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Cholesterol Metabolism in Rats Sensitive to High Cholesterol Diet

  • Nozomu Takeuchi
  • Masami Ito
  • Yuichi Yamamura
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 67)

Abstract

There was great individual variation in the elevations of serum cholesterol concentrations in a Wistar strain of rats by the ingestion of a large amount of cholesterol, although their cholesterol concentrations were almost identical while under the feeding of a regular stock diet. Their serum total phospholipid and dextran precipitable beta-lipoproteins showed the same tendencies, but serum triglyceride concentration was not affected by the dietary supplement in both groups.

So, the rats with the different elevation rates of serum cholesterol concentrations were divided into good, normo and poor responding groups to cholesterol ingestion by the degrees of the elevations and bred for several generations. Serum lipid levels in the descendants from hyperresponding rats were not different from those from hyporesponding rats during the observed period, when they were given a stock diet. However, the response of serum cholesterol level to oral cholesterol ingestion in the former was larger than that in the latter. Therefore, it is suggested that the susceptibility of serum cholesterol to cholesterol ingestion may be heritable from parents to their offsprings.

By the results of the tracer experiments, it was demonstrated that neither hepatic cholesterol synthesis nor absorption was affected in hyperresponding rats. On the other hand, a half life of labeled cholesterol was prolonged in this selected group. The relative fractional turnover rate was 17.8 per cent in hyporesponding rats and 15.8 per cent in hyperresponding rats. Excretion of the radioactivity from labeled cholesterol into the bile in good responding rats with bile fistula was slower than that in poor responding rats.

When 1 g per 100 g body weight of glucose was given to the rats after 40 hours fasting, hepatic cholesterol synthesis increased at the same rate in both groups of rats, but the induction of hepatic cholesterol 7α-hydroxylation in hyperresponding groups was slower than that in hyporesponding groups. The distribution rates of the radioactivities into livers seemed to be delayed in good responders after the labeled cholesterol was ingested orally. It means that some disturbances in cholesterol transport may exist which induce the metabolic abnormality in such animals.

It was shown that cholesterol metabolism was impaired in aged animals as compared with young ones. Serum cholesterol concentrations were elevated in good responders more than in poor responders by aging. The inborn errors of cholesterol metabolism in such animals might be emphasized from the fact of the impairment of cholesterol metabolism by the aging process.

Keywords

Bile Acid Serum Cholesterol Cholesterol Synthesis Serum Cholesterol Level Cholesterol Metabolism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Cox, G.E., C.B. Taylor and D. Patton. 1963. Origin of plasma cholesterol in man. Arch. Pathol. 76:60–88.PubMedGoogle Scholar
  2. 2.
    Dietchy, J.M. and J.D. Wilson. 1970. Regulation of cholesterol metabolism. New Engl. J. Med. 282: 1128–1138 and 1179–1183.CrossRefGoogle Scholar
  3. 3.
    Danielsson, H. and T.T. Tchen. 1970. Steroid metabolism. In: Metabolic Pathway II. Ed. by D.M. Greenberg, Academic Press, New York, pp. 117–168.Google Scholar
  4. 4.
    Taylor, C.B., B. Mikkelson, J.A. Anderson, D.T. Forman and S.S. Choi. 1965. Human serum cholesterol synthesis. Exp. Mol. Path. 4: 480–488.CrossRefGoogle Scholar
  5. 5.
    Gould, R.G. 1951. Lipid metabolism and atherosclerosis. Amer. J. Med. 11:209–227.PubMedCrossRefGoogle Scholar
  6. 6.
    Taylor, C.B. and R.G. Gould. 1950. Effect of dietary cholesterol on rate of cholesterol synthesis in the intact animal measured by means of radioactive carbon. Circulation 2:467–468.Google Scholar
  7. 7.
    Bhattathiry, E.P. and M.D. Siperstein. 1963. Feedback control of cholesterol synthesis in man. J. Clin. Invest. 42:1613–1618.PubMedCrossRefGoogle Scholar
  8. 8.
    Wilson, J.D. 1962. Relation between dietary cholesterol and bile acid excretion in the rat. Am. J. Physiol. 203:1029–1037.PubMedGoogle Scholar
  9. 9.
    Beher, W.T., K.K. Casazza, M.E. Beher, A.M. Filus and J. Bertasius. 1970. Effect of cholesterol on bile acid metabolism in the rat. Proc. Soc. Exp. Biol. Med. 134:595–602.PubMedGoogle Scholar
  10. 10.
    Frantz, I.D. and B.T. Hinkelman. 1955. Acceleration of hepatic cholesterol synthesis by Triton WR 1339. J. Exp. Med. 101: 225–232.PubMedCrossRefGoogle Scholar
  11. 11.
    Radding, CM. and D. Steinberg. 1960. Studies on the synthesis and secretion of serum lipoproteins by rat liver slices. J.Clin Invest. 39:1560–1569.PubMedCrossRefGoogle Scholar
  12. 12.
    Kandutsch, A.A. and S.E. Saucier. 1969. Prevention of cyclic and triton-induced increase in hydroxy methyl glutaryl coenzyme A reductase and sterol synthesis by puromycin. J.Biol. Chem. 244:2299–2305.PubMedGoogle Scholar
  13. 13.
    White, L.W. and H. Rudney. 1970. Regulation of 3-hydroxy-3-methyl glutarate and mevalonate biosynthesis by rat liver homogenates. Effect of fasting, cholesterol feeding, and Triton administration. Biochemistry 9:2725–2731.Google Scholar
  14. 14.
    Yamamoto, R.S., L.B. Crittenden, L. Sokoloff and G.E. Jay Jr. 1963. Genetic variations in plasma lipid content in mice. J. Lipid Res. 4:413–418.PubMedGoogle Scholar
  15. 15.
    Bruell, J.H. 1963. Additive inheritance of serum cholesterol level in mice. Science 142:1664–1666.PubMedCrossRefGoogle Scholar
  16. 16.
    Weibust, R.S. and G. Schlager, 1968. A genetic study of blood pressure, hematocrit and plasma cholesterol in aged mice. Life Sci. 7: (part II) 1111–1119.PubMedCrossRefGoogle Scholar
  17. 17.
    Patton, N.M., R.V. Brown and C.C. Middleton. 1975. Atherosclerosis in familial lines of pigeons fed exogenous cholesterol. Atherosclerosis 21:147–154.PubMedCrossRefGoogle Scholar
  18. 18.
    Wartman, A.M. and W.E. Conner. 1973. The cholesterol balance and turnover in genetically hypercholesterolemic pigeons. J. Lab. Clin. Med. 82:793–808.PubMedGoogle Scholar
  19. 19.
    Prichard, R.W., T.B. Clarkson, H.B. Lofland and H. D. Goodman. 1964. Pigeon atherosclerosis. Am. Heart J. 67:715–717.PubMedCrossRefGoogle Scholar
  20. 20.
    Clarkson, T.B., H.B. Lofland, B.C. Bullock and H.D. Goodman. 1971. Genetic control of plasma cholesterol. Studies on Squirrel monkeys. Arch. Pathol. 92:37–45.Google Scholar
  21. 21.
    Morris, M.D. and C.D. Fitch. 1968. Spontaneous hyperbetalipoproteinemia in the Rhesus monkey. Biochem. Med. 2:209–215.CrossRefGoogle Scholar
  22. 22.
    Younger R.K., H.W. Scott, W.H. Butts and S.E. Stephenson Jr. 1969. Rapid production of experimental hypercholesterolemia and atherosclerosis in the rhesus monkey:comparison of five dietary regimens. J.Surg. Res. 9:263–271.PubMedCrossRefGoogle Scholar
  23. 23.
    Thompson J.S. 1969.Atheromata in an inbred strain of mice. J. Atheroscler. Res. 10:113–122.PubMedCrossRefGoogle Scholar
  24. 24.
    Stout, C. and M.E. Groover Jr. 1969. Spontaneous versus experimental atherosclerosis. Ann. N.Y. Acad. Sci. 162:89–98.PubMedCrossRefGoogle Scholar
  25. 25.
    Dieterich R.A., W. Van Pelt and W. Galster. 1973. Diet-induced cholesterolemia and atherosclerosis in wild rodents. Atherosclerosis 17:345–352.PubMedCrossRefGoogle Scholar
  26. 26.
    Leffler, H.H. and C.H. McDougald. 1963. Estimation of cholesterol in serum. Am. J. Clin. Pathol. 39:311–315.Google Scholar
  27. 27.
    Haeflmayr, J. and R. Freed. 1966. Eine Methode Zur routin maessigen Bestimmung des Lipidphosphors und der Phosphatide. Med. Ernabr. 7:1–4.Google Scholar
  28. 28.
    Fletcher, M.J. 1968. A colorimetric method for estimating serum triglycerides. Clin. China. Acta. 22:397–399.Google Scholar
  29. 29.
    Takeuchi, N. and Y. Yamamura. 1972. The effect of plasmapheresis on cholesterol synthesis in the rat: Relationship to protein synthesis. J. Lab. Clin. Med. 79:801–813.PubMedGoogle Scholar
  30. 30.
    Lowry, O.H., N.J. Rosenbrough, A.L. Farr and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–276.PubMedGoogle Scholar
  31. 31.
    Sadahiro, R., N. Takeuchi, A. Kumagai and Y. Yamamura. 1970. Studies on cholesterol metabolism in experimental diabetic rat. End. Japon. 17:225–232.CrossRefGoogle Scholar
  32. 32.
    Mitropoulos, K.A. and S. Balasubramaniam. 1972. Cholesterol 7 α-hydroxylase in rat liver microsomal preparations. Biochem. J. 128:1–9.PubMedGoogle Scholar
  33. 33.
    Lofland, H.B., T.B. Clarkson, R.W. StClair and N.D. M. Lehner. 1972. Studies on the regulation of plasma cholesterol levels in Squirrel monkeys of two genotypes. J.Lipid Res. 33: 39–47.Google Scholar
  34. 34.
    Bell, F.P., H.B. Lofland and T.B. Clarkson. 1970. Plasma cholesterol turnover and esterification in the pigeon. Lipids 5:153–155.PubMedCrossRefGoogle Scholar
  35. 35.
    West C.E. and G.K. Roberts. 1974. Cholesterol metabolism in two strains of rabbits differing in their cholesterolemic response to dietary cholesterol. Biochem.Soc.Trans. 2:1275–1277.Google Scholar
  36. 36.
    Adams, W.C., E.M. Gaman and A.S. Feigenbaum. 1972. Breed differences in the response of rabbits to atherogenic diet. Atherosclerosis 16:405–411.PubMedCrossRefGoogle Scholar
  37. 37.
    Takeuchi, N., M. Yamamoto, A. Kumagai and Y. Yamamura. 1970. Alterations of cholesterol metabolism induced by anabolic steroid administration to rat. Endocrinol. Japon. 17:195–202.CrossRefGoogle Scholar
  38. 38.
    Lindstedt, S., J. Avigan, D.S. Goodman, J. Sjoevall and D. Steinberg. 1965. The effect of dietary fat on the turnover of cholic acid and on the composition of the biliary bile acids in man. J. Clin. Invest. 44:1754–1765.PubMedCrossRefGoogle Scholar
  39. 39.
    Bieberdorf, F.A. and J.D. Wilson. 1965. Studies on the mechanism of action of unsaturated fats on cholesterol metabolism in the rabbit. J.Clin. Invest. 44:1834–1844.PubMedCrossRefGoogle Scholar
  40. 40.
    Goldstein, J.L. and M.S. Brown. 1974. Hyperlipidemia in coronary heart disease: a biochemical genetic approach. J. Lab. Clin. Med. 85:15–25.Google Scholar
  41. 41.
    Brown, M.S., S.E. Dana and J.L. Goldstein. 1974. Regulation of 3-hydroxy-3-methylglutaryl Coenzyme A reductase activity in cultured human fibroblast. J.Biol. Chem. 249:789–796.PubMedGoogle Scholar
  42. 42.
    Miettinen, T.A., R. Pelkonen, E.A. Nikkilae and O. Heinonen. 1967. Low excretion of fecal bile acid in a family with hypercholesterolemia. Acta Med. Scand. 182:645–650.PubMedCrossRefGoogle Scholar
  43. 43.
    Kottke, B.A. 1969. Differences in bile acid excretion, primary hypercholesterolemia compared to combined hypercholesterolemia and hypertriglyceridemia. Circulation 15:13–20.CrossRefGoogle Scholar
  44. 44.
    Lewis, B. and N.B. Myant, 1967. Studies in the metabolism of cholesterol in subjects with normal plasma cholesterol levels and in patients with essential hypercholesterolemia.Clin.Sci. 32:201–213.PubMedGoogle Scholar
  45. 45.
    Nestel, P.J. and E. M. Monger. 1967. Turnover of plasma esterified cholesterol in normocholesterolemic and hypercholesterolemic subjects and its relation to body fluid. J.Clin.Invest. 46:967–974.PubMedCrossRefGoogle Scholar
  46. 46.
    Grundy, S. M. and E.H. Ahrens. 1969. Mesurements of cholesterol turnover and synthesis and absorption in man carried out by isotope kinetic and sterol balance method. J.Lipid Res. 10:91–107.PubMedGoogle Scholar
  47. 47.
    Samuel, P. and W. Perl. 1970. Long-term decay of serum cholesterol radioactivity, body cholesterol metabolism in normals and patients with hyperlipoproteinemia and atherosclerosis. J.Clin.Invest. 49:346–357.PubMedCrossRefGoogle Scholar
  48. 48.
    Langer, T., W. Stroler and R.I. Levy. 1972. The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia. J.Clin.Invest. 51:1528–1536.PubMedCrossRefGoogle Scholar
  49. 49.
    Simons, L.A., D. Reichl, N.B. Myant and M. Mancini, 1975. The metabolism of the apoprotein of plasma low density lipoprotein in familial hyperbetalipoproteinaemia in the homozygous form. Atherosclerosis 21:283–298.PubMedCrossRefGoogle Scholar
  50. 50.
    Gotto, A.M. W.V. Brown, R.I. Levy, M.E. Biembaumer and D.S. Fredrickson, 1972. Evidence for the identity of the major apoprotein in low density and very low density lipoproteins in normal subjects and patients with familial hyperlipoproteinemia, J.Clin.Invest. 51: 1486–1496.PubMedCrossRefGoogle Scholar
  51. 51.
    Slack, J. and G.L. Mills. 1970. Anomalous low density lipoproteins in familial hyperlipoproteinemia. Clin.Chim.Acta 29:15–25.PubMedCrossRefGoogle Scholar
  52. 52.
    Ruderman, N.B., A.L. Jones, R.M. Krause and E. Shafrir. 1970. A biochemical and morphologic study of very low density lipoproteins in carbohydrate-induced hypertriglyceridemia. J.Clin.Invest. 50:1355–1368.CrossRefGoogle Scholar
  53. 53.
    Patton, N.M., R.V. Brown and C.C. Middleton, 1974. Familial cholesterolemia in pigeons. Atherosclerosis 19:308–314.CrossRefGoogle Scholar
  54. 54.
    Imai, Y. and H. Matsumura. 1973. Genetic studies on induced and spontaneous hypercholesterolemia in rats. Atherosclerosis 18: 59–64.PubMedCrossRefGoogle Scholar
  55. 55.
    Zucker, L. M. and T.F. Zucker. 1961. Fatty a new mutation in the rat. J.Hered. 52:295–278.Google Scholar
  56. 56.
    Zucker, T.F. and L.M. Zucker. 1962. Hereditary obesity in the rat associated with high serum fat and cholesterol. Proc. Soc. Exp. Biol. Med. 110:165–171.Google Scholar
  57. 57.
    Bray, G.A. 1968. Lipogenesis from glucose and pyruvate in fat cells from genetically obese rats. J.Lip id Res. 9:681–686.Google Scholar
  58. 58.
    Uchida, K. personal communication.Google Scholar
  59. 59.
    Sellers, E.A. and D.G. Baker. 1960. Coronary atherosclerosis in rats exposed to cold. Canad.Med. Ass. J. 83:6–13.PubMedGoogle Scholar
  60. 60.
    Bondjers, G. and T. Bjoernheden. 1970. Experimental atherosclerosis induced by mechanical trauma in rats. Atherosclerosis 12:301–306.PubMedCrossRefGoogle Scholar
  61. 61.
    Weibust, R. S. 1973. Inheritance of plasma cholesterol levels in mice. Genetics 73:303–312.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1976

Authors and Affiliations

  • Nozomu Takeuchi
    • 1
  • Masami Ito
    • 1
  • Yuichi Yamamura
    • 1
  1. 1.The Third Department of Internal MedicineOsaka University HospitalFukushima, OsakaJapan

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