The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglycerides |
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Authors: | Moen Corina J A Tholens Aart P Voshol Peter J de Haan Willeke Havekes Louis M Gargalovic Peter Lusis Aldons J van Dyk Ko Willems Frants Rune R Hofker Marten H Rensen Patrick C N |
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Institution: | Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. cmoen@lumc.nl |
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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(3)H]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(3)H]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 (3)H-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. |
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Keywords: | congenic mice lipoproteins lipoprotein lipase triglyceride hydrolysis lipoprotein clearance |
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