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.
Moen, C. J., Tholens, A. P., Voshol, P. J., de Haan, W., Havekes, L. M., Gargalovic, P., Lusis, A. J., Willems van Dijk, K., Frants, R. R., Hofker, M. H., & Rensen, P. C. (2007). The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglycerides. Journal of Lipid Research, 48(10), 2182-2192. https://doi.org/10.1194/jlr.M700009-JLR200