Abstract
The interactive effect of high dietary levels of oxidized cholesterol on exogenous cholerterol and linoleic acid metabolism was examined in male 4-wk-old Sprague-Dawley rats given high-cholesterol diets. The rats were pair-fed purified diets free of or containing either 0.5% cholesterol alone or both 0.5% cholesterol and 0.5% oxidized cholesterol mixture (containing 93% oxidized cholesterol) for 3 wk. Hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity was reduced in rats given cholesterol alone or both cholesterol and oxidized cholesterol. However, hepatic cholesterol 7α-hydroxylase activity was lowered only when rats were given both cholesterol and oxidized cholesterol, although dietary cholesterol increased this activity. Reflecting this effect, acidic steroid excretion was lowest among the groups of rats given cholesterol and oxidized cholesterol. On the other hand, the activity of hepatic Δ6 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 Δ6 desaturation index, 20∶3n-6+20∶4n-6/18∶2n-6, in liver and serum phosphlipids tended to be higher in the group fed both cholesterol and oxidized cholesterol than in the one fed cholesterol alone. Thus, dietary oxidized cholesterol significantly modulated exogenous cholesterol metabolism and promoted linoleic acid desaturation even when it was given at high levels together with a high cholesterol diet.
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Abbreviations
- Chol:
-
0.5% cholesterol added
- cholesterol:
-
cholest-5-en-3β-0.5% oxidized cholesterol-added
- HDL:
-
high depsity lipoprotein
- HMG-CoA:
-
3-hydroxy-3-methylglutaryl coenzyme A
- 7β-hydroxycholesterol:
-
cholest-5-en-3β, 7β-diol
- PC:
-
phosphatidylcholine
- PE:
-
phosphatidylethanolamine
- TBARS:
-
thiobarbituric acid-reactive substances
References
Tanaka, M., and Kanamaru, S. (1993) Capillary Gas Chromatography Quantification of Cholesterol in Copper-Oxidized Low-Density Lipoprotein, Biol. Pharm. Bull. 16, 538–543.
Dzeletovic, S., Babiker, A., Lund, E., and Diczfalusy, U. (1995) Time Course of Oxysterol Formation During in vitro Oxidation of Low Density Lipoprotein, Chem. Phys. Lipids 78, 119–128.
Patel, R.P., Diszfalusy, U., Dzeletovic, S., Wilson, M.T., and Darley-Usmar, V.M. (1996) Formation of Oxysterols During Oxidation of Low Density Lipoprotein by Peroxynitrite, Myoglobin, and Copper, J. Lipid Res. 37, 2361–2371.
Smith, L.L., and Johnson, B.H. (1989) Biological Activities of Oxysterols, Free Radiacal Biol. Med. 7, 285–352.
Paniangvait, P., King, A.J., Jones, A.D., and German, B.G. (1995) Cholesterol Oxides in Foods of Animal Origin, J. Food Sci. 60, 1159–1174.
Peng, S.-K., Phillips, G.A., Xia, G.-Z., and Morin, R.J. (1987) Transport of Cholesterol Autoxidation Products in Rabbit Lipoproteins, Atherosclerosis 64, 1–6.
Osada, K., Sasaki, E., and Sugano, M. (1994) Lymphatic Absorption of Oxidized Cholesterol in Rats, Lipids 29, 555–559.
Osada, K., Kodama, T., Cui, L., Ito, Y., and Sugano, M. (1994) Effects of Dietary Oxidized Cholesterol on Lipid Metabolism in Differently Aged Rats, Biosci. Biotechnol. Biochem. 58, 1062–1069.
Osada, K., Kodama, T., Noda, S., Yamada, K., and Sugano, M. (1995) Oxidized Cholesterol Modulates Age-Related Change in Lipid Metabolism in Rats, Lipids 30, 405–413.
American Institute of Nutrition. (1977) Report of the AIN Ad Hoc Committee on Standards for Nutritional Studies. J. Nutr. 107, 1340–1348.
Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951) Protein Measurement with Folin Phenol Reagent, J. Biol. Chem. 193, 265–275.
Folch, J., Lees, M., and Sloane-Stanley, G.H. (1957) A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissues, J. Biol. Chem. 226, 497–506.
Ide, T., Okamatsu, H., and Sugano, M. (1978) Regulation by Dietary Fats of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase in Rat Liver, J. Nutr. 108, 601–612.
Yagi, K. (1976) A Simple Fluorometric Assay for Lipoperoxides in Blood Plasma, Biochem. Med. 15, 212–216.
Ohkawa, H., Ohishi, N., and Yagi, K. (1979) Assay for Lipid Peroxides in Animal Tissue by Thiobarbituric Acid Reaction, Anal. Biochem. 95, 351–358.
Ikeda, I., Tomari, Y., and Sugano, M. (1989) Interrelated Effects of Dietary Fiber and Fat on Lymphatic Cholesterol and Triglyceride Absorption in Rats, J. Nutr. 119, 1383–1387.
Sugano, M., Yamada, Y., Yoshida, K., Hashimoto, Y., Matsuo, T., and Kimoto, M. (1988) The Hypocholesterolemic Action of the Undigested Fraction of Soybean Protein in Rats, Atherosclerosis 72, 115–122.
Osada, K., Kodama, T., Yamada, K., and Sugano, M. (1993) Oxidation of Cholesterol by Heating, J. Agric. Food Chem. 41, 1198–1202.
Duncan, D.B. (1955) Multiple Range and Multiple F Tests, Biometrics. 11, 1–42.
Osada, K., Sasaki, E., and Sugano, M. (1994) Inhibition of Cholesterol Absorption by Oxidized Cholesterol in Rats, Biosci. Biotechnol. Biochem. 58, 782–783.
Naseem, S.M., and Heald, F.P. (1987) Cytotoxicity of Cholesterol Oxides and Their Effects on Cholesterol Metabolism in Cultured Human Aortic Smooth Muscle Cells, Biochem. Int. 14, 71–84.
Tanaka, R.D., Edwards, P.A., Lan, S.-F., and Fogelman, A.M. (1983) Regulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Activity in Avian Myeloblasts, J. Biol. Chem. 258, 13331–13339.
Erickson, S.K., Shrewsbury, M.A., Gould, R.G., and Cooper, A.D. (1980) Studies on the Mechanisms of the Rapid Modulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase in Intact Liver by Mevalonolactone and 25-Hydroxycholesterol, Biochim. Biophys. Acta. 620, 70–79.
Vargas, R.E., Allred, J.B., Biggert, M.D., and Naber, E.C. (1986) Effect of Dietary 7-Ketocholesterol, Pure, or Oxidized Cholesterol on Hepatic 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Activity, Energy Balance, Egg Cholesterol Concentration, and 14C-Acetate Incorporation into Yolk Lipids of Laying Hen, Poultry Sci 65, 1333–1342.
Böstrom, H. (1983) Binding of Cholesterol to Cytochromes P-450 from Rabbit Liver Microsomes, J. Biol. Chem. 258, 15091–15094.
Joyce, M., and Eliott, W.H. (1986) Competitive Inhibitors of Rabbit Hepatic Microsomal Steroid 12α-Hydroxylase, Biochim. Biophys. Acta. 879, 202–208.
Botham, K., Beckett, G.J., Percy-Robb, I.W., and Boyd, G.S. (1980) Bile Acid Synthesis in Isolated Rat Liver Cells. The Effect of 7α-Hydroxycholesterol, Eur. J. Biochem. 103, 299–305.
Reddy, B.S., Narasawa, T., Weisburger, J.H., and Wynder, E.L. (1976) Promoting Effect of Sodium Deoxycholate on Colon Adenocarcinomas in Germfree Rats, J. Natl. Cancer Inst. 56, 441–442.
Kawalek, J.C., Hallmark, R.K., and Andrews, A.W. (1983) Effect of Lithocholic Acid on the mutagenicity of Some Substituted Aromatic Amines, J. Natl. Cancer Inst. 71, 293–298.
Grag, M.L., Snoswell, A.M., and Sabine, J.R. (1986) Influence of Dietary Cholesterol on Desaturase Enzymes of Rat Liver Microsomes, Prog. Lipid Res. 25, 639–644.
Hochgraf, E., Mokady, S., and Cogan, U. (1997) Dietary Oxidized Linoleic Acid Modifies Lipid Composition of Rat Liver Microsomes and Increases Their Fluidity, J. Nutr. 127, 681–686.
Brown, M.S., and Goldstein, J.L. (1986) A Receptor-Mediated Pathway for Cholesterol Homeostasis, Science 232, 34–47.
Phillips, M.C., Johnson, W.J., and Rothblat, G.H. (1987) Mechanisms and Consequences of Cellular Cholesterol Exchange and Transfer, Biochim. Biophys. Acta. 906, 223–276.
Cho, B.H.S., Egwin, O.O., and Fahey, G.C., Jr. (1986) Effects of Pure and Auto-Oxidized Forms of Cholesterol on Plasma, Liver Lipids and Hepatic Lipogenesis in Chicks, Comp. Biochem. Physiol. 83B, 767–770.
Erickson, S.K., Shrewsbury, M.A., Brooks, C., and Meyer, D.J. (1980) Rat Liver Acyl-Coenzyme A:Cholesterol Acyltransferase: Its Regulation in vivo and Some of Its Properties in vitro, J. Lipid Res. 21, 930–941.
Dievon, C.A., Engelhorn, S.C., and Steinberg, D. (1980) Secretion of Very Low Density Lipoprotein Enriched in Cholesterol Esters by Cultured Rat Hepatocytes During Stimulation of Intracellular Cholesterol Esterification, J. Lipid Res. 21, 1065–1071.
Suckling, K.E., Tocher, D.R., Smelie, C.G., and Boyd, G.S. (1983) In vitro Regulation of Bovine Adrenal Cortical Acyl-CoA: Cholesterol Acyltransferase and Comparison with the Rat Liver System, Biochim. Biophys. Acta. 753, 422–429.
Jamal, Z., Suffolk, R.A., Boyd, G.S., and Suckling, K.E. (1985) Metabolism of Cholesteryl Esters in Monolayers of Bovine Adrenal Cortical Cells. Effect of an Inhibitor of Acyl-CoA: Cholesterol Acyltransferase, Biochim. Biophys. Acta. 834, 230–237.
Emanuel, H.a., Hassel, C.A., Addis, P.B., Bergmann, S.D., and Zavoral, J.H. (1991) Plasma Cholesterol Oxidation Products (Oxysterol) in Human Subjects Fed a Meal Rich in Oxysterols, J. Food Sci. 56, 843–847.
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Osada, K., Kodama, T., Yamada, K. et al. Dietary oxidized cholesterol modulates cholesterol metabolism and linoleic acid desaturation in rats fed high-cholesterol diets. Lipids 33, 757–764 (1998). https://doi.org/10.1007/s11745-998-0267-x
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DOI: https://doi.org/10.1007/s11745-998-0267-x