Title
The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglycerides
Author
TNO Kwaliteit van Leven
Moen, C.J.A.
Tholens, A.P.
Voshol, P.J.
de Haan, W.
Havekes, L.M.
Gargalovic, P.
Lusis, A.J.
van Dyk, K.W.
Frants, R.R.
Hofker, M.H.
Rensen, P.C.N.
Publication year
2007
Abstract
The Hyplip2 congenic mouse strain contains part of chromosome 15 from MRL/MpJ on the BALB/cJ background. Hyplip2 mice show increased plasma levels of cholesterol and predominantly triglycerides (TGs) and are susceptible to diet-induced atherosclerosis. This study aimed at elucidation of the mechanism(s) explaining the hypertriglyceridemia. Hypertriglyceridemia can result from increased intestinal or hepatic TG production and/or by decreased LPL-mediated TG clearance. The intestinal TG absorption and chylomicron formation were studied after intravenous injection of Triton WR1339 and an intragastric load of olive oil containing glycerol tri[3H]oleate. No difference was found in intestinal TG absorption. Moreover, the hepatic VLDL-TG production rate and VLDL particle production, after injection of Triton WR1339, were also not affected. To investigate the LPL-mediated TG clearance, mice were injected intravenously with glycerol tri[3H]oleate-labeled VLDL-like emulsion particles. In Hyplip2 mice, the particles were cleared at a decreased rate (half-life of 25 ± 6 vs. 11 ± 2 min; P < 0.05) concomitant with a decreased uptake of emulsion TG-derived 3H-labeled fatty acids by the liver and white adipose tissue. The increased plasma TG levels in Hyplip2 mice do not result from an enhanced intestinal absorption or increased hepatic VLDL production but are caused by decreased LPL-mediated TG clearance. Copyright © 2007 by the American Society for Biochemistry and Molecular Biology, Inc.
Subject
Biomedical Research
Congenic mice
Lipoprotein clearance
Lipoprotein lipase
Lipoproteins
Triglyceride hydrolysis
Animals
Chylomicrons
Female
Genetic Techniques
Hypertriglyceridemia
Lipase
Lipoprotein Lipase
Lipoproteins
Lipoproteins, VLDL
Mice
Mice, Congenic
Postprandial Period
Triglycerides
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DOI
https://doi.org/10.1194/jlr.m700009-jlr200
TNO identifier
240204
ISSN
0022-2275
Source
Journal of Lipid Research, 48 (48), 2182-2192
Document type
article