scholarly journals Effects of hypothyroidism on the metabolism of lipid emulsion models of triacylglycerol-rich lipoproteins in rats

1991 ◽  
Vol 273 (2) ◽  
pp. 375-381 ◽  
Author(s):  
T G Redgrave ◽  
C L Elsegood ◽  
J C L Mamo ◽  
M J Callow
Keyword(s):  
Apolipoprotein E ◽  
Lipoprotein Lipase ◽  
Lipid Emulsion ◽  
Hepatic Lipase ◽  
Plasma Cholesterol ◽  
Cholesteryl Oleate ◽  
Hormone Analogue ◽  
Apolipoprotein C ◽  
Heparin Plasma

Methimazole-treated hypothyroid rats were injected intravenously with triacylglycerol/cholesteryl oleate/cholesterol/phospholipid emulsions designed to model the composition of chylomicrons. Compared with controls, hypothyroidism decreased the clearance rates of emulsion cholesteryl oleate. Clearance of emulsion triolein was affected much less and could be accounted for by residual triolein in remnants, suggesting that triacylglycerol lipolysis by lipoprotein lipase was unaffected by hypothyroidism but that clearance of remnants from plasma was decreased. Assays in vitro showed increased activities of lipoprotein lipase and hepatic lipase in hypothyroid rats. Emulsions were incubated with post-heparin plasma lipoprotein lipase to prepare remnants in vitro. The clearance from plasma of pre-formed remnants was slower after injection into hypothyroid rats than in control rats. Uptake of remnant cholesteryl oleate by the liver was significantly decreased in the hypothyroid rats. Treatment of hypothyroid rats for 7 days with 3,3′,5′-tri-iodo-L-thyronine (T3) reversed the inhibition of hepatic remnant uptake and normalized plasma cholesterol. A thyroid hormone analogue with decreased hypermetabolic side-effects, L-94901, attenuated plasma cholesterol and improved but did not normalize remnant clearance. Emulsions incubated with plasma from hypothyroid rats had a decreased ratio of apolipoprotein E/apolipoprotein C compared with control rats or hypothyroid rats treated with T3. The change in the apolipoprotein E/apolipoprotein C ratio probably accounts for the defect in remnant clearance in hypothyroidism.

scholarly journals Interaction of lipoprotein lipase with native and modified heparin-like polysaccharides

1980 ◽  
Vol 189 (3) ◽  
pp. 625-633 ◽  
Author(s):  
Gunilla Bengtsson ◽  
Thomas Olivecrona ◽  
Magnus Höök ◽  
Johan Riesenfeld ◽  
Ulf Lindahl
Keyword(s):  
Lipoprotein Lipase ◽  
Chondroitin Sulphate ◽  
Hepatic Lipase ◽  
Anticoagulant Activity ◽  
Heparan Sulphate ◽  
Binding Affinities ◽  
Dermatan Sulphate ◽  
Heparin Plasma ◽  
Heparin Fractions

1. Lipoprotein lipase (EC 3.1.1.34), which was previously shown to bind to immobilized heparin, was now found to bind also to heparan sulphate and dermatan sulphate and to some extent to chondroitin sulphate. 2. The relative binding affinities were compared by determining (a) the concentration of NaCl required to release the enzyme from polysaccharide-substituted Sepharose; (b) the concentration of free polysaccharides required to displace the enzyme from immobilized polysaccharides; and (c) the total amounts of enzyme bound after saturation of immobilized polysaccharides. By each of these criteria heparin bound the enzyme most efficiently, followed by heparan sulphate and dermatan sulphate, which were more efficient than chondroitin sulphate. 3. Heparin fractions with high and low affinity for antithrombin, respectively, did not differ with regard to affinity for lipoprotein lipase. 4. Partially N-desulphated heparin (40–50% of N-unsubstituted glucosamine residues) was unable to displace lipoprotein lipase from immobilized heparin. This ability was restored by re-N-sulphation or by N-acetylation; the N-acetylated product was essentially devoid of anticoagulant activity. 5. Partial depolymerization of heparin led to a decrease in ability to displace lipoprotein lipase from heparin–Sepharose; however, even fragments of less than decasaccharide size showed definite enzyme-releasing activity. 6. Studies with hepatic lipase (purified from rat post-heparin plasma) gave results similar to those obtained with milk lipoprotein lipase. However, the interaction between the hepatic lipase and the glycosaminoglycans was weaker and was abolished at lower concentrations of NaCl. 7. The ability of the polysaccharides to release lipoprotein lipase to the circulating blood after intravenous injection into rats essentially conformed to their affinity for the enzyme as evaluated by the experiments in vitro.

Activities of post-heparin plasma lipoprotein lipase and hepatic lipase during pregnancy and lactation

1980 ◽  
Vol 10 (6) ◽  
pp. 469-474 ◽  
Author(s):  
PAAVO K. J. KINNUNEN ◽  
TAPIO RANTA ◽  
CHRISTIAN EHNHOLM ◽  
J ESKO A. NIKKILÄ ◽  
MARKKU SEPPÄLÄ
Keyword(s):  
Lipoprotein Lipase ◽  
Hepatic Lipase ◽  
Plasma Lipoprotein ◽  
Heparin Plasma ◽  
Pregnancy And Lactation

scholarly journals Lipolysis generates platelet dysfunction after in vivo heparin administration

2002 ◽  
Vol 103 (4) ◽  
pp. 433-440 ◽  
Author(s):  
Elijah W. MURIITHI ◽  
Philip R. BELCHER ◽  
Stephen P. DAY ◽  
Mubarak A. CHAUDHRY ◽  
Muriel J. CASLAKE ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Cardiopulmonary Bypass ◽  
Lipoprotein Lipase ◽  
Whole Blood ◽  
Ex Vivo ◽  
Hepatic Lipase ◽  
Platelet Factor 4 ◽  
Platelet Factor

Heparin, when administered to patients undergoing operations using cardiopulmonary bypass, induces plasma changes that gradually impair platelet macroaggregation, but heparinization of whole blood in vitro does not have this effect. The plasma changes induced by heparin in vivo continue to progress in whole blood ex vivo. Heparin releases several endothelial proteins, including lipoprotein lipase, hepatic lipase, platelet factor-4 and superoxide dismutase. These enzymes, which remain active in plasma ex vivo, may impair platelet macroaggregation after in vivo heparinization and during cardiopulmonary bypass. In the present study, proteins were added in vitro to hirudin (200units·ml-1)-anticoagulated blood from healthy volunteers, and the platelet macroaggregatory responses to ex vivo stimulation with collagen (0.6μg·ml-1) were assessed by whole-blood impedance aggregometry. Over a 4h period, human lipoprotein lipase and human hepatic lipase reduced the platelet macroaggregatory response from 17.0±2.3 to 1.5±1.3 and 1.2±0.6Ω respectively (means±S.D.) (both P<0.01; n = 6). Other lipoprotein lipases also impaired platelet macroaggregation, but platelet factor-4 and superoxide dismutase did not. Platelet macroaggregation showed an inverse linear correlation with plasma concentrations of non-esterified fatty acids (r2 = 0.69; two-sided P<0.0001; n = 8), suggesting that heparin-induced lipolysis inhibits platelet macroaggregation. Lipoprotein degradation products may cause this inhibition by interfering with eicosanoids and other lipid mediators of metabolism.

scholarly journals Hepatic lipase function and the accumulation of β-very-low-density lipoproteins in the plasma of cholesterol-fed rabbits

1993 ◽  
Vol 293 (3) ◽  
pp. 745-750 ◽  
Author(s):  
S Chang ◽  
J Borensztajn
Keyword(s):  
Lipoprotein Lipase ◽  
Hepatic Lipase ◽  
Low Density Lipoproteins ◽  
High Cholesterol Diet ◽  
Low Density ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Very Low Density Lipoproteins

The accumulation of cholesterol-rich beta-very-low-density lipoproteins (beta-VLDL) in the plasma of rabbits fed on a high-fat high-cholesterol diet is due to a defect in the clearance of these lipoprotein remnants from circulation by the liver. In view of the evidence that hepatic lipase participates in the process of rapid removal of remnants from circulation, and considering that rabbits are naturally deficient in hepatic lipase, we examined whether this defect in the clearance of beta-VLDL could be reversed by exogenous hepatic lipase. We report that treatment in vitro of [3H]cholesterol-labelled beta-VLDL, or rat chylomicrons, with hepatic lipase resulted in the formation of particles that were rapidly cleared from circulation by the liver when injected intravenously into hypercholesterolaemic rabbits. These results are consistent with the notion that, in addition to the well-established requirement for lipoprotein lipase activity, the generation of remnants capable of being efficiently taken up by the liver also requires the action of hepatic lipase. Lipoprotein lipase acts on triacylglycerol-rich lipoproteins to transform them into particles (remnants) which bind to the surface of liver cells, where they become accessible to hepatic lipase. Hepatocyte endocytosis of these remnants occurs only after further modification by hepatic lipase. According to this scheme, the results presented suggest that the accumulation of beta-VLDL in the circulation of rabbits fed on a high-fat high-cholesterol diet is the result of the saturation of the available hepatic lipase by abnormally high levels of lipoprotein-lipase-generated chylomicron remnants.

Preferential in vivo accumulation of sn-2,3-diacylglycerols in postheparin plasma of rats

1977 ◽  
Vol 55 (10) ◽  
pp. 1075-1081 ◽  
Author(s):  
N. Morley ◽  
A. Kuksis ◽  
A. G. D. Hoffman ◽  
G. Kakis
Keyword(s):  
Portal Vein ◽  
Lipoprotein Lipase ◽  
Hepatic Lipase ◽  
Water Interface ◽  
Substrate Complex ◽  
Enzyme Substrate ◽  
Oil Water ◽  
Hydrolysis Of

The stereochemical course of in vivo hydrolysis of triacylglycerols by lipoprotein lipase was investigated by determining the structure of diacylglycerol intermediates in postheparin plasma of rats which had been fed [3H]glycerol-labeled Intralipid 2 h before an injection of heparin or had been given an injection of a mixture of [3H]glycerol-Intralipid and heparin. During the clearance of both the natural chylomicrons and the artificial emulsion, sn-2,3-diacylglycerols (60–80%) were found to be the dominant enantiomers. Similar results were obtained when the contribution of the hepatic lipase was altered, either by tying off the mesentery artery and portal vein before injection of heparin, or by injection of heparin directly into the portal vein. These findings are consistent with a preferential release of the acyl group from the sn-1 position of the triacylglycerol molecule as demonstrated previously in vitro. A preferential orientation of the substrate in the enzyme–substrate complex or at the oil–water interface is discussed as a possible basis for these effects.

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