Alterations in plasma lipid, lipoprotein and apolipoprotein concentrations in copper-deficient rats

In the first experiment, 32 weanling male Sprague-Dawley rats were randomly divided into two treatment groups, namely, a copper-adequate (8 mg Cu/kg diet) or a copper-deficient (0.85 mg Cu/kg diet) group. These animals were used for the plasma lipoprotein determinations. In the second experiment, 20 similar rats were assigned to the two treatments and were used for plasma and blood volume determinations. Feed and distilled water were provided ad libitum. After 7 weeks, plasma was obtained by heart puncture. Plasma lipoproteins were partitioned and purified by ultracentrifugation and agarose-column chromatography into high, low and very low density lipoprotein fractions (HDL, LDL, VLDL). The apolipoprotein profile of HDL fraction was established by polyacrylamide gel electrophoresis. The markedly reduced liver copper content of rats fed the copper-deficient diet confirmed that they were indeed copper-deficient. Significant elevations in protein and cholesterol contents of HDL and LDL fractions and in triglyceride content of LDL fraction were observed in the copper-deficient rats. In addition, the apolipoprotein E concentration of the HDL fraction was significantly increased in the copper-deficient rats. In the second experiment, the hematocrit was markedly reduced and the plasma volume was significantly increased in the rats fed the copper-deficient diet. Data derived from this study and previous studies suggest that the hypercholesterolemia associated with copper deficiency was due mainly to an impairment in the cholesterol degradation process.