Hepatic iron (Fe) retention in copper (Cu)-deficient rats is a potential risk factor for hypercholesterolemia

In rats, Cu deficiency is associated with hypercholesterolemia and with hep atic Fe retention. Dietary saturated fat is also associated with hyperchole sterolemia and with elevated hepatic Fe. In contrast, dietary unsaturated f at is considered hypocholesterolemic.Is the cholesterol-lowering nature of unsaturated fat due to its inability to raise hepatic Fe? We therefore hypo thesized that the mechanism of raising blood cholesterol is dependent on th e ability to elevate liver Fe. The present study was undertaken to determin e whether dietary manipulations that are able to raise hepatic Fe such as C u deficiency, saturated fat, or Fe supplementation have also the ability to elevate blood cholesterol. Weanling male, Sprague-Dawley rats were fed a C u-deficient (0.7 mu g Cu/g diet) or Cu-adequate (6.9 mu g Cu/g) diet contai ning either saturated (beef tallow) or unsaturated (corn oil) fat. The diet s were either Fe adequate (44 mu g Fe/g) or supplemented (87 mu gFe/g). Rat s were fed their respective diets for four weeks. There was a direct relati onship between the concentrations of liver Fe and blood cholesterol. The lo west liver Fe (96 +/- 9 mu g/g) was found in rats fed the Fe and Cu-adequat e diet containing unsaturated fat. Their blood cholesterol was low (114 +/- 6 mg/dl). Beef tallow and high Fe in the Cu-adequate diet elevated hepatic Fe (192 +/- 10 mu g/g) and elevated blood cholesterol (140 +/- 3 mg/dl). T he highest concentration of liver Fe (296 +/- 9 mu g/g) was associated with the highest concentration of blood cholesterol (225 +/- 5 mg/dl). This was achieved by feeding a Cu-deficient diet which contained beef tallow and wa s supplemented with Fe. Based on these data, it is concluded that nutrients which raise hepatic Fe have the potential to increase blood cholesterol. I n addition, cholesterol-lowering properties of unsaturated fat may be due t o its inability to raise hepatic Fe.