Title
Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice
Author
Gaubius Instituut TNO
van Vlijmen, B.J.M.
Mensink, R.P.
van 't Hof, H.B.
Offermans, R.F.G.
Hofker, M.H.
Havekes, L.M.
Publication year
1998
Abstract
Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidentic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VDL) remnant metabolism, to study the effects of dietary fish oil on serum lipids and VLDL kinetics under highly standardized conditions. For this, female APOE*3-Leiden mice were fed a fat- and cholesterol-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 VLDL (-80%). LDL and HDL cholesterol levels were not affected by fish oil feeding. VLDL-apoB kinetic studies showed that fish oil feeding resulted in a significant 2-fold increase in VLDL-apoB fractional catabolic rate (FCR). Hepatic VLDL-apoB production was, however, not affected by fish oil feeding. VLDL-triglyceride turnover studies revealed that fish oil significantly decreased hepatic VLDL-triglyceride production rate (- 60%). A significant increase in VLDL-triglyceride FCR was observed (+70%), which was not related to increased lipolytic activity. We conclude that APOE*3-Leiden mice are highly responsive to dietary fish oil. The observed strong reduction in serum very low density lipoprotein (VLDL) is primarily due to an effect of fish oil to decrease hepatic VLDL triglyceride production rate and to increase VLDL-apoB fractional catabolic rate.
Subject
Dietary fish oil
Hypertipidemia
n-3 fatty acids
Transgenic mice
VLDL metabolism
Animals
Apolipoprotein E3
Apolipoproteins B
Apolipoproteins E
Cholesterol
Cholesterol, Dietary
Dietary Fats
Female
Fish Oils
Humans
Hyperlipidemias
Kinetics
Lipoproteins
Lipoproteins, HDL
Lipoproteins, IDL
Lipoproteins, LDL
Lipoproteins, VLDL
Mice
Mice, Transgenic
Triglycerides
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TNO identifier
234472
ISSN
0022-2275
Source
Journal of Lipid Research, 39 (39), 1181-1188
Document type
article