

For three weeks, male Sprague-Dawley rats at either four weeks (young) or eight months (adult) of age were pairfed one of the purified diets free of or containing either 0.2% of oxidized cholesterol mixture (cholesterol oxidation products) or 0.2% of cholesterol. Although the food intake was similar, dietary oxidized cholesterol lowered body weight gain in young rats, but did not increase relative liver weight, in contrast to the enlargement seen with dietary cholesterol. Oxidized cholesterol, compared to cholesterol, tended to reduce the activity of hepatic 3-hydroxy-3-methylglutaryl CoA reductase and cholesterol 7α-hydroxylase, particularly the latter in aged rats, and prevented the rise in the concentration of liver cholesterol at both ages. It also tended to increase the activity of hepatic δ6 desaturase, particularly in young rats. Moreover, oxidized cholesterol in relation to cholesterol influenced liver and serum lipid concentrations in different ways, and increased lipid peroxidation at both ages. The ratio of splenic CD4⁺/CD8⁺ T-lymphocytes increased with age, but the influence of cholesterol and oxidized cholesterol was comparable. Thus, oxidized cholesterol may specifically disturb growth and age-related changes in the lipid metabolism in rats.