Dimeric lipoprotein lipase is bound to triglyceride-rich plasma lipoproteins

Zambón, Alberto; Schmidt, Ida G.; Beisiegel, Ulrike; Brunzell, John D.

doi:10.1016/s0022-2275(20)37488-5

Cited by 55 publications

(17 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differences in molar ratio estimations may result from differences in identified lipoprotein species and differences between groups with conceivably different LPL mass and VLDL particle concentrations. It should be noted that calculated ranges of Zambon et al (36) and ours overlap.…”

Section: Discussionsupporting

confidence: 47%

“…Based on these findings, they argued that there was a frequency of 1 LPL homodimer per 800 LDL particles in postheparin plasma (assuming half of the LPL molecules were on LDL). Zabon and coworkers (36) showed that dimeric postheparin lipoprotein lipase was bound to triglyceride-rich particles and that differences with previous studies resulted from the use of a lipase inhibitor. It was found that the postheparin LPL-dimer/apoB molar ratio in the d Ͻ 1.006 g/mL was 1 on 100 to 500 VLDL particles.…”

Section: Discussionmentioning

confidence: 96%

“…LPL binding to lipoproteins is known to be disrupted by high salt concentrations and centrifugal forces (40). Recently, Zambon et al (36) showed that ex vivo lipolysis in postheparin whole plasma was extensive when no LPL inhibitor was used. Thus, it is possible that part of the observed phenomena could be due to ex vivo changes.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotein lipase activity

Beek

Barlingen

Ruijter-Heijstek

et al. 1998

Journal of Lipid Research

View full text Add to dashboard Cite

The acute effects of intravenous heparin administration (50 U/kg body weight) on apolipoprotein (apo)B-48 and apoB-100-containing lipoproteins in relation to postheparin lipase activities were studied in ten healthy normolipidemic volunteers. Five subjects returned to receive sham injections 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 Ͻ 1.006 g/mL and 1.006 Ͻ d Ͻ 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) activities after 20 min, and significantly reduced apoB-48 concentrations in d Ͻ 1.006 g/mL fractions only. ApoB-100 concentrations showed a trend to decrease in d Ͻ 1.006 g/mL fractions and to increase in 1.006 Ͻ d Ͻ 1.019 g/mL fractions. LPL activity was related to the percentual disappearance of apoB-48 ( r ϭ 0.81, P ϭ 0.004) and apoB-100 ( r ϭ 0.91, P Ͻ 0.001) in d Ͻ 1.006 g/mL fractions. When little LPL was released (LPL activity Ͻ 120 mU/mL) by heparin, apoB-48 was preferentially eliminated over apoB-100. However, when abundant LPL was released (LPL activity Ͼ 140 mU/mL), comparable percentual reductions for apoB-48 and apoB-100 were seen. Pharmacokinetic analysis revealed first-order kinetics for the clearance of apoB-48 in d Ͻ 1.006 g/mL fractions, but zero-order kinetics for apoB-100 clearance.Under conditions of artificially enhanced lipolysis, the first catabolic step of apoB-48-containing lipoproteins and hepatic VLDL showed different pharmacokinetics. ApoB-48-containing 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 lipolysis is modulated by lipoprotein lipase activity.

show abstract

Section: Discussionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotein lipase activity

Beek

Barlingen

Ruijter-Heijstek

et al. 1998

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…The latter is not easy to comprehend, taking into account that the greatest part of LPL is anchored at the surface of the capillary endothelium (19). However, recent studies have convincingly demonstrated that a substantial amount of LPL is associated with circulating lipoproteins in human plasma (20)(21)(22)(23)(24). Thus, one can now consider the possibility that VLDL-bound LPL might facilitate the action of CETP by improving the efficiency of VLDL as CE acceptors.…”

mentioning

confidence: 99%

“…This concept led us to investigate the putative effect of physiological amounts of VLDLbound LPL on the CETP-mediated CET from HDL to VLDL and to determine to what extent it was due to the lipolytic action of LPL. The latter aspect is of particular interest inasmuch as the question as of whether or not the VLDL-bound LPL is lipolytically active has been a matter of controversies (22,23). We therefore measured CET in various experiments where several types of VLDL were used as CE acceptors.…”

mentioning

confidence: 99%

VLDL-bound lipoprotein lipase facilitates the cholesteryl ester transfer protein-mediated transfer of cholesteryl esters from HDL to VLDL

Pruneta

Pulcini²,

Lalanne³

et al. 1999

Journal of Lipid Research

View full text Add to dashboard Cite

In recent years, it has been established that lipoprotein lipase (LPL) is partly associated with circulating lipoproteins. This report describes the effects of physiological amounts of very low density lipoprotein (VLDL)-bound LPL on the cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester transfer (CET) from high density lipoprotein (HDL) to VLDL. Three patients with severe LPL deficiency exhibited a strong decrease in net mass CET that was more than 80% lower than that of common hypertriglyceridemic subjects. Recombination experiments showed that this was due to an abnormal behavior of the VLDL fraction. Replacement of the latter by normal VLDL totally normalized net mass CET. We therefore prepared VLDL containing controlled amounts of bound LPL that we used as CE acceptors in experiments involving unidirectional radioisotopic CET measurements. These were carried out either in the absence or in the presence of inhibitors of LPL lipolytic activity. When LPL-induced lipolysis was totally blocked, the stimulating effect of the enzyme on the CETP-dependent CET was only reduced by about 50%, showing that it did not entirely result from its lipolytic action. These data were dependent upon neither the type of LPL inhibitor (E600 or THL) nor the source of CETP (delipidated plasma or partially purified CETP). Thus, in addition to the well-known stimulating effect of LPL-dependent lipolysis on CET, our work demonstrates that physiological amounts of VLDLbound LPL may facilitate CET through a mechanism partially independent of its lipolytic activity. -Pruneta, V., T. Pulcini, F. Lalanne, C. Marçais, F. Berthezène, G. Ponsin, and P. Moulin. VLDL-bound lipoprotein lipase facilitates the cholesteryl ester transfer protein-mediated transfer of cholesteryl esters from HDL to VLDL.

show abstract

Severe Hypertriglyceridemia With Pancreatitis

2014

View full text Add to dashboard Cite

IMPORTANCE Recurrent pancreatitis is a potentially fatal complication of severe hypertriglyceridemia. Genetic defects and lifestyle risk factors may render this condition unresponsive to current treatments. OBSERVATIONS We report this first case of long-term management of intractable near-fatal recurrent pancreatitis secondary to severe hypertriglyceridemia by a novel use of lomitapide, an inhibitor of microsomal triglyceride transfer protein, recently approved for treatment of familial homozygous hypercholesterolemia. The patient had been hospitalized many times for pancreatitis since age 15 years. Her serum triglyceride level averaged 3900 mg/dL while she received therapy with approved lipid drugs. She is homozygous for a coding mutation (P234L) in lipoprotein lipase, leaving her unable to metabolize triglycerides in chylomicrons and very low density lipoproteins (VLDL). Lomitapide reduces the secretion of chylomicrons and VLDL. Lomitapide, which was started when she was 44 years old after near-fatal pancreatitis, lowered her fasting triglyceride level from greater than 3000 mg/dL to a mean (SD) of 903 (870) mg/dL while she received 30 mg/d and to 524 (265) mg/dL while she received 40 mg/d; eliminated chronic abdominal pain; and prevented pancreatitis. However, fatty liver, present before treatment, progressed to steatohepatitis and fibrosis after 12 to 13 years. CONCLUSIONS AND RELEVANCE Lomitapide prevented pancreatitis in severe intractable hypertriglyceridemia but at a potential long-term cost of hepatotoxicity.

show abstract

Dimeric lipoprotein lipase is bound to triglyceride-rich plasma lipoproteins

Cited by 55 publications

References 28 publications

Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotein lipase activity

Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotein lipase activity

VLDL-bound lipoprotein lipase facilitates the cholesteryl ester transfer protein-mediated transfer of cholesteryl esters from HDL to VLDL

Severe Hypertriglyceridemia With Pancreatitis

Contact Info

Product

Resources

About