Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Tumor necrosis factor (TNF), a protein homologous to cachectin, has been implicated in mediating cachexia. This effect at least in part has been suggested to occur through the influence of the hormone on adipose tissue metabolism. Using fully differentiated 3T3-L1 adipocytes as a model system, we have been investigating the effects of recombinant TNF (rTNF) on key features of adipocyte metabolism. Exposure of fully differentiated 3T3-L1 adipocytes to recombinant tumor necrosis factor resulted in a dose and time-dependent suppression of the activity of lipoprotein lipase. The loss in activity results from an effect on the synthesis of the enzyme, as determined by a decreased incorporation of [35S]methionine into immunoprecipitable lipoprotein lipase. No effect of rTNF on the half-life of the enzyme was observed. General protein synthesis, as judged by [35S]methionine incorporation into acid-insoluble protein, was minimally affected by exposure of the cells to rTNF; this was further confirmed by sodium dodecyl sulfate-polyacrylamide gel analysis of total cellular protein. As opposed to our previously reported results with crude preparations of TNF, no effect on either the ability of the adipocytes to synthesize and store or mobilize triacylglycerol was observed. Our results are consistent with the hypothesis that other hormones present in crude preparations of TNF acting either alone or synergistically with TNF play a major role in the further metabolic derangements associated with adipose tissue during cachexia.
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PMID:Regulation of lipoprotein lipase synthesis by recombinant tumor necrosis factor--the primary regulatory role of the hormone in 3T3-L1 adipocytes. 380 Mar 96

Mycoplasma fermentans is one of several Mycoplasma species that have been reported to stimulate tumor necrosis factor (TNF) secretion from monocytes. This activity has been associated primarily with the mycoplasma membrane fraction. In this article, we have characterized a membrane protein that stimulates TNF and interleukin 1 beta secretion. The TNF-releasing activity partitioned into the Triton X-114 detergent phase, suggesting that the molecules is hydrophobic. The secretion of TNF is elevated in the presence of serum, which suggests that a serum component may play a role in the interaction between this mycoplasma protein and monocytes. Treatment of monocytes with monoclonal anti-CD14 antibody had no effect on the levels of TNF-releasing activity. By using the monocyte Western blot (immunoblot) technique, we have determined the molecular mass of the active molecule to be 48 kDa. This molecule appears to be distinct from the recently described family of variable lipoproteins of M. fermentans. Mycoplasma particulate material treated with proteinase K lost all inducing activity, whereas lipoprotein lipase-treated samples retained some level of activity.
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PMID:A 48-kilodalton Mycoplasma fermentans membrane protein induces cytokine secretion by human monocytes. 752 Apr 21

We demonstrated for the first time that 9,10-dimethyl-1,2-benzanthracene (DMBA)-treated hamsters showed hypertriglyceridemia followed by cachexia. Hypertriglyceridemia is believed to be caused in part by the decreased lipoprotein lipase (LPL) activity, and by cytokines such as tumor necrosis factor (TNF)-alpha. In addition, TNF-alpha action is associated with the LPL activity. Therefore, we determined the content of triglyceride (TG), LPL, and TNF-alpha in the serum from DMBA-treated hamsters. Elevated TG concentration in the serum of tumor-bearing hamsters was more remarkable and preceded the increase in other lipids, whereas the activity of LPL, the key enzyme of TG metabolism in vivo, was drastically reduced. TNF-alpha, known as an endogenous inhibitor of LPL activity, was detected in both the sera and the extract of tumors from DMBA-treated hamsters, whereas it was not detectable in any control samples. Pre-incubation of control sera with exogenous recombinant human TNF-alpha resulted in a potent inhibition of endogenous LPL activity in a dose-dependent manner in vitro. Therefore, the presence of TNF-alpha might lead to the increase in plasma TG mediated by LPL in tumor-bearing hamsters.
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PMID:Hypertriglyceridemia associated with tumor necrosis factor-alpha in hamster cheek-pouch carcinogenesis. 756 Apr 16

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with a hypercatabolic condition. Plasma levels of classical hormones and humoral mediators (prostaglandin E2 and tumor necrosis factor-alpha) are early perturbed after tumor transplantation (Tessitore, L., Costelli, P. and Baccino, F.M. (1993) Humoral mediation for cachexia in tumour-bearing rats. Br. J. Cancer, 67, 16-23). Enhanced protein degradation rates and alteration of lipoprotein lipase activity mainly account for the wasting of protein and adipose mass, respectively. However, the daily intragastric administration of eicosapentaenoic acid (1.5 g/kg body wt) to AH-130 bearing rats was completely ineffective either in preventing tissue waste or in reducing tumor growth. The low degree of differentiation and the high growth rate of the AH0130 hepatoma probably account for this lack of effect.
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PMID:Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth. 758 74

As part of an ongoing search for diabetes susceptibility loci, we tested linkage with non-insulin-dependent diabetes mellitus (NIDDM) for 19 candidate loci or regions chosen for their potential to affect directly or indirectly the action of insulin. Loci were associated with insulin resistance, known effects on lipid metabolism, or effects on glucose metabolism or insulin action. Loci included the insulin-responsive (GLUT4) glucose transporter, hexokinase 2, glucagon, growth hormone, insulin receptor substrate 1 (IRS1), phosphoenolpyruvate carboxykinase, hepatic and muscle forms of pyruvate kinase, hepatic phosphofructokinase, the apolipoprotein B and the apolipoprotein A2 cluster, lipoprotein lipase, hepatic triglyceride lipase, the very-low-density-lipoprotein receptor, and the Pima insulin resistance locus on chromosome 4. For several candidates, no specific informative marker was available; consequently, we tested the surrounding region with highly informative markers. These regions included the diabetes-associated ras-like gene, rad, and the cholesterol ester-transfer gene, both mapped to chromosome 16. Additionally, we tested for linkage with markers at the tumor necrosis factor-alpha gene and the Friedreich's ataxia region. All regions were tested for linkage with microsatellite polymorphisms in > 450 individuals from a minimum of 16 Caucasian families under parametric (LINKAGE 5.1) and nonparametric (affected pedigree member) models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Linkage analysis of 19 candidate regions for insulin resistance in familial NIDDM. 758 21

We assessed the role of catecholamines in mediating the hypertriglyceridemia induced by lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF alpha) in rats by employing specific adrenoreceptor antagonists. Pretreatment with phentolamine, an alpha-antagonist, but not propranolol, a beta-antagonist, suppressed the hypertriglyceridemia induced by either low dose LPS (100 ng/100 g BW) or high dose LPS (50 micrograms/100 g BW). Prazosin, an alpha 1-selective antagonist, significantly suppressed the low dose LPS-induced hypertriglyceridemia by inhibiting hepatic triglyceride secretion, but did not affect the increase in lipolysis. In contrast, yohimbine, an alpha 2-selective antagonist, partially suppressed the high dose LPS-induced hypertriglyceridemia by inhibiting the decrease in postheparin lipoprotein lipase activity. Treatment with phentolamine and propranolol did not affect the hypertriglyceridemia induced by TNF alpha. In summary, these findings suggest that catecholamines via alpha-adrenergic, but not beta-adrenergic, receptors are mediators of the hypertriglyceridemia induced by either low or high dose LPS in rats. alpha 1-Adrenergic receptors are involved in mediating the increased hepatic triglyceride secretion induced by low dose LPS, whereas alpha 2-adrenergic receptors are involved in mediating the decrease in lipoprotein lipase activity induced by high dose LPS. The hypertriglyceridemia induced by either low or high dose LPS may be regulated by a mechanism unrelated to TNF alpha in rats.
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PMID:Alpha-adrenergic receptors mediate the hypertriglyceridemia induced by endotoxin, but not tumor necrosis factor, in rats. 798 54

Cytokines induce a number of changes in lipid metabolism that can produce hyperlipidemia. Leukemia inhibitory factor (LIF), a recently discovered cytokine, has been suggested to play a role in the cancer cachexia syndrome through its ability to decrease lipoprotein lipase (LPL) activity. This study explores the mechanism by which LIP decreases LPL activity in cultured adipocytes and determines its effects on fatty acid synthesis and lipolysis to see if it shares the same catabolic effects on fat cells as seen with other cytokines, such as tumor necrosis factor (TNF). LIF decreased LPL activity in cultured adipocytes by 44% compared with an 85% decrease produced by TNF. Although the percent decrease in LPL activity is not as great in LIF-incubated adipocytes as in TNF-incubated adipocytes, the half-maximal doses for both cytokines are similar. LPL messenger RNA levels paralleled LPL activity in the LIF-treated adipocytes, suggesting that the effect of LIF on LPL activity is predominantly mediated through transcriptional regulation. In contrast to TNF, LIF tended to increase the de novo synthesis of fatty acids. Acetyl coenzyme-A carboxylase messenger RNA levels paralleled the changes seen in fatty acid synthesis for both cytokines. LIF caused a small increase in lipolysis, whereas TNF increased lipolysis by greater than 2-fold. These results demonstrate that the catabolic effects of LIF are weaker than those of TNF and are predominantly directed toward decreasing LPL activity, which may contribute to the hyperlipidemia associated with infection, inflammation, and cancer.
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PMID:Leukemia inhibitory factor induces changes in lipid metabolism in cultured adipocytes. 801 46

Fragments of human adipose tissue were maintained in culture for 1 week in a medium containing 1 mU/ml insulin and 100 ng/ml dexamethasone. Under these conditions lipoprotein lipase activity was present in human adipose tissue fragments which converted [14C]glucose to 14CO2 and [14C]triglyceride. Both metabolic parameters studied were affected by human tumor necrosis factor and brefeldin A. When fragments of human adipose tissue after 1 week in culture were incubated with nicotine tartrate for 20 h, a slight but significant increase in lipoprotein lipase activity was observed, and an increased conversion of [14C]glucose to 14CO2 and [14C]triglyceride occurred. Nicotine was taken up by human adipose tissue, but no conversion to cotinine was observed. Our data demonstrate a direct effect of nicotine on human adipose tissue metabolism. Furthermore, it is suggested that weight loss in smokers is a multifactorial phenomenon, and one of the important factors to be considered is the direct effect of nicotine within the tissue.
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PMID:Metabolic effects of nicotine on human adipose tissue in organ culture. 818 67

Hyperlipidemia is prominent among the disturbances in intermediary metabolism that occur subsequent to infections by microorganisms. The response to such infections is known to involve several cell types and is mediated by cytokines. We hypothesized that metabolic lipid disturbances seen during infection in cystic fibrosis (CF) patients may partly be the result of excessive tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine known to cause a large spectrum of pathophysiologic alterations, including impaired lipid metabolism. Therefore, we determined the circulating concentration of TNF-alpha and analyzed its relationship to lipid and lipoprotein levels, as well as lipoprotein lipase activity, in 31 CF patients. Plasma TNF-alpha values were significantly (p < 0.01) elevated in patients with CF compared with controls. The CF subjects were found to have decreased plasma cholesterol (25%), LDL cholesterol (35%), and HDL cholesterol (19%) concentrations, whereas plasma triglycerides were significantly increased (p < 0.001). The apo A-I level was reduced (p < 0.005), whereas apo B levels were normal. Low levels of the major essential fatty acids were found in the plasma of the CF patients, and the triene/tetraene ratio confirmed their essential fatty acid deficiency. Postheparin lipolytic activity was lower in CF patients than in controls, and the decreased activity was accounted for primarily by a decline in hepatic lipase. A significant positive correlation (p < 0.001, r = 0.70) was found between TNF-alpha and plasma triglyceride levels. However, no association was noted between TNF-alpha and essential fatty acid, cholesterol, or lipoprotein cholesterol levels, or with lipoprotein lipase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circulating tumor necrosis factor-alpha levels and lipid abnormalities in patients with cystic fibrosis. 823 19

The effects of multicytokine inducer, OK-432, on tumor-induced metabolic alterations were studied by assessing three key regulatory enzymes of gluconeogenesis, de novo fatty acid synthesis and the triglyceride clearance pathways. Two Klinish Einheit (KE) of OK-432 was subcutaneously injected on alternate days, for 10 days, into Fischer 344 rats with or without methylcholanthrene-induced sarcoma. At the time of sacrifice, the tumors accounted for approximately 23% of their total body weight. The injections of OK-432 did not affect the amount of food intake in either the tumor bearers or the controls. The tissue lipoprotein lipase activities in the epididymal fat pads of the tumor bearers were significantly decreased compared with the controls (P < 0.01). Phosphoenolpyruvate carboxykinase activity in the liver was significantly increased (P < 0.01), while malic enzyme activity tended to be decreased in the tumor bearers compared with the controls. However, there were no significant differences in those activities depending on the OK-432 injections, even though OK-432 induced tumor necrosis factor (TNF) and increased cytotoxic activities in the mesenteric lymph nodes as well as in the spleen. Thus, although the role of monokines in inducing cancer cachexia is not yet clearly understood, OK-432 was not able to revert the tumor-induced metabolic alterations which lead to tissue wasting and cancer cachexia.
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PMID:The effects of a biological response modifier, OK-432, on tumor-induced alterations in the host metabolism. 836 14


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