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)

Infection causes disturbances in lipid metabolism that may be mediated by cytokines. Therefore we studied plasma lipids, lipoproteins, triglyceride (TG) metabolism, and serum cytokines in three groups: patients with the acquired immunodeficiency syndrome (AIDS) without active secondary infection, patients with evidence of human immunodeficiency virus infection but without clinical AIDS (HIV+), and controls. Plasma TGs and FFA were increased in AIDS, while plasma cholesterol, high density lipoprotein (HDL) cholesterol, apolipoprotein-A-1 (Apo-A-1), low density lipoprotein (LDL) cholesterol, and Apo-B-100 levels were decreased. Increased TG levels in AIDS were primarily due to increases in very low density lipoprotein of normal composition; in addition, LDL and HDL were TG enriched. In HIV+, TGs and FFA were not increased, but total cholesterol, HDL cholesterol, Apo-A-1, and Apo-B-100 were significantly decreased. Interferon-alpha (IFN alpha) and C-reactive protein levels were increased in AIDS, but tumor necrosis factor and haptoglobin levels were not. There was a significant correlation between plasma TGs and IFN alpha levels (r = 0.477; P less than 0.01), but not between TGs and tumor necrosis factor, C-reactive protein, haptoglobin, or P-24 antigen. In addition, there was no relationship between circulating IFN alpha levels and plasma cholesterol, HDL cholesterol, Apo-A-1, LDL cholesterol, Apo-B-100, or FFA. TG clearance time and postheparin lipase were significantly decreased in AIDS and HIV+. There was a strong correlation between serum IFN alpha levels and TG clearance time in AIDS and HIV+ (r = 0.783; P less than 0.001). In summary, decreases in cholesterol and cholesterol containing lipoproteins (including HDL) in both AIDS and HIV+ precede the appearance of hypertriglyceridemia and are not related to IFN alpha or TG levels. Our data raise the possibility that with development of AIDS, subsequent increases in IFN alpha may contribute to increases in plasma TG levels in part by decreasing the clearance of TG.
 ...
PMID:Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. 137 35

Cytokines like tumor necrosis factor (TNF), interferon-gamma (IFN-gamma), and interleukin-1 (IL-1) are known to interfere with the differentiation of cultured cell lines of adipocyte precursors. In the present study, the effect of mouse and rat IFN-gamma, as well as human IL-1 beta, was investigated on rodent preadipocytes in primary cultures, either in the presence of fetal bovine serum (FBS, 10%) or in serum-free defined medium. IFN-gamma exerted an antiproliferative action that was more pronounced when cells reached confluency than during the growth phase of the culture. Morphological observation and quantifications of undifferentiated and differentiating cells revealed that IFN-gamma caused a decrease in the proportion of cells devoid of lipid droplets which would correspond to fibroblast-like cells, whereas preadipocytes remained unaffected. IFN-gamma induced a marked retardation of adipoconversion, resulting in a partial inhibition of lipoprotein lipase (LPL) activity and a severe decrease in glycerol-3-phosphate dehydrogenase (GPDH) activity. The antiproliferative and anti-LPL effects of IFN-gamma were neutralized by adding anti-IFN-gamma antibodies, while these antibodies prevented only partially the depressing effect of IFN-gamma on GPDH activity. Contrary to IFN-gamma, IL-1 beta slightly enhanced the proliferation in preadipocyte cultures. IL-1 beta also depressed adipoconversion, inhibited markedly LPL activity, and partially reduced GPDH activity. These results show that the influence of cytokines on adipoconversion observed in preadipocyte cell lines can be found in normal preadipocytes in culture.
 ...
PMID:Interferon-gamma and interleukin-1 beta inhibit adipoconversion in cultured rodent preadipocytes. 157 4

The release of tumor necrosis factor (TNF), interleukin-1 beta (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) from freshly harvested monocytes and lymphocytes attached to plastic beads was investigated. Previous studies had shown that freshly harvested endothelial cells attached to microcarrier beads release an endothelium-derived relaxing factor. Attachment of freshly harvested lymphocytes and monocytes to plastic beads created a dense network, consisting of 25% monocytes and 75% lymphocytes as shown by flow cytometry. Viability of cells was 90%. Monocytes were characterized by phagocytosis and non-specific esterase stain. Freshly harvested cells stimulated with lipoprotein lipase (LPS) released TNF and IL-1. Non-stimulated cells also produced GM-CSF five hours after collection of blood.
 ...
PMID:Cytokine production from freshly harvested human mononuclear cells attached to plastic beads. 158 69

We previously showed that indomethacin blocked the effect of tumor necrosis factor (TNF) and other cytokines on lipolysis. We now show that TNF stimulates prostaglandin (PG) production, enhances lipolysis and decreases lipoprotein lipase (LPL) activity in 3T3-F442A adipocytes and indomethacin blocks these activities, suggesting that the actions of TNF are mediated by PG's. However, exogenous PGE2 at the levels induced by TNF is not sufficient to affect lipolysis or LPL activity and low doses of indomethacin and flurbiprofen block PG production without affecting TNF's action. Interleukin-1 and interferon-alpha and gamma induce lipolysis and decrease LPL activity but do not stimulate much PG production. These results demonstrate that cytokines enhance lipolysis and decrease LPL activity in 3T3 adipocytes by a PG independent mechanism.
 ...
PMID:Cytokines stimulate lipolysis and decrease lipoprotein lipase activity in cultured fat cells by a prostaglandin independent mechanism. 163 69

To investigate whether interleukin 6 (IL-6) might be a potential mediator of the depleted fat reserves observed in malignancy-associated cachexia, we measured lipoprotein lipase (LPL) activity in adipose tissue of mice after administration of IL-6 or tumor necrosis factor and in cultured adipocytes after addition of these cytokines. Injection of IL-6 i.p. reduced adipose tissue LPL activity by 53% within 4.5 to 5.5 h. Injection of tumor necrosis factor elevated serum IL-6 levels and reduced adipose tissue LPL activity by 70%. Both human and murine IL-6 reduced heparin-releasable LPL activity in 3T3-L1 adipocytes in a dose-dependent manner; half-maximal inhibition of LPL activity was achieved with 5000 hybridoma growth factor units/ml. Thus, IL-6 reduces adipose LPL activity and may contribute to the loss of body fat stores associated with some cases of cancer cachexia. Since tumor necrosis factor increases circulating IL-6, some of its effects may be mediated or potentiated by IL-6.
 ...
PMID:Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L1 adipocytes: a possible role for interleukin 6 in cancer cachexia. 163 23

Apolipoprotein E (apoE) is an important constituent of plasma lipoproteins and a ligand for several lipoprotein receptors. It is produced mainly in the liver but also in several peripheral tissues like brain, adrenal glands, kidney, and macrophages. Some of these tissues also coexpress lipoprotein lipase (LPL), an important enzyme in the metabolism of lipids and lipoproteins. This suggested a possible coordinate expression of these genes and led us to analyze whether adipocytes, a major source of LPL, could also synthesize apoE. Northern blotting experiments showed that apoE mRNA is found in differentiated mouse 3T3-L1 adipocytes as well as biopsies of human adipose tissue maintained in organ culture but not in undifferentiated 3T3-L1 preadipocytes. [35S]Methionine pulse-labeling experiments revealed that apoE protein is produced in human adipose tissue and differentiated mouse 3T3-L1 adipocytes but not in preadipocytes. In biosynthetic labeling experiments, most apoE was found to be cell associated even after prolonged chase periods. Heparin treatment of the cultured cells did not enhance apoE secretion. During differentiation of 3T3-L1 cells, the onset of apoE gene expression was later than that of LPL. The apoE mRNA and intracellular apoE protein concentrations increased linearly with time of differentiation, at least through day 11, whereas LPL showed highest expression at day 7 and then declined. The increase in apoE mRNA correlated with the cellular lipid content. Inhibition of lipid accumulation in differentiated cells by biotin deprivation decreased apoE expression. Cholesterol-loading experiments suggested that apoE mRNA expression is regulated by the intracellular free cholesterol content of 3T3-L1 adipocytes. In contrast, the LPL mRNA level was not influenced by biotin deprivation or cholesterol loading. Human recombinant tumor necrosis factor, a potent inhibitor of LPL gene transcription, had no effect on adipocyte apoE mRNA levels. Therefore, although apoE and LPL are both expressed in adipocytes in a differentiation-dependent manner, the time course of their expression differs as do their responses to cellular lipid content and tumor necrosis factor. We conclude that these genes are not coordinately regulated in adipocytes.
 ...
PMID:Apolipoprotein E gene expression in mouse 3T3-L1 adipocytes and human adipose tissue and its regulation by differentiation and lipid content. 170 37

A rise in plasma triglycerides has been noted after thermal injury in a number of animal species including humans. In this study we identified a factor, tumor necrosis factor, which was responsible for increased plasma triglycerides during thermal injury that was induced by scalding. Two strains of mice that differed genetically in susceptibility to lipopolysaccharides were used. These were CH3HEB/HeJ (LPS-) and CH3HEB/FeJ (LPS+). A 15% total body surface area was burned; this resulted in an increase of plasma triglycerides of 126% of preburn levels in the LPS+ strain 24 hours after burn injury. No change in triglycerides was noted in the LPS- mice at any time after burn injury. Sera from LPS+ mice at 1 to 2 hours after burn injury was injected into nonburned animals of the same strain; this caused a 62% +/- 5% increase in plasma triglycerides 24 hours after injection. When thermally injured LPS+ mice were injected with anti-tumor necrosis factor-alpha at 1 hour after injury, they did not show a rise in plasma triglycerides at any time between 24 to 72 hours after injury. Hepatic secretion of triglycerides was also measured 1 day after burn; the average secretion of triglycerides was significantly reduced (2.69 +/- 0.36 mg/kg/hr, compared with 3.83 +/- 0.15 mg/kg/hr for the control). We conclude that tumor necrosis factor, a cytokine that inhibits lipoprotein lipase, causes hypertriglyceridemia during thermal injury in spite of a decreased secretion of triglycerides. This is the first report that demonstrates that hypertriglyceridemia that is secondary to thermal injury is induced by tumor necrosis factor.
 ...
PMID:Tumor necrosis factor mediates hypertriglyceridemia during thermal injury in mice genetically susceptible to lipopolysaccharides. 175 82

Fully differentiated 3T3-L1 adipocytes were chronically exposed to 5 nM tumor necrosis factor-alpha (TNF). This resulted in the development of an insulin resistance based on the inability of insulin to stimulate hexose uptake. Western blot analysis for glucose transporter protein in isolated membrane fractions indicated a total depletion of GLUT4 protein (insulin-responsive glucose transporter) in cells chronically treated with TNF. Plasma membrane content of GLUT1 protein (growth-related glucose transporter) was similar in both control and TNF-treated cells; however, the GLUT1 content of the intracellular membrane compartment had decreased markedly after TNF treatment. Continuous exposure to TNF resulted in an 85-90% decrease in the mRNA content for both GLUT4 and 422 (aP2, a lipid binding protein) genes relative to age matched controls, whereas insulin receptor mRNA levels declined by at least 50%. This was preceded by a marked decrease in mRNA accumulation for C/EBP, a transcription factor proposed to control expression of both GLUT4 and 422. The specificity of these observations was demonstrated by the lack of an effect of the chronic TNF treatment on either beta-actin or lipoprotein lipase mRNA content. The decreased content of GLUT4 and C/EBP mRNA was judged to be regulated at least in part at the level of transcription, based on the results of transcription run-on assays. Thus, the lack of response to insulin appeared due to a suppression of GLUT4 expression as well as a decreased intracellular content of GLUT1.
 ...
PMID:Transcriptional repression of the GLUT4 and C/EBP genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. 193 8

Previous studies demonstrated that administration of tumor necrosis factor (TNF) to diabetic rats rapidly increases serum triglyceride levels and stimulates hepatic lipogenesis without affecting the activity of adipose tissue lipoprotein lipase or serum insulin levels. The purpose of this study was to determine the mechanism by which TNF increases serum triglyceride levels and stimulates hepatic fatty acid synthesis in diabetic animals. The maximal increase (approximately 2-fold) in serum triglyceride levels in diabetic rats is seen with a dose of 10 micrograms TNF/200 g body wt, and the half-maximal effect is observed with 5 micrograms TNF/200 g body wt. The clearance of labeled triglyceride-rich lipoproteins from the circulation is not affected by TNF administration (triglyceride t 1/2; diabetic vs. TNF-administered diabetic, 3.5 +/- 0.7 vs. 4.0 +/- 0.6 min, respectively; NS). The production of triglyceride, measured by the Triton WR-1339 technique, is increased twofold in diabetic animals after TNF administration. These results indicate that the rapid increase in serum triglyceride levels after TNF treatment is accounted for by increased hepatic lipoprotein secretion. TNF administration did not alter either the amount or activation state of hepatic acetyl-CoA carboxylase, a key regulatory enzyme in fatty acid synthesis. There was also no change in the hepatic levels of fatty acyl-CoA, an allosteric inhibitor of acetyl-CoA carboxylase. However, there was a 71% increase in hepatic citrate concentrations. Citrate is an allosteric activator of acetyl-CoA carboxylase, and changes in hepatic citrate concentrations have been shown to mediate changes in the rates of fatty acid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tumor necrosis factor-increased hepatic very-low-density lipoprotein production and increased serum triglyceride levels in diabetic rats. 197 29

The effects of (human recombinant) tumor necrosis factor-alpha on phosphatidylinositol breakdown, release of 1,2-diacylglycerols, mobilization of arachidonate from diacylglycerol and prostaglandin synthesis were examined in a model osteoblast cell line (MC3T3-E1). Tumor necrosis factor-alpha (10 nM) caused a specific (30%) decrease in the mass of phosphatidylinositol (and no other phospholipids) within 30 min of exposure. Tumor necrosis factor-alpha doubled the rate of incorporation of [32P]orthophosphoric acid into phosphatidylinositol, indicating that the turnover of inositol phosphate was enhanced, and increased the content of diacylglycerol in parallel with phosphatidylinositol breakdown. The cytokine (10-50 nM; 4 h) also promoted a specific release of 24-34% of the [3H]arachidonate from prelabeled phosphatidylinositol, a release of 80% of the 3H-fatty acid from the diacylglycerol pool, and a 30-fold increase in the synthesis of prostaglandin E2. The tumor necrosis factor-alpha induced liberation of [3H]arachidonate from diacylglycerol, cellular arachidonate release and the synthesis of prostaglandin E2 were each blocked by an inhibitor of diacylglycerol lipase, the compound RHC 80267 (30 microM). Therefore, we conclude that, in the MC3T3-E1 cell line, tumor necrosis factor-alpha activates a phosphatidylinositol-specific phospholipase C (phosphatidylinositol inositolphosphohydrolase; EC 3.1.4.3) to release diacylglycerol, and increases the metabolism of diacylglycerol to liberate arachidonate for prostaglandin synthesis.
 ...
PMID:Tumor necrosis factor-alpha stimulates phosphatidylinositol breakdown by phospholipase C to coordinately increase the levels of diacylglycerol, free arachidonic acid and prostaglandins in an osteoblast (MC3T3-E1) cell line. 200 18


1 2 3 4 5 6 7 8 9 10 Next >>