The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞

Autor: Corina J.A. Moen, Aart P. Tholens, Peter J. Voshol, Willeke de Haan, Louis M. Havekes, Peter Gargalovic, Aldons J. Lusis, Ko Willems van Dȳk, Rune R. Frants, Marten H. Hofker, Patrick C.N. Rensen
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Zdroj: Journal of Lipid Research, Vol 48, Iss 10, Pp 2182-2192 (2007)
Druh dokumentu: article
ISSN: 0022-2275
DOI: 10.1194/jlr.M700009-JLR200
Popis: 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.
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