PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “LIPOPROTEIN LIPASE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1999

Linkage of low-density lipoprotein size to the lipoprotein lipase gene in heterozygous lipoprotein lipase deficiency.

Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in the LpL gene. LDL particle size was smaller among the heterozygous subjects, compared with controls. Among heterozygous subjects, 44% were classified as affected by LDL subclass phenotype B, compared with 8% of normal family members. Plasma triglyceride levels were significantly higher, and high-density lipoprotein cholesterol (HDL-C) levels were lower, in heterozygous subjects, compared with normal subjects, after age and sex adjustment. A highly significant LOD score of 6.24 at straight theta=0 was obtained for linkage of LDL particle size to the LpL gene, after adjustment of LDL particle size for within-genotype variance resulting from triglyceride and HDL-C. Failure to adjust for this variance led to only a modest positive LOD score of 1.54 at straight theta=0. Classifying small LDL particles as a qualitative trait (LDL subclass phenotype B) provided only suggestive evidence for linkage to the LpL gene (LOD=1. 65 at straight theta=0). Thus, use of the quantitative trait adjusted for within-genotype variance, resulting from physiologic covariates, was crucial for detection of significant evidence of linkage in this study. These results indicate that heterozygous LpL deficiency may be one cause of small LDL particles and may provide a potential mechanism for the increase in coronary disease seen in heterozygous LpL deficiency. This study also demonstrates a successful strategy of genotypic specific adjustment of complex traits in mapping a quantitative trait locus.

Adolescent↗
PubMed1989

Assessment of lipoprotein activators of skim milk lipoprotein lipase and the relationship between lipoprotein lipase activity and milk fat synthesis.

Bovine plasma and lipoproteins isolated by gel filtration chromatography were examined for their ability to activate skim milk lipoprotein lipase. Addition of equal amounts of protein from either triglyceride-rich lipoprotein, low density lipoprotein, high density lipoprotein or plasma to a lipoprotein lipase assay resulted in 6.0, 2.2, 2.5, or 1.1% hydrolysis of radiolabelled triglyceride emulsion. Lipoprotein lipase activity in skim milk was evaluated as an indicator of mammary lipid secretory capacity. Skim milk lipoprotein lipase activity was significantly lower immediately prepartum as compared with activity immediately postpartum (.2 vs. 5.4% of substrate hydrolyzed). Skim milk lipoprotein lipase was significantly higher during the final 12 d of lactation than in samples obtained 12 d after machine milking was terminated (5.6 vs. less than 1% of substrate hydrolyzed). Although skim milk lipoprotein lipase activity appeared positively related to mammary lipid secretory capacity during the time immediately surrounding initiation and cessation of copious milk production, activity between those periods was not correlated to milk fat percentage, milk fat yield, or stage of lactation.

Animals↗
PubMed1989

Secretion and degradation of lipoprotein lipase in cultured adipocytes. Binding of lipoprotein lipase to membrane heparan sulfate proteoglycans is necessary for degradation.

Equilibrium-binding data of highly purified 125I-labeled avian lipoprotein lipase to cultured avian adipocytes demonstrate the presence of a class of high affinity binding sites. Analysis of the binding function yielded an association constant of 0.62 x 10(8)M-1 and a maximum binding capacity of 2.1 micrograms/60-mm dish. From a time course of dissociation of 125I-lipoprotein lipase from adipocytes at 4 degrees C, a dissociation rate constant of 6.1 x 10(-5)s-1 was obtained. Pretreatment of cells with heparinase and heparitinase resulted in a quantitative suppression of the high affinity binding component, establishing that lipoprotein lipase is bound to cell surface heparan sulfate proteoglycans. At 37 degrees C, cell surface-bound 125I-lipoprotein lipase is internalized and either degraded or recycled to the medium. The degradation rate constant for 125I-lipoprotein lipase was estimated to be 0.78 h-1. The degradation rate constant was reduced 6-fold when cells were exposed to 100 microM chloroquine, indicating that most of the degradation occurs within the lysosomal compartment. By using cells that had been pulsed with Trans35S-label for 1 h, it was demonstrated that acute treatment with endoglycosidases for up to 1 h resulted in a new lipoprotein lipase secretion rate which was 6-fold higher than that of control cells. Degradation of newly synthesized lipoprotein lipase was essentially blocked 30 min after the initiation of the chase. In other studies it was observed that there were no additive effects of chloroquine and either endoglycosidase or heparin treatment on total lipoprotein lipase levels (intracellular, cell surface, and medium) in adipocyte cultures. These experiments support the hypothesis that the release of lipoprotein lipase from its receptor prevents its internalization and degradation and enhances enzyme efflux from the adipocyte. A new model of lipoprotein lipase secretion in cultured adipocytes is proposed: Newly synthesized lipoprotein lipase is transported to the cell surface where it binds to specific heparan sulfate proteoglycan receptors. The enzyme is either released to the medium or internalized via the receptor, in which case the enzyme is degraded or recycled to the cell surface. Major determinants of enzyme efflux from the cell surface include the number and integrity of receptors, the association constant of the enzyme-receptor complex, and the presence in the medium of competing molecules with high affinity for lipoprotein lipase. In this model, modulation of lipoprotein lipase degradation rate may be a significant mechanism for acute regulation of enzyme efflux independent of changes in the rate of enzyme synthesis.

Adipose Tissue↗
PubMed1988

Role of lipoprotein lipase activity on lipoprotein metabolism and the fate of circulating triglycerides in pregnancy.

The mechanism that induces maternal hypertriglyceridemia in late normal pregnancy, and its physiologic significance are reviewed as a model of the effects of sex steroids on lipoprotein metabolism. In the pregnant rat, maternal carcass fat content progressively increases up to day 19 of gestation, then declines at day 21. The decline may be explained by the augmented lipolytic activity in adipose tissue that is seen in late pregnancy in the rat. This change causes maternal circulating free fatty acids and glycerol levels to rise. Although the liver is the main receptor organ for these metabolites, liver triglyceride content is reduced. Circulating triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels are highly augmented in the pregnant rat, indicating that liver-synthesized triglycerides are rapidly released into the circulation. Similar increments in circulating VLDL-triglycerides are seen in pregnant women during the third trimester of gestation. This increase is coincident with a decrease in plasma postheparin lipoprotein lipase activity, indicating a reduced removal of circulating triglycerides by maternal tissues or a redistribution in their use among the different tissues. During late gestation in the rat, tissue lipoprotein lipase activity varies in different directions; it decreases in adipose tissue, the liver, and to a smaller extent the heart, but increases in placental and mammary gland tissue. These changes play an important role in the fate of circulating triglycerides, which are diverted from uptake by adipose tissue to uptake by the mammary gland for milk synthesis, and probably by the placenta for hydrolysis and transfer of released nonesterified fatty acids to the fetus. After 24 hours of starvation, lipoprotein lipase activity in the liver greatly increases in the rat in late pregnancy; this change is not seen in virgin animals. This alteration is similar to that seen in liver triglyceride content and plasma ketone body concentration in the fasted pregnant rat. In the fasting condition during late gestation, heightened lipoprotein lipase activity is the proposed mechanism through which the liver becomes an acceptor of circulating triglycerides, allowing their use as ketogenic substrates, so that both maternal and fetal tissues may indirectly benefit from maternal hypertriglyceridemia. Changes in the magnitude and direction of lipoprotein lipase activity in different tissues during gestation actively contribute both to the development of hypertriglyceridemia and to the metabolic fate of circulating triglycerides.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1986

Purification and characterization of lipoprotein lipase from human postheparin plasma and its comparison with purified bovine milk lipoprotein lipase.

Lipoprotein lipase [EC 3.1.1.34, LpL] was purified from human postheparin plasma (PHP) almost to homogeneity (a 210,000-fold purification) using columns of heparin-Sepharose, hydroxylapatite, and concanavalin A-Sepharose, and its properties were compared with the purified bovine milk LpL. The specific activity of the PHP-LpL was 26 mmol free fatty acids (FFA)/h/mg of protein at 37 degrees C; close to that of bovine milk LpL (35 mmol FFA/h/mg). For both enzyme preparations, the pH optimum (about 8.7) and the inhibition by sodium chloride were almost the same. The apparent Michaelis constants were also similar; 2.5 mM for human PHP-LpL and 2.1 mM for bovine milk LpL. The apparent molecular weight of the purified human PHP-LpL was 58,000 by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate, slightly larger than that of the bovine milk LpL (56,000). Although the amino acid composition of the two LpL preparations had only slight differences, antibody raised against bovine milk LpL cross-reacted very weakly with purified human PHP-LpL. With 1% bovine serum albumin, bovine milk LpL was highly stable, but the human PHP-LpL was unstable; it lost 60% of its activity within 60 min at 0 degrees C. In the absence of apolipoprotein C-II (apo C-II), the activity of human PHP-LpL was very weak. However, human PHP-LpL was activated by apo C-II more strongly than bovine milk LpL; the fold activation of human PHP-LpL by apo C-II was 7-8 times that of bovine milk LpL. The apparent Km value of human PHP-LpL for apo C-II (1.00 +/- 0.58 microM) was larger than that of bovine milk LpL (0.15 +/- 0.03 microM).

Amino Acids↗
PubMed1989

Structural features of lipoprotein lipase. Lipase family relationships, binding interactions, non-equivalence of lipase cofactors, vitellogenin similarities and functional subdivision of lipoprotein lipase.

A structural homology between lipoprotein lipase, pancreatic lipase and hepatic lipase is known and indicates that all three lipases are members of a common protein family. Lipoprotein lipase and pancreatic lipase utilize small protein co-factors, apolipoprotein C-II and co-lipase, respectively, but comparisons reveal no homology between the co-factor molecules. Hence, they do not show the same relationship as their target enzymes. Neither do screenings detect any extensive similarities between lipoprotein lipase, serine hydrolases, or apolipoproteins. Scannings against data bank proteins show that a 105-residue segment of lipoprotein lipases exhibits a 35-40% residue identity with a sub-region of Drosophila vitellogenins. One fifth of the conserved amino acid residues (8 of 40) are glycine, a pattern which is typical of distantly related forms of protein families. This supports a true relationship between large segments of Drosophila vitellogenins and lipases. Physiological and functional aspects of the vitellogenin/lipoprotein lipase similarities are given. The region concerned is entirely within the N-terminal domain of lipoprotein lipase and constitutes the segment where the similarity to hepatic and pancreatic lipases is most pronounced. Within this lipase region a 10-residue putative lipid-binding site exists for which further similarities have been found to the otherwise not closely related lingual/gastric lipases, prokaryotic lipases and lecithin-cholesterol acyltransferase. Another segment in lipoprotein lipase, where the heparin-binding site has been mapped, exhibits a correlation between strength of heparin binding and extent of basic residues among members of the lipase family. It further exhibits weak similarities with the 'Zn-finger' DNA-binding segment of steroid hormone receptors and may indicate convergence in a binding interaction. Thus, a functional subdivision of lipoprotein lipase into different segments can be distinguished.

Amino Acid Sequence↗
PubMed2000

Lipoprotein lipase gene variation is associated with adipose tissue lipoprotein lipase activity, and lipoprotein lipid and glucose concentrations in overweight postmenopausal women.

Adipose tissue lipoprotein lipase (LPL) activity is under strong genetic control in both mice and humans. This study determines whether common DNA variation in the LPL gene (PvuII and HindIII polymorphisms) is associated with adipose tissue LPL activity and metabolic risk factors in a homogeneous population of 75 overweight postmenopausal women (body mass index >25 kg/m2; age: 51-69 years old). The allele frequencies for the presence of the cut-sites for LPL HindIII and PvuII were 0.71 and 0.49, respectively. There were no associations between the HindIII polymorphism and any of the measured variables. Age, body mass index, percent body fat, waist-hip ratio, visceral and subcutaneous fat area, and gluteal (GLT) and abdominal (ABD) adipocyte size did not differ by LPL PvuII genotype. However, adipose tissue LPL activity at both GLT and ABD sites was higher in women without the LPL PvuII cut-site (-/-) compared with women who were heterozygous (+/-) or homozygous (+/+) for the cut-site (P<0.05). Total and LDL cholesterol were lower in women without the LPL PvuII cut-site (-/-) compared with women who were heterozygous or homozygous for the cut-site (P<0.05), whereas triglyceride and HDL levels were similar between LPL PvuII genotypes. Fasting glucose, but not insulin, was lower in women without the LPL PvuII cut-site (-/-). These data suggest that the LPL PvuII polymorphism is a possible marker for a functional mutation that is found in the LPL gene and that alters LPL activity in older overweight women.

Adipocytes↗
PubMed1987

The kinetics of heparin inhibition of the esterase and basal lipase activities of lipoprotein lipase.

The kinetics of inhibition of the esterase and lipase activities of bovine milk lipoprotein lipase (LPL) were compared. The esterase LPL activity against emulsified tributyrylglycerol was not affected by the enzyme activator apolipoprotein C-II (C-II) and amounted to about 15% of the "plus activator" lipase enzyme activity. Heparin at concentrations of 20 micrograms/ml inhibited 25% of the esterase activity. The reaction followed Henri-Michaelis-Menten kinetics and the inhibition by heparin followed a linear, intersecting, noncompetitive kinetic model. On the other hand, the basal lipase activity of LPL against emulsified trioleoylglycerol (TG) was very sensitive to inhibition by heparin: 1 microgram/ml inhibited about 80% of the reaction and 3 micrograms/ml drove the reaction to zero. The velocity curve for the uninhibited basal LPL activity was sigmoidal with an apparent nH(TG) of 2.94. Heparin inhibited the lipase activity competitively: heparin decreased nH(TG) and increased[TG]0.5 6.4-fold, while TG decreased the nH(Heparin) from 2.14 to 0.95 and caused a 3-fold increase in [Heparin]0.5. C-II, at concentrations lower than 2.5 X 10(-8) M (i.e., lower than KA), countered the inhibitory effects of heparin: at constant inhibitor concentrations, C-II increased nH(TG) from 1.78 to 2.52 and decreased [TG]0.5 about 10-fold; it also increased the apparent Vmax. At the lower C-II concentrations, nH(C-II) was approximately equal to 1.0 and increasing the TG concentrations decreased [C-II]0.5 from 3.8 X 10(-8) to 8.5 X 10(-9) M, with no effect on the nH(C-II). At the higher C-II concentrations, nH(C-II) was 2.5 and TG decreased [C-II]0.5 about 2-fold with no effect on the nH(C-II). In the absence of heparin, C-II had no effect on nH(TG) nor on [TG]0.5, but it increased the apparent Vmax. On the other hand, TG had no effect on nH(C-II) nor on [C-II]0.5, but at any given C-II concentration, the reaction velocity increased with increasing TG concentrations. It is concluded that TG and heparin as well as C-II and heparin are mutually exclusive and that lipoprotein lipase is a multisite enzyme, possibly a tetramer, with three high-affinity catalytic sites, and an equal number of sites for C-II and heparin per oligomer. However, LPL differs from classical allosteric enzymes in that its activator has no effect on substrate cooperativity nor on [S]0.5; its only effect is to increase Vmax by increasing the catalytic rate constant kp by inducing conformational changes in the enzyme.

Animals↗
PubMed1985

Postheparin plasma lipoprotein lipase activity in heterozygotes of familial lipoprotein lipase deficiency.

Serum lipoprotein pattern, apoproteins and two postheparin triglyceride lipases were analyzed in a patient with familial lipoprotein lipase (LPL) deficiency and her family. Serum of the patient showed extreme hyperchylomicronemia and her postheparin plasma LPL activity was distinctly decreased. None of heterozygotes had any type of hyperlipoproteinemia. The mother and brother of the patient had moderately decreased LPL activity. There were no consistent changes in hepatic triglyceride lipase (H-TGL) activity among heterozygotes. These results suggest that assay of LPL may be helpful for detection of heterozygotes in familial LPL deficiency.

Adult↗
PubMed1985

Purification and characterization of human lipoprotein lipase and hepatic triglyceride lipase. Reactivity with monoclonal antibodies to hepatic triglyceride lipase.

Human lipoprotein lipase and hepatic triglyceride lipase were purified to homogeneity from post-heparin plasma. These enzymes were purified 250,000- and 100,000-fold with yields of 27 +/- 15 and 19 +/- 6%, respectively. Molecular weight determination by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and reducing agents yielded Mr of 60,500 +/- 1,800 and 65,200 +/- 400, respectively, for lipoprotein lipase and hepatic triglyceride lipase. These lipase preparations were shown to be free of detectable antithrombin by measuring its activity and by probing of Western blots of lipases with a monospecific antibody against antithrombin. In additions, probing of Western blots with concanavalin A revealed no glycoproteins corresponding to the molecular weight of antithrombin. Four stable hybridoma-producing distinct monoclonal antibodies (mAb) to hepatic triglyceride lipase were isolated. The specificity of one mAb, HL3-5, was established by its ability to immunoprecipitate hepatic triglyceride lipase catalytic activity. Interaction of HL3-5 with this lipase did not inhibit catalytic activity. The three other mAb interacted with hepatic triglyceride lipase only after denaturation of the enzyme with detergents. The relatedness of these two enzymes was examined by comparing under the same conditions the thermal inactivation, the sensitivity to sulfhydryl and reducing agents, amino acid composition, and the mobility of peptide fragments generated by cyanogen bromide cleavage. The results of these studies strongly support the view that the two enzymes are different proteins. Immunological studies confirm this conclusion. Four mAb to hepatic triglyceride lipase did not interact with lipoprotein lipase in Western blots, enzyme-linked immunosorbent assay, and immunoprecipitation experiments. These immunological studies demonstrate that several epitopes of the hepatic triglyceride lipase protein moiety are not present in the lipoprotein lipase molecule.

Amino Acids↗
PubMed2004

Cardiac-specific knock-out of lipoprotein lipase alters plasma lipoprotein triglyceride metabolism and cardiac gene expression.

Fatty acids are the primary energy source for the heart. The heart acquires fatty acids associated with albumin or derived from lipoprotein lipase (LpL)-mediated hydrolysis of lipoprotein triglyceride (TG). We generated heart-specific LpL knock-out mice (hLpL0) to determine whether cardiac LpL modulates the actions of peroxisome proliferator-activated receptors and affects whole body lipid metabolism. Male hLpL0 mice had significantly elevated plasma TG levels and decreased clearance of postprandial lipids despite normal postheparin plasma LpL activity. Very large density lipoprotein-TG uptake was decreased by 72% in hLpL0 hearts. However, heart uptake of albumin-bound free fatty acids was not altered. Northern blot analysis revealed a decrease in the expression of peroxisome proliferator-activated receptor alpha-response genes involved in fatty acid beta-oxidation. Surprisingly, the expression of glucose transporters 1 and 4 and insulin receptor substrate 2 was increased and that of pyruvate dehydrogenase kinase 4 and insulin receptor substrate 1 was reduced. Basal glucose uptake was increased markedly in hLpL0 hearts. Thus, the loss of LpL in the heart leads to defective plasma metabolism of TG. Moreover, fatty acids derived from lipoprotein TG and not just albumin-associated fatty acids are important for cardiac lipid metabolism and gene regulation.

Animals↗
PubMed1997

Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase.

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the import of triglyceride-derived fatty acids by muscle, for utilization, and adipose tissue (AT), for storage. Relative ratios of LPL expression in these two tissues have therefore been suggested to determine body mass composition as well as play a role in the initiation and/or development of obesity. To test this, LPL knockout mice were mated to transgenics expressing LPL under the control of a muscle-specific promoter (MCK) to generate induced mutants with either relative (L2-MCK) or absolute AT LPL deficiency (L0-MCK). L0-MCK mice had normal weight gain and body mass composition. However, AT chemical composition indicated that LPL deficiency was compensated for by large increases in endogenous AT fatty acid synthesis. Histological analysis confirmed that such up-regulation of de novo fatty acid synthesis in L0-MCK mice could produce normal amounts of AT as early as 20 h after birth. To assess the role of AT LPL during times of profound weight gain, L0-MCK and L2-MCK genotypes were compared on the obese ob/ob background. ob/ob mice rendered deficient in AT LPL (L0-MCK-ob/ob) also demonstrated increased endogenous fatty acid synthesis but had diminished weight and fat mass. These findings reveal marked alterations in AT metabolism that occur during LPL deficiency and provide strong evidence for a role of AT LPL in one type of genetic obesity.

Adipose Tissue↗