Comparison of the effects of dietary n-3 and n-6 polyunsaturated fatty acids on very-low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnants

The effects of chylomicron remnants enriched in n - 3 or n - 6 polyunsatura ted fatty acids (derived from fish or corn oil respectively) on the secreti on of very-low-density lipoprotein (VLDL) lipid and apolipoprotein B (apoB) by rat hepatocytes in culture was investigated. Remnants were prepared in vivo from chylomicrons obtained from rats given an oral dose of fish or cor n oil and incubated with cultured hepatocytes for up to 16 h. The medium wa s then removed and the secretion of cholesterol and triacylglycerol into th e whole medium or the rho < 1.050 g/ml fraction during the following 7-24 h was determined. After exposure of the cells to fish-oil as compared with c orn-oil remnants, secretion of both cholesterol and triacylglycerol into th e whole medium was decreased by 25-35%, and secretion into the rho < 1.050 g/ml fraction was decreased by 20-25 %. In addition, the levels of apoB48 f ound in the rho < 1.050 g/ml fraction were significantly lower in cells tre ated with fish-oil rather than corn-oil remnants, although the levels of ap oB100 remained unchanged. The expression of mRNA for apoB, as determined by reverse-transcriptase PCR, however, was not significantly changed after ex posure of the cells to both types of remnants. These results demonstrate th at the effects of dietary n - 3 polyunsaturated fatty acids in depressing h epatic VLDL secretion occur directly when they are delivered to the liver f rom the intestine in chylomicron remnants, and that the secretion, but not the synthesis, of apoB is targeted.