Male Sprague-Dawley rats, 4 weeks (young) or 8 months (adult) of age, were fed one of three purified diets free of or containing either 0.5% cholesterol or 0.5% oxidized cholesterol (92°!cl oxidized cholesterol) for 3 weeks. Feeding of oxidized cholesterol caused a significant reduction of food intake, body weight gain, and relative liver weight in rats of both ages. The activity of the HMG-CoA reductase and cholesterol 7~-hydroxylase of liver microsomes, the key enzymes in cholesterol synthesis and catabolism, respectively, was lowered by oxidized cholesterol compared to the diet free of cholesterol in both ages, and the difference was significantly in the adult. On the other hand, the activity of A6-desaturase of liver microsomes, a key enzyme in linoleic acid metabolism to arachidonic acid, was significantly increased by oxidized cholesterol in adult rats, leading to the increase in linoleic acid desaturation index [(20:3n-6 + 20:4n-6)/18:2n-6] in liver phospholipids. Oxidized cholesterol reduced the concentration of cholesterol in serum and liver. Also, the fecal excretion of acidic steroids was lower in rats fed the oxidized cholesterol diet than in those fed the cholesterol-free diet. Thus, oxidized cholesterol significantly influenced cholesterol and fatty acid metabolism in particular in adult rats.Lipid peroxidation is considered to be implicated in a number of human disorders. 1) Similarly, oxidized cholesterol displays a wide range of untoward effects. Oxidized cholesterols are readily formed in foods when it is exposed to air, free radicals, and high temperatures. In fact, processed foods such as egg products, meat products, butter, dairy products, pancake mix, French fries, and seafoods contain various types of oxidized cholesterols at the ppm level. 2 -4) Approximately 30% of oxidized cholesterols is absorbed in rats (unpublished observation). Several oxidation products of cholesterol have been reported to have various biological activities such as cytotoxicity,5) mutagenicity,5) carcinogenicitY,6) atherogenicity,7) and inhibition of cholesterol biosynthesis. 8 ) However, the information is mainly based on observations in vitro, and their effects in vivo are not well understood.Numerous epidemiological studies show an aged-related increase in coronary heart disease. The development of this disease is largely associated with the elevation of serum cholesterol, presumably due to the disturbance of cholesterol homeostasis with age. 9,10) Since cholesterol metabolism is modulated with age, the effects of dietary oxidized cholesterol on cholesterol metabolism may be different in young and adult individuals. Choi et al. 1 1) showed that cholesterol levels in serum and liver were increased and the activities of both 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and cholesterol 7a-hydroxylase in rat liver were decreased with age. Therefore, in this communication, we studied the effects of oxidized cholesterols on the metabolism of cholesterol and fatty acid using young (4 weeks old) and adult (8 month...