Stereospecificity of lipases. Enzymic hydrolysis of enantiomeric alkyl diacylglycerols by lipoprotein lipase, lingual lipase and pancreatic lipase.
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Adipose Tissue↗
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Results for “LIPOPROTEIN LIPASE”
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[Lipoprotein lipase and lecithin-cholesterol-acyltransferase activity when lipoprotein metabolism is experimentally altered].
Lipoproteinlipase (LPL) and lecithin-cholesterol-acyltransferase (LCAT) activity was studied in rats in conditions of drug-induced (Clofibrat, cholestyramine, aethinyloestradiol) changes in lipid metabolism. Comparison of enzyme activity in three models of changed lipoprotein metabolism has revealed that the only model used (with aethinyloestradiol) leads to the uniform changes (decrease) in LPA and LCAT. Clofibrat increased LPL activity, with LCAT activity remaining unaffected. Cholestyramine caused no changes in LPL activity, but increased LCAT activity. The results obtained suggest that synergism in LPL and LCAT activity changes is registered only when lipolysis of triglyceride-saturated lipoproteins leads to the increase in the number of particles, similar in their structure and properties to high density lipoproteins, the basic LCAT structure.
Animals↗
[Lipoproteins lipase and its effect on very low density lipoproteins].
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Animals↗
Lipoprotein lipase affects the survival and differentiation of neural cells exposed to very low density lipoprotein.
Lipoprotein lipase (LPL) is a key enzyme involved in the metabolism of lipoproteins, providing tissues like adipose tissue or skeletal muscle with fatty acids. LPL is also expressed in the brain, fulfilling yet unknown functions. Using a neuroblastoma cell line transfected with a NEO- or a LPL-expression vector, we have developed a model to study the function of LPL in neurons exposed to native or copper-oxidized lipoproteins. The addition to the culture media of VLDL with 10 microm copper sulfate led to a significant reduction in the viability of NEO transfectants whereas LPL-transfectants were protected from this injury. In the presence of VLDL and CuSO(4), LPL transfectants were even able to display significant neurite extension. This neuritogenic effect was also observed in LPL transfectants exposed to native lipoproteins. However, addition of VLDL particles oxidized with CuSO(4) prior to their addition to the culture media resulted in neurotoxic effects on LPL transfectants. These findings suggest that the presence of LPL in cultured neuronal cells modulates the physiological response of neurons following exposure to native or oxidized lipoproteins. LPL could thus play a key role in the differentiation of Neuro-2A cells and in the pathophysiological effects of oxidative stress in several neurodegenerative disorders.
Cell Differentiation↗
Reduced plasma lipoprotein lipase activity in patients with malignancy-associated weight loss.
Post-heparin plasma lipoprotein lipase activity was measured in 28 cancer patients with varying degrees of weight loss, and in 16 normal volunteers. Total lipoprotein lipase activity was decreased by 35.4% (P less than 0.001) in the cancer group. The component lipase activities, hepatic (HLPL), and peripheral (PLPL), were decreased by 40% (P less than 0.001) and 38% (P less than 0.005) respectively. In addition, the level of total peripheral lipoprotein lipase correlated well with the percent body weight lost by these patients (r = 0.6, P less than 0.01). Regardless of extent of disease, patients with lung cancer showed the lowest enzyme activity (mean 191 mU/ml +/- 30 SEM, P less than 0.001) and the greatest percent of weight loss (mean 16%), while patients with breast cancer had nearly normal lipase activity (mean 315 mU/ml +/- 50 SEM, normal 340 mU/ml +/- 22 SEM, P less than 0.10) and minimal weight loss (mean 8.4%). Fasting serum triglycerides were significantly elevated in the patient group (mean 120 mg/dl +/- 9.7 SEM) as compared to normal (mean 71 mg/dl +/- 7 SEM, P less than 0.001). The mean fasting insulin level was elevated in the patient group (13 mU/ml +/- 3.0 SEM), although in the majority of the patients it was found within the normal range (4-24 mU/ml). We conclude that the significant decrease in the total LPL activity may be responsible in part for the characteristic hypertriglyceridemia present in cancer patients.
Adult↗
Hepatic and extrahepatic uptake of intravenously injected lipoprotein lipase.
Rats were injected intravenously with 125I-labeled bovine lipoprotein lipase. The lipase disappeared within minutes from the blood due to uptake both in the liver (about 50% of the injected dose) and in extrahepatic tissues. Lipase enzyme activity disappeared in parallel to the 125I radioactivity. Thus, there was no inactivation of lipase in the circulating blood. Similar results were obtained when lipoprotein lipase purified from guinea pigs was injected into guinea pigs. Using supradiphragmatic rats we could show that the extrahepatic uptake was saturable and that the amounts of lipase that could be bound far exceeded the amounts of endogenous lipase expected to be present on the endothelium. When the lipase was denatured before injection, its removal in supradiaphragmatic rats became slower, and in intact rats the fraction of the uptake that occurred in extrahepatic tissues was much decreased. It is concluded that recognition by the extrahepatic receptors depends on the native conformation of the lipase. The extrahepatic uptake was strongly impeded by injection of heparin prior to injection of the lipase, and the uptake could to a large extent be reversed by injection of heparin after the lipase. Even after 1 h lipase that had been taken up by extrahepatic tissues reappeared immediately in the blood on injection of heparin. This was true both for enzyme activity and for enzyme radioactivity. Thus, internalization-inactivation-degradation occur only slowly in extrahepatic tissues. It is possible that the extrahepatic binding occurs to the enzyme's physiological receptors. The hepatic uptake was not dependent on the native conformation of the lipase, was less sensitive to heparin, could not be reversed by heparin and was not saturable. The enzyme was not rapidly inactivated after uptake; its activity could be detected in liver homogenates even after 1 h. Degradation to acid-soluble products in the liver was relatively slow; the t1/2 for native lipase was about 1 h. In comparison, in parallel experiments asialofetuin was degraded with a t1/2 of about 15 min.
Animals↗
Expression and regulation of the lipoprotein lipase gene in human adrenal cortex.
Lipoprotein lipase (LPL), an enzyme which hydrolyzes triglycerides and participates in the catabolism of remnant lipoproteins, plays a crucial role in energy and lipid metabolism. The goal of this study was to analyze the expression and regulation of the LPL gene in human adrenals. Reverse transcriptase-polymerase chain reaction amplification and sequence analysis demonstrated the presence of LPL mRNA in fetal and adult human adrenal cortex. Furthermore, the human adrenocortical carcinoma cell line, NCI-H295, expresses LPL mRNA and protein, which is localized to the outer cellular membrane as demonstrated by immunofluorescence confocal microscopy and can be released in the medium by heparin addition. To asses whether the LPL gene is regulated by agents regulating adrenal steroidogenesis, NCI-H295 cells were treated with activators of second messenger systems. Whereas the calcium-ionophore A23187 did not affect LPL gene expression, treatment with phorbol 12-myristate 13-acetate decreased LPL mRNA levels in a time- and dose-dependent manner. This decrease after phorbol 12-myristate 13-acetate was associated with diminished heparin-releasable LPL mass and activity in the culture medium. Addition of the cAMP analog 8-Br-cAMP to NCI-H295 cells resulted in a rapid, but transient dose-dependent induction of LPL mRNA. Treatment with the protein synthesis inhibitor cycloheximide gradually induced, whereas simultaneous addition of cAMP and cycloheximide superinduced LPL mRNA levels. Nuclear run-on analysis indicated that the effects of cAMP and cycloheximide occurred at the transcriptional and post-transcriptional level, respectively. Transient co-transfection assays demonstrated that the first 230 base pairs of the proximal LPL promoter contain a cAMP-responsive element activated by protein kinase A and transcription factors belonging to the CREB/CREM family. These data indicate that LPL is expressed in human adrenal cortex and regulated in NCI-H295 adrenocortical carcinoma cells by activators of the protein kinase A and protein kinase C second messenger pathways in a manner comparable to P450scc, which catalyzes the first step in adrenal steroidogenesis. These observations suggest a role for LPL in adrenal energy and/or lipid metabolism and possibly in steroidogenesis.
8-Bromo Cyclic Adenosine Monophosphate↗
Lipoprotein lipase: cellular origin and functional distribution.
Lipoprotein lipase (LPL, E.C. 3.3.1.34) is the enzyme responsible for hydrolysis of triacylglycerols in plasma lipoproteins, making the fatty acids available for use by subjacent tissues. LPL is functional at the surface of endothelial cells, but it is not clear which cells synthesize the enzyme and what its distribution is within tissues and vessels. We have searched for specific cell expression of the LPL gene by in situ hybridization using a RNA probe and for the corresponding protein distribution by immunocytochemistry on cryosections of some LPL-producing tissues of guinea pigs. In white and brown adipose tissues, heart and skeletal muscle, and lactating mammary gland, there was positive hybridization for LPL mRNA over all members of the major cell types, indicating that mature and immature adipocytes, muscle cells, and mammary epithelial cells are main sources of LPL. In large vessels, LPL expression was detected in some smooth muscle cells in the media layer. There was no positive hybridization for LPL mRNA over endothelial cells in any of the tissues studied, but there was immunoreaction for LPL protein at endothelial surfaces of all blood vessels. In the kidney, there was strong immunofluorescence at the vascular endothelium, particularly in the glomeruli, but little or no LPL mRNA was detected in the surrounding cells. These observations suggest that in some tissues LPL is synthesized by parenchymal cells and spreads along the vascular mesh. Transfer to the vascular endothelium is, however, not the only route taken by LPL. In the mammary gland most of the enzyme protein appeared to be secreted, partly in association with milk fat droplets.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
Acute effect of physical exercise on glycogen content and lipoprotein lipase activity in untrained diabetic rats.
The effect of acute physical exercise on skeletal muscle glycogen content and on lipoprotein lipase activity of muscle, adipose and lung tissues was studied in streptozotocin diabetic and control rats. Rats were accustomed to treadmill running for two weeks after streptozotocin treatment. For an exercise bout of moderate intensity rats were randomly divided into two groups: one was sacrificed immediately after exercise and the other 24 hours afterwards. In addition there was a nonexercised sedentary group. No depletion of glycogen was observed after exercise in the vastus lateralis muscle of control (nondiabetic) rats. No difference in glycogen utilization was found in soleus muscle between diabetic and control rats. In diabetic rats a slight decrease occurred in the lipoprotein lipase activity in adipose tissue immediately after exercise, while in control rats there was a significant decline 24 hours after exercise. In soleus muscle a slight but significant increase of lipoprotein lipase activity occurred 24 hours after exercise in diabetic rats but not in control rats. The results suggest that nonketotic streptozotocin diabetes of short duration does not influence muscle glycogen in the resting state, but glycogen utilization is disturbed in white muscle during moderate treadmill running in untrained diabetic rats. The increase in lipoprotein lipase activity after physical exercise in red muscle of diabetic rats occurs during the recovery phase.
Adipose Tissue↗
Lipoprotein lipase activity/mass ratio is higher in omental than in subcutaneous adipose tissue.
BACKGROUND: Lipoprotein lipase (LPL) is important for lipid deposition in adipose tissue (AT) and responds rapidly to changes in the nutritional state. Animal experiments indicate that short-term regulation of LPL is mainly post-translational. Different processing of LPL in different AT depots may play a role in the distribution of lipids in the body. MATERIALS AND METHODS: Lipoprotein lipase mRNA, mass and activity were measured in pieces of omental adipose tissue (OAT) and subcutaneous adipose tissue (SAT) from 15 subjects undergoing gastrointestinal surgery (four male and 11 female subjects, mean age 54 +/- 5 years, BMI 28 +/- 2 kg m(-2)). RESULTS: Lipoprotein lipase activity was higher in OAT than in SAT (18 +/- 2.1 compared with 12 +/- 1.6 mU g(-1), P < 0.01), whereas LPL mass was lower in OAT than in SAT (100 +/- 9 compared with 137 +/- 16 mU g(-1), P < 0.05). Consequently, the specific LPL activity (ratio of activity over mass) was approximately twofold greater in OAT compared with SAT. There was correlation between LPL mRNA and LPL activity in SAT (P < 0.05) and a similar tendency in OAT (P = 0.08). There were strong correlations (P < 0.01) for mRNA abundance as well as for LPL activity between the two depots. In contrast there was no correlation between the LPL mass and LPL mRNA or activity in any of the depots. CONCLUSIONS: These results indicate that long-term regulation, as reflected in the mRNA abundance, is similar in the two types of adipose tissue. The displayed activity reflects the mRNA abundance and the fraction of newly synthesized LPL molecules which the post-translational mechanism allows to become/remain active. This fraction was on average twofold greater in OAT compared with SAT.
Abdomen↗
Lipoprotein lipase activity of rat cardiac muscle. The intracellular distribution of the enzyme between fractions prepared from cardiac muscle and cells isolated from the hearts of fed and starved animals.
1. Subcellular fractions, characterized by using morphological, compositional and enzymic markers, were prepared from rat heart tissue and cells isolated from the hearts of fed and 24 h-starved rats. 2. The lipoprotein lipase activity of fractions from whole tissue and isolated cells was determined in either fresh fractions or in acetone/diethyl ether powders of the fractions. 3. Lipoprotein lipase activity was present in all the fractions from tissue and cells, but was found to be of highest relative specific activity in the microsomal () fractions. 4. In fractions prepared from the isolated cells of hearts from starved rats the proportion of the total lipoprotein lipase present and its relative specific activity in the microsomal fraction were greater than in the equivalent fractions from fed animals. 5. The enhancement of lipoprotein lipase activity as a result of the acetone/diethyl ether powder preparation of fractions was most extensive in the microsomal fractions. 6. Investigation of the microsomal fraction showed that the lipoprotein lipase activity present was in two pools, one of which was within endoplasmic-reticulum vesicles. 7. The observations were consistent with the possibility that the cardiac-muscle cell could be the origin of the lipoprotein lipase activity functional in triacylglycerol uptake by the heart.
Animals↗
Inhibition of lipoprotein lipase by plasma from children with the steroid responsive nephrotic syndrome.
The study was designed to investigate the hyperlipidaemia associated with the steroid responsive nephrotic syndrome in children and in particular to examine the mechanism for the delayed clearance of the circulating triglyceride-rich lipoproteins. The possibility that plasma from patients with steroid responsive nephrotic syndrome may contain an inhibitor of lipoprotein lipase activity was studied by examining the effect of the addition of plasma from patients, on normal postheparin lipoprotein lipase activity. Plasma from children with steroid responsive nephrotic syndrome significantly inhibited lipoprotein lipase activity (p less than 0.001), whereas that from patients with familial hypercholesterolaemia and normal children had no significant effect. The inhibition of lipoprotein lipase activity by plasma from patients with steroid responsive nephrotic syndrome correlated significantly with their increased plasma cholesterol and reduced plasma albumin concentrations (p less than 0.001 and less than 0.02, respectively), but there was no significant correlation with plasma triglyceride concentrations. Thus, the degree of inhibition probably reflected the severity of the condition at the time of study. Neither the cholesterol, albumin nor triglyceride concentrations appeared to directly influence the lipoprotein lipase activity of postheparin plasma.
Adolescent↗
Effect of the calcium channel antagonist nitrendipine on lipoprotein lipase and hepatic lipase in the normal rat.
Several observations indicate that a low lipoprotein lipase (LPL)/hepatic lipase (HL) ratio clusters with clinical and laboratory features of atherosclerosis. Antihypertensive treatment can unfavourably interfere with lipid metabolism, counteracting the beneficial effects of lowering blood pressure. We have evaluated the effects of the Ca2+ channel antagonist nitrendipine on tissue LPL and HL in the normal rat. At the dose of 40 mg/day administered intragastrically, a 5-day nitrendipine treatment induced a significant decrease in HL activity in the liver, in comparison to control animals: 656 +/-82 mU/g tissue vs. 814+/-38 mU/g 3 h after the last administration; 640+/-70 mU/g vs. 893+/-101 mU/g 8 h after administration. LPL activity in heart was increased by active treatment: 2542+/-298 vs. 2115+/-244 mU/g in controls 3 h after administration, P < 0.05. At variance, LPL mass, measured 8 h after administration, was decreased in heart of treated rats: 2.38+/-0.4 microg/g tissue vs. 3.88+/-0.3 microg/g in controls. The ratio between heparin-releasable and residual LPL in heart was unaffected by the drug. No changes were observed in LPL activity and mass in soleus muscle or in periepididymal adipose tissue. Our results indicate that nitrendipine, at the dose used, induces changes in lipolytic enzymes of rat tissues that could be beneficial in relation to atherosclerosis. These data encourage further investigations in humans, at the usual therapeutical doses.
Adipose Tissue↗
Depletion of lipoprotein lipase after heparin administration.
Some or most of the turnover of lipoprotein lipase (LPL) occurs by dissociation from vascular endothelial sites in extrahepatic tissues and further degradation in the liver. Heparin greatly enhances this dissociation and delays but does not abolish uptake in the liver, raising the possibility that heparin could lead to accelerated catabolism of functional LPL. To investigate this, we determined time curves for heparin (anti-factor Xa activity) and for LPL and hepatic lipase after injection in rats of two doses of conventional unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The high dose (250 U/kg) of both heparins resulted in similar initial levels of LPL activity in plasma, but at 30 minutes the activity with LMWH had declined by more than 80%, whereas with UFH it remained essentially unchanged during this time. In contrast, time curves for heparin activity in blood were similar for the two heparins. The low dose (50 U/kg) led to lower initial levels of LPL activity with LMWH in spite of slower elimination of heparin activity from the blood. These results agree with previous studies that indicate that LMWH has a similar ability as UFH to release LPL, but a lesser ability to delay its removal by the liver. Only slight differences were noted in the time curves for hepatic lipase with the two heparins. To assess the possible depletion of the lipases, we administered a second large dose of conventional heparin. One hour after the first injection, the second injection resulted in lower plasma LPL activities in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Comparison of the effect of homologous and heterologous albumin on the activity of lipoprotein lipase and liver triglyceride lipase in rabbit plasma].
Changes in the activity of blood plasma lipoprotein lipase (EC 3.1.1.34, LPL and hepatic triacylglycerol lipase EC 3.1.1.3, H-TGL) were studied in rabbits injected intravenously by homologous and heterologous albumins (bovine, fraction Y, Sigma, BSA) alone and in combination with heparin. Rabbit albumin enhanced the effect of heparin on the LPL activity, while heterologous protein, to the contrary, diminished it. The in vitro experiments showed that BSA caused a more distinct effect on the LPL activity as compared with that of rabbit albumin. The activity of H-TGL was not significantly altered under the influence of both proteins.
Animals↗
Sensitive non-radioisotopic method for measuring lipoprotein lipase and hepatic triglyceride lipase in post-heparin plasma.
In this method for measuring lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) in post-heparin plasma, we determine the released free fatty acids enzymically. After release, they are extracted by Dole 's method (J. Biol. Chem. 235: 2595-2599, 1960), solubilized with Triton X-100, then measured with an enzymic kit (NEFA Kit-K; Nippon Shoji Kaisha Ltd.) after residual turbidity is removed by centrifugation with chloroform. A 5-microL sample of post-heparin plasma suffices to measure the activity of LPL and H-TGL; thus the method is as sensitive as the radioisotopic method. Selective assay of LPL and H-TGL, by adding sodium dodecyl sulfate to inactivate H-TGL or NaCl to inactivate LPL, is also feasible. The mean activities +/- SD of LPL and H-TGL in plasma of normal healthy men were respectively 9.4 +/- 2.3 mumol/h per milliliter (157 +/- 38 U/L) and 20.1 +/- 10.4 (335 +/- 173 U) mumol/h per milliliter (U/L).
Adult↗
[Subcellular localization of rat adipocyte lipoprotein lipase].
The sub-cellular localisation in rat fat cells of lipoprotein lipase is discussed in this paper. The lipoprotein lipase was found with maximum activity in the microsomal fraction. Some special features of this activity in membrane fraction are pointed out.
Adipose Tissue↗
Heparan sulphate and the binding of lipoprotein lipase to porcine thoracic aorta endothelium.
Purified bovine milk lipoprotein lipase was shown to bind to intact porcine aortic endothelium in a specific, saturable fashion. The binding was reversed by exogenous heparin. A single class of binding sites was involved and at saturation 1.24 x 10(11) molecules of lipoprotein lipase/cm2 were bound. This represents 0.51 x 10(6) enzyme molecules per endothelial cell at a density of 1.2 x 10(3) molecules/micrometers 2. The enzyme binding was reduced by prior trypsinisation of the endothelial surface under conditions that removed cell surface glycosaminoglycan chains. The porcine endothelium was shown to have available at its surface 5.4 x 10(11) chains of heparan sulphate plus heparin-like glycosaminoglycans/cm2. Such an excess suggests that lipoprotein lipase may interact with approximately one in four of the available heparan sulphate chains.
Animals↗