Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resident peritoneal macrophages release arachidonic acid when challenged by zymosan, a phagocytosable particle. The present study was designed to investigate the pathways for arachidonic acid mobilization in zymosan-stimulated macrophages. Experiments were conducted with [3H]arachidonic acid-labeled macrophages to establish the relative contribution of acyltransferases, phospholipase A2, and diacylglycerol lipase to overall arachidonic acid release. Upon zymosan stimulation, [3H]arachidonic acid incorporation into phospholipids was significantly enhanced. Stimulus-induced activation of arachidonic acid incorporated was not observed immediately, but was found 5 min after cell challenge. On the other hand, the results indicated a rapid accumulation of intracellular free [3H]arachidonic acid that paralleled the appearance of both [3H]glycerol-labeled lysophosphatidylcholine and [3H]glycerol-labeled lysophosphatidylinositol, the by-products of phospholipase A2 action on phosphatidylcholine and phosphatidylinositol, respectively. A transient accumulation of [3H]arachidonate-carrying diacylglycerol was also observed. However, no appreciable alterations in the levels of [3H]monoacylglycerol were found. The phospholipase A2 inhibitor nordihydroguaiaretic acid substantially prevented the zymosan-induced arachidonic acid release. In contrast, RHC 80267, a diacylglycerol lipase inhibitor, though preventing diacylglycerol breakdown, did not have any effect on [3H]arachidonic acid release From these results, it is concluded that: (1) the phospholipase A2 pathway controls arachidonic acid release upon zymosan stimulation; (2) the diacylglycerol lipase pathway appears not to be involved in arachidonic acid release by stimulated cells; (3) the acyltransferases play a remarkable role in controlling free arachidonic acid levels, but they do not participate in the increase of free fatty acid levels observed upon cell stimulation.
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PMID:Pathways for arachidonic acid mobilization in zymosan-stimulated mouse peritoneal macrophages. 164 16

During the first half of gestation in the rat, maternal net body weight increases rapidly, whereas in the second half of gestation, the mass of maternal structures declines, coincident with the rate of maternal fat accumulation. Enhanced maternal food intake, extrahepatic tissue lipoprotein lipase (LPL) activity, and adipose tissue lipogenesis are responsible for the progressive accumulation of maternal fat. However, during late gestation, decreased fat synthesis in maternal adipose tissue, enhanced lipolytic activity, and decreased LPL activity deplete maternal fat depots. These changes, plus enhanced endogenous production of triglyceride-rich lipoproteins, are also responsible for maternal hypertriglyceridemia. This condition benefits the offspring in two ways: 1) enhanced LPL activity in maternal liver when fasting increases triglyceride consumption for ketone body synthesis, giving the basis for accelerated starvation; and 2) induction of LPL activity in the mammary gland before parturition diverts maternal circulating triglycerides to milk synthesis in preparation for lactation. The magnitude of the maternal-fetal glucose transfer was higher than that of any of the other substrates studied, including alanine, and despite actions to spare glucose, this transfer causes maternal hypoglycemia, which is especially intense in the fasting condition. This increases sympathoadrenal activity in the mother, which may contribute to her active gluconeogenesis. Glycerol was a more efficient glucose precursor than alanine and pyruvate, and whereas glycerol placental transfer is very small, it is proposed that the fetus benefits from this product of adipose tissue lipolysis when it is previously converted into glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intermediary metabolism in pregnancy. First theme of the Freinkel era. 174 73

The enzyme lipoprotein lipase (LPL) is responsible for the hydrolysis of triglycerides into free fatty acids and glycerol. Its synthesis is induced as the murine bone marrow stromal cell clone, BMS2, undergoes adipocyte differentiation. The murine genomic LPL promoter has been cloned, sequenced, and characterized by functional and structural assays. The transcriptional start points have been mapped by S1 nuclease and primer extension techniques. Comparison of the 1.7-kb of LPL 5'-flanking sequence between mouse and man reveals 65% identity or greater with conservation of many potential protein-recognition motifs. Using constructs linking this region to the luciferase-encoding reporter gene, transient transfection experiments have documented the promoter function of this sequence in a number of cell lines. Based on a battery of restriction endonucleases, at least 260 bp immediately adjacent to and including the 5'-untranslated region of the first exon are hypersensitive to exogenous nuclease digestion, consistent with an altered chromatin structure. Protein-DNA interactions are detected within this area at the octamer binding protein 1 site and immediately 5' to the translation initiation site based on ExoIII footprinting and gel retention assays.
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PMID:Cloning and characterization of the promoter of the murine lipoprotein lipase-encoding gene: structural and functional analysis. 174 95

Earlier studies have shown that bradykinin stimulated release of catecholamines from chromaffin cells by an influx of calcium through dihydropyridine-insensitive channels, and also that bradykinin stimulated (poly)phosphoinositide hydrolysis. To investigate membrane-bound second messengers in chromaffin cells, and to elucidate any role these may play in stimulus-secretion coupling, we have studied the influence of bradykinin on diacylglycerol and phosphatidic acid (PA). Using equilibrium labelling of primary cultures of chromaffin cells with [3H]arachidonic acid or [3H]glycerol, we found no influence of bradykinin (10 nM) on labelled diacylglycerol formation, either in the presence or absence of inhibitors of diacylglycerol lipase or kinase. However, when we used cells prelabelled with 32Pi for 2.5 h, we found that bradykinin produced a substantial stimulation of label found in PA, with an EC50 value of about 1 nM. This bradykinin stimulation of [32P]PA formation was only partially dependent on extracellular calcium, in contrast to the smaller response to nicotine, which was completely dependent on extracellular calcium. Short (10 min) pretreatment with tetradecanoylphorbol acetate (TPA) almost completely eliminated the bradykinin-stimulated formation of inositol phosphates, but failed to affect bradykinin stimulation of label in PA, suggesting that PA production in response to bradykinin is not downstream of phospholipase C activation. TPA alone failed to stimulate [32P]PA substantially, whereas long-term (24 or 48 h) treatment with TPA failed to attenuate the response to bradykinin. Diacylglycerol kinase inhibitors were also without effect on the bradykinin stimulation of [32P]PA. These results suggest that bradykinin stimulates PA production by a mechanism independent of the activation of protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of bradykinin on diacylglycerol and phosphatidic acid accumulation in cultured bovine adrenal chromaffin cells. 186 Nov 47

This study was designed to understand the reasons for the increase in serum pseudocholinesterase activity in diabetes mellitus. Streptozotocin-induced diabetic rats were used for the study. Serum pseudocholinesterase activity increased with the induction of diabetes (381.5 units/l +/- 11.8) compared to the non-diabetic rats (243.1 units/l +/- 7.2). Serum triglycerides, total low density lipoprotein and glycerol also increased concurrently with the development of diabetes. Insulin treatment of the diabetic rats normalized serum glucose concomitant with the reduction of pseudocholinesterase activity, triglycerides, total low density lipoprotein and glycerol. Heparin injection appeared to activate lipoprotein lipase in the diabetic rats by showing a marked fall in serum triglyceride and total low density lipoprotein levels but not in pseudocholinesterase activity. Administration of tetraisopropylpyrophosphoramide a specific pseudocholinesterase inhibitor, inhibited serum and adipose tissue pseudocholinesterase activity by greater than 80% and liver greater than 50%. Concurrent with the inhibition of pseudocholinesterase activity serum triglyceride, low density lipoprotein and glycerol decreased significantly. In normal rats treatment with tetraisopropylpyrophosphoramide also reduced serum lipoproteins markedly, while glycerol only showed a marginal decrease. Glycerol was used as a marker of adipose tissue lipolysis and total low density lipoprotein which is defined as lipoproteins of density less than 1.063 (LDL + VLDL).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between serum pseudocholinesterase and triglycerides in experimentally induced diabetes mellitus in rats. 186 86

Lipogenic activities of perirenal adipose tissue were investigated in early (wk 3) and midlactation (wk 19 to 26) cows that received a duodenal rapeseed oil infusion (1.0 to 1.1 kg/d). In midlactation, oil infusion resulted in a decreased rate of fatty acid synthesis from acetate and a decreased rate of the activities of fatty acid synthetase and glucose-6-phosphate dehydrogenase, whereas lipoprotein lipase activity tended to increase. The rate of glucose incorporation into glyceride-glycerol and the activities of glycerol-3-phosphate dehydrogenase and malic enzyme were not significantly affected. Fatty acid C14:0 content of perirenal adipose tissue was decreased, and fatty acid C18:2 and C18:3 contents were increased in oil-infused cows. In early lactation, rates of acetate incorporation into fatty acids and activities of fatty acid synthetase and lipoprotein lipase were very low. Activities of glucose-6-phosphate dehydrogenase and glycerol-3-phosphate dehydrogenase were lower in the early than in the midlactation trial. Oil infusion did not change the measured parameters. In both trials, percentages and yields of milk fatty acids C18:1, C18:2, and C18:3 were increased, whereas those of C14:0 and C16:0 were decreased by oil. Calculated transfer rates of absorbed fatty acid C18:2 from oil to milk fat were 16 to 26%. Results suggested that oil fatty acids affected adipose and mammary de novo lipogenesis in a direct way without affecting fatty acid esterification in adipose tissue or total fat secretion in mammary tissue.
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PMID:Duodenal rapeseed oil infusion in early and midlactation cows. 5. Milk fatty acids and adipose tissue lipogenic activities. 189 93

We have studied the capacity of human neutrophils to release arachidonic acid from diacylglycerol, employing 1-stearoyl-2-[1-14C]arachidonoyl-sn-glycerol and 1-[1-14C]stearoyl-2-arachidonoyl-sn-glycerol as exogenous substrates. We have found that arachidonic acid is removed from diacylglycerol by the sequential action of two enzymes. First, the sn-1 position is split by 1-diacylglycerol lipase activity, and then, arachidonic acid is released from the resulting 2-monoacylglycerol by a 2-monoacylglycerol lipase. The specific activity of the 2-monoacylglycerol lipase, using 2-[1-14C]arachidonoyl-sn-glycerol as exogenous substrate, was at least 9-fold higher than that of 1-diacylglycerol lipase, indicating that the action of the 1-diacylglycerol lipase is the rate-limiting step in arachidonic acid release from diacylglycerol. Postnuclear supernatants from A23187-treated cells showed a 2.5-fold increase in both lipase activities. The arachidonic acid-releasing diacylglycerol lipase system showed an optimum pH of 4.5 and was not inhibited by EGTA or stimulated by Ca2+, Mg2+, Mn2+, Zn2+, or Co2+. However, arachidonic acid release was inhibited by Hg2+, suggesting the involvement of sulfhydryl groups in catalytic activity. The subcellular distribution of both 1-diacylglycerol lipase and 2-monoacylglycerol lipase activities was examined in resting and A23187-treated human neutrophils by fractionation of postnuclear supernatants on continuous sucrose gradients. Both lipases were localized mainly in the membrane of gelatinase-containing granules, which were resolved from cytosol, plasma membrane, phosphasomes, and specific and azurophilic granules. When neutrophils were stimulated by the calcium ionophore A23187, a drastic shift of the 1-diacylglycerol lipase and 2-monoacylglycerol lipase toward the plasma membrane was detected. This shift was due to fusion of gelatinase-containing granules with the plasma membrane upon neutrophil stimulation. As a result of the membrane fusion process, the capacity to release arachidonic acid from diacylglycerol was increased. This translocation from the membrane of gelatinase-containing granules to the plasma membrane may play an important role in regulating the diacylglycerol level in stimulated human neutrophils.
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PMID:Arachidonic acid release from diacylglycerol in human neutrophils. Translocation of diacylglycerol-deacylating enzyme activities from an intracellular pool to plasma membrane upon cell activation. 190 58

Fasted 1-day-old rat liver has high heparin-releasable (endothelial) lipoprotein lipase (LPL) activity, and its hepatocytes synthesize LPL protein. To test the physiological role of this LPL, we perfused the isolated organ with a 0.8 mM triacylglycerol (TAG) (Intralipid + glycerol tri[3H]oleate) 6.3% serum medium. Samples of the recirculated perfusate were taken at different times to determine 3H in TAG, free fatty acid (FFA), and water-soluble (WS) fractions. In the medium [3H]TAG disappeared and [3H]FFA and [3H]WS fractions appeared linearly with time. This TAG hydrolysis was 1) absent when medium was recirculated without liver, 2) not affected by chloroquine addition, 3) inhibited by anti-LPL immunoglobulins, 4) absent when serum was omitted from the medium, and 5) restituted when apolipoprotein CII was added to the medium without serum. Therefore, lysosomal lipase is not involved in this TAG hydrolysis, the features of which are characteristic of LPL, not of the so-called "hepatic endothelial lipase." Thus LPL activity enables the neonatal rat liver to hydrolyze and take up circulating TAG, i.e., has the same function as extrahepatic LPL.
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PMID:Lipoprotein lipase enables triacylglycerol hydrolysis by perfused newborn rat liver. 192 50

Long chain fatty acids (FA) and 2-monoacylglycerols (MG) are produced by lipoprotein lipase (LPL) from plasma triacylglycerols (TG) in capillaries of adipose tissue and transported to adipocytes for TG synthesis. It is widely proposed FA may be transported in cells by FA-binding protein. Mode of transport of MG has received little attention. Our findings in tissues and model membranes indicate that FA (as 1:1 acid-soaps) and MG can be transported in vivo by lateral movement in an interfacial continuum (IFC) of the outer leaflets of plasma and intracellular membranes of capillary endothelium and adipocytes. We postulate that FA and MG enter the IFC in capillaries and flow in the IFC across endothelium and extracellular space to sites in adipocytes where MG are hydrolyzed by MG-lipase (MGL) to FA and glycerol, and FA are esterified in endoplasmic reticulum or transferred to inner mitochondrial membrane for oxidation. FA and MG produced by hormone-sensitive lipase also enter the IFC. These MG flow in the IFC to sites of MGL activity, and the FA flow in the IFC to capillaries for transport to other tissues by albumin, or to mitochondria for heat production.
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PMID:Transport of fatty acids and monoacylglycerols in white and brown adipose tissues. 195 50

Factors contributing to fasting hypertriglyceridaemia were studied in 20 patients with non-insulin-dependent diabetes--nine with normal triglyceride concentrations [fasting triglyceride 0.94 (range 0.58-1.23) mmol l-1] and eleven with mild fasting hypertriglyceridaemia [fasting triglyceride 2.4 (1.82-4.0) mmol l-1]. The patients with hypertriglyceridaemia were more obese [body mass index 29.0 (24.6-33.8) vs. 25.7 (21.9-30.1) kg m-2, P less than 0.05] and demonstrated impaired glucose disposal in response to exogenous insulin at isoglycaemia [insulin sensitivity index, SIp 0.7 (0.27-2.5) vs. 2.4 (0.62-5.1) ml m-2 min per mU l-1, P less than 0.001]. Basal non-esterified fatty acid (NEFA) and glycerol concentrations were higher and were suppressed to a lesser extent during isoglycaemic hyperinsulinaemia. Fasting glucose and apolipoprotein B concentrations were higher in the hypertriglyceridaemic patients, but lipoprotein lipase activities were similar in the two groups. When the effect of obesity was removed (by weight-matching six normotriglyceridaemic with seven hypertriglyceridaemic patients) basal NEFA and glycerol concentrations and the suppression of NEFA in response to insulin remained significantly different between the two groups. We propose that defects in both the glucoregulatory and antilipolytic actions of insulin contribute to mild fasting hypertriglyceridaemia in NIDDM, and that these defects cannot be attributed solely to obesity. These disorders of insulin action may also have important implications for the postprandial metabolism of triglyceride-rich lipoproteins and hence atherogenesis.
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PMID:Determinants of mild fasting hypertriglyceridaemia in non-insulin-dependent diabetes. 200 44


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