Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Heparin can cause an artifactual elevation in the concentration of unbound (free) thyroxine (T4) in the plasma, particularly when measured by equilibrium dialysis. The lipase released into the plasma by heparin acts on substrate (triglycerides; TG) in the plasma in vitro to release nonesterified (free) fatty acids (FFA), which, in high concentrations, inhibit the binding of T4 to its plasma binding proteins. This artifact occurs only in the presence of sufficient substrate (serum TG greater than approximately 180 mg/dL), and is most pronounced in methods requiring long incubation times. We observed this artifact in a patient receiving intralipid and subcutaneous (sc) heparin. Plasma-free T4, when measured by equilibrium dialysis, was elevated, but was normalized when the in vitro generation of FFA during equilibrium dialysis was prevented by prior treatment of the sample with protamine to inhibit lipoprotein lipase and with an antibody to hepatic triglyceride lipase. This observation caused us to investigate formally whether heparin, at standard sc doses or at iv doses even lower than those that are commonly used to flush iv lines (100-300 U), could also cause this artifact. We gave increasing doses of heparin at weekly intervals to each of three normal volunteers and measured FFA generation in their plasma (supplemented with 250 mg/dL triglycerides) under conditions simulating equilibrium dialysis. We found that, indeed, iv doses of heparin as low as 0.08 U/kg (5.6 U in a 70-kg subject) as well as a standard dose of sc heparin (5000 U) could release significant lipase activity into the plasma and, in the setting of sufficient substrate, cause enough in vitro generation of FFA to artifactually increase the serum-free T4 concentration when measured by equilibrium dialysis. These results indicate that equilibrium dialysis may not always be the best method for assessing serum-free T4 concentrations in hospitalized patients, and should be taken into account when interpreting previous studies demonstrating inhibitors of T4-serum protein binding in sera from hospitalized patients.
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PMID:Extremely low doses of heparin release lipase activity into the plasma and can thereby cause artifactual elevations in the serum-free thyroxine concentration as measured by equilibrium dialysis. 873 76

A sucrose-rich diet (SRD) causes hypertriglyceridemia in nonpregnant rats. To determine whether a SRD further enhances gestational hypertriglyceridemia, female rats were divided into the following two groups: 1) rats fed a SRD (63 g sucrose/100 g), and 2) rats that received the same diet except that the sucrose was replaced by an equal amount of cornstarch (CD). Half of the rats were mated and studied at d 20 of gestation. Body weight increase did not differ between virgin rats fed either diet, but the final body weight of pregnant rats fed SRD was lower than that of rats fed CD due to fewer fetuses per litter and lower fetal and placental weights. The SRD enhanced plasma glucose and insulin concentrations in virgin but not in pregnant rats; plasma triglycerides and FFA concentrations and the rate of triglyceride secretion into the plasma were higher in pregnant than in virgin rats fed SRD, but the increase in liver triglycerides due to SRD was higher in virgin rats. Both removal rate of a fat emulsion and adipose tissue lipoprotein lipase activity (LPL) were lower in virgin rats fed SRD than in those fed CD. They were lower in pregnant than in virgin rats fed CD. Placental and fetal liver triglyceride concentration and placental LPL were higher in rats fed SRD than in those fed CD. Both the increased triglyceride secretion by the liver and the decreased triglyceride removal from blood resulting in maternal hypertriglyceridemia may contribute to the negative effect of SRD on the developing fetus.
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PMID:A sucrose-rich diet affects triglyceride metabolism differently in pregnant and nonpregnant rats and has negative effects on fetal growth. 885 8

In order to compare the influence of a single bout of exercise on HDL-C metabolism with normal variability, 12 male runners (mean age: 24.9 +/- 4 yr) who ran 15-30 miles per week underwent exercise (E) and control (C) experimental conditions. During the E trial subjects ran on a motor driven treadmill at 75% (42.5 +/- 4.7 ml.kg-1.min-1) VO2max until 800 Kcals were expended. The C trial consisted of no exercise. Subjects were instructed to follow the same diet and keep a four d food diary during each experimental condition. Fasted blood samples were obtained at the same time of day in each condition at time points corresponding to 24 h pre-exercise (24 PRE), 6 h post- (6 h) and 24 h post-exercise (24 h). Plasma was analyzed for HDL-C, HDL2-C and HDL3-C (mg.dl-1). In addition post-heparin plasma samples were analyzed for lipoprotein lipase (LPL) and hepatic lipase (HL) activity (mumol.FFA-1.ml-1). All values were adjusted for changes in plasma volume and compared to Baseline. HDL-C levels were unaltered following the C trial. However, following the E trial, HDL-C increased (p < 0.01) above baseline values at 24 h. The increase in HDL-C was reflected in the HDL3-C subfraction (p < 0.05). Analysis of lipolytic activity revealed an overall greater LPL activity (p < 0.05) in the E trial vs the C trial. In addition, a decrease in HL was observed at 24 h (p < 0.05) but was not different between experimental conditions. These data suggest that exercise and not normal variability are responsible for alterations in lipolytic activity and corresponding increases in HDL-C levels.
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PMID:Comparison of exercise and normal variability on HDL cholesterol concentrations and lipolytic activity. 885 3

Acromegaly is associated with changes in lipoprotein metabolism and an excess in cardiovascular mortality. We have examined low density lipoprotein (LDL) subfraction distribution in 24 patients with active acromegaly and in controls matched for age, sex and body mass index. LDL was subfractionated by density gradient ultracentrifugation. The concentration of small dense LDL-III was significantly higher in the acromegalic patients compared to the controls (94.2 +/- 44.9 versus 67.2 +/- 30.4 mg/dl, P < 0.05) and there was a concomitant reduction in the intermediate subfraction LDL-II (124.8 +/- 31.3 versus 149.9 +/- 30.0 mg/dl, P < 0.05). Univariate analysis showed that both growth hormone (GH) and insulin-like growth factor (IGF)-I correlated with LDL-III and inversely with LDL-II. Acromegalic patients were found to have lower hepatic lipase (HL) and lipoprotein lipase (LPL) activities than controls (HL: 13.29 +/- 6.56 versus 21.58 +/- 7.27 micromol FFA released/ml/h, P < 0.001: LPL: 7.22 +/- 3.04 versus 11.53 +/- 7.85 micromol FFA released/ml/h, P < 0.05) whereas plasma cholesteryl ester transfer protein (CETP) activity was significantly increased (8.15 +/- 1.81 versus 5.54 +/- 1.86 pmol/microl/h, P < 0.001). Both GH and IGF-I were significantly associated with HL, LPL and CETP activities. Multivariate analysis on this relatively small sample size showed that in normal subjects, triglyceride and HL activity were the major determinants of LDL-III. In contrast, GH and HDL were the main determinants in acromegaly, accounting for 32 and 24% in the variability of LDL-III respectively. In conclusion, GH excess has a direct effect on LDL subfraction distribution.
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PMID:LDL subfractions in acromegaly: relation to growth hormone and insulin-like growth factor-I. 906 18

A line of transgenic rats (heterozygotes) carrying a chimeric gene comprising a regulatory portion of murine whey acidic protein and a structural portion of human GH (hGH) genes developed severe obesity with age. To characterize physiological mechanisms that lead to fat accumulation, an array of parameters related to obesity were studied. Blood hGH levels were continuously low, endogenous rat GH secretion was suppressed, and the pulsatility in peripheral GH levels was absent. Plasma glucose, insulin, triglyceride, and FFA levels in the male transgenic rats significantly exceeded those in nontransgenic littermates at 12 and 17 weeks, but not at 7 weeks, of age. All symptoms except hyperlipidemia were restored to normal by treatment with an antidiabetic agent, thiazolidinedione (troglitazone), for 1 week from 17 weeks of age. As phenotypic expression of obesity was already evident before aberration of physiological parameters, it was assumed that animals had a condition in which obesity or hyperlipidemia caused hyperinsulinemia. Gene expression and enzymatic activity of lipoprotein lipase in the adipose tissue in the transgenic rats were not different from those in normal rats. In contrast, the gene expression level of glycerol-3-phosphodehydrogenase was markedly elevated, suggesting that glycerol synthesis was much enhanced in the adipocytes of the transgenic rats. In an i.p. glucose tolerance test, the transgenic rats were not hyperglycemic at 7 weeks of age; however, the animal became hyperglycemic at 15-17 weeks of age. Finally, treatment with recombinant hGH for 1 week to produce pulsatile secretion reduced the size of epididymal and kidney fat pads and restored normal weight gain. These observations suggest that continuously low peripheral GH levels with the lack of pulsatile secretion resulted in obesity and noninsulin-dependent diabetes mellitus.
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PMID:Obesity and insulin resistance in human growth hormone transgenic rats. 964 76

It is currently thought that the effects of PPARgamma activation on glucose homeostasis may be due to the effect of this nuclear receptor on the production of adipocyte-derived signalling molecules, which affect muscle glucose metabolism. Potential signalling molecules derived from adipocytes and modified by PPARgamma activation include TNFalpha and leptin, which both interfere with glucose homeostasis. In addition to its effects on these proteins, PPARgamma also profoundly affects fatty acid metabolism. Activation of PPARgamma will selectively induce the expression of several genes involved in fatty acid uptake, such as lipoprotein lipase, fatty acid transport protein and acyl-CoA synthetase, in adipose tissue without changing their expression in muscle tissue. This co-ordinate regulation of fatty acid partitioning by PPARgamma results in an adipocyte 'FFA steal' causing a relative depletion of fatty acids in the muscle. Based on the well established interference of muscle fatty acid and glucose metabolism it is hypothesized that reversal of muscle fatty acid accumulation will contribute to the improvement in whole body glucose homeostasis.
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PMID:PPARgamma activators improve glucose homeostasis by stimulating fatty acid uptake in the adipocytes. 969 45

The enzymatic fundamentals of lipid metabolism of equine have not been thoroughly investigated at this point in time. It is still unclear why ponies in contrast to horses may become hyperlipaemic when coming negative energy balance. In this study, the activities of the triglyceride-cleaving key enzymes of ponies are large bred horses were investigated in order to obtain insight into the aetiology of the syndrome. The objective of the study was to measure the activities of hormone-sensitive lipase (HSL), lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in ponies and horses in ex vivo in vitro assays. Norepinephrine (NE) stimulated pony adipocytes to release FFA in a linear fashion (4.57 +/- 2.09 nmol FFA.10(5) cells-1.min-1). This was not observed in horses. Lipolysis was significantly higher in fat cells of ponies than in horses when adenosine deaminase (ADA) and NE were added (12.71 +/- 3.12 vs. 1.96 +/- 1.22 nmol FFA.10(5) cells-1.min-1). Relative inhibition of lipolysis by the action of insulin was comparable in adipocytes of horses and ponies. However, absolute FFA release in pony fat cells was as high as the maximal NE and ADA stimulated lipolysis in horse adipocytes. Postheparin plasma lipase activities in ponies and horses did not differ between the sub-species. This finding was supported by the results obtained from measurement of LPL activity in adipose and muscle tissue showing only a tendency of increased activities in pony explants when compared to horse tissue incubations. This study further supports the hypothesis that differences in regulation of TG release from fat stores rather than clearance of TG from plasma is causative for the development of hyperlipaemia in ponies. Abbreviations used: ADA, adenosine deaminase; BW, body weight; FFA, free fatty acid; HSL, hormone-sensitive lipase; HTGL, hepatic triglyceride lipase; LPL, lipoprotein lipase; NE, norepinephrine; SDS, sodium dodecyl sulfate; TG, triglyceride; VLDL, very low density lipoprotein.
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PMID:Studies on equine lipid metabolism. 2. Lipolytic activities of plasma and tissue lipases in large horses and ponies. 1008 66

Plasma TGs, FFAs, and muscle TG are oxidizable lipid fuel sources for skeletal muscle metabolism during prolonged exercise. Plasma FFAs are a major fuel oxidized by skeletal muscle, and their rate of use by muscle depends on several factors, including plasma FFA availability, transport from plasma to the mitochondria, and intracellular metabolism. Mobilization of FFAs from adipose tissue is the first committed step in FFA metabolism, and it depends on the rate of adipose tissue lipolysis. Adipose tissue lipolysis increases with exercise duration and exercise intensity up to intensities of approximately 60% to 65%. Evidence suggests that FFAs are transported from plasma to the mitochondria by FFA transporter proteins that include the plasma membrane and cytosolic FABPPM and FABPC. Plasma FFA use can also be regulated at the mitochondrial transport step by changing the activity of carnitine palmitoyltransferase (CPT-1). Although results from biopsy and tracer studies indicate that muscle TG contribute to skeletal muscle oxidative metabolism during exercise, their exact contribution is difficult to ascertain. Evidence shows that muscle TG use depends on exercise intensity, duration, and mode. The contribution of plasma TG to skeletal muscle metabolism is small. The rate of use of plasma TG is dependent on lipoprotein lipase activity, which is correlated with the oxidative capacity of the muscle fibers. Dietary manipulations can modulate substrate use during exercise and can potentially affect exercise performance. High carbohydrate availability before exercise is associated with an increase in blood glucose and plasma insulin concentrations, which can ultimately decrease the rate of adipose tissue lipolysis and the availability of plasma FFAs. Increased glucose flux has also been shown to decrease lipid oxidation by directly inhibiting the transport of FFAs across the mitochondrial membranes. High lipid availability can be changed by short-term or long-term exposure to high-fat diets. Because carbohydrate reserves are diminished with exposure to high-fat diets, improvements in exercise performance have been difficult to measure under these conditions.
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PMID:Role of fats in exercise. Types and quality. 1041 Aug 36

Heparin given intravenously enhances lipolysis, although fasting lipids are not markedly altered in long-term administration. In the present study we investigated heparin-induced acute perturbation of VLDL subclass metabolism. Eight men were examined during a control study and during an 8.5 h infusion of heparin. 2H3-leucine was used as tracer and kinetic constants derived using a non-steady-state model. Heparin infusion increased both plasma lipoprotein and hepatic lipase activity and raised plasma FFAs two-fold (P < 0.001). The fractional catabolic rate (FCR) of VLDL1 apo B increased on heparin (25.7 +/- 4.2 and 10.8 +/- 1.7 pools/d, heparin vs. control, P < 0.02). The FCR of VLDL2 apo B increased to 12.6 +/- 1.9 pools/d on heparin vs. 8.8 +/- 1.1 pools/d during the control (NS). Total VLDL apo B production was not significantly changed (824 +/- 45 and 692 +/- 91 mg/d, heparin vs. control, NS). We conclude that during heparin infusion, the catabolism of especially large triglyceride-rich VLDL1 apo B is greatly increased. However, although the FFA levels were high during the heparin study, the production of total VLDL apo B did not rise. These findings are consistent with the known action of heparin on lipoprotein lipase but indicate that acute increase in plasma FFA levels does not lead to a rise in VLDL apo B production.
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PMID:Effect of heparin-stimulated plasma lipolytic activity on VLDL APO B subclass metabolism in normal subjects. 1053 94

During the first two-thirds of gestation, the mother is in an anabolic condition, increasing her fat depots thanks to both hyperphagia and enhanced lipogenesis. During the last third of gestation, the mother switches to a catabolic condition. Glucose is the most abundant nutrient crossing the placenta, which causes maternal hypoglycemia despite an increase in the gluconeogenetic activity. Adipose tissue lipolytic activity becomes enhanced, increasing plasma levels of FFA and glycerol that reach the liver; consequently there is an enhanced production of triglycerides that return to the circulation in the form of very low density lipoproteins (VLDL). Glycerol is also used as a preferential gluconeogenetic substrate, saving other more essential substrates, like amino acids, for the fetus. Under fasting conditions, fatty acids are converted into ketone bodies throughout the beta-oxidation pathway, and these compounds easily cross the placental barrier and are metabolized by the fetus. An enhanced liver production of VLDL-triglycerides together with a decrease in adipose tissue lipoprotein lipase (LPL) and an increase in plasma activity of cholesterol ester transfer protein causes both an intense increment in these lipoproteins and a proportional enrichment of triglycerides in both low and high density lipoproteins. Maternal triglycerides do not cross the placenta, but the presence of LPL and other lipases allows their hydrolysis, releasing fatty acids to the fetus. Under fasting conditions, the maternal liver uses circulating triglycerides as ketogenic substrates. Around parturition there is an induction of LPL activity in the mammary glands, driving circulating triglycerides to this organ for milk synthesis, allowing essential fatty acids derived from the mother's diet to become available to the suckling newborn.
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PMID:Metabolic adaptations in pregnancy and their implications for the availability of substrates to the fetus. 1080 38


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