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PubMed1999

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

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 VLDL-bound LPL may facilitate CET through a mechanism partially independent of its lipolytic activity.

Animals↗
PubMed2002

Determinants of HDL particle size in patients with the null (P207L) or defective (D9N) mutation in the lipoprotein lipase gene: the Québec LipD Study.

The aim of the present study was to examine the impact of the defective D9N and the null P207L mutations in the lipoprotein lipase (LPL) gene on high density lipoprotein (HDL) particle size in relation to specific environmental factors such as obesity, gender and menopausal status. Analyses were carried out in 118 heterozygous carriers of the D9N mutation and 88 heterozygous for the P207L mutation. HDL particle size was measured on whole plasma by non-denaturing 4-30% polyacrylamide gradient gel electrophoresis. Although carriers of the P207L mutation presented a more deteriorated lipoprotein-lipid profile compared with carriers of the D9N mutation, there was no difference in HDL particle size between the P207L and D9N carriers (81.9+/-4.5 vs. 82.7+/-4.4 A, respectively, P=0.2). Multivariate analyses indicated that waist circumference (P=0.001) and HDL cholesterol levels (P<0.001) were independent predictors of HDL particle size among carriers of the defective D9N mutation. On the other hand, gender (P=0.03), plasma cholesterol (P=0.01) and TG (P=0.04) levels were significant predictors of HDL particle size among carriers of the null P207L mutation in multivariate analyses. These results suggest that the nature of the mutation in the LPL gene modifies the relationship of HDL particle size to other metabolic variables and secondary factors such as abdominal obesity and gender.

Adult↗
PubMed1981

The relationship between the levels of free fatty acids, lipoprotein lipase, carboxylesterase, N-acetyl-beta-D-glucosaminidase, somatic cell count and other mastitis indices in bovine milk.

A large-scale survey of milks from healthy and mastitic bovine quarters was undertaken to establish the influence of mastitic infection on milk lipase activity and free fatty acid (FFA) level. Mastitic milks tended to have higher FFA levels, but lower lipoprotein lipase activities compared with milk from healthy quarters. These effects became significant at relatively severe levels of infection. The elevated FFA was attributable to higher FFA levels on secretion and to greater lipolysis during storage. Levels of carboxylesterase activity increased with severity of mastitis and showed high positive correlation with mastitis indices. Marked increases in carboxylesterase, N-acetyl-beta-D-glucosaminidase and phospholipase occurred following the induction of mastitis by intramammary infusion of Escherichia coli endotoxin, in parallel with changes in somatic cell count and other mastitis indices. Relativity little change in lipoprotein lipase activity was observed.

Acetylglucosaminidase↗
PubMed2001

Lipoprotein lipase during continuous heparin infusion: tissue stores become partially depleted.

Lipoprotein lipase (LPL) and hepatic lipase (HL) are located at vascular surfaces in extrahepatic tissues and in the liver, respectively. Heparin displaces the enzymes into the circulating blood. Animal studies have shown that the liver takes up and degrades LPL. To explore whether heparin leads to a depletion of tissue stores, we followed the lipase activities in plasma during an 8-hour primed infusion of heparin in 10 healthy subjects. After an initial peak, the HL activity decreased slowly after a time curve similar to that for activated partial thromboplastin time. The time curve for LPL was different. After the initial peak, the activity dropped by almost 80%, from 30 to 120 minutes, and then leveled off to a plateau that corresponded to about 15% of the peak level. A second bolus of heparin was given to 4 subjects after 4 hours. The plasma LPL activity increased, but only to about 35% of the original peak level. We conclude that when heparin releases LPL into plasma, the lipase becomes liable to be taken up and degraded by the liver. After less than 1 hour, the stores of LPL have been exhausted, and recruitment of lipase into plasma depends on a slow but stable delivery of newly synthesized molecules.

Aged↗
PubMed1986

Plasma lipoprotein cholesterol and triglycerides and lipoprotein lipase activity in epididymal white adipose tissue of rats fed high sucrose or high corn oil diets.

The present study was undertaken to compare plasma lipoprotein lipid composition, as well as white adipose tissue lipoprotein lipase activity, in rats fed purified diets high in either sucrose or corn oil. The experimental diets (65% of calories as sucrose or corn oil, 15% as the opposite nutrient, and 20% as casein) were given ad libitum for 4 weeks. An additional group was fed a nonpurified diet as a reference diet. Both sucrose and oil diets were spontaneously consumed in isocaloric amounts by the animals. Despite energy intakes that were 35% lower than that of the reference group, the sucrose and oil groups exhibited final body weights that were only 6 and 9% lower, respectively, than that of the reference group, and accumulated more fat in the epididymal depots. Postprandial as well as fasting total cholesterol levels were similar in the sucrose and oil groups, while the high-density lipoprotein to total cholesterol ratio was highest in the animals fed corn oil. In both the fasted and fed states, plasma total triglyceride levels were 73% higher in the sucrose group than in the corn oil group. The largest triglyceride differences due to diet were observed in the chylomicron + very-low-density lipoprotein fraction. The oil-fed rats accumulated large amounts of triglycerides in their livers. Postprandial lipoprotein lipase activity in epididymal adipose tissue was almost twice as high in the sucrose group as in the oil group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1975

Lipoprotein lipase of ovarian follicles in the domestic chicken (Gallus domesticus) (38537).

A lipase, bearing the characteristics of adipose tissue lipoprotein lipase (LPL) has been characterized in avian ovarian granulosa cells. The activity is low in cells from follicles weighing less than 0.5 g; in heavier follicles which have entered the rapid growth phase, significant activity (1 mumole fatty acid/mg protein/hr) could be identified. Granulosa LPL provides follicular tissues with the requisite enzyme system to hydrolyze very low density lipoprotein triglyceride en route to the oocyte.

Adipose Tissue↗
PubMed2002

Molecular modeling of the dimeric structure of human lipoprotein lipase and functional studies of the carboxyl-terminal domain.

Lipoprotein lipase (LPL) plays a key role in lipid metabolism. Molecular modeling of dimeric LPL was carried out using insight ii based upon the crystal structures of human, porcine, and horse pancreatic lipase. The dimeric model reveals a saddle-shaped structure and the key heparin-binding residues in the amino-terminal domain located on the top of this saddle. The models of two dimeric conformations - a closed, inactive form and an open, active form - differ with respect to how surface-loop positions affect substrate access to the catalytic site. In the closed form, the surface loop covers the catalytic site, which becomes inaccessible to solvent. Large conformational changes in the open form, especially in the loop and carboxyl-terminal domain, allow substrate access to the active site. To dissect the structure-function relationships of the LPL carboxyl-terminal domain, several residues predicted by the model structure to be essential for the functions of heparin binding and substrate recognition were mutagenized. Arg405 plays an important role in heparin binding in the active dimer. Lys413/Lys414 or Lys414 regulates heparin affinity in both monomeric and dimeric forms. To evaluate the prediction that LPL forms a homodimer in a 'head-to-tail' orientation, two inactive LPL mutants - a catalytic site mutant (S132T) and a substrate-recognition mutant (W390A/W393A/W394A) - were cotransfected into COS7 cells. Lipase activity could be recovered only when heterodimerization occurred in a head-to-tail orientation. After cotransfection, 50% of the wild-type lipase activity was recovered, indicating that lipase activity is determined by the interaction between the catalytic site on one subunit and the substrate-recognition site on the other.

Amino Acid Substitution↗
PubMed1983

Interaction of synthetic N-5-dimethylaminonaphthalene-1-sulfonyl-apolipoprotein C-II peptides with lipoprotein lipase.

Synthetic fragments of apo-C-II, specifically labeled on their NH2-terminals with the 5-dimethylaminonaphthalene-1-sulfonyl (dansyl or DNS) fluorophore, have been prepared by solid phase peptide synthesis. When a complex is formed between bovine milk lipoprotein lipase and N-dansyl-apo-C-II peptides, resonance energy transfer occurs from the tryptophan residues of the enzyme to the dansyl-labeled peptides upon excitation at 280 nm. In the absence of lipid, the association constant increases 10-fold when the length of the DNS peptide is increased from apo-C-II-DNS(64-78) (0.04 X 10(6) M-1) to apo-C-II-DNS(60-78) (0.3 X 10(6) M-1). In the presence of lipid, the association constants are dependent on peptide chain length, and increase from 0.4 X 10(6) M-1 for apo-C-II-DNS(64-78) to 2.2 X 10(7) M-1 for apo-C-II-DNS(43-78). The interactions are specific for lipoprotein lipase, are disrupted by guanidinium chloride, are not affected by 1.0 M NaCl, and are competitive with the corresponding nondansylated peptide. Apolipoproteins C-III and A-I, at 5 to 1 molar ratios, had no effect on the interaction. These findings demonstrate the importance of the COOH-terminal region in the lipoprotein lipase-apo-C-II interaction and show that activation of the enzyme involves a specific protein-protein interaction.

Amino Acids↗
PubMedDate not supplied

[Influence of rapeseed oil on lipoprotein lipase activity in pigs (author's transl)].

Toxic activities in various animal species have shown for rapeseed oil. In this paper the influence of this oil on lipoprotein lipase activity of heart, liver and lung of pigs has been examined. The animals were fed with rapeseed oil with 40% erucic acid for 7, 15, 20 and 40 days. The control animals received olive oil. The results have shown a slight increase in the lipoprotein lipase activity in the heart of the pig after 20 days with rapeseed oil. In the liver this increase is particularly large in the pigs having been fed for 15 days both with rapeseed oil and olive oil. No differences were observed in the lung in the test and control animals with the only exception of animals fed for 20 days.

Animals↗
PubMed2001

Recycling of apolipoprotein E and lipoprotein lipase through endosomal compartments in vivo.

We have recently described a novel recycling pathway of triglyceride-rich lipoprotein (TRL)-associated apolipoprotein (apo) E in human hepatoma cells. We now demonstrate that not only TRL-derived apoE but also lipoprotein lipase (LPL) is efficiently recycled in vitro and in vivo. Similar recycling kinetics of apoE and LPL in normal and low density lipoprotein receptor-negative human fibroblasts also indicate that the low density lipoprotein receptor-related protein seems to be involved. Intracellular sorting mechanisms are responsible for reduced lysosomal degradation of both ligands after receptor-mediated internalization. Immediately after internalization in rat liver, TRLs are disintegrated, and apoE and LPL are found in endosomal compartments, whereas TRL-derived phospholipids accumulate in the perinuclear region of hepatocytes. Subsequently, substantial amounts of both proteins can be found in purified recycling endosomes, indicating a potential resecretion of these TRL components. Pulse-chase experiments of perfused rat livers with radiolabeled TRLs demonstrated a serum-induced release of internalized apoE and LPL into the perfusate. Analysis of the secreted proteins identified approximately 80% of the recycled TRL-derived proteins in the high density lipoprotein fractions. These results provide the first evidence that recycling of TRL-derived apoE and LPL could play an important role in the modulation of lipoproteins in vivo.

Animals↗
PubMed1981

Relationship between plasma high-density lipoprotein concentrations and lipoprotein lipase and hepatic lipase activities in children with hyperlipidaemia.

1. Significant positive correlations were found between the lipoprotein lipase and hepatic lipase activities of post-heparin plasma samples and plasma high-density-lipoprotein (HDL) cholesterol concentrations in 21 children with hyperlipidaemia and six normal adult males. 2. A significant positive correlation was also observed between the two lipase activities and the ratio of HDL cholesterol to apoprotein AI (apo AI) concentrations. 3. These findings provide further evidence that a significant proportion of HDL and possibly the HDL, subfraction is formed during the clearance of triglyceride-rich lipoproteins.

Adolescent↗
PubMed1997

Combined effects of sphingomyelin and cholesterol on the hydrolysis of emulsion particle triolein by lipoprotein lipase.

Sphingomyelin (SM) is one of the major lipids in lipoproteins. However, its function in lipoprotein metabolism is unknown. In an attempt to understand the role that this lipid plays in modulation of lipoprotein lipase (LPL)-mediated hydrolysis, triolein-based emulsion particles containing 15% (physiological concentration) and 30% of the phospholipid content as SM together with phosphatidyl choline were used as substrate for the enzyme. Using a continuous fluorescence displacement assay to measure triglyceride (triolein) hydrolysis, it is shown that LPL activity was not modified by physiological concentrations of SM. However, under these assay conditions the presence of 30% SM inhibited LPL hydrolysis. SM and cholesterol (a normal component of the lipoprotein surface monolayer) become closely associated in phospholipid monolayers and bilayers. Incorporation of cholesterol into emulsion particles containing only PC increased LPL activity, but this increase was reduced by the additional presence of a physiological concentration (15%) of SM. These model studies suggest that the ratio, cholesterol:SM, in the monolayer may regulate the hydrolytic activity of the LPL. The production of ceramide by sphingomyelinase pre-treatment of emulsion particles containing SM leads to a two- to three-fold increase in LPL activity. This effect was dependent on sphingomyelinase concentration and time of pre-incubation and was not seen with cholesterol containing substrates. The ability of apolipoprotein CII to enhance LPL-catalysed triolein hydrolysis was not affected by the presence of SM; however, the stimulatory effect of this apolipoprotein was attenuated by pre-treatment of emulsion particles with sphingomyelinase. In summary, physiological concentrations of SM can inhibit the hydrolysis of cholesterol-containing emulsion particles; while pre-treatment of SM containing emulsion particles with sphingomyelinase in the absence of cholesterol can increase LPL-mediated triglyceride hydrolysis.

Animals↗
PubMed1986

Heparin-binding apoproteins. Effects on lipoprotein lipase and hepatic uptake of remnants.

Apoprotein-free heparin-binding and non-binding chylomicrons were used as substrates to test the effects on lipoprotein lipase activity of (a) chylomicron protein I; (b) the mixture of proteins I, II and apoprotein E and (c) human beta 2-glycoprotein I. No activation of the enzyme was observed with any of those apoproteins. When rats were injected simultaneously with [3H]cholesterol-labelled heparin-binding chylomicrons (containing proteins I and II) and [14C]cholesterol-labelled non-binding chylomicrons, no differences were detected between the rates of removal from circulation of those two types of particles. Clearance of chylomicrons from circulation was accompanied by the incorporation of 3H and 14C labels into the livers at similar rates. It is concluded that proteins I, II and apoprotein E have no effect on the degradation of chylomicrons by lipoprotein lipase and that the hepatic recognition of remnants does not appear to be affected by proteins I and II.

Animals↗
PubMed2000

Circulating lipoprotein profiles are modulated differently by lipoprotein lipase in obese humans.

BACKGROUND: Several genetic analyses have suggested that lipoprotein lipase (LpL) genotypes causing decreased LpL activity correlate with increased triglyceride concentrations and risk for coronary artery disease. In contrast, in some other studies LpL activity was positively correlated with plasma low-density lipoprotein (LDL) cholesterol concentrations. OBJECTIVE: To assess whether these different associations represent physiologic differences in lipoprotein metabolism. METHODS: We correlated postheparin lipase activities, postprandial lipemia, and fasting lipoprotein concentrations in obese (BMI > or = 30 kg/m2, n = 26) and non-obese (BMI < or = 30 kg/m2, n = 57) individuals. LpL was measured using specific inhibitory antibodies. RESULTS: Surprisingly, LpL activity was significantly correlated with triglyceride area under the curve after a fat load in the non-obese, but not the entire group. Moreover, in non-obese individuals, LpL activity correlated directly (r = 0.40) and hepatic lipase activity correlated inversely (r = -0.32) with high-density lipoprotein (HDL) cholesterol concentrations. These relationships were not found in the obese group, in whom LpL correlated with LDL cholesterol concentrations (r = 0.54). CONCLUSIONS: We conclude that postheparin LpL activity relates to different lipoproteins in obese and non-obese individuals. In obesity, greater LpL activity may enhance conversion of very-low-density lipoprotein cholesterol to LDL cholesterol, whereas in non-obese individuals the correlation is with HDL cholesterol. Whether this is due to differences in the source of LpL (muscle or fat), or to other associated alterations in lipoprotein metabolism is unknown. These results may explain the non-uniformity of correlations between LpL and atherogenic lipoproteins in different populations.

Adult↗
PubMed1989

Lipoprotein lipase with a defect in lipid interface recognition in a case with type I hyperlipidaemia.

Defective lipoprotein lipase (LpL) was found in the postheparin plasma (PHP) of a patient with severe hypertriglyceridaemia. The patient was a 14-year-old girl with a maximum plasma triglyceride (TG) level of 3600 mg d-1 who had been suffering from recurrent pancreatitis. The patient's LpL purified from the PHP by heparin-Sepharose and phenyl-Sepharose chromatographies hydrolysed tributryrin, but not triolein emulsified with Triton X-100 and phosphatidylcholine (PC), or in chylomicrons, whereas normal LpL hydrolysed these substrates. Moreover, unlike normal LpL, LpL from the patient did not associate with VLDL, as shown by Sepharose 4B column chromatography. The patient's LpL hydrolysed triolein emulsified with lysophospholipid at a normal rate in the presence of apolipoprotein CII. These findings suggest that this patient has LpL with a normal catalytic site for tributyrin but with a defect in lipid interface recognition resulting in loss of ability to recognize VLDL or chylomicrons, but not of triolein emulsified with lysophospholipid.

Adolescent↗
PubMed1984

Glycosaminoglycan: cell interactions; their role in lipoprotein lipase secretion from isolated cardiac muscle cells.

When cardiac muscle cells from mature rats were incubated in vitro in the presence of heparin (8.7 nmole ml-1) lipoprotein lipase activity appeared in the incubation medium. The intracellular activity of the enzyme remained unchanged. Other glycosaminoglycans (heparan sulphate, dermatan sulphate, keratan sulphate and chrondroitin 6-sulphate) at the same or higher concentrations were totally ineffective in producing any enzyme redistribution between cells and medium. The release seen in the presence of heparin was blocked by the presence of cycloheximide. Cycloheximide by contrast had no effect on the release observed in the presence of dexamethasone, The action of endogenous glycosaminoglycans are unlikely therefore to have a significant role to play in the movement of lipoprotein lipase in heart tissue in vivo.

Animals↗
PubMed2003

Overexpression of lipoprotein lipase in transgenic Watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity.

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of the triglyceride-rich lipoproteins and plays a critical role in lipoprotein and free fatty acid metabolism. Genetic manipulation of LPL may be beneficial in the treatment of hypertriglyceridemias, but it is unknown whether increased LPL activity may be effective in lowering plasma cholesterol and improving insulin resistance in familial hypercholesterolemic patients. To test the hypothesis that stimulation of LPL expression may be used as an adjunctive therapy for treatment of homozygous familial hypercholesterolemia, we have generated transgenic (Tg) Watanabe heritable hyperlipidemic (WHHL) rabbits that overexpress the human LPL transgene and compared their plasma lipid levels, glucose metabolism, and body fat accumulation with those of non-Tg WHHL rabbits. Overexpression of LPL dramatically ameliorated hypertriglyceridemia in Tg WHHL rabbits. Furthermore, increased LPL activity in male Tg WHHL rabbits also corrected hypercholesterolemia (544 +/- 52 in non-Tg versus 227 +/- 29 mg/dl in Tg, p < 0.01) and reduced body fat accumulation by 61% (323 +/- 27 in non-Tg versus 125 +/- 21ginTg, p < 0.01), suggesting that LPL plays an important role in mediating plasma cholesterol homeostasis and adipose accumulation. In addition, overexpression of LPL significantly suppressed high fat diet-induced obesity and insulin resistance in Tg WHHL rabbits. These results imply that systemic elevation of LPL expression may be potentially useful for the treatment of hyperlipidemias, obesity, and insulin resistance.

Adipose Tissue↗