Ext1 heterozygosity causes a modest effect on postprandial lipid clearance in humans
| Autor: | Erin M. Foley, Michiel A. J. van de Sande, Julia J. Witjes, Michael W.T. Tanck, J. Han M. Levels, Philip L.S.M. Gordts, Erik S.G. Stroes, Max Nieuwdorp, Marjolein A.W. van den Boogert, Geesje M. Dallinga-Thie, Jeff Esko, Kristin I. Stanford, H. Carlijne Hassing, Hans L. Mooij, Sophie J. Bernelot Moens, John J.P. Kastelein |
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| Přispěvatelé: | Internal medicine, ICaR - Circulation and metabolism, Other departments, 01 Internal and external specialisms, Graduate School, Amsterdam Cardiovascular Sciences, Cardiology, Amsterdam Public Health, Epidemiology and Data Science, Amsterdam institute for Infection and Immunity, Experimental Vascular Medicine, Vascular Medicine, Amsterdam Gastroenterology Endocrinology Metabolism |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Heterozygote multiple exostoses Biochemistry & Molecular Biology Multiple Sclerosis Knockout QD415-436 Familial hypercholesterolemia Biology Medical Biochemistry and Metabolomics Compound heterozygosity N-Acetylglucosaminyltransferases Cardiovascular Biochemistry chemistry.chemical_compound Mice Endocrinology Internal medicine Retinyl palmitate medicine Animals Humans 2.1 Biological and endogenous factors Aetiology triglycerides Mice Knockout familial hypercholesterolemia Area under the curve Cell Biology Middle Aged hereditary multiple exostoses medicine.disease Postprandial Period Postprandial Heart Disease chemistry LDL receptor Mutation heparan sulfates Female Biochemistry and Cell Biology Patient-Oriented and Epidemiological Research hereditary Chylomicron Lipoprotein |
| Zdroj: | Mooij, H L, Moens, S J, Gordts, P L, Stanford, K I, Foley, E M, van den Boogert, M A, Witjes, J J, Hassing, H, Tanck, M W, van de Sande, M A, Levels, J, Kastelein, J J, Stroes, E S, Dallinga-Thie, G M, Esko, J D & Nieuwdorp, M 2015, ' Ext1 heterozygosity causes a modest effect on postprandial lipid clearance in humans ', Journal of Lipid Research, vol. 56, no. 3, pp. 665-673 . https://doi.org/10.1194/jlr.M053504 Journal of Lipid Research, 56(3), 665-673. American Society for Biochemistry and Molecular Biology Inc. Journal of lipid research, vol 56, iss 3 Journal of Lipid Research, Vol 56, Iss 3, Pp 665-673 (2015) Journal of Lipid Research, 56(3), 665-673 Journal of lipid research, 56(3), 665-673. American Society for Biochemistry and Molecular Biology Inc. |
| ISSN: | 0022-2275 |
| DOI: | 10.1194/jlr.M053504 |
| Popis: | Elevated nonfasting TG-rich lipoprotein levels are a risk factor for CVD. To further evaluate the relevance of LDL-receptor (LDLr) pathway and heparan sulfate proteoglycans (HSPGs) in TG homeostasis, we analyzed fasting and postprandial TG levels in mice bearing combined heterozygous mutations in both Exostosin (Ext) 1 and Ldlr, in subjects with hereditary multiple exostosis (HME) due to a heterozygous loss-of-function mutation in EXT1 or EXT2 (N = 13), and in patients with heterozygous mutations in LDLR [familial hypercholesterolemia (FH)] and SNPs in major HSPG-related genes (n = 22). Mice bearing a homozygous mutation in hepatic Ext1 exhibited elevated plasma TGs similar to mice lacking other key enzymes involved in HSPG assembly. Compound heterozygous mice lacking Ldlr and Ext1 showed synergy on plasma TG accumulation and postprandial clearance. In human subjects, a trend was observed in HME patients toward reduced postprandial TG clearance with a concomitant reduction in chylomicron clearance [area under the curve (AUC)retinyl ester (RE) HME, 844 +/- 127 vs. controls, 646 +/- 119 nM/h, P = 0.09]. Moreover, in FH subjects with a high HSPG gene score, retinyl palmitate excursions were higher (AUC-RE, 2,377 +/- 293 vs. 1,565 +/- 181 nM/h, P |
| Databáze: | OpenAIRE |
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