Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotein lipase activity
| Autor: | A. van Beek, Geesje M. Dallinga-Thie, F.C. de Ruijter-Heijstek, Hans Jansen, H. H. J. J. Van Barlingen, D.W. Erkelens, T.W.A. de Bruin |
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| Přispěvatelé: | Other departments, Interne Geneeskunde, RS: NUTRIM School of Nutrition and Translational Research in Metabolism |
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Lipoprotein lipase Very low-density lipoprotein Apolipoprotein B biology Chemistry nutritional and metabolic diseases Chylomicron remnant clearance Cell Biology Protein degradation digestive system Biochemistry Endocrinology Internal medicine medicine biology.protein lipids (amino acids peptides and proteins) Hepatic lipase Lipase Chylomicron |
| Zdroj: | Journal of lipid research, 39(2), 322-332. American Society for Biochemistry and Molecular Biology Inc. Journal of Lipid Research, 39(2), 322-332. American Society for Biochemistry and Molecular Biology, Inc. |
| ISSN: | 0022-2275 |
| DOI: | 10.1016/s0022-2275(20)33894-3 |
| Popis: | The acute effects of intravenous heparin adminis- tration (50 U/kg body weight) on apolipoprotein (apo)B-48 and apoB-100-containing lipoproteins in relation to posthep- arin lipase activities were studied in ten healthy normolipi- demic volunteers. Five subjects returned to receive sham in- jections with saline. Lipoproteins were separated from plasma by density gradient ultracentrifugation at baseline, 3, and 20 min postheparin. ApoB-48 and apoB-100 in d , 1.006 g/mL and 1.006 , d , 1.019 g/mL fractions were quantitatively measured after electrophoresis on 5% SDS polyacrylamide gels and Coomassie-blue staining. No significant changes were observed after saline injections. Heparin administration released lipoprotein lipase (LPL) and hepatic lipase (HL) ac- tivities after 20 min, and significantly reduced apoB-48 con- centrations in d , 1.006 g/mL fractions only. ApoB-100 con- centrations showed a trend to decrease in d , 1.006 g/mL fractions and to increase in 1.006 , d , 1.019 g/mL frac- tions. LPL activity was related to the percentual disappear- ance of apoB-48 ( r 5 0.81, P 5 0.004) and apoB-100 ( r 5 0.91, P , 0.001) in d , 1.006 g/mL fractions. When little LPL was released (LPL activity , 120 mU/mL) by heparin, apoB-48 was preferentially eliminated over apoB-100. However, when abundant LPL was released (LPL activity . 140 mU/mL), comparable percentual reductions for apoB-48 and apoB-100 were seen. Pharmacokinetic analysis revealed first-order ki- netics for the clearance of apoB-48 in d , 1.006 g/mL frac- tions, but zero-order kinetics for apoB-100 clearance. Un- der conditions of artificially enhanced lipolysis, the first catabolic step of apoB-48-containing lipoproteins and hepatic VLDL showed different pharmacokinetics. ApoB-48-contain- ing lipoproteins were the preferred substrate for LPL, and only when abundant LPL was present, clearance of hepatic VLDL occurred.— van Beek, A. P., H. H. J. J. van Barlingen, F. C. de Ruijter-Heijstek, H. Jansen, D. W. Erkelens, G. M. Dallinga-Thie, and T. W. A. de Bruin. Preferential clearance of apoB-48-containing lipoproteins after heparin-induced li- polysis is modulated by lipoprotein lipase activity. J. Lipid Res. 1998. 39: 322-332. Triglycerides (TG) in plasma are transported by two different types of apoB-containing triglyceride-rich lip- oproteins (TRL), chylomicrons, and hepatic VLDL. Chylomicrons, with apoB-48 as their structural protein, are synthesized by the intestine and carry dietary tri- glycerides. Hepatic VLDL, with apoB-100 as major pro- tein component, bring endogenous triglycerides to pe- ripheral tissues. In the postprandial state, both apoB-48 and apoB-100 levels are increased (1-3), and both chy- lomicrons and hepatic VLDL compete for lipoprotein lipase in the "common lipolytic pathway" (4). The first catabolic step of TRL, hydrolysis of core TG, requires these particles to bind to the vascular endothelium, the site of lipase action. Several studies have contributed evidence that chylomicrons are preferentially lipolyzed over VLDL, thereby temporarily impeding normal li- polytic degradation of VLDL (5, 6). It has been known for over 50 years that intravenous heparin administration to human subjects leads to en- hanced hydrolysis of triglycerides (7), due to the re- lease of two key enzymes in lipoprotein catabolism, lip- oprotein lipase (LPL) and hepatic lipase (HL) (8). Heparin-induced lipolysis has been used to study the contribution of LPL and HL to apolipoprotein metabo |
| Databáze: | OpenAIRE |
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