The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglycerides.

C.J. Moen*, A.P. Tholens, P.J. Voshol, W. de Haan, L.M. Havekes, P. Gargalovic, A.J. Lusis, K. Willems van Dijk, R.R. Frants, M.H. Hofker, P.C. Rensen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective - The Hyplip2 congenic mouse strain contains part of chromosome 15 from MRL/MpJ on BALB/cJ (B/c) background. Hyplip2 mice show elevated plasma levels of cholesterol and predominantly triglycerides (TG), and are susceptible to diet-induced atherosclerosis. This study aimed at elucidation of the mechanism(s) explaining the hypertriglyceridemia. Methods and Results - Hypertriglyceridemia can result from an increased intestinal or hepatic TG production and/or by a decreased LPL-mediated TG clearance. The intestinal TG absorption and chylomicron formation was studied after i.v. injection of Triton WR1339 and 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 i.v. with glycerol tri[3H]oleate-labeled VLDL-like emulsion particles. In Hyplip2 mice, the particles were cleared at a decreased rate (t(1/2) 25+/-6 vs 11+/-2 min, p<0.05) concomitant with decreased uptake of emulsion-TG derived 3H-labeled fatty acids by the liver and white adipose tissue. Conclusion - 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.
Original languageEnglish
Pages (from-to)2182-2192
JournalJournal of Lipid Research
Issue number10
Publication statusPublished - 1 Jan 2007

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