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Research paper| Volume 31, ISSUE 3, P259-271, November 1978

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Copper deficiency and cholesterol metabolism in the rat

  • Kenneth G.D. Allen
    Footnotes
    Affiliations
    Department of Biochemistry, University of North Dakota and United States Department of Agriculture, Science and Education Administration, Human Nutrition Laboratory, Grand Forks, ND 58201 U.S.A.
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  • Leslie M. Klevay
    Affiliations
    Department of Biochemistry, University of North Dakota and United States Department of Agriculture, Science and Education Administration, Human Nutrition Laboratory, Grand Forks, ND 58201 U.S.A.
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  • Author Footnotes
    ∗ Present address: Department of Food Science and Nutrition, Colorado State University, Fort Collins, C080523, U.S.A.
DOI:https://doi.org/10.1016/0021-9150(78)90062-X
Copper deficiency and cholesterol metabolism in the rat
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      Abstract

      The influence of copper deficiency on both 3H incorporation into plasma and liver lipids following [3H]mevalonate injection, and the excretion of biliary steroids from cannulated bile ducts was examined in the rat in two separate experiments. Copper-deficient rats exhibited a significant hypercholesterolemia (129% increase, P < 0.001) at 181 days. Four hours after [3H]mevalonate injection, 3H incorporation into plasma free and esterified cholesterol was elevated 162% (P < 0.005) and 80% (P < 0.025), respectively, and 3H incorporation into liver total lipids and cholesterol esters was depressed 18% (P < 0.04) and 43% (P < 0.005, respectively, in copper-deficient rats. Hepatic copper concentration of deficient rats showed a significant negative correlation with 3H incorporation into plasma cholesterol (r= −0.83, P < 0.02) and cholesterol ester (r = −0.70, P < 0.08). Total hepatic cholesterol remained unchanged by deficiency despite the significant increase in total plasma cholesterol burden of copper deficient rats (82%, P < 0.001). Copper deficiency failed to impair biliary steroid excretion. The 56% (P < 0.001) increase in bile acid excretion in the first 8 hours was paralleled by the 62% (P < 0.005) increase in plasma cholesterol concentration of deficient rats.
      The observations suggest a more rapid synthesis and clearance of cholesterol to the plasma pool, with this cholesterol being unavailable for excretion as biliary steroids, in copper-deficient rats.

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      References

        • Fredrickson D.S.
        • Levy R.I.
        Familial hyperlipoproteinemia.
        in: Stanbury J.B. Wyngaarden J.B. Fredrickson D.S. The Metabolic Basis of Inherited Disease. 3rd edition. McGraw-Hill, New York, NY1972: 545-614
        • Kannel W.B.
        • Dawber T.R.
        • Friedman G.D.
        • Glennon W.E.
        • McNamara P.M.
        Risk factors in coronary heart disease.
        Ann. Intern. Med. 1964; 61: 888

      3. Anon., Vital Statistics of the United States 1967, Department of Health, Education, and Welfare, Washington, D.C., Vol. 2, Part A, Tables 1–7.

        • Ross R.
        • Glomset J.A.
        The pathogenesis of atherosclerosis.
        New Engl. J. Med. 1976; 295: 369
        • Ross R.
        • Glomset J.A.
        The pathogenesis of atherosclerosis.
        New Engl. J. Med. 1976; 295: 420
        • Allen K.G.D.
        • Klevay L.M.
        Hypercholesterolemia in rats caused by copper deficiency.
        J. Nutr. 1976; 106: xxii
        • Lei K.Y.
        Cholesterol metabolism in copper-deficient rats.
        Nutr. Rep. Int. 1977; 15: 597
        • Allen K.G.D.
        • Klevay L.M.
        Cholesterolemia and cardiovascular abnormalities in rats caused by copper deficiency.
        Atherosclerosis. 1978; 29: 81
        • Klevay L.M.
        Coronary heart disease — The zinc/copper hypothesis.
        Amer. J. Clin. Nutr. 1975; 28: 764
        • Hart E.B.
        • Steenbock H.
        • Waddell J.
        • Elvehjem C.A.
        Iron in nutrition, Part 7 (Copper as a supplement to iron for hemoglobin building in the rat).
        J. Biol. Chem. 1928; 77: 797
        • Pinnell S.R.
        • Martin G.R.
        The cross linking of collagen and elastin — Enzymatic conversion of lysine in peptide linkage to α-aminoadipic-σ-semialdehyde (allysine) by an extract from bone.
        in: 3rd edition. Proc. Nat. Acad. Sci. (U.S.A.). 61. 1968: 708
        • Ullrich V.
        • Duppel W.
        Iron- and copper-containing monooxygenases.
        in: 3rd edition. The Enzymes. Vol. 12. Academic Press, New York, NY1975: 296
        • Whale K.W.J.
        • Davies N.T.
        Effect of dietary copper deficiency in the rat on fatty acid composition of adipose tissue and desaturase activity of liver microsomes.
        Brit. J. Nutr. 1975; 34: 105
        • Caughey W.S.
        • Wallace W.J.
        • Volpe J.A.
        • Yoshikawa S.
        Cytochrome c oxidase.
        in: 3rd edition. The Enzymes. Vol. 13. Academic Press, New York, NY1976: 299
      15. Nutrient Requirements of Domestic Animals. 2nd edition. Nutrient Requirements of Laboratory Animals. National Academy of Sciences, Washington, DC1972: 56 (Number 10)
      16. Nutrient Requirements of Domestic Animals. 2nd edition. Nutrient Requirements of Laboratory Animals. National Academy of Sciences, Washington, DC1972: 70 (Number 10)
        • Allen K.G.D.
        • Klevay L.M.
        • Springer H.L.
        The zinc and copper content of seeds and nuts.
        Nutr. Rep. Int. 1977; 16: 227
        • Gloster J.
        • Fletcher R.F.
        Quantitative analysis of serum lipids with thin-layer chromatography.
        Clin. Chim. Acts. 1966; 13: 235
        • Carpenter K.J.
        • Gotsis A.
        • Hegsted D.M.
        Estimation of total cholesterol in serum by a micro method.
        Clin. Chem. 1957; 3: 233
        • Kleinman L.I.
        • Radford E.P.
        • Torelli G.
        Urea and inulin clearances in undisturbed unanesthetized rats.
        Amer. J. Physiol. 1965; 208: 578
        • Cole J.F.
        • Klevay L.M.
        • Zavon M.R.
        Endrin and dieldrin — A comparison of hepatic excretion in the rat.
        Toxicol. Appl. Pharmacol. 1970; 16: 547
        • Roschlau P.
        • Bernt E.
        • Gruber W.
        Enzymatic determination of total cholesterol in serum.
        Z. Klin. Chem. Klin. Biochem. 1974; 12: 403
        • Turnberg L.A.
        • Anthony-Mote A.
        The quantitative determination of bile salts in bile using thinlayer chromatography and 3a-hydroxysteroid dehydrogenase.
        Clin. Chim. Acta. 1969; 24: 253
        • Snedecor G.W.
        Statistical Methods.
        in: 5th edition. Iowa State University Press, Ames, IA1956: 45
        • Snedecor G.W.
        Statistical Methods.
        in: 5th edition. Iowa State University Press, Ames, IA1956: 160
        • Siperstein M.D.
        • Guest M.J.
        Studies on the site of the feed-back control of cholesterol synthesis.
        J. Clin. Invest. 1960; 39: 642
        • Hellstrom K.H.
        • Siperstein M.D.
        • Bricker L.A.
        • Luby L.J.
        Studies of the in vivo metabolism of mevalonic acid in the normal rat.
        J. Clin. Invest. 1973; 52: 1303
      28. (Anon)
        Blood volumes.
        in: Altman P.L. Dittmer D.S. Respiration and Circulation. Committee on Biological Handbooks. Federation of American Societies for Experimental Biology (FASEB), Bethesda, MD1971: 381
        • Danielsson H.
        Mechanism of bile acid synthesis.
        in: The Bile Acids. Vol. 2. Plenum Press, New York, NY1973: 1
        • Suzuki M.
        • Mitropoulos K.A.
        • Myant N.B.
        The electron transport mechanism associated with the 12α-hydroxylation of C27 steroids.
        Biochem. Biophys. Res. Commun. 1968; 30: 516
        • Owen C.A.
        • Hazelrig J.B.
        Copper deficiency and copper toxicity in the rat.
        Amer. J. Physiol. 1968; 215: 334
        • Miettinen T.A.
        Clinical implications of bile acid metabolism in man.
        in: The Bile Acids. Vol. 2. Plenum Press, New York, NY1973: 283
        • Goldstein J.L.
        • Brown M.S.
        Atherosclerosis — The low-density lipoprotein hypothesis.
        Metabolism. 1977; 26: 1257
        • Brown M.S.
        • Goldstein J.L.
        Receptor-mediated control of cholesterol metabolism.
        Science. 1976; 191: 150
        • Stein O.
        • Stein Y.
        The removal of cholesterol from Landschütz ascites cells by high-density apolipoprotein.
        Biochim. Biophys. Acta. 1973; 326: 232
        • Hsia S.L.
        • Chao Y.S.
        • Hennekens C.H.
        • Reader W.B.
        Decreased serum cholesterol-binding reserve in premature myocardial infarction.
        Lancet. 1975; 2: 1000
        • Miller G.J.
        • Miller N.E.
        Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease.
        Lancet. 1975; 1: 16
        • Klevay L.M.
        The ratio of zinc to copper of diets in the United States.
        Nutr. Rep. Int. 1975; 11: 237
        • Klevay L.M.
        • Vo-Khactu K.P.
        • Jacob R.A.
        The ratio of zinc to copper of cholesterol lowering diets.
        in: Hemphill D.D. Trace Substances in Environmental Health-IX. Missouri University Press, Colombia, MO1976: 131-138
        • Brown E.D.
        • Howard M.D.
        • Smith J.C.
        The copper content of regular, vegetarian and renal diets.
        in: Fed. Proc.36. 1977: 1122
        • Wolf W.R.
        • Holden J.
        • Greene F.E.
        Daily intake of zinc and copper from self selected diets.
        in: Fed. Proc.36. 1977: 1175
        • Guthrie B.E.
        • Robinson M.F.
        Daily intakes of manganese, copper, zinc and cadmium by New Zealand women.
        Brit. J. Nutr. 1977; 38: 55
      43. (Anon)Recommended Dietary Allowances. National Academy of Sciences, Washington, DC1974: 95-96
        • Darby W.J.
        • Friberg L.
        • Mills C.F.
        • Parizek J.
        • Ramalingaswami V.
        • Ronaghy H.A.
        • Sandstead H.H.
        • Underwood E.J.
        • Rao N.M.
        • Parr R.
        • Bengoa J.M.
        • DeMaeyer E.M.
        • Mertz W.
        Trace Elements in Human Nutrition.
        in: WHO Technical Report Series, No. 532. World Health Organization, Geneva1973: 15-19
        • Dietschy J.M.
        • Wilson J.D.
        Regulation of cholesterol metabolism.
        New Engl. J. Med. 1970; 282: 1128
        • Dietschy J.M.
        • Wilson J.D.
        Regulation of cholesterol metabolism.
        New Engl. J. Med. 1970; 282: 1179
        • Dietschy J.M.
        • Wilson J.D.
        Regulation of cholesterol metabolism.
        New Engl. J. Med. 1970; 282: 1241
        • Nervi F.O.
        • Weis H.J.
        • Dietschy J.M.
        The kinetic characteristics of inhibition of hepatic cholesterogenesis by lipoproteins of intestinal origin.
        J. Biol. Chem. 1975; 250: 4145

      Article info

      Publication history

      Accepted: August 11, 1978
      Received in revised form: July 31, 1978
      Received: March 6, 1978

      Identification

      DOI: https://doi.org/10.1016/0021-9150(78)90062-X

      Copyright

      © 1978 Published by Elsevier Inc.

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