EFFECTS OF DIETARY FISH-OIL ON SERUM-LIPIDS AND VLDL KINETICS IN HYPERLIPIDEMIC APOLIPOPROTEIN E-ASTERISK-3-LEIDEN TRANSGENIC MICE

Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. Zn th e present study we therefore used hyperlipidemic apolipoprotein (APO) E3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VLDL) remnant metabolism, to study the effects of dietary fish oil on serum lipids and VLDL kinetics under highly standardized conditions, For this, female APOE3-Leiden mice were fed a fat-and cho lesterol-containing diet supplemented with either 0, 3 or 6% w/w (i.e. 0, 6, or 12% of total energy) of fish oil, Fish oil-fed mice showed a significant dose-dependent decrease in serum cholesterol (up to -43%) and triglyceride levels (up to -60%), mainly due to a reduction of VL DL (-80%). LDL and HDL cholesterol levels were not affected by fish oi l feeding. VLDL-apoB kinetic studies showed that fish oil feeding resu lted in a significant 2-fold increase in VLDL-apoB fractional cataboli c rate (FCR), Hepatic VLDL-apoB production was, however, not affected by fish oil feeding, VLDL-triglceride turnover studies revealed that f ish oil significantly decreased hepatic VLDL-triglyceride production r ate (-60%), A significant increase in VLDL-triglyceride FCR was observ ed (+70%), which was not related to increased lipolytic activity. We c onclude that APOE3-Leiden mice are highly responsive to dietary fish oil. The observed strong reduction in serum very low density lipoprote in (VLDL) is primarily due to an effect of fish oil to decrease hepati c VLDL triglyceride production rate and to increase VLDL-apoB fraction al catabolic rate.