Effect of dietary copper concentrations on dyslipidemia in SOD1−/− mice

Abstract

We previously observed dyslipidemia in Cu,Zn‐superoxide dismutase knockout mice (SOD1−/−). This study was conducted to test if the dyslipidemic phenotype in the SOD1−/− mice was ameliorated by feeding a high level of dietary Cu. Weanling male SOD1−/− mice and their wild‐type (WT) controls (3‐wk old, n = 7–10 per genotype by treatment) were fed a Torula‐yeast based, Cudeficient (< 1 mg/kg) diet (BD) or BD plus Cu (as CuSO4·5H2O) at 10 and 100 mg/kg for 6 wk. Compared with the 10 mg Cu/kg diet, the BD elevated (P < 0.05) plasma cholesterol and non‐esterifed fatty acid concentrations. However, neither the BD nor the high Cu diet (100 mg/kg) removed the genotype differences in body weight, plasma lipid profiles, or hepatic lipid profiles, although the high Cu diet decreased the relative difference in hepatic triglyceride concentration between the SOD1−/− and WT mice. Meanwhile, the BD aggravated (P < 0.05) the genotype differences in hepatic cholesterol and triglyceride concentrations. Hepatic nuclear sterol regulatory element‐binding protein‐1 and ‐2 were affected (P < 0.05) by the high Cu diet in an opposite way, but the genotype difference in these two key lipogenesis regulatory proteins remained. In conclusion, dyslipidemia in the SOD1−/− mice was not likely attributed to Cu deficiency, and could not be ameliorated by a high dietary Cu supplementation (supported in part by NIH 53018).