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)

Previous studies have demonstrated that some cytokines induce a coordinate catabolic response in adipose cells which leads to decreased fat storage. The mechanisms by which cytokines cause these effects are unknown. The primary purpose of the present study was to determine the effects of TNF, IL-1, IFN-alpha and IFN-alpha on the mRNA levels of the key enzymes involved in fat metabolism in 3T3-F442A adipocytes. TNF, IL-1, IFN-alpha and IFN-gamma decreased lipoprotein lipase activity and increased lipolysis in adipocytes. TNF, IFN-alpha and IFN-gamma decreased fatty acid synthesis while IL-1 increased fatty acid synthesis. However, the cytokine effects on mRNA levels were not always consistent with the observed changes in activity and were unique for each cytokine. Specifically, while all cytokines decreased LPL activity, only TNF and IFN-gamma decreased LPL mRNA levels. In addition, while TNF, IFN-alpha and IFN-gamma decreased fatty acid synthesis, only TNF significantly decreased the mRNA levels of both acetyl CoA carboxylase and fatty acid synthase, the key enzymes in fatty acid synthesis. IFN-alpha and IFN-gamma decreased fatty acid synthase mRNA levels without significantly altering acetyl CoA carboxylase mRNA. IL-1 caused a slight increase in fatty acid synthesis and increased acetyl CoA carboxylase mRNA levels. Finally, while all cytokines increased lipolysis, hormone sensitive lipase mRNA levels were decreased by TNF, IFN-alpha and IFN-gamma treatment. These results indicate that the regulation of adipocyte lipid metabolism by cytokines is complex and that coordinate changes in mRNA levels cannot account for the observed metabolic changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines induce catabolic effects in cultured adipocytes by multiple mechanisms. 782 85

The regulation of macrophage lipoprotein lipase (LPL) by cytokines is of potentially crucial importance in the pathogenesis of atherosclerosis. The effect of combinations of interleukin 1 (IL-1), 6 (IL-6), and 11 (IL-11), interferon gamma (INF-gamma), leukaemia inhibitory factor (LIF) and tumour necrosis factor alpha (TNF-alpha) on the expression of LPL in macrophages was studied using the murine J774.2 cell line. The suppression of heparin-releasable LPL activity produced by combinations of IL-1 and IL-11, IL-1 and TNF-alpha, IL-11 and TNF-alpha, and, IL-11 and INF-gamma was substantially lower than that expected from the additive action of the corresponding two cytokines. By contrast, co-exposure of cells to LIF and IFN-gamma, IL-6 and LIF, and INF-gamma and TNF-alpha resulted in a more than additive, synergistic, suppression of LPL activity with the maximum reduction and maximum degree of synergism produced by combinations of IFN-gamma and TNF-alpha. The synergism between IFN-gamma and TNF-alpha was observed over a range of complementary dose combinations and also occurred when the cells were exposed first to INF-gamma (priming), washed, and then stimulated subsequently with TNF-alpha. The reduction in LPL activity by combinations of IFN-gamma and TNF-alpha and the priming action of IFN-gamma were accompanied by a comparable decrease in LPL mRNA concentrations, thereby indicating that the major control responsible for the changes in LPL activity was being exerted at the level of mRNA metabolism (decreased transcription or RNA stability). These results suggest that the modulation of macrophage LPL function in atherosclerosis by cytokine combinations may be more important than the presence or absence of any given cytokine.
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PMID:Synergism between interferon gamma and tumour necrosis factor alpha in the regulation of lipoprotein lipase in the macrophage J774.2 cell line. 950 44

The regulation of macrophage lipoprotein lipase (LPL) by cytokines is potentially of crucial importance in the pathogenesis of atherosclerosis and in septic shock. The effect of combinations of lipopolysaccharide (LPS) and cytokines on the expression of LPL in macrophages was studied using the murine J774.2 cell line. The suppression of heparin-releasable LPL activity produced by combinations of LPS and interleukin 1 (IL-1), IL-11 or tumour necrosis factor alpha(TNF-alpha) was substantially less than that expected from the simple additive action of the corresponding two effectors. By contrast, co-exposure of the cells to LPS and interferon gamma(IFN-gamma) resulted in a more than additive, synergistic, suppression of LPL activity which was, additionally, also observed when the rat alveolar macrophage NR8383 cell line was studied. This synergistic action was also observed when J774.2 macrophages were exposed initially to IFN-gamma (priming), washed and then treated with LPS. A comparison of the LPL activity and mRNA levels produced by the synergistic action of LPS and IFN-gamma and the priming action of IFN-gamma indicated that a combination of mRNA metabolism (transcription or RNA stability), translation and post-translational mechanisms were responsible for the observed changes in LPL activity. These data, therefore, suggest that combinations of LPS and cytokines may be more important than the presence or absence of any given single effector in the modulation of LPL function during infection.
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PMID:Synergism between lipopolysaccharide and interferon gamma in the regulation of lipoprotein lipase in macrophages. 1034 80

In a clinical trial for adeno-associated virus serotype 1 (AAV-1)-mediated gene transfer to muscle for lipoprotein lipase (LPL) deficiency, 1 subject from the high-dose cohort experienced a transient increase in the muscle enzyme creatine phosphokinase (CPK) 4 weeks after gene transfer. Simultaneously, after an initial downward trend consistent with expression of LPL, plasma triglyceride levels returned to baseline. We characterized B- and T-cell responses to the vector and the transgene product in the subjects enrolled in this study. IFN-gamma enzyme-linked immunosorbent spot (ELISpot) and intracellular cytokine staining assays performed on peripheral blood mononuclear cells (PBMCs) from the subject who experienced the CPK elevation showed the activation of capsid-specific CD4(+) and CD8(+) T cells. Four of 8 subjects had detectable T-cell responses to capsid with dose-dependent kinetics of appearance. Subjects with detectable T-cell responses to capsid also had higher anti-AAV-1 IgG3 antibody titer. No subject developed B- or T-cell responses to the LPL transgene product. These findings suggest that T-cell responses directed to the AAV-1 capsid are dose-dependent. Whether they also limit the duration of expression of the transgene at higher doses is unclear, and will require additional analyses at later time points.
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PMID:AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells. 1972 32