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)

Each day more than 150 g of triglycerides are transported from the intestine in chylomicrons and from the liver in VLDL. The triglycerides are hydrolyzed by lipoprotein lipase at the vascular endothelium in extrahepatic tissues. This releases fatty acids and monoglycerides which can move across aqueous barriers and cell membranes to reach metabolic sites in tissue cells. At the endothelial cell the enzyme is anchored to heparin sulfate proteoglycans. The enzyme is located in a position where it can freely interact with lipoproteins from the circulating blood. The hydrolysis is a rapid and efficient process. A chylomicron containing more than a million triglyceride molecules can be unloaded in less than 10 minutes. As a consequence of triglyceride hydrolysis the lipoproteins are reduced to remnant particles. Some of these are rapidly removed from plasma but some are remodeled into LDL and HDL, lipoproteins that are catabolized slowly and therefore dominate in plasma. The activity of LPL is regulated in a tissue-specific manner and this directs the destination of triglyceride transport. The enzyme binds fatty acids which provides a mechanism for product control of the reaction. When the tissue can no longer assimilate the fatty acids, the lipase reaction is stopped and the lipoprotein returns to the circulating blood. In addition to its catalytic action, lipoprotein lipase can also serve as a ligand for binding of lipoproteins to cell surfaces and to receptors. Hence, the lipase has a dual role in lipoprotein metabolism, mediating both unloading of triglycerides in extrahepatic tissues and particle catabolism in the liver.
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PMID:[The great Scandinavian Medical Jahre Prize 1994. Role of lipoprotein lipase in lipoprotein metabolism]. 783 Nov 8

We analyzed the molecular defects in the lipoprotein lipase gene of a patient with type I hyperlipidemia suffering from recurrent pancreatitis, indicative for lipoprotein lipase deficiency. Postheparin lipoprotein lipase activity in the patient was decreased by 70%. Direct genomic sequencing revealed compound heterozygosity for two mutation: the well-known Gly188-->Glu and a new Val69-->Leu substitution. Val69 is situated in a conserved hydrophobic region of the lipoprotein lipase protein, and the substitution with leucine gives rise to a 80% decrease in specific catalytic activity, as supported by site-directed mutagenesis experiments, followed by expression in COS-cells. The combination of both defects in the lipoprotein lipase gene was incidentally associated with severe clinical expression of disease, and triglyceride levels of more than 30 mmol/l were measured. In our patient, triglyceride levels wer usually below 10 mmol/l. We, therefore, postulate that the residual LPL activity in our patient is usually sufficient to keep the triglyceride level within bounds and expression of disease occurred only when conditions such as alcohol abuse or poor compliance to diet were present.
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PMID:A compound heterozygote for lipoprotein lipase deficiency, Val69-->Leu and Gly188-->Glu: correlation between in vitro LPL activity and clinical expression. 791 54

Using mature adipocytes and preadipocytes from genetically obese Zucker rats, we investigated the cells' ability to maintain abnormal fat storage capacity when withdrawn from their in vivo environment. Long-term adipocyte cultures from obese rats displayed an increase in both glucose consumption (GC) and enzyme activities, including fatty acid synthase (4-fold), glycerol-3-phosphate dehydrogenase (4.5-fold), lipoprotein lipase (LPL; 6-fold), and malic enzyme (2.5-fold). Fully differentiated obese predipocytes exhibited a twofold increase in these enzyme activities, together with higher glucose metabolism. In obese cells, LPL mRNA was increased in both adipocytes (6-fold) and differentiated preadipocytes (2-fold). Insulin mediated an increase in GC and lipogenic enzymes in both adipocytes and preadipocytes regardless of the genotype; this effect was more marked in obese cells. Examining cultured adipocytes from rats fed a high-fat diet, we showed that the nutritional effect upon GC and lipogenic enzymes was abolished after culture. These results demonstrated that fatty mutation may be intrinsically expressed in prolonged cultured mature adipocytes and in newly differentiated adipocytes.
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PMID:Evidence for a sustained genetic effect on fat storage capacity in cultured adipose cells from Zucker rats. 794 24

Lipoprotein lipase is the extrahepatic lipase responsible for the hydrolysis of triglycerides in chylomicrons and very low-density lipoproteins. Its enzymic activity and its location on the surface of endothelial cells are affected by the presence of fatty acids, implying that the protein possesses binding sites for that ligand. In this study, we examine the binding of fatty acids to LpL and describe factors that must be considered when the dissociation constant of the acceptor-ligand equilibrium is close to the critical micelle concentration of the fatty acid. The interaction of fatty acids with lipoprotein lipase (LpL) was studied by two methods. A new direct method, based on the LpL-induced increase in the apparent critical micelle concentration of the sodium soap of the fatty acid, indicates the presence of multiple high-affinity binding sites. In the second method, the specific binding of fatty acids to LpL was measured by quantitating the blue shift in the tryptophan fluorescence of LpL that occurs upon binding the ligand. Both methods suggest the existence of 4-6 fatty acid binding sites on LpL with a dissociation constant on the order of 10(-6)-10(-7) M. Further analysis of the blue shift indicates that at higher concentrations of fatty acid, large complexes are formed consisting of 260-310 molecules of fatty acid per LPL monomer. In contrast, no large complexes are formed with fatty acids that form crystals above their solubility limit.
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PMID:Interactions between fatty acids and lipoprotein lipase: specific binding and complex formation. 794 38

Interleukin-11/adipogenesis inhibitory factor (IL-11/AGIF) inhibits adipogenesis and suppresses lipoprotein lipase (EC3.1.1.34, LPL) activity in adipocytes (1,2). We investigated the mechanism of suppression of LPL activity in 3T3-L1 adipocytes by IL-11/AGIF. Incubation of adipocytes with 50 ng/ml of IL-11/AGIF led to a 75% decrease in LPL activity within 8 hours, whereas LPL mRNA level decreased by less than 30%. The LPL synthesis, as judged by the incorporation of 35S-label into immunoprecipitable LPL, decreased at almost the same rate over the same time period as enzyme activity. The degradation rate was not significantly affected by IL-11/AGIF. These data suggest that regulation of the synthesis of the enzyme protein is at least one of the main steps in the suppression of LPL by IL-11/AGIF in 3T3-L1 adipocytes.
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PMID:Regulation of lipoprotein lipase synthesis in 3T3-L1 adipocytes by interleukin-11/adipogenesis inhibitory factor. 803 20

This study evaluated the respective and interactive effects of chronic dl-fenfluramine treatment, an anorectic serotoninergic agonist, and gonadectomy on lipoprotein lipase activity in adipose tissue and skeletal muscle. Male and female Sprague-Dawley rats were gonadectomised. These as well as intact animals were treated with dl-fenfluramine or a placebo for 28 days. Gonadectomy brought about an increase in final body weight of females (16-18%, P < 0.0001), but a decrease in that of male animals (9-13%, P < 0.001). These changes were proportional to those of food intake. The increase in body weight of gonadectomised female rats was paralleled by that of retroperitoneal adipose tissue and vastus lateralis muscle weights, whereas in male rats, gonadectomy diminished muscle weight only. Lipoprotein lipase activity was doubled (P < 0.0001) by gonadectomy in adipose tissue of female rats, but remained unaltered by the surgery in male animals. Enzyme activity in muscle was unaffected by gonadectomy in both genders. Treatment with dl-fenfluramine reduced weight gain in males and females, whether they had been gonadectomised or not. A concomitant reduction was observed in adipose tissue mass and lipoprotein lipase activity, which was reduced to 50-65% of the activity measured in placebo-treated animals (P < 0.01). The drug remained without effect on muscle weight and lipoprotein lipase activity in either gender. Thus removal of gonadal steroids had divergent effects on LPL activity with regard to gender and tissue. In addition, dl-fenfluramine treatment was followed by decreased enzyme activity in adipose tissue, but not in muscle, this pattern being independent of the nature or presence of gonadal steroids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue- and gender-specific modulation of lipoprotein lipase in intact and gonadectomised rats treated with dl-fenfluramine. 808 32

The purpose of the present study was to characterize the time course of adaptation (i.e., circulating metabolites and hormones, fat pad mass, lipoprotein lipase) to a high-fat diet in obesity-prone (OP) and obesity-resistant (OR) male Wistar rats. Delineation of OP and OR was based on body weight gain (upper tertile for OP; lower tertile for OR) after 1 wk on a high-fat diet (60% of kcal from corn oil). Rats were killed after 1, 2, or 5 wk of the dietary period. Increased body weight and percent body fat in OP rats at 1 wk could not be accounted for by increased retroperitoneal or epididymal fat pad weight. Plasma nonesterified fatty acids and triglycerides, as well as blood concentrations of glucose, lactate, and glycerol, were similar throughout the study. Plasma insulin was significantly greater in OP vs. OR rats and low-fat diet (LFD; 20% of kcal from corn oil) controls at 5 wk only, and blood beta-hydroxybutyrate (mM) was significantly higher in OR compared with OP and LFD rats at 1, 2, and 5 wk. Lipoprotein lipase mRNA and activity were significantly greater in epididymal fat pad and significantly lower in gastrocnemius muscle of OP vs. OR rats at 1 wk. Results suggest that early (i.e., 1 wk) differences in body weight and fat weight between OP and OR rats are not due to fat deposition in retroperitoneal or epididymal fat depots, and tissue-specific changes in LPL (increase in epididymal fat pad and decrease in gastrocnemius muscle) that occur in OP compared with OR rats after 1 wk on a high-fat diet provide a metabolic environment favoring fat storage.
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PMID:Time course of adaptation to a high-fat diet in obesity-resistant and obesity-prone rats. 809 9

We have recently demonstrated that macrophage conditioned medium (MP medium) and beta VLDL enhance cholesterol esterification in cultured aortic smooth muscle cells by LDL receptor mediated and other pathways (Stein, O. et al. (1993) Arteroscl. Thromb. 13, 1350-1358). In view of the presence of extracellular non-lipoprotein cholesteryl ester (in the form of lipid droplets) in the atheroma, the effect of MP medium on the cellular uptake of liposomal cholesteryl linoleyl ether (CLE) or cholesteryl ester (CE) was studied. After 4 h incubation in MP medium, the uptake of liposomal [3H]CLE was up to 10-fold higher than in the presence of control medium of the same composition but not conditioned with macrophages (DV medium). Similar results were seen also with HSF derived from LDL receptor negative donors. The MP medium-stimulated uptake of liposomal [3H]CE resulted also in hydrolysis of 70-90% of the labeled compound, indicating that the [3H]CE was intracellular. While the MP medium effect on liposomal [3H]CLE uptake was evident after 4 h, its effect on [3H]cholesterol esterification by SMC in the presence of beta VLDL could be demonstrated only after 24 h. Addition of apoE to MP medium resulted in a small (30-40%) increase in the uptake of liposomal [3H]CLE; however, it was augmented more than 4-fold when apoE was added to DV medium. The MP medium effect on the uptake of liposomal [3H]CLE was interfered with by heparin, anti-LPL antibody or heparinase, while these treatments did not affect [3H]cholesterol esterification in the presence of beta VLDL. These results suggest that the interaction between SMC and two potential sources of lipids in atheroma, i.e., lipoproteins and non-lipoprotein lipid droplets, could be governed by different components of the MP medium. In the case of the lipid droplets, as modeled here in the form of liposomes, macrophage-derived lipoprotein lipase could play a major role in cholesteryl ester transfer into SMC.
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PMID:Murine macrophages secrete factors that enhance uptake of non-lipoprotein [3H]cholesteryl ester by aortic smooth muscle cells. 819 1

Binding studies at 37 degrees C showed that lipoprotein lipase-treated very low density lipoproteins (LPL-VLDL) and very low density lipoproteins (VLDL), once taken up via the low density lipoprotein (LDL) receptor, are poorly degraded by HepG2 cells as compared with LDL. Determination of the initial endocytotic rate for LPL-VLDL and VLDL as compared to LDL shows that LPL-VLDL and VLDL are internalized at a similar rate as LDL. Incubation of cells with labeled LDL, LPL-VLDL, and VLDL at 18 degrees C for 4.5 h resulted in the accumulation of these particles in the early endosomes, without subsequent transport to the lysosomes and degradation. After washing the cells and a temperature shift to 37 degrees C, the labeled LDL present in the early endosomes is transported to the lysosomal compartment almost completely within 15 min. Strikingly, for LPL-VLDL and for VLDL, only about 50% or less of the label was moved to the lysosomal compartment within 45 min. However, once present in the lysosomes, VLDL and LPL-VLDL are degraded about 1.6-fold more rapidly than LDL. Retroendocytosis accounts for less than 10% of the internalized LDL, whereas a higher rate of retroendocytosis, up to 20 and 40%, respectively, was observed for LPL-VLDL and VLDL. To evaluate the effect of the inefficient transport of VLDL and LPL-VLDL to the lysosomal compartment on cellular cholesterol homeostasis, acyl-CoA:cholesterol acyltransferase (ACAT) activity was measured. Incubation with 30 micrograms/ml of LDL induced a 2.5-fold increase in ACAT activity, whereas the incubation with similar amounts of both VLDL and LPL-VLDL failed to stimulate this enzyme. We conclude that both a slower transport to the lysosomal compartment and a higher rate of retroendocytosis, possibly as the consequence of the longer residence time in the early endosomes, are responsible for the poor degradation of VLDL and LPL-VLDL by HepG2 cells.
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PMID:Inefficient degradation of triglyceride-rich lipoprotein by HepG2 cells is due to a retarded transport to the lysosomal compartment. 825 28

Although there have been a number of studies of effects of diet and hormones on lipoprotein lipase (EC 3.1.1.34; LPL) activity and levels of LPL mRNA (Raynolds et al. 1990), there have been no studies which have investigated effects of different dietary fatty acids on LPL gene expression. In the present study male Wistar Albino rats were pair-fed diets containing 50 g fat/kg of different fatty acid composition for 2 weeks. The diets fed were (1) a mixed oil (450 g saturated fatty acids, 420 g monounsaturated fatty acids, 130 g polyunsaturated fatty acids/kg; n 8), (2) maize oil (n 8), or (3) fish oil (n 8). Animals were killed, RNA was extracted from liver and perirenal and epididymal fat pads, and analysed by 'Northern methodology'. Samples were hybridized to a human cDNA probe for LPL (Gotoda et al. 1989). Two transcripts were identified in epididymal and perirenal adipose tissue which were approximately 3.7 and 1.7 kb in size. The results suggested that (1) fish oil-fed animals had significantly greater production of LPL mRNA in epididymal adipose tissue compared with maize oil-fed animals (P < 0.05), (2) maize oil-fed animals had significantly greater production of LPL mRNA in perirenal fat compared with the other dietary groups (P < 0.05), (3) expression in the liver was not significant. Rats fed on a fish oil diet had significantly reduced plasma triacylglycerol concentrations compared with the mixed-oil group (P < 0.05), but there were no significant differences in plasma cholesterol. The differences in LPL could not be explained directly by the changes in plasma immunoreactive-insulin and glucose-dependent insulinotrophic polypeptide levels in the three groups.
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PMID:Pretranslational regulation of the expression of the lipoprotein lipase (EC 3.1.1.34) gene by dietary fatty acids in the rat. 829 11


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