Effects of cholesterol on viability and (n – 6) fatty acid metabolism in cultured human monocyte-like cells (U937)

Effects of supplementation of growth-promoting cholesterol on metabolism of the cytotoxic (n – 6) polyunsaturated fatty acids in cultured human monocyte-like cells (U937) have been examined. U937 cells were incubated in 5% delipidated fetal bovine serum containing 0 or 38.7 μM cholesterol. The rate of uptake and the distribution of metabolites of (n – 6) fatty acids (such as 18:2(n – 6), 18:3(n – 6), and20:3(n – 6), and20:4(n – 6)) were examined by adding radiolabelled fatty acid at a level of 1 μg/mL (3.3 μM for 20-carbon fatty acids and 3.6 μM for 18-carbon fatty acids). For assessing the cytotoxicity, (n – 6) fatty acids were added to medium at a concentration of 5 μg/mL (16.4 μM for 20-carbon fatty acids and 17.9 μM for 18-carbon fatty acids). Cholesterol supplementation suppressed the uptake of all (n – 6) fatty acids and reduced the cytotoxic effects of 18:2(n – 6), 20:3(n – 6), and 20:4(n – 6), but not 18:3(n – 6). In addition, cholesterol supplementation increased peroxide production and metabolism of (n – 6) fatty acids in U937 cells. Thus, the differential suppressive effect of cholesterol on the cytotoxicity of different fatty acids could not be attributed to an inhibitory effect on fatty acid Δ6- and Δ5-desaturation, or to an antioxidant effect on peroxide formation.Key words: (n – 6) fatty acid metabolism, cytotoxicity, peroxides.