Effect of copper deficiency on the apolipoprotein E-rich high density lipoproteins in rats

Twenty-four male weanling Sprague-Dawley rats were randomly divided into two treatments, namely a copper-adequate (8 mg Cu/kg diet) or a copper-deficient (0.85 mg Cu/kg diet) group. Feed and distilled-demineralized water were provided ad libitum. After 7 wk, plasma high density lipoproteins (HDL) were isolated by ultracentrifugation and agarose column chromatography. A heparin-Sepharose affinity column chromatographic method was used to subfractionate HDL into apolipoprotein E (apoE) -rich and apoE-poor subfractions. Significantly higher protein and cholesterol contents of HDL and the second retained (RII) subfraction (apoE-rich) were observed in copper-deficient than in control rats. The apoE contents of HDL and the apoE-rich (RII) subfraction were about threefold higher in copper-deficient rats. The increase in apoE in the HDL fraction was due primarily to the increased apoE concentration of the RII subfraction. In addition to a higher apoE concentration, apolipoprotein A-I concentration was also higher in the RII subfraction of the copper-deficient rats as compared to controls. However, the percentage of these apolipoproteins remained unaltered by copper deficiency. The present data suggest that the hypercholesterolemia observed in copper deficiency was associated with marked increases in cholesterol and apolipoprotein contents of the apoE-rich HDL.