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

Chylomicron "remnants" are formed by the selective removal of triglyceride catalyzed by lipoprotein lipase. To investigate a possible defect in the clearance of these remnants in the pathophysiology of broad-beta disease (type III hyperlipoproteinemia), subjects with this disorder and comparison subjects with endogenous hypertriglyceridemia (and type IV lipoprotein patterns) ingested an oral fat load (corn oil: cocoa butter, 1:1, 50 g/sq M) containing retinyl ester, 100 mg, with or without 15 muCi 15-(14) C-retinol (43.7 mCi/mg). The content of triglyceride and vitamin A was sequentially determined in chylomicrons (Sf more than 400) and very low density lipoproteins (VLDS, Sf20-400) over the ensuing 24-72 hr. Vitamin A was chosen as a marker for exogenous sterol assimilation since, like cholesterol, it is absorbed in the small intestine and cosecreted in esterified form with triglyceride in the chylomicron core; however, unlike cholesterol, once having been removed by the liver, it cannot be recycled inot VLDL, but subsequently circulates only as a complex with the high density retinol binding protein. Thus measurements of the vitamin A/triglyceride ratio in Sf greater than 20 lipoproteins reflected the relative efficiency of vitamin A versus triglyceride removal within these lipoproteins. These studies confirmed the intital concentration of exogenous vitamin A in chylomicrons but invariably disclosed an increasing proportion of the remaining Sf greater than 20 vitamin A in VLDL 24 hr after its ingestion. The vitamin A/triglyceride ratio also invariably increased between 6 and 24 hr in the Sf20-30 subfraction, reflecting the formation of vitamin A-rich "remnants" as intermediate species in the catabolism of chylomicrons and VLDL. Among those with mild to moderate endogenous hypertriglyceridemia the Sf greater than 400 vitamin A/triglyceride ratio declined between 6 and 24 hr, reflecting the efficient passage of the vitamin A through this fraction and/or continued secretion of Sf greater than 400 particles rich in triglyceride. Among those with severe endogenous hypertriglyceridemia, both the peak and decline in the Sf greater than 400 vitamin A/triglyceride ratio were delayed. However, among those with broad-beta disease, an increasing vitamin A/triglyceride ratio between 6 and 24 hr was frequent within all VLDL subfractions and invariable among lipoproteins of Sf greater than 400 regardless of the degree of antecedent hypertriglyceridemia. Although additional experiments disclosed a similar delay in both vitamin A and triglyceride assimilation when basal triglyceride levels were high in these subjects, marked reduction of triglyceride levels did not correct the rise in the Sf greater than 400 vitamin A/triglyceride ratio between 6 and 24 hr. Experiments employing preparative electrophoresis confirmed the identity of VLDL containing a high vitamin A/triglyceride ratio with the beta-VLDL which accumulate in broad-beta disease...
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PMID:Delayed clearance of chylomicron remnants following vitamin-A-containing oral fat loads in broad-beta disease (type III hyperlipoproteinemia). 18 57

We have recently reported that the apolipoprotein (apo) B-100-apo(a) complex, the protein moiety of lipoprotein(a) [Lp(a)], has a high affinity for triglyceride(TG)-rich particles (TRP) and that this complex can affiliate with endogenous TG-rich lipoproteins. To shed more light on the apo B-100-apo(a) complex associated with plasma TRP during postprandial lipidemia, we fed five male subjects presenting with primary hypoalphalipoproteinemia (HP) and four male controls a single fat meal (60 g/m2) containing saturated fatty acids (SFA) and, 6 weeks later, an isocaloric meal containing omega-3 polyunsaturated fatty acids. The subjects were phenotyped for plasma Lp(a) and apo C-III levels, apo(a) and apo E isoforms, and lipoprotein lipase and hepatic lipase activities. Vitamin A was included in the meal as a marker of intestinally derived TRP. Following the SFA meal, three of the HP subjects showed a decrease in plasma levels of Lp(a) that lasted 10 to 12 hours in the presence of an increased hypertriglyceridemic response. Two HP subjects who had low preprandial lipoprotein lipase activity and elevated plasma apo C-III levels showed an increase in plasma Lp(a) levels along with the hypertriglyceridemic excursion. However, in all cases, inclusive of the controls, there was an elevation in plasma levels of TRP of Sf greater than 1,000 that contained apo B-100-apo(a) 6 to 8 hours after the meal. This TRP excursion appeared not to be related to the basal levels of plasma Lp(a), high-density lipoprotein (HDL) cholesterol, TGs, or apo(a) and apo E isoforms, and it did not coincide with the retinyl ester peak.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postprandial lipoprotein(a) response to a single meal containing either saturated or omega-3 polyunsaturated fatty acids in subjects with hypoalphalipoproteinemia. 146 Nov 42

[3H]Retinol and [14C]oleic acid labelled fresh chyle was obtained from thoracic duct cannulated rats. The labelled compounds were fed dispersed in either a small amount of egg phosphatidylcholine to produce a lipid-poor chyle, or in a soy bean lipid emulsion to produce a lipid-rich chyle. Small amounts (100 microliters, 24 and 172 micrograms triacylglycerol, respectively) of fresh labelled chyle preparations were injected i.v. into fed recipient animals, which were killed after 10, 20 or 30 min. At 20 min, more [3H]retinyl ester remained in plasma in the rats injected with lipid-rich than in those injected with lipid-poor chyle. The difference was, however, smaller than the difference in the hepatic uptake of 3H. Both the uptake of 3H by the liver and the hydrolysis of [3H]retinyl ester after the uptake, was faster in the group that had been injected with the lipid-poor chyle. The 3H/14C ratios of the serum and liver lipids in relation to that of the injected material did not differ between the two groups, indicating that the proportion of the [14C]triacylglycerol that underwent hydrolysis before clearance of remnants by the liver did not differ. Particularly in the heart, but also in adipose tissue, lungs and kidneys the 3H radioactivity after injecting lipid-rich chyle was highest at 10 min and then decreased with time, being similar in the two groups at 30 min. The results suggest that the formation of remnants from lipoproteins formed after a fat meal requires a longer time for the interaction with endothelial-bound lipoprotein lipase. The uptake by the spleen was also 6-9-fold higher than in the group receiving lipid-poor chyle, indicating that the reticuloendothelial system participates in the metabolism of chyle lipoproteins after a fat meal.
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PMID:Metabolism in vivo of [14C]oleic acid and [3H]retinol of lipid-poor and lipid-rich chyle. 162 25

This report describes a series of experiments that attempt to characterize the lipidemia accompanying retinoic acid administration. After feeding young adult male Sprague-Dawley rats, 1.2 Retinol Equivalents (R.E.) retinyl acetate plus supplemental retinoic acid (100 microgram/g dry diet) for three days and fasting for 6-8 hr, triglyceride, cholesterol, and phospholipid content of various serum lipoprotein fractions were determined. When compared to unsupplemented controls, both the serum very low density lipoprotein (VLDL) and the high density lipoprotein (HDL) fractions of the retinoic acid-fed rats were found to harbor an elevated triglyceride content. While VLDL cholesterol and phospholipid content were also elevated, total serum cholesterol and phospholipids were not statistically altered. The detergent Triton WR-1339 was used to depress serum triglyceride clearance in order to assess the effects of retinoic acid feeding on serum triglyceride levels. Triglyceride accumulation started earlier after Triton treatment and was greater when rats were fed 100 microgram/g retinoic acid for three days prior to testing. Red and white gastrocnemius muscle, cardiac ventricular muscle, and perirenal adipose tissue were removed from rats following retinoic acid feeding. Analysis of these tissues for lipoprotein lipase (EC 3.1.1.3) activity showed a decrease in adipose tissue, a large depression in both areas of gastrocnemius muscle and no change in cardiac muscle as a result of retinoic acid feeding.
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PMID:Hyperlipidemia in rats fed retinoic acid. 727 11

Heparin is a well-known, widely used anticoagulant drug. In addition to its anticoagulant properties, however, it also has a marked influence on fat metabolism. Postprandial lipoproteins may contribute significantly to the development of coronary heart disease. Therefore, it is important to evaluate the effects of heparin on these lipoproteins. The effect of continuous heparin administration on postprandial lipoprotein metabolism was studied in 11 patients with thromboembolic disease. Results were compared with those in a group of six patients given no heparin. Two vitamin A-fat loading tests were done: the first, 5 days before heparin was started and the second, on the fourth day of continuous heparin drip of 1000 U/h, maintaining PTT levels at twice the baseline. To study the effect of acute heparin, an additional fat loading test was done in five patients on the first day of heparin treatment. Vitamin A, specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). The concentrations of chylomicron (Sf > 1000)- and nonchylomicron (Sf < 100)-retinyl palmitate were measured for 10 h postprandially. Four days of continuous intravenous heparin administration increased the area below the chylomicron RP curve from 11091 +/- 4393 to 17684 +/- 5949 micrograms/l.h (P < 0.003). When measured on the first day of heparin treatment in five patients, the area of the chylomicron fraction was reduced from 16678 +/- 6895 to 10474 +/- 3893 micrograms/l.h (P < 0.05). Postheparin lipoprotein lipase activity was significantly lower on the fourth day of heparin, administration than before treatment: 1.8 +/- 1.1 vs. 4.1 +/- 1.3 mumol/FFA per ml per h, respectively (P < 0.0005). In the six control patients with thromboembolic disease in whom heparin therapy was not indicated, no changes in postprandial lipoprotein levels or in lipolytic activity during hospitalization were found. The study demonstrates that 4 days of heparin administration causes an accumulation of chylomicrons in the circulation, most probably as a result of a marked decrease in serum lipolytic activity.
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PMID:Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and accumulation of chylomicrons in circulation. 816 26

The effect of a single oral fat meal (60 g fat/m2 body surface area) enriched in either saturated (SFA) or polyunsaturated ([PUFA] omega-6 or omega-3) fatty acids on postprandial lipoprotein levels was studied in four men with primary hypoalphalipoproteinemia (HP) and in four age- and sex-matched controls. Vitamin A was included in the meal to label intestinally derived triglyceride-rich particles (TRP) with retinyl palmitate (RP). The HP subjects were either mildly hypertriglyceridemic (group A) or normotriglyceridemic (group B) and were phenotyped for post-heparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities and apolipoprotein (apo) E isoforms. Postprandial total plasma triglyceride (TG), high-density lipoprotein (HDL) cholesterol, and RP and TG concentrations in the chylomicron (Sf > 1,000) and nonchylomicron (Sf > 1,000) fractions were evaluated for 24 hours after the meal. At each time point, HDL composition and size and apolipoprotein distributions were also measured. Following the SFA meal, HP subjects had maximal plasma TG levels at 8 hours (4 hours in controls) with a slow return to baseline levels at 12 to 24 hours (8 to 12 hours for controls). In contrast, after the omega-6 meal plasma TG levels decreased in group A subjects, while group B subjects and controls showed only a small increase. The results after the omega-6 meal were intermediate between the SFA and the omega-3 meal. When compared with group B, subjects in group A showed higher levels of RP-associated TRP, slower clearance rates, 30% to 50% lower fasting LPL activity, and 1.5-fold to twofold higher fasting plasma apo C-III levels. The major preprandial HDL subclass in HP subjects was HDL3, which showed a relative decrease in cholesterol esters (CE) and an increase in TG levels following the SFA meal. After the omega-3 meal, HDL of group A subjects showed a decrease in TG, a reciprocal increase in CE, and either no changes or minor changes in phospholipid (PL) and free-cholesterol (FC) levels. The results show that HP subjects with mild preprandial hypertriglyceridemia respond to a single fat meal differently than subjects with normotriglyceridemia, and that this difference is the result of HP in addition to other factors such as low LPL and HTGL activities, high plasma apo C-III levels, and apo E2 phenotype.
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PMID:Hypoalphalipoproteinemia: postprandial response of subjects with preprandial normotriglyceridemia and hypertriglyceridemia to various diets. 847 23

Familial combined hyperlipidaemia (FCH) is not a single entity with a clearly defined cause but can occur through an increased fatty acid flux from adipose cells, lipoprotein lipase dysfunction or apolipoprotein CIII abnormalities. A dynamic model of the metabolic processes of FCH has been used to describe how lipolysis of adipose cells may ultimately contribute to the formation of atherosclerotic plaques. Elevated circulating levels of chylomicrons are broken down to produce atherogenic remnants. One of the roles of lipoprotein lipase is in the low density lipoprotein (LDL) receptor-like protein-mediated uptake of lipoprotein remnants in the liver and up to 20% of FCH patients show a genetic abnormality of this enzyme. Vitamin A loading and measurement of chylomicron retinyl palmitate levels has further demonstrated impaired chylomicron remnant metabolism in these patients. Macrophages located in the vascular walls engulf remnants but are unable to metabolize their cholesterol. These cells contribute to atherosclerotic plaques. In terms of atherogenic potential, triglyceride levels are found to be higher and the hypertriglyceridaemia more severe in fed than in fasted patients. A case study of a patient with abetalipoproteinaemia suggests that the hypertriglyceridaemia seen in patients with FCH may be the result of an abnormality in microsomal triglyceride transport protein function. Studies also suggest a direct relationship between the post-prandial triglyceride levels and LDL cholesterol levels in the fasting state of patients with FCH and sporadic hypercholesterolaemia.
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PMID:Metabolic basis for hypertriglyceridaemia in familial combined hyperlipidaemia. 971 61

Vitamin A plays an important role in reducing infectious disease morbidity and mortality by enhancing immunity, an effect that is partly mediated by macrophages. Thus, knowing how these cells take up vitamin A is important. The results in the present study demonstrate that J774 macrophages efficiently take up chylomicron remnant retinyl esters and retinol-binding protein (retinol-RBP) bound retinol by specific and saturable mechanisms. The binding of (125)I-RBP to plasma membrane vesicles demonstrated that the macrophage receptor had a similar binding affinity, as was discovered previously for other cells. The B(max) for the macrophages was smaller than the values reported for placenta, bone marrow, and kidney, but larger than that reported for liver. The J774 cells also bound and took up [(3)H]retinol-RBP. Approximately 50 to 60% of the uptake may compete with excess unlabeled retinol-RBP and approximately 30 to 40% with excess transtyrethin. Following the uptake of [(3)H]retinol-RBP, an extensive esterification occurred: After 5 hours of incubation, 77.8 +/- 3.9% (SD; n = 3) of the cellular radioactivity was recovered as retinyl esters. The J774 cells also demonstrated saturable binding of chylomicron remnant [(3)H]retinyl esters, and a continuous uptake at 37 degrees C followed by an extensive hydrolysis of the retinyl esters. Binding could be inhibited by approximately 50% by excess unlabeled low density lipoprotein (LDL). In addition, lipoprotein lipase increased the binding of chylomicron remnant [(3)H]retinyl esters by approximately 30% and the uptake of chylomicron remnant [(3)H]retinyl ester by more than 300%. Furthermore, because sodium chlorate reduced binding with 40% and uptake with 55%, the results suggest that proteoglycans are involved in the uptake. Thus, the results suggest that both LDL receptor and LDL-related protein are involved in the uptake of chylomicron remnant [(3)H]retinyl ester in macrophages.
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PMID:Uptake of vitamin A in macrophages from physiologic transport proteins: role of retinol-binding protein and chylomicron remnants. 1553 9