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Interaction of size-fractionated heparins with lipoprotein lipase and hepatic lipase in the rat.

ABSTRACT: Heparin and heparin partially depolymerized by enzymic digestion were separated into six size fractions. Hep 1 (tetrasaccharides), with a mean M(r) of 1200, did not release significant amounts of either lipoprotein lipase (LPL) or hepatic lipase (HL) on intravenous injection into rats. Hep 2 (mainly octa- and deca-saccharides), with a mean M(r) of 2400-3000, released both lipases. To evoke the same plasma activity of LPL and HL required about 10 times more by weight, or about 40 times more molecules, of this heparin than of hep 5 (mean M(r) 12,000, similar to conventional heparin). Hep 5 impeded binding and degradation of 125I-labelled bovine LPL by perfused rat livers. In contrast, hep 2 had no detectable effect on these processes. This demonstrates a difference between the sites in the liver that mediate binding, uptake and degradation of LPL, and the extrahepatic sites that bind functional LPL, and the hepatic sites that bind functional HL. After injection of 3.25 mg of hep 5/kg body weight, plasma LPL activity rapidly rose and then remained high for at least 1 h. With hep 2, plasma LPL also rose rapidly, but then decreased to almost basal by 1 h. When a labelled triacylglycerol emulsion was injected 1 h after the heparins, the fractional catabolic rate was enhanced in the rats that had received conventional heparin, as expected from the high plasma LPL activity, but decreased compared with controls in rats that had received hep 2, indicating that available LPL had been depleted through enhanced transport to and uptake in the liver.

SUBMITTER: Liu G

PROVIDER: S-EPMC1132856 | biostudies-other | 1992 Aug

REPOSITORIES: biostudies-other

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Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size.

Project description:The structural features responsible for the activities of hepatic lipase (HL) can be clarified by in vivo comparisons of naturally occurring variants. The coding sequence of HL from C57BL/6J (B6) and SPRET/EiJ (SPRET) mice differs by four amino acids (S106N, A156V, L416V, S480T); however, these changes are not predicted to influence HL function. To test for allelic effects, we generated SPRET-HL transgenics with physiological levels of HL mRNA and HL activity that was parallel in female transgenics and about 70% higher in male transgenics, toward tri-[3H]oleate, compared with B6 controls. We found no correlation between activity levels and plasma lipids. However, significant allelic effects on plasma lipids were observed. Compared with B6-HL, SPRET-HL mediated reductions in total cholesterol (TC) and VLDL-, LDL- and HDL-cholesterol and HDL-triglyceride (TG) in fed males, and SPRET-HL decreased total TG and VLDL- and HDL-TG levels in fasted males. Fasted female transgenics had reduced TC compared with controls. We also found allele and sex effects on lipoprotein particle size. Male transgenic mice had increased VLDL and decreased LDL size, and female transgenic mice had decreased HDL size compared with control animals. These findings demonstrate highly divergent effects of naturally occurring HL coding sequence variants on lipid and lipoprotein metabolism.

| S-EPMC2853430 | biostudies-literature

High-density lipoprotein subpopulation profiles in lipoprotein lipase and hepatic lipase deficiency.

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| S-EPMC5064856 | biostudies-literature

Size-fractionated heparins have differential effects on human neutrophil function in vitro.

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| S-EPMC3749185 | biostudies-literature

Neuronal Lipoprotein Lipase Deficiency Alters Neuronal Function and Hepatic Metabolism.

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| S-EPMC1131138 | biostudies-other

Regulation of plasma lipid homeostasis by hepatic lipoprotein lipase in adult mice.

Project description:LPL is a pivotal rate-limiting enzyme to catalyze the hydrolysis of TG in circulation, and plays a critical role in regulating lipid metabolism. However, little attention has been paid to LPL in the adult liver due to its relatively low expression. Here we show that endogenous hepatic LPL plays an important physiological role in plasma lipid homeostasis in adult mice. We generated a mouse model with the Lpl gene specifically ablated in hepatocytes with the Cre/LoxP approach, and found that specific deletion of hepatic Lpl resulted in a significant decrease in plasma LPL contents and activity. As a result, the postprandial TG clearance was markedly impaired, and plasma TG and cholesterol levels were significantly elevated. However, deficiency of hepatic Lpl did not change the liver TG and cholesterol contents or glucose homeostasis. Taken together, our study reveals that hepatic LPL is involved in the regulation of plasma LPL activity and lipid homeostasis.

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Effect of protamine on lipoprotein lipase and hepatic lipase in rats.

Project description:The polycation protamine impedes the catabolism of triglyceride-rich lipoproteins and this has been suggested to be due to intravascular inactivation of lipoprotein lipase. We have made intravenous injections of protamine to rats and found that both lipoprotein lipase and hepatic lipase activities were released to plasma. The effect of protamine was more short-lived than that obtained by injection of heparin. The release of hepatic lipase by protamine was as effective as the release by heparin, while the amount of lipoprotein lipase released by protamine was only about one-tenth of that released by heparin. This was not due to inactivation of lipoprotein lipase, since injection of an excess of heparin 10 min after injection of protamine released as much lipoprotein lipase activity to plasma as in controls. The results in vivo differed from those obtained in model experiments in vitro. Protamine was able to almost quantitatively release both lipoprotein lipase and hepatic lipase from columns of heparin-agarose. The displacement was dependent on the total amount of protamine that had passed over the column, indicating that it was due to occupation by protamine of all available binding sites. Our results in vivo showed that the binding sites for lipoprotein lipase were not blocked as efficiently as those for hepatic lipase, indicating that the binding structures were not identical. It was concluded that the impaired turnover of lipoproteins by protamine probably was due to prevention of binding of the lipoproteins to endothelial cell surfaces rather than to impaired lipase function.

| S-EPMC1137426 | biostudies-other

Species differences in lipoprotein lipase and hepatic lipase activities: comparative studies of animal models of lifestyle-related diseases.

Project description:Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) have an important role in lifestyle-related diseases. To evaluate species differences, we compared LPL and HTGL activities in different animal models of lifestyle-related diseases using the same assay kit. Normal animals (JW rabbits, ICR mice, and SD rats), a hypercholesterolemic animal model (WHHLMI rabbits), and obese animal models (KK-Ay mice and Zucker fatty rats) fed standard chow were used in this study. Plasma was prepared before and after an intravenous injection of heparin sodium under fasting and feeding. LPL and HTGL activities were measured with the LPL/HTGL activity assay kit (Immuno-Biological Laboratories) using an auto-analyzer. Only in mice, high HTGL activity was observed in pre-heparin plasma. In normal animals, LPL and HTGL activities were high in ICR mice and SD rats but low in JW rabbits. Compared to normal animals, LPL activity was high in Zucker fatty rats and WHHLMI rabbits at both fasting and feeding, while LPL activity after feeding was low in KK-Ay mice. HTGL activity was higher in fasted and fed WHHLMI rabbits and fasted Zucker fatty rats, but was lower in fed KK-Ay mice. Gender difference was observed in HTGL activity in SD rats and LPL activity in WHHLMI rabbits but not in ICR mice. In conclusion, this simple assay method was effective for measuring LPL and HTGL activities of experimental animals, and the activities are highly regulated depending on animal species, animal models, feeding/fasting conditions and genders.

| S-EPMC6699980 | biostudies-literature

Hepatic lipase gene -514C>T variant is associated with exercise training-induced changes in VLDL and HDL by lipoprotein lipase.

Project description:Our objective was to test the hypothesis that a common polymorphism in the hepatic lipase (HL) gene (LIPC -514C>T, rs1800588) influences aerobic exercise training-induced changes in TG, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) through genotype-specific increases in lipoprotein lipase (LPL) activity and that sex may affect these responses. Seventy-six sedentary overweight to obese men and women aged 50-75 yr at risk for coronary heart disease (CHD) underwent a 24-wk prospective study of the LIPC -514 genotype-specific effects of exercise training on lipoproteins measured enzymatically and by nuclear magnetic resonance, postheparin LPL and HL activities, body composition by dual energy x-ray absorptiometry and computer tomography scan, and aerobic capacity. CT genotype subjects had higher baseline total cholesterol, HDL-C, HDL(2)-C, large HDL, HDL particle size, and large LDL than CC homozygotes. Exercise training elicited genotype-specific decreases in VLDL-TG (-22 vs. +7%; P < 0.05; CC vs. CT, respectively), total VLDL and medium VLDL, and increases in HDL-C (7 vs. 4%; P < 0.03) and HDL(3)-C with significant genotype×sex interactions for the changes in HDL-C and HDL(3)-C (P values = 0.01-0.02). There were also genotype-specific changes in LPL (+23 vs. -6%; P < 0.05) and HL (+7 vs. -24%; P < 0.01) activities, with LPL increasing only in CC subjects (P < 0.006) and HL decreasing only in CT subjects (P < 0.007). Reductions in TG, VLDL-TG, large VLDL, and medium VLDL and increases in HDL(3)-C and small HDL particles correlated significantly with changes in LPL, but not HL, activity only in CC subjects. This suggests that the LIPC -514C>T variant significantly affects training-induced anti-atherogenic changes in VLDL-TG, VLDL particles, and HDL through an association with increased LPL activity in CC subjects, which could guide therapeutic strategies to reduce CHD risk.

| S-EPMC3233892 | biostudies-literature

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