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PubMed1992

Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden.

Association studies were carried out on a sample of 87 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms (PvuII, HindIII and Serine447-Stop) at the lipoprotein lipase (LPL) gene locus on among-individual differences in plasma lipid traits and progression of atherosclerosis. Significant linkage disequilibrium was detected between any two of these polymorphisms, with the Stop447 allele being only found on the same chromosome as the rare alleles (no cutting sites) of the PvuII and HindIII polymorphisms. In the healthy individuals, weak associations were found between genotypes of the HindIII polymorphism and triglycerides and the PvuII polymorphism and high density lipoprotein cholesterol explaining 7.4% and 5.6% of sample variance (P = 0.03 and 0.09), respectively. No associations were found between these traits and genotypes of the Serine447-Stop substitution, and thus it is unlikely to be the cause of the associations seen with the PvuII and HindIII polymorphisms even though it truncates the enzyme amino acid sequence. The presence of the rare allele, H-, of the HindIII polymorphism was associated with a smaller variance in triglycerides and both cholesterol and triglycerides in the very low density lipoprotein fraction, and with larger interdependent variation between these lipid traits, and also between LPL activity and these lipid traits. This implies that the H- allele, rather than the Stop447 allele, has the major impact on interdependence between traits which are directly or indirectly influenced by LPL activity. In the healthy individuals who were carriers of the apolipoprotein E2 allele, the inter-dependence between LPL activity and lipid traits was significantly smaller, and that between high density lipoprotein cholesterol and both cholesterol and triglycerides in the very low density lipoprotein fraction was much larger compared with non-carriers (P < 0.05). No significant associations were found between lipid traits or lipase activity and genotypes of the Serine447-Stop substitution. However, in the patients, global severity of coronary atherosclerosis at the first angiography was significantly associated with haplotype combinations of the HindIII and the Serine447-Stop polymorphisms, with the H-Stop haplotype being associated with the highest median score (P = 0.02). The data suggest that variation at the LPL gene locus is associated with a pleiotropic effect, that is not directly mediated by changes in lipids, on severity of coronary atherosclerosis.

Adult↗

PubMed2003

Lipoprotein lipase and atherosclerosis.

Lipoprotein lipase (LPL) is a rate-limiting enzyme that hydrolyzes circulating triglyceride-rich lipoprotein such as very low density lipoproteins and chylomicrons. A decrease in LPL activity is associated with an increase in plasma triglycerides (TG) and decrease in high density lipoprotein (HDL) cholesterol. The increase in plasma TG and decrease in HDL cholesterol are risk factors of coronary heart disease. However, whether LPL directly or indirectly promotes or protects against atherosclerosis remains unclear as two contrary views exist in this regard: one where LPL promotes atherosclerosis and one where LPL protects against atherosclerosis. Many studies have been carried out to investigate whether LPL is an anti-atherogenic or atherogenic enzyme by using animals with genetic defects or with an excess of this enzyme. From these studies, much evidence has been acquired showing that LPL is an anti-atherogenic enzyme. We hypothesized that elevating LPL activity would cause a reduction of plasma TG and increase in HDL cholesterol, resulting in protection against the development of atherosclerosis. To test this hypothesis, we studied the effects of the LPL activator NO-1886 in animals. NO-1886 has been shown to increase LPL mRNA in adipose tissue and myocardium, and increase LPL activity in adipose tissue, myocardium and skeletal muscle, resulting in an elevation of postheparin plasma LPL activity and LPL mass in rats. NO-1886 has also been shown to decrease plasma TG levels accompanied by a concomitant rise in HDL cholesterol. Long-term administration of NO-1886 to rats and rabbits with experimental atherosclerosis inhibited the development of atherosclerotic lesions in coronary arteries and aortae. The results of multiple regression analysis in these studies suggest that the increase in plasma HDL cholesterol and the decrease in TG protect against atherosclerosis. We have determined in our studies that the atherogenic lipid profile is changed to an anti-atherogenic lipid profile by increasing LPL activity, resulting in protection against the development of atherosclerosis. Therefore, we believe that high activity of LPL is anti-atherogenic, whereas a low activity of LPL is atherogenic.

Animals↗

PubMed1987

Lipoprotein lipase in diabetes.

Lipoprotein lipase has a central role in the metabolism of both triglyceride-rich particles and high density lipoproteins, and it is one determinant of both serum triglyceride and HDL concentrations. In man the enzyme activity in both adipose tissue and skeletal muscle is insulin dependent, and therefore it varies in diabetes according to ambient insulin level and insulin sensitivity. In insulin deficiency (untreated Type 1 diabetes) the enzyme activity in both adipose tissue and muscle tissue is low but increases upon insulin therapy. In chronically insulin-treated patients with good control, the enzyme activity in postheparin plasma is increased. In untreated Type 2 diabetic patients, the average enzyme activity in adipose tissue and postheparin plasma is normal or subnormal. Therapy with oral agents or insulin, resulting in good glycemic control, is followed by an increase of LPL activity in both adipose tissue and postheparin plasma. In both Types 1 and 2 diabetes, changes of LPL activity are associated with relevant alterations in lipoprotein pattern. In insulin deficiency with low LPL, serum total and VLDL triglyceride levels are elevated, and HDL concentration is reduced. In chronically insulin-treated patients with high LPL activity, VLDL triglyceride concentrations are normal or subnormal, and HDL level is increased. In untreated Type 2 diabetic patients subnormal LPL activity may contribute to the elevation of serum triglycerides and to the reduction of HDL level.

Diabetes Mellitus↗

PubMed1995

Endothelin-1, but not endothelin-3, suppresses lipoprotein lipase gene expression in brown adipocytes differentiated in culture.

The effect of endothelins on lipoprotein lipase activity and lipoprotein lipase mRNA levels was studied in brown adipocytes differentiated in culture. Lipoprotein lipase activity was determined in two fractions; lipoprotein lipase released by heparin (10 IU/ml, 1 h) into the medium (heparin-releasable fraction) and lipoprotein lipase activity remaining in cells (extractable fraction). Time-course studies showed that endothelin 1 (10(-7) M) progressively decreased both lipoprotein lipase fractions (heparin-releasable, extractable), until nadir at 24 h. Endothelin-1 reduced both lipoprotein lipase activities (heparin-releasable, extractable) in a concentration-dependent manner, whereas endothelin-3 did not produce any significant changes in either of them. Northern blot analysis revealed that endothelin-1 (10(-7)-10(-11) M) caused a concentration-dependent decrease in lipoprotein lipase mRNA obtained from cells on day 9. Furthermore, pretreatment of brown adipocytes with endothelin ETA receptor antagonist FR139317 antagonized the endothelin-1-induced reduction of lipoprotein lipase activity and lipoprotein lipase mRNA. These results suggest that endothelin-1 decreases lipoprotein lipase activity by inhibiting the lipoprotein lipase gene expression in brown adipocytes differentiated in culture, possibly through endothelin ETA receptors on cell membranes. Because of marked reduction of lipoprotein lipase activity and its mRNA as a marker of adipogenic differentiation, endothelin-1 may have an inhibitory role in the differentiation of brown adipocytes.

Adipocytes↗

PubMed1999

Lipoprotein hydrolysis and fat accumulation in chicken adipose tissues are reduced by chronic administration of lipoprotein lipase monoclonal antibodies.

The lipoprotein lipase (LPL) catalyzed hydrolysis of plasma lipoproteins is a rate-limiting step in the lipid transport into peripheral tissues. The aim of the present study was to isolate monoclonal antibodies against chicken adipose LPL and to investigate whether chronic infusion of the LPL monoclonal antibodies inhibits adipose LPL activity and consequently reduces fat accumulation in broiler chickens. The LPL catalyzed very low density lipoprotein (VLDL) hydrolysis was completely inhibited by the addition of 100 microg/mL of monoclonal antibodies (CLP10, CLP14, CLP16) in the in vitro incubation with plasma VLDL and LPL. A single injection of CLP10 and CLP16 into chickens fed or starved for 24 h elevated plasma triacylglycerol concentrations for 24 h, whereas that of CLP14 was ineffective. Intravenous injection every other day and continuous infusion by osmotic minipump with CLP16 maintained higher plasma triacylglycerol concentration for 5 d than that of the control group and extensively reduced LPL activity in adipose tissues and abdominal fat pad weight. Lipoprotein lipase mRNA and protein levels in adipose tissue were not modified by chronic administration of anti-LPL antibody. The results indicate that chronic administration of anti-LPL antibodies is effective in retarding fatness in broiler chickens, and the antibodies are a proper subject for studies of lipoprotein metabolism.

Adipose Tissue↗

PubMedDate not supplied

Rat heart lipoprotein lipase.

Rat heart lipoprotein lipase was highly purified by affinity chromatography using heparin-Sepharose 4B. When extracts of acetone powder were applied to columns, lipase activity was firmly bound to the gel matrix and was later eluted with 1.5 M NaCl. At this stage the eluted enzyme was purified 1500-fold. Disc gel electrophoresis yielded a single protein band corresponding with the enzyme activity. The apparent molecular weight was 60,000. The purified enzyme was highly unstable; however, its activity could be partially stabilized by glycerol or ethylene glycol. In studying the purified enzyme we observed: (i) a cofactor in serum was required for full enzymatic activity; ApoLp-Glu could be substituted for this cofactor; (ii) ApoLp-Ser was inhibitory to lipase activity; (iii) NaCl and protamine sulfate also markedly inhibited the lipase activity; (iv) heparin stimulated the enzymatic activity.

Animals↗

PubMed1992

Trp64----nonsense mutation in the lipoprotein lipase gene.

A lipoprotein lipase (LpL) gene defect has been identified, a G----A transition at nucleotide position 446 of exon 3, resulting in a premature termination codon (Trp----stop) at amino acid residue 64. This defect was identified in a Type I hyperlipoproteinemic subject with an amino acid residue 194 defect in the other allele. Plasma lipoprotein values as well as LpL mass and activity in postheparin plasma were determined in the subjects with the residue 64 defect and in other LpL-deficient heterozygotes. LpL mass levels in both the Type I and the other subject with a 64 LpL defect were markedly reduced. This may be explained by rapid degradation of LpL protein or decreased secretion from the 64 defective allele. Alternatively, the marked reduction or absence of mass associated with the 64 defect may be due to synthesis of a severely truncated protein which escapes immunologic detection.

Amino Acid Sequence↗

PubMed1988

Substrate specificity studies of partially purified rabbit heart lipoprotein lipase.

Rabbit heart lipoprotein lipase (LPL) was partially purified by affinity chromatography. The purified enzyme was characterized by salt inhibition, the requirement of a serum co-factor and an alkaline pH optimum. Because of the known hypocholesterolemic effect of dietary polyunsaturated fat in this and other species, the fatty acyl substrate specificity of this lipase was also studied. Both saturated and unsaturated fatty acid chain hydrolysis were investigated using synacyl and mixed acyl triglyceride emulsion substrates. It was found that trans, monounsaturated and some saturated fatty acids were more favorably hydrolyzed than polyunsaturated cis fatty acids. Positional specificity was also observed. The physiological significance of these findings may relate to a) the production of lipoprotein remnant particles relatively enriched in polyunsaturated fatty acids, especially when consumed in the diet and b) the subsequent preferential delivery of these fatty acids to the liver.

Animals↗

PubMed1997

Lipoprotein lipase, LDL receptors and apo-lipoproteins in human fetal membranes at term.

Ultrastructurally, all cells of human fetal membranes strongly exhibit a large amount of lipid deposits throughout pregnancy. Their origin and function is still unknown. The aim of this study was to investigate the localization of key components of lipid metabolism in this tissue. Using immunohistochemical techniques, the distribution of lipoprotein lipase (LPL), low density lipoprotein receptors (LDL receptors), and apo-lipoprotein B and E was investigated in 20 human fetal membranes at term. In addition, electron microscopy was used to study the intracellular localization of lipoprotein-sized particles. Amnionic epithelium and trophoblast cells reacted strongly for LPL. LDL receptors and apo-lipoproteins were present in amnionic epithelium and fibroblasts of the amnion. In none of the investigated cells were lipoprotein-sized particles identified. Similar results were obtained in all 20 cases. The findings indicate that lipoprotein from the amniotic fluid or from the maternal circulation may serve as substrate for lipids in human fetal membranes.

Amnion↗

PubMed1985

Combined lipase deficiency (cld/cld) in mice. Demonstration that an inactive form of lipoprotein lipase is synthesized.

Combined lipase deficiency, cld, is a recessive mutation within the T/t complex of mouse chromosome 17. Mice homozygous for this defect display severe functional deficiencies of lipoprotein lipase and the related hepatic lipase. They develop massive hyperchylomicronemia and die within 3 days when allowed to suckle. Heart, diaphragm muscle, and brown adipose tissue of 1-day-old cld/cld and unaffected mice incorporated in vivo [35S]methionine into a protein that could be immunoprecipitated by antilipoprotein lipase serum. The immunoprecipitated protein in all tissues had the same Mr as bovine lipoprotein lipase as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proportion of radioactivity in the lipoprotein lipase band to that in total protein was 0.02% in tissues of cld/cld mice and 0.01% in tissues of unaffected mice. There was 2-6 times more lipoprotein lipase-like protein (determined by immunoassay) in tissues of defective mice than in those of unaffected mice. These findings indicate that the cld mutation did not cause deletion of the structural gene for lipoprotein lipase. Lipoprotein lipase activity in heart, diaphragm muscle, brown adipose tissue, and lung of cld/cld mice was less than 5% of that in tissues of unaffected mice. This low activity could be inhibited more than 85% by antilipoprotein lipase serum, but not by nonimmune serum. It is concluded that tissues in cld/cld mice synthesize a lipoprotein lipase-like protein which has subnormal catalytic activity.

Adipose Tissue, Brown↗

PubMed1986

Regulation of the secretion of lipoprotein lipase by mouse macrophages.

The regulation of the secretion of lipoprotein lipase was studied in primary cultures of mouse peritoneal macrophages and in the murine macrophage cell line J774. As previously reported, both cell types secrete a lipase with the characteristics of lipoprotein lipase. Incubation of macrophages with insulin, insulin-like growth factor, and L-thyroxine had no effect on lipoprotein lipase secretion. Incubation with dexamethasone and with several agents which increase intracellular cyclic AMP led to a decrease in lipoprotein lipase secretion by mouse peritoneal macrophages. These results suggest that the hormonal regulation of lipoprotein lipase in macrophages is different from that in adipose tissue and heart muscle. Incubation of the macrophages with heparin caused a marked increase in the secretion of lipoprotein lipase. Short incubations with heparin (5 min) caused a release of the enzyme into the media, while longer incubations caused a 2-8-fold increase in net lipoprotein lipase secretion which was maximal after 2-16 h depending on cell type, and persisted for 24 h. The effect of heparin was dose-dependent and specific (it was not duplicated by other glycosaminoglycans). The mechanism of heparin-induced increase in lipoprotein lipase secretion was explored. The increase was not caused by the release of a presynthesized intracellular pool of lipoprotein lipase or by the stabilization of lipoprotein lipase by heparin after secretion. The heparin-induced increase in lipoprotein lipase secretion was dependent on protein synthesis. The secretion of lipoprotein lipase by macrophages in response to low levels of heparin may be a significant factor in the formation of atherosclerotic lesions.

1-Methyl-3-isobutylxanthine↗

PubMedDate not supplied

[Gestational or essential hypertension in pregnant women limits the capacity to stock triglycerides by the placenta despite raised lipoprotein-lipase activity].

Placenta lipoprotein lipase (LPL) activity as well as serum VLDL and placenta lipids composition were determined in pregnant hypertensive women at term. 46 patients aged from 29 +/- 2 years with gravidic hypertension (HTA-G) and 38 patients with essential hypertension (HTA-E) aged 30 +/- 1 years were compared with 20 normotensive women aged 27 +/- 1 years. Serum triacylglycerols (TG) concentrations were 1.3-fold higher in the both hypertensive patients compared with controls. However, serum phospholipids (PL) and total cholesterol (TC) values were similar in the three groups. VLDL mass and their apolipoproteins, unesterified cholesterol (UC) and cholesteryl esters (CE) contents were significantly increased in hypertensive women compared with controls. In HTA-G and HTA-E patients, respectively. TG-VLDL concentrations were increased by +43% and +36% compared with those of controls (P < 0.01). In placenta, the values were lower 2.2- and 1.9-fold for TG, 2.8 and 2.5-fold for PL and two- and threefold for TC, in HTA-G and HTA-E patients than in controls. Placenta LPL activity was 2.7-fold higher in HTA-G and HTA-E patients compared with that of controls. In conclusion, although placenta LPL activity is higher it is not permit a decrease of serum TG-VLDL on the one hand, and an increase of placenta ability in TG storage on the other hand.

Adult↗

PubMed2006

Fasting decreases free fatty acid turnover in mice overexpressing skeletal muscle lipoprotein lipase.

Skeletal muscle lipoprotein lipase (LPL) overexpression in mice results in whole-body insulin resistance and increased intramuscular triglyceride stores, but decreased plasma triglyceride concentration and unchanged plasma free fatty acid (FFA) concentration. The effects of skeletal muscle LPL overexpression and fasting duration on FFA kinetics are unknown. Transgenic mice with muscle-specific LPL overexpression (MCKhLPL) and control mice (Con) were studied at rest during a 50-minute constant infusion of [9,10- 3H]palmitate to determine FFA kinetics after both 4 and 16 hours of fasting. FFA concentration was not different between groups after the 4-hour (Con, 0.80 +/- 0.06 mmol/L; MCKhLPL, 0.83 +/- 0.07 mmol/L) and 16-hour (Con, 0.83 +/- 0.04 mmol/L; MCKhLPL, 0.80 +/- 0.07 mmol/L) fast. FFA turnover (Ra) was not significantly different between MCKhLPL and Con groups after the 4-hour fast (Con Ra = 2.52 +/- 0.36 micromol/min; MCKhLPL Ra = 2.37 +/- 0.27 micromol/min). However, FFA turnover was significantly decreased after the 16-hour fast in MCKhLPL mice vs controls (Con Ra = 2.89 +/- 0.52 micromol/min; MCKhLPL Ra = 1.64 +/- 0.17 micromol/min; P < .05). The significantly lower FFA Ra in MCKhLPL vs control mice was due to a decrease in MCKhLPL FFA turnover from the 4- to 16-hour fast, whereas FFA turnover was unchanged in controls. The changes in FFA appearance after the 16-hour fast in MCKhLPL mice are most likely explained by increased reliance by skeletal muscle on plasma triglyceride as a fuel. These data suggest increased skeletal muscle LPL expression decreases dependence on plasma FFA during prolonged fasting in mice.

Animals↗

PubMed1986

Production and use of an inhibitory monoclonal antibody to human lipoprotein lipase.

Studies were performed to produce a monoclonal antibody to human lipoprotein lipase, verify the specificity of the antibody for lipoprotein lipase, and use this antibody for detection of lipoprotein lipase protein in human post-heparin plasma. Partially purified lipoprotein lipase from human milk was used as an antigen for the production of anti-lipoprotein lipase antibodies in mice. The spleen was removed from the animal having the highest titer of inhibitory antibodies to lipoprotein lipase and the cells were fused mouse myeloma cells. Culture media from the resulting hybridomas were screened for their ability to inhibit lipoprotein lipase catalytic activity. This screening procedure thus identified only those hybridomas which produced antibodies directed against lipoprotein lipase. One monoclonal antibody, from one clone, was selected for detailed study. The specificity of this antibody for lipoprotein lipase protein was established by three methods. First, post-heparin plasma lipoprotein lipase activity and immunoreactivity detected by an enzyme-linked immunosorbent assay (ELISA) co-eluted during heparin-agarose and phenyl-Sepharose chromatography. Second, the antibody detected a protein which was released into the circulation after intravenous injection of heparin into humans. Third, both immunoreactive lipoprotein lipase protein and lipoprotein lipase enzymatic activity were lost by heat-inactivation of lipoprotein lipase. The use of active enzyme as an antigen and the procedure used to screen the monoclonal antibody-producing hybridomas allowed the production of an inhibitory anti-human lipoprotein lipase monoclonal antibody. This antibody is useful for detection of lipoprotein lipase protein in plasma and should allow for immunohistochemical staining of active lipoprotein lipase enzyme in tissues. Moreover, the methods described for screening hybridomas may be modified and used to produce specific antibodies against other partially purified enzymes.

Adult↗

PubMed1983

Metabolic abnormalities in multiple symmetric lipomatosis: elevated lipoprotein lipase activity in adipose tissue with hyperalphalipoproteinemia.

Lipoprotein lipase activity in lipomatous tissue, post-heparin lipoprotein lipase activity in plasma, and the composition and concentration of serum lipoproteins were studied in 15 patients with Multiple Symmetric Lipomatosis (MSL). Extremely elevated lipoprotein lipase activity in adipose tissue was found in MSL patients. Total and hepatic post-heparin plasma lipolytic activity was normal, while a moderate but statistically significant increase of extrahepatic lipolytic activity was present. An abnormal composition of serum lipoproteins, characterized by a significant increase in high density lipoproteins, namely HDL2 subfraction, and apoprotein A-I, was demonstrated. A concomitant decrease in and abnormal composition of low density lipoproteins were found. This lipoprotein pattern is consistent with a newly recognized type of hyperalphalipoproteinemia. Significant correlations were found between serum HDL2 cholesterol values and lipoprotein lipase activity in adipose tissue (as well as between serum VLDL-triglyceride and HDL2 cholesterol values). These observations confirm the role of adipose tissue lipoprotein lipase in triglyceride-rich lipoprotein catabolism. The elevated levels of lipoprotein lipase activity in adipose tissue, in addition to a previously demonstrated decrease in adrenergic-stimulated lipid mobilization, could account for both the abnormal fat accumulation in lipomatous fat cell and for hyperalphalipoproteinemia in MSL patients. The occurrence of MSL in two brothers suggests an inherited enzymatic defect, indicating MSL as a "triglyceride storage disease in adipose tissue".

Adipose Tissue↗

PubMed1998

The Ser447-Ter mutation of the lipoprotein lipase gene relates to variability of serum lipid and lipoprotein levels in monozygotic twins.

Studies on monozygotic twins support a role for genetic determinants of plasma lipid, lipoprotein, and apolipoprotein levels. Gene variants of the enzyme lipoprotein lipase have been shown to associate with dyslipidemia and coronary artery disease. We assessed the gene-environment interaction by investigating the relationship between the lipoprotein lipase gene and plasma lipid, lipoprotein, and apolipoprotein variability and levels among 54 male monozygotic twin pairs (aged 18-28 years). The Ser447-Ter mutation (C-->G transversion) was associated with significantly smaller within-pair differences in plasma high density lipoprotein-cholesterol (CG [n = 10] vs. CC [n = 44], 3.7+/-5.3 mg/dl vs. 6.4+/-5.2 mg/dl, P < 0.03) and total cholesterol (CG [n = 10] vs. CC [n = 44], 7.9+/-9.4 mg/dl vs. 15.8+/-12.7 mg/dl, P < 0.05), indicating attenuated variability in response to environmental stimuli. This observation of a restrictive variability gene effect further supports a role for the lipoprotein lipase gene in the genetic regulation of lipids and lipoproteins and suggests that the Ser447-Ter mutation exerts multiple effects. This study also raises the possibility of a genetically determined responsiveness to dyslipidemia therapies.

Adolescent↗

PubMed1985

Importance of the different steps of glycosylation for the activity and secretion of lipoprotein lipase in rat preadipocytes studied with monensin and tunicamycin.

Lipoprotein lipase synthesized by cultured rat preadipocytes is present in three compartments: an intracellular, a surface-related 3-min heparin-releasable, and that secreted into the culture medium. 30 min after addition of 6 microM monensin, the lipoprotein lipase activity in the heparin-releasable compartment starts to decrease; by 4 h of monensin treatment the lipoprotein lipase activity in the heparin-releasable pool and in the culture medium is about 10% of that found in control dishes. The intracellular activity, which had been identified as lipoprotein lipase by an antiserum to lipoprotein lipase, increases slowly and doubles by 24 h. However, since the cellular compartment accounts for 10-25% of total activity, this increase does not account for the missing enzyme activity. To determine whether this enzyme molecule is synthesized but is not active, incorporation of labeled leucine, mannose and galactose into immunoadsorbable lipoprotein lipase was studied in control, monensin- or tunicamycin-treated cells. Addition of tunicamycin (5 micrograms/ml) for 24 h caused a 30-50% reduction in immunoadsorbable lipoprotein lipase, but the enzyme activity was reduced by 90%. On the other hand, 4 h monensin treatment reduced both incorporation of [3H]leucine into immunoadsorbable lipoprotein lipase and heparin-releasable and medium lipoprotein lipase activity by 57 to 77%. The immunoadsorbable lipoprotein lipase in the intracellular compartment has a [14C]mannose to [3H]galactose ratio of 0.15 and this ratio increased 6-fold in monensin-treated cells. The intracellular lipoprotein lipase in monensin-treated cells had the same affinity for both the native and synthetic substrate as the lipoprotein lipase in control cells, yet its spontaneous secretion into the culture medium and its release by 3 min heparin treatment was markedly decreased. The present results indicate that: the presence of asparagine-linked oligosaccharide (formation of which is inhibited by tunicamycin) is mandatory for the expression of lipoprotein lipase activity; lipoprotein lipase is active also in a high mannose form; and terminal glycosylation and oligosaccharide processing, which is inhibited by monensin, may be important for the appearance of heparin-releasable lipoprotein lipase and secretion of lipoprotein lipase into the medium.

Adipose Tissue↗

PubMed1996

Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis.

Although it has been known for over 50 years that lipoprotein lipase (LPL) hydrolyzes triglyceride in chylomicrons, during the past half decade there has been a reinterest in the physiologic and pathophysiologic actions of this enzyme. In part, this has coincided with clinical studies implicating increased postprandial lipemia as a risk factor for atherosclerosis development. In addition, the recent creation of genetically altered mice with hypertriglyceridemia has focused the interest of geneticists and physiologists on the pathophysiology of triglyceride metabolism. As reviewed in this article, it is apparent that the lipolysis reaction is only partially understood. Several factors other than LPL are critical modulators of this process, in part, because the reaction requires the lipoproteins to interact with the arterial or capillary wall. Among the factors that affect this are the apolipoprotein composition of the particles, the size of the lipoproteins, and how LPL is displayed along the endothelial luminal surface. Zilversmit's observation that LPL activity is found in greater amounts in atherosclerotic than normal arteries has led to a large number of experiments linking LPL with atherogenesis. In medium and large arteries LPL is found on the luminal endothelial surface and in macrophage-rich areas within the plaque. LPL actions in both of these locations probably have major effects on the biology of the blood vessel. Possible atherogenic actions for this LPL based on in vitro experiments are reviewed.

Animals↗