Oxidation affects the regulation of hepatic lipid synthesis by chylomicronremnants

The effects of native and oxidized chylomicron remnants on lipid synthesis in normal and oxidatively stressed liver cells were investigated using MET murine hepatocytes (MMH cells), a nontransformed mouse hepatocyte cell line that maintains a highly differentiated hepatic phenotype in culture. Lipid synthesis was determined by measuring the incorporation of [H-3]oleate int o cholesteryl ester, triacylglycerol, and phospholipid by the cells. The fo rmation of cholesteryl ester and phospholipid was decreased by chylomicron remnants in a dose-dependent manner, while triacylglycerol synthesis was in creased. Exposure of MMH cells to mild oxidative stress by incubation with CuSO4 (2.5 muM) for 24 h led to significantly increased incorporation of [H -3]oleate into triacylglycerol and phospholipid, but not cholesteryl ester, in the absence of chylomicron remnants. In the presence of the lipoprotein s, however, similar effects to those found in untreated cells were observed . Oxidatively modified chylomicron remnants prepared by incubation with CuS O4 (10 muM, 18 h, 37 degreesC) did not influence cholesteryl ester or phosp holipid synthesis in MMH cells, but had a similar effect to that found with native remnants on triacylglycerol synthesis. These findings show that hep atic lipid metabolism is altered by exposure to mild oxidative stress and b y lipids from the diet delivered to the liver in chylomicron remnants, and these effects may play a role in the development of atherosclerosis, (C) 20 01 Elsevier Science Inc.