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

Serum lipoproteins and apolipoproteins were studied in 14 hypertriglyceridaemic (HTG) patients during a 24-week period of treatment with gemfibrozil, and after a 6-week washout period. A marked decrease in very low density lipoprotein (VLDL) cholesterol and triglyceride was observed. There was an increase in high density lipoprotein (HDL) cholesterol, particularly the HDL3 component. A slight increase in low density lipoprotein (LDL) cholesterol was observed after 12 weeks, but this had almost disappeared after 24 weeks. The treatment resulted in an increase in serum apolipoprotein A-II levels and a reduction in serum apo C-III and apo E. VLDL subfractionation by density gradient centrifugation in four subfractions of decreasing size (A, B, C and D) showed a predominant reduction of the large subfractions A, B and C, while the decrease in VLDL-D was less marked. Percentage changes from the baseline level of VLDL-A and VLDL-D cholesterol were found to be inversely correlated with percentage changes in HDL and LDL cholesterol, respectively. This might reflect a transfer of cholesterol from VLDL-A to HDL, and from VLDL-D to LDL. The above data suggest fibrate-induced stimulation of lipoprotein lipase, and indicate that the enhanced transfer of cholesterol from VLDL to LDL, induced by fibrates in HTG patients, is less pronounced after a prolonged period of treatment.
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PMID:Serum lipoproteins, apolipoproteins and very low density lipoprotein subfractions during 6-month fibrate treatment in primary hypertriglyceridaemia. 225 11

Mechanisms responsible for hypertriglyceridemia in Tangier disease were elucidated by an analysis of the plasma post-heparin lipolytic activities and the structural and metabolic properties of very low (VLDL) and low (LDL) density lipoproteins. The levels of lipoprotein lipase activity in six Tangier patients were significantly lower (P less than 0.001) than in 40 control subjects (8.1 +/- 3.3 (+/- S.D.) vs. 14.1 +/- 3.7 units/ml). In contrast, the levels of hepatic triacylglycerol lipase were higher (P less than 0.01) than in normal controls (14.4 +/- 3.9 vs. 9.3 +/- 4.0 units/ml). Because kinetic parameters such as Km or Vmax cannot be obtained with naturally occurring triacylglycerol-rich lipoproteins, the pseudo-first-order rate constant (k1) of triacylglycerol hydrolysis was used to assess the effectiveness of triacylglycerol-rich lipoproteins as substrates for lipoprotein lipase. The k1 values for Tangier VLDL (k1 = 0.017 +/- 0.002 min-1) were significantly lower (P less than 0.001) than the k1 values (0.036 +/- 0.008 min-1) for control VLDL. Both the Tangier and control LDL2 are similar in their resistance to the action of lipoprotein lipase, as shown by their low k1 values (0.002 +/- 0.001 and 0.001 +/- 0.001 min-1, respectively). The major compositional difference between the lipoproteins of Tangier disease and normal subjects was a significant increase in the percent content of apolipoprotein A-II in all lipoprotein particles with d less than 1.063 g/ml, with the greatest increase occurring in VLDL and the lowest in LDL2. These results were interpreted as indicating that, in Tangier disease, there is a lower reactivity of VLDL with lipoprotein lipase which may in part be attributed to the abnormal apolipoprotein composition. This finding, in conjunction with the reduced levels of lipoprotein lipase activity, may explain the hypertriglyceridemia in Tangier disease.
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PMID:Studies on the mechanism of hypertriglyceridemia in Tangier disease. Determination of plasma lipolytic activities, k1 values and apolipoprotein composition of the major lipoprotein density classes. 310 93

High-density lipoprotein (HDL) metabolism was studied in eight sedentary men before and after 14 and 32-48 weeks of exercise training. Subjects rode stationary bicycles 1 hour daily, 5 days each week for 14 weeks (n = 8), and 4 days each week thereafter for a total of 32-48 weeks (n = 7) of training. HDL metabolism was assessed with 125I-radiolabeled autologous HDL while subjects consumed defined diets. Maximal oxygen uptake increased 26 +/- 7% (p less than 0.001) after 14 weeks but did not increase further with more prolonged training. Body weight and estimated body fat did not change. HDL cholesterol increased 5 +/- 3 mg/dl, and triglycerides decreased 19 +/- 23 mg/dl after 14 weeks (p less than 0.025 for both), but there were no additional changes with continued training. Postheparin plasma lipoprotein lipase activity was 22% higher than baseline activity after both 14 (p less than 0.025) and 32 or more weeks of exercise. In contrast, hepatic triglyceride lipase activity was 16 +/- 8% and 15 +/- 8% lower than baseline at each measurement (p less than 0.005 for both). The disappearance rate of triglycerides after an intravenously administered fat solution was 24 +/- 24% higher at 14 weeks and 49 +/- 18% (p less than 0.005) higher after more prolonged training. Total and low-density lipoprotein cholesterol and apolipoprotein A-I and A-II concentrations at the end of study were not different from initial values. Plasma volume was 8% above initial values at both post-training measurements. The biological half-life of apolipoprotein A-I was unchanged at 14 weeks but was 10 +/- 13% longer (p = 0.07) and increased in all but one subject at the end of the study. Half-life for apolipoprotein A-II was 8 +/- 8% (p = 0.031) and 11 +/- 14% (p = 0.06) above baseline at 14 and 32 or more weeks, respectively. The synthetic rates for apolipoproteins A-I and A-II were not different from baseline values at 32-48 weeks. We conclude that 8-11 months of exercise training in previously sedentary men enhances fat tolerance and increases HDL cholesterol concentrations by prolonging HDL survival. The changes in HDL apolipoprotein survival, however, do not approximate the differences previously noted between elite endurance athletes and sedentary men. Changes in HDL cholesterol concentration were not large and suggest that the potential for exercise-related changes in HDL may be modest in many subjects.
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PMID:Modest changes in high-density lipoprotein concentration and metabolism with prolonged exercise training. 338 8

Lipoprotein lipase is the rate-limiting factor for hydrolyzing triglycerides to glycerol and fatty acids. Carnitine is a cofactor in the transport of long-chain fatty acids through the mitochondrial membrane for oxidation. To assess these determinants of fat utilization during total parenteral nutrition, lipoprotein and hepatic lipase activities and carnitine concentrations of nine newborn infants, operated on because of gastrointestinal anomalies during the first day of life, were measured with specific methods. Total parenteral nutrition was built up in 3 days whereafter the infants received 3 g/kg of fat at a constant rate of infusion for 24 h/day. Lipoprotein lipase activity of post-heparin plasma increased from 14 to 35 mumol free fatty acids/ml/h during parenteral nutrition whereas hepatic lipase activity remained unchanged at 40 mumol free fatty acids/ml/h. Serum free carnitine and acylcarnitine levels decreased significantly during parenteral nutrition; urinary excretion of carnitine decreased also. In addition, serum cholesterol and phospholipids increased markedly during parenteral nutrition whereas serum triglycerides, free fatty acids, and blood beta-hydroxybutyrate remained unchanged. Serum apolipoprotein A-I concentrations were unaltered, apolipoprotein A-II underwent a transient increase, and apolipoprotein B increased monotonically during parenteral nutrition. The results suggest that under the present circumstances neither lipoprotein lipase activity nor carnitine resources are rate-limiting for the utilization of fat in newborn infants during total parenteral nutrition.
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PMID:Postheparin plasma lipases and carnitine in infants during parenteral nutrition. 392 Jun 39

The conversion of pig high-density lipoproteins (HDL) (mainly HDL3) to fractions of lower densities was studied by incubating pig plasma for 24 h at 37 degrees C in the presence and absence of lipoprotein lipase from bovine milk, lecithin:cholesterol acyltransferase, cholesteryl ester transfer protein and triacylglycerol-rich particles (very-low-density lipoproteins (VLDL) or Intralipid). The results can be summarized as follows. In the presence of lipoprotein lipase and at a VLDL/HDL mass ratio of 2, the F-1.210 of pig HDL was shifted from 3.3 to 4.2, which is characteristic for human HDL2. This shift was caused by the excessive increase in the free fatty acid content in HDL. If 50 g/l of bovine serum albumin were added prior to incubation, the flotation rate of HDL remained in the HDL2a region. If lecithin:cholesterol acyltransferase was active in fasting pig plasma during incubation, we observed only a negligible increase of F-1.210 in HDL. If pig lipoproteins were incubated with human lipoprotein-free serum as a source of cholesteryl ester transfer activity, a slight increase in the flotation rate of HDL was observed, which was amplified in the presence of active lecithin:cholesterol acyltransferase. Pig HDL was converted to a fraction with F-1.210 of 4.2, which is typical for human HDL2, only if active lecithin:cholesterol acyltransferase, cholesteryl ester transfer protein and triacylglycerol-rich particles were present in the incubation mixture. From our results we also concluded that apolipoprotein A-II plays no role in the HDL2 formation.
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PMID:Factors affecting the conversion of high-density lipoproteins: experiments with pig and human plasma. 400 82

Apolipoprotein and lipid composition of differently sized chylomicrons from healthy volunteers was determined. During their intravasal catabolism the chylomicrons lose triacylglycerol and apolipoproteins. Decreasing particle size results in a loss of apolipoprotein C and apolipoprotein E peptides and an increase in apolipoproteins B and A-I, which constitutes more than 20% of the moiety of small chylomicrons. The C peptides do not seem to behave as a functional entity. Apolipoprotein C-III, the inhibitor of lipolytic activities, is catabolized independently of the other C peptides. Albumin constitutes about 15-25% of the protein moiety of all chylomicrons. The different chylomicron fractions were incubated with lipolytic activities of lipoprotein lipase and hepatic triacylglycerol lipase. At lower substrate concentrations the reactions were of first-order. Large chylomicrons were the favored substrate for both enzymes with Michaelis Menten constant Km = 1.1 mM for hepatic triacylglycerol lipase and 0.48 mM for lipoprotein lipase. After incubation with hepatic triacylglycerol lipase or lipoprotein lipase the shape of chylomicrons differs from that of control particles as demonstrated by electron microscopy. C peptides were completely dissociated and found in the infranatant. In the enzyme assay with triolein gum arabic substrate several apolipoproteins showed an influence on the activities of hepatic triacylglycerol lipase and lipoprotein lipase. Apolipoprotein C-III peptides were the most effective inhibitors of both enzymes. Also, apolipoprotein A-II, A-I and apolipoprotein C-I inhibited lipoprotein lipase activity, whereas only apolipoprotein A-II was able to decrease hepatic triacylglycerol activity.
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PMID:Characterization of human chylomicrons. 715 Jun 20

During a cross-over study with young female volunteers, the effects of a combination of 30 micrograms ethinylestradiol (EE) and 150 micrograms desogestrel (DG) or 3-keto-desogestrel (KDG) upon lipid metabolism were investigated on day 3 of the first cycle (day 3/I) and on day 21 of the third cycle of treatment (day 21/III). As compared to the control cycle, total cholesterol (CH), low-density lipoprotein CH (LDL-CH), and the apolipoproteins A-II and B were reduced already on day 3/I, the effects being more pronounced with the DG-containing formulation. On day 21/III of treatment with EE/DG, the levels of total CH, LDL-CH and apolipoprotein B did not differ from controls, while apolipoprotein A-II was significantly increased. The effects of EE/KDG were similar, except that on LDL-CH which was still reduced on day 21/III. The serum concentrations of total triglycerides (TG), very low-density lipoprotein CH (VLDL-CH), VLDL-TG, LD-TG, high-density lipoprotein CH (HDL-CH), HDL-TG, and apolipoprotein A-I were not significantly affected on day 3/I, but elevated on day 21/III. As during treatment with EE/KDG the peak level of KDG was higher than with EE/DG, the results indicate a more pronounced antagonistic effect of EE/KDG on some EE-induced changes on lipoproteins during the first days of intake. These short-term changes possibly reflect a rapid enhancement of hepatic uptake of remnants and LDL by EE. During long-term treatment, the other effects of EE, e.g. the stimulation of hepatic synthesis of TG, VLDL, and HDL and the inhibition of hepatic lipoprotein lipase, become apparent.
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PMID:Short- and long-term effects on lipid metabolism of oral contraceptives containing 30 micrograms ethinylestradiol and 150 micrograms desogestrel or 3-keto-desogestrel. 759 Jun 42

Apolipoprotein A-I plays an essential structural and functional role in HDL metabolism and apolipoprotein A-II has important effects on HDL metabolism and function. Kinetic studies in humans have established that variation in plasma HDL-cholesterol and apolipoprotein A-I concentrations is primarily determined by variation in the rate of apolipoprotein A-I catabolism. In contrast, plasma apolipoprotein A-II levels are primarily determined by the rate of apolipoprotein A-II production. Genetic factors play an important role in modulating the plasma levels of HDL-cholesterol and apolipoproteins A-I and A-II. Studies in humans have established that mutations in genes encoding enzymes that esterify cholesterol (lecithin : cholesterol acyltransferase), transfer cholesterol (cholesteryl ester transfer protein) and hydrolyze lipids (hepatic lipase, lipoprotein lipase) regulate HDL-cholesterol and apolipoprotein A-I levels by modifying the lipid content (and therefore the size) of HDL particles. Recent studies in transgenic and knockout animals have confirmed the key role of HDL lipid-modifying proteins in HDL, apolipoprotein A-I and apolipoprotein A-II metabolism and have expanded our understanding of the role of lipid modification in determining plasma concentrations of HDL-cholesterol and apolipoprotein A-I, as well as the potential functional roles of apolipoprotein A-II.
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PMID:Unravelling high density lipoprotein-apolipoprotein metabolism in human mutants and animal models. 881 7

The peroxisome proliferator-activated receptors (PPARs) [alpha, delta (beta) and gamma] form a subfamily of the nuclear receptor gene family. All PPARs are, albeit to different extents, activated by fatty acids and derivatives; PPAR-alpha binds the hypolipidemic fibrates whereas antidiabetic glitazones are ligands for PPAR-gamma. PPAR-alpha activation mediates pleiotropic effects such as stimulation of lipid oxidation, alteration in lipoprotein metabolism and inhibition of vascular inflammation. PPAR-alpha activators increase hepatic uptake and the esterification of free fatty acids by stimulating the fatty acid transport protein and acyl-CoA synthetase expression. In skeletal muscle and heart, PPAR-alpha increases mitochondrial free fatty acid uptake and the resulting free fatty acid oxidation through stimulating the muscle-type carnitine palmitoyltransferase-I. The effect of fibrates on the metabolism of triglyceride-rich lipoproteins is due to a PPAR-alpha dependent stimulation of lipoprotein lipase and an inhibition of apolipoprotein C-III expressions, whereas the increase in plasma HDL cholesterol depends on an overexpression of apolipoprotein A-I and apolipoprotein A-II. PPARs are also expressed in atherosclerotic lesions. PPAR-alpha is present in endothelial and smooth muscle cells, monocytes and monocyte-derived macrophages. It inhibits inducible nitric oxide synthase in macrophages and prevents the IL-1-induced expression of IL-6 and cyclooxygenase-2, as well as thrombin-induced endothelin-1 expression, as a result of a negative transcriptional regulation of the nuclear factor-kappa B and activator protein-1 signalling pathways. PPAR activation also induces apoptosis in human monocyte-derived macrophages most likely through inhibition of nuclear factor-kappa B activity. Therefore, the pleiotropic effects of PPAR-alpha activators on the plasma lipid profile and vascular wall inflammation certainly participate in the inhibition of atherosclerosis development observed in angiographically documented intervention trials with fibrates.
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PMID:Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. 1043 61

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. PPARalpha, the first identified PPAR family member, is principally expressed in tissues exhibiting high rates of beta-oxidation such as liver, kidney, heart and muscle. PPARgamma, on the other hand, is expressed at high levels in adipose tissue. PPARs are activated by dietary fatty acids and eicosanoids, as well as by pharmacological drugs, such as fibrates for PPARalpha and glitazones for PPARgamma. PPARalpha mediates the hypolipidemic action of fibrates in the treatment of hypertriglyceridemia and hypoalphalipoproteinemia. PPARalpha is considered a major regulator of intra- and extracellular lipid metabolism. Upon fibrate activation, PPARalpha down-regulates hepatic apolipoprotein C-III and increases lipoprotein lipase gene expression, key players in triglyceride metabolism. In addition, PPARalpha activation increases plasma HDL cholesterol via the induction of hepatic apolipoprotein A-I and apolipoprotein A-II expression in humans. Glitazones exert a hypotriglyceridemic action via PPARgamma-mediated induction of lipoprotein lipase expression in adipose tissue. PPARs play also a role in intracellular lipid metabolism by up-regulating the expression of enzymes involved in conversion of fatty acids in acyl-coenzyme A esters, fatty acid entry into mitochondria and peroxisomal and mitochondrial fatty acid catabolism. These observations have provided the molecular basis leading to a better understanding of the mechanism of action of fibrates and glitazones on lipid and lipoprotein metabolism and identify PPARs as attractive targets for the rational design of more potent lipid-lowering drugs.
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PMID:Regulation of lipid and lipoprotein metabolism by PPAR activators. 1077 55


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