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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.
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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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