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)

The presence of cachectin or tumor necrosis factor (TNF) associated with hypertriglyceridemia was demonstrated in the serum of patients with pulmonary tuberculosis. The hyperlipidemia that accompanies this infection may be mediated by the TNF inhibition of lipoprotein lipase activity. This sequence of events may be sufficient to explain, in part, the complex metabolic changes and emaciation observed in tuberculosis patients.
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PMID:The role of cachectin/TNF in the pathogenesis of tuberculosis. 314 96

Thioglycollate-elicited mouse peritoneal macrophages spontaneously secrete lipoprotein lipase during culture. Exposure of the cultures to 50 ng/ml of recombinant human tumor necrosis factor (rTNF) for 48 h resulted in a 69% reduction in lipoprotein lipase activity in the culture medium with a concomitant decrease in cellular enzyme activity. The decrease in enzyme activity was not the result of rTNF-dependent reduction in the total protein synthesis, since the presence of rTNF did not affect [3H]leucine incorporation into cellular proteins. The effect of rTNF on lipoprotein lipase was reversible; upon TNF withdrawal, enzyme activity returned to basal levels after 60 h. The reduction of lipoprotein lipase in rTNF-treated cultures could be completely prevented by preincubation with a specific antiserum against recombinant human TNF. The late onset of decrease of lipoprotein lipase (LPL) activity suggests that rTNF might induce a mediator, which in turn suppresses LPL production. While rTNF was very effective in reducing lipoprotein lipase activity in mouse peritoneal macrophages, it did not affect lipoprotein lipase activity when added to the murine J774 cell line and to CT2 macrophage-like cells, a variant of the J774 cell line.
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PMID:Modulation of lipoprotein lipase activity in mouse peritoneal macrophages by recombinant human tumor necrosis factor. 319 26

Human monocyte-derived macrophages secrete lipoprotein lipase (LPL) in culture. The regulation of human macrophage LPL production is poorly understood. Since bacterial lipopolysaccharide (LPS) alters production of several macrophage secretory products, its effect on human monocyte-derived macrophage LPL was tested. LPS treatment produced a dramatic dose-dependent decrease in LPL activity in macrophage-conditioned media. At 100 ng/ml LPS, medium LPL activity dropped by 60%. The effect of LPS on macrophage LPL activity was rapid, was blocked by polymixin B, and was not due to cytotoxicity. LPS lowers (by about 60%) the steady state level of LPL mRNA, suggesting that its effect is exerted at the level of mRNA metabolism. Since LPS stimulates macrophage production of cachectin/tumor necrosis factor (TNF), a potent inhibitor of LPL production by the 3T3-L1 adipocyte-like cell line, it was determined whether TNF reduces macrophage LPL levels. Treatment of human macrophages with up to 1000 U/ml of recombinant human TNF had no effect on macrophage LPL activity. When TNF was added in combination with LPS, no additional effect on LPL activity was observed over that seen with LPS alone. Furthermore, the LPS effect was not blocked by a monoclonal anti-TNF antibody. Thus, bacterial LPS potently decreases macrophage LPL activity and mass independent of an autocrine effect of TNF.
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PMID:Bacterial lipopolysaccharide reduces macrophage lipoprotein lipase levels: an effect that is independent of tumor necrosis factor. 323 20

Exposure of rat heart cell cultures, consisting mainly of nonbeating mesenchymal cells, to 50 ng/ml of bacterial lipopolysaccharide (LPS) for 24 h resulted in a more than 80% reduction in lipoprotein lipase activity. The loss of enzymic activity was accompanied by a concomitant reduction in enzyme protein, as shown by immunoblotting. Addition of LPS to the culture medium resulted also in the production of tumor necrosis factor (TNF), and the fall in lipoprotein lipase in LPS-treated cultures could be prevented by an antibody to TNF. Addition of recombinant human TNF to the heart cell cultures also depressed lipoprotein lipase activity. LPS treatment of preadipocytes in culture resulted in a fall in lipoprotein lipase activity and TNF production. Since TNF is known as a macrophage product, the cultures were tested for phagocytic capacity, and only 0.2-1.3% of the cells were shown to engulf Staphylococcus albus. Immunofluorescent staining with monoclonal antibodies OX-1, which identify leukocyte common antigen, was negative, and only 0.1 +/- 0.07% of the cells were positive after staining with OX-42 antibody to iC3b receptor. Both antibodies stained more than 98% of rat peritoneal macrophages used as controls. Since LPS treatment of macrophages at numbers comparable to or exceeding the number of phagocytic cells present in the heart cell cultures did not induce measurable amounts of TNF, it is suggested that in the heart cell cultures, TNF may be produced by cells other than macrophages.
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PMID:Lipoprotein lipase in heart cell cultures is suppressed by bacterial lipopolysaccharide: an effect mediated by production of tumor necrosis factor. 328 93

Levels of mRNA for lipoprotein lipase (LPL) in guinea pig epididymal adipose tissue, heart and liver were determined by dot blot analysis of total RNA using a cDNA probe complementary to the coding region, and compared to the LPL activity. For adipose tissue we also measured the incorporation of radioactivity into immunoprecipitable LPL after pulse-labeling with [35S]methionine. LPL activity was 93%, LPL mRNA 82% and LPL synthesis 85% lower in epididymal fat pads from animals fasted for 48 h compared to rigorously fed animals. In contrast, neither LPL activity nor LPL mRNA levels differed in heart. A single dose of tumor necrosis factor (TNF) decreased LPL activity and LPL mRNA in fat pads with no effects in heart. In the liver, TNF caused a marked increase in LPL mRNA levels, which are normally very low. Northern-blot analysis confirmed a previous observation that the patterns of mRNA species differ between heart, in which a 3.8-kb mRNA dominates, and adipose tissue, in which the LPL mRNAs of 3.3 and 2.1 kb occur in similar abundance as the 3.8-kb species.
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PMID:Tissue-specific regulation of guinea pig lipoprotein lipase; effects of nutritional state and of tumor necrosis factor on mRNA levels in adipose tissue, heart and liver. 339 78

Previous studies have demonstrated that cachectin/tumor necrosis factor (TNF) inhibits lipoprotein lipase (LPL) activity in cultures of 3T3-L1 cells. To determine whether TNF also inhibits LPL in human adipocytes, primary cultures of isolated human adipocytes were exposed to a spectrum of concentrations of recombinant human TNF. TNF concentrations up to 1000 pM had no effect on either LPL activity or LPL immunoreactive mass in the human adipocytes. Specific binding of 125I-labeled TNF was demonstrated in human adipocytes, and a TNF concentration of 100 pM competed for approximately 50% of the 125I-labeled TNF binding sites. In contrast, the same TNF in the same concentrations progressively inhibited LPL activity and immunoreactive mass in 3T3-L1 cells. Thus, human adipocytes respond to TNF in a different manner than 3T3-L1 cells. TNF may not cause the cachexia of cancer or chronic infection by directly inhibiting LPL in adipose tissue.
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PMID:Recombinant human tumor necrosis factor does not inhibit lipoprotein lipase in primary cultures of isolated human adipocytes. 341 Dec 49

Lipopolysaccharide (LPS) modulates macrophage functions and induces the synthesis and secretion of tumor necrosis factor (TNF) and interleukin 1 (IL-1) in these cells. The latter two factors but not LPS suppress lipoprotein lipase (LPL) synthesis and secretion in adipocytes. Since the regulation of LPL secretion in macrophages is rather poorly understood, we investigated the effect of the macrophage activator LPS on LPL secretion by macrophages. LPS suppressed in a dose- and time-dependent manner the heparin-induced secretion of LPL from the macrophage-like tumor cell line J774.1 and from bone marrow derived mononuclear phagocytes (BMM). Suppression of LPL secretion from J774.1 and that from BMM reached about 66 and 50%, respectively, within 8 h of exposure to 500 ng/ml LPS. LPS did not inhibit the enzymic activity of LPL when added directly to the cell free enzyme assay system. Human recombinant TNF (1000 U/ml) and murine recombinant IL-1 (100 U/ml) did not affect LPL secretion or cell proliferation in the J774.1 cell line over a period of 72 and 24 h, respectively. Thus LPS regulates macrophage secretion of LPL in a mechanism independent of the induction of autocrine production of TNF and IL-1, and possesses a disparate pattern of regulation to that expressed by adipose tissue cells.
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PMID:Bacterial lipopolysaccharide suppresses the expression of lipoprotein lipase in murine macrophages: a process independent of tumor necrosis factor or interleukin 1. 349 89

A single dose of recombinant murine tumor necrosis factor (TNF) suppressed lipoprotein lipase activity in adipose tissue of fed rats, mice, and guinea pigs for 48 h, even though TNF itself is rapidly metabolized in vivo. Immunoprecipitation of [35S]lipoprotein lipase from fat pads pulse-labeled with [35S]methionine showed a decrease in relative synthesis of the enzyme, which correlated to the decrease in activity. There was no decrease in general protein synthesis and no change in distribution of the enzyme between adipocytes and extracellular locations in the tissue. This is in contrast to fasting in which case there is redistribution of the enzyme within the tissue, decrease in general protein synthesis, but no change in relative synthesis of lipoprotein lipase. TNF did not decrease lipoprotein lipase activity in any tissue other than the adipose but increased the activity in several cases, most markedly in the liver. No [35S]methionine was incorporated into lipoprotein lipase by liver slices from normal or TNF-treated animals. Thus, the increased activity can not be ascribed to enhanced hepatic synthesis of the enzyme. There was an increase in lipoprotein lipase activity in plasma, which correlated to the increase in liver. Thus, TNF suppresses lipoprotein lipase synthesis in adipocytes, but not in other tissues, and has some as yet undefined effect on lipoprotein lipase turnover in extrahepatic tissues, which results in increased transport of active lipase through plasma to the liver.
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PMID:Multiple effects of tumor necrosis factor on lipoprotein lipase in vivo. 359 77

The hyperlipidemia accompanying infection has been attributed to production of tumor necrosis factor. This cytokine inhibits adipose tissue lipoprotein lipase, which could decrease clearance of lipoproteins. Infections also increase hepatic lipogenesis. We now have demonstrated that tumor necrosis factor-alpha stimulates lipid synthesis in vivo. 2 h after administration of tumor necrosis factor (25 micrograms/200 g), plasma triglycerides increase 2.2-fold and remain elevated for 17 h. Plasma cholesterol also increases, but this effect appears after 7 h. Tumor necrosis factor rapidly stimulates incorporation of tritiated water into fatty acids in the liver (1-2 h), which persists for 17 h. Also, tumor necrosis factor stimulates hepatic sterol synthesis. Of note, tumor necrosis factor treatment does not stimulate lipid synthesis in other tissues, including adipose tissue. Labeled fatty acids rapidly increase in the plasma, raising the possibility that stimulation of hepatic lipogenesis by tumor necrosis factor contributes to the hyperlipidemia of infection.
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PMID:Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo. 359 72

Tumor necrosis factor is a monokine, which causes cytolysis of many transformed cells. In this study we have found that in addition to cytotoxicity recombinant Escherichia coli-derived human tumor necrosis factor, like cachectin, inhibited the lipoprotein lipase of 3T3-L1 preadipocytes. Both effects were inhibited by monoclonal anti-tumor necrosis factor antibodies. Monoclonal antibodies against recombinant human tumor necrosis factor were produced by fusing splenocytes of immune mice with P3X63Ag8 653 myeloma cells. The monoclonal antibodies, namely BG 2-4, were of IgG2a, IgG, and IgG2a subclasses. These monoclonal antibodies neutralized the cytotoxicity of natural and recombinant human tumor necrosis factor but not that of rabbit or mouse tumor necrosis factor. They also neutralized the cachectin activity of human tumor necrosis factor in the 3T3-L1 embryonic cell assay. These results indicate that the functional structure(s) of human tumor necrosis factor responsible for the cytotoxicity and cachectin activities are likely to be closely related.
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PMID:Production and characterization of monoclonal antibodies against recombinant human tumor necrosis factor/cachectin. 372 42


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