Abstract

Experiments were conducted with suckling male C57BL mice and Sprague-Dawley rats to investigate the relationship between copper deficiency and elevated serum cholesterol. Brindled mice, which have a genetic defect that affects copper distribution, were compared to their normal brothers. Dietary copper deficiency was produced in dams heterozygous for the brindled gene, in normal mouse dams and in rat dams. The subsequent male offspring were compared to those from copper-supplemented dams. Copper deficiency, as assessed by liver copper levels or ceruloplasmin activity, was demonstrated in 12-d-old rats, brindled mice, and in genotypically normal mice from dams fed the copper-deficient diet. However, serum cholesterol levels were not elevated in these “copper-deficient” rats or mice. In one experiment serum cholesterol levels of brindled mice were significantly lower than that of their littermate controls. An additional study was done with older mice. Their dams were fed a low copper diet from parturition throughout lactation, and the pups were fed the same copper-deficient diet for 4 wk after weaning. The 7-wk-old male copper-deficient mice had liver copper levels below 1 µg/g, but no elevation in serum cholesterol was observed. The failure to demonstrate a rise in serum cholesterol in these perinatal models may be due in part to less severe hepatic copper deficiency because of neonatal copper reserves in liver.

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