The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞

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 mechanis...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2007-10-01
Series:Journal of Lipid Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520424630
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author 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
author_facet 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
author_sort Corina J.A. Moen
collection DOAJ
description 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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spelling doaj.art-0b85f06617064831b97c73353612aa912022-12-21T22:12:42ZengElsevierJournal of Lipid Research0022-22752007-10-01481021822192The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞Corina J.A. Moen0Aart P. Tholens1Peter J. Voshol2Willeke de Haan3Louis M. Havekes4Peter Gargalovic5Aldons J. Lusis6Ko Willems van Dȳk7Rune R. Frants8Marten H. Hofker9Patrick C.N. Rensen10Department of Human Genetics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Human Genetics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Netherlands Organization for Applied Scientific Research Quality of Life, Gaubius Laboratory, Leiden, The NetherlandsDepartment of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Netherlands Organization for Applied Scientific Research Quality of Life, Gaubius Laboratory, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The NetherlandsDepartments of Microbiology, Immunology, and Molecular Genetics; Medicine; and Human Genetics, University of California Los Angeles, Los Angeles, CADepartments of Microbiology, Immunology, and Molecular Genetics; Medicine; and Human Genetics, University of California Los Angeles, Los Angeles, CADepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Human Genetics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Molecular Genetics, University Maastricht, Maastricht, The Netherlands; Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Netherlands Organization for Applied Scientific Research Quality of Life, Gaubius Laboratory, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsThe 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.http://www.sciencedirect.com/science/article/pii/S0022227520424630congenic micelipoproteinslipoprotein lipasetriglyceride hydrolysislipoprotein clearance
spellingShingle 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
The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞
Journal of Lipid Research
congenic mice
lipoproteins
lipoprotein lipase
triglyceride hydrolysis
lipoprotein clearance
title The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞
title_full The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞
title_fullStr The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞
title_full_unstemmed The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞
title_short The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞
title_sort hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglyceridess⃞
topic congenic mice
lipoproteins
lipoprotein lipase
triglyceride hydrolysis
lipoprotein clearance
url http://www.sciencedirect.com/science/article/pii/S0022227520424630
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