首页> 外文期刊>Molecular and Cellular Biology >Recombinant human cachectin/tumor necrosis factor but not interleukin-1 alpha downregulates lipoprotein lipase gene expression at the transcriptional level in mouse 3T3-L1 adipocytes.
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Recombinant human cachectin/tumor necrosis factor but not interleukin-1 alpha downregulates lipoprotein lipase gene expression at the transcriptional level in mouse 3T3-L1 adipocytes.

机译:重组人类Cachectin /肿瘤坏死因子,但白介素-1α不能在小鼠3T3-L1脂肪细胞的转录水平下调脂蛋白脂肪酶基因的表达。

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Lipoprotein lipase (LPL) is synthesized primarily in muscle and adipose tissue and by hydrolyzing triglycerides in chylomicrons and very low density lipoprotein allows uptake of the resultant free fatty acids by these tissues. This report describes the cloning of the mouse LPL gene from which probes were derived to study the regulation of LPL synthesis in the 3T3-L1 adipocyte cell culture system. Preconfluent 3T3-L1 preadipocytes had very small amounts of LPL mRNA (less than 1 pg/micrograms of RNA). At confluency, LPL mRNA levels increased to 5 to 15 pg/micrograms of RNA. After insulin and dexamethasone were added, LPL activity and mRNA levels rose in parallel. Peak mRNA levels were reached within 4 to 10 days, achieving LPL mRNA concentrations of 150 to 500 pg/micrograms of RNA. This represents a 15- to 50-fold increase over confluent cells. Two cytokines known to diminish adipose tissue LPL activity were studied to see how their effects were regulated. Recombinant human cachectin/tumor necrosis factor diminished both LPL activity and LPL mRNA levels. The effect on LPL activity compared with mRNA levels was quicker, at a lower dose, and more complete (95 versus 75% maximum effect). The effect of recombinant human cachectin tumor necrosis factor on LPL mRNA levels was shown by nuclear run-on experiments to be exerted transcriptionally. It was also independent of new protein synthesis. Recombinant human interleukin-1 alpha diminished only LPL activity but not mRNA levels. This study suggests that during times of stress, cytokines secreted by activated macrophages can alter energy balance by affecting transcriptional and posttranscriptional processes in adipocytes.
机译:脂蛋白脂肪酶(LPL)主要在肌肉和脂肪组织中合成,并通过水解乳糜微粒中的甘油三酸酯,并且非常低密度的脂蛋白允许这些组织吸收所得的游离脂肪酸。该报告描述了小鼠LPL基因的克隆,从中克隆了探针以研究3T3-L1脂肪细胞培养系统中LPL合成的调控。融合前的3T3-L1前脂肪细胞具有非常少量的LPL mRNA(少于1 pg /微克RNA)。汇合时,LPL mRNA水平增加至5至15 pg /微克RNA。加入胰岛素和地塞米松后,LPL活性和mRNA水平平行上升。在4至10天内达到峰值mRNA水平,使LPL mRNA浓度达到150至500 pg /微克RNA。这表示比融合细胞增加了15到50倍。研究了两种已知会降低脂肪组织LPL活性的细胞因子,以了解它们的作用是如何调节的。重组人恶病质/肿瘤坏死因子减少了LPL活性和LPL mRNA水平。与mRNA水平相比,对LPL活性的影响更快,剂量更低且更完整(最大影响为95%相对于75%)。核运行实验表明重组人恶病质素肿瘤坏死因子对LPL mRNA水平的影响是转录作用。它也独立于新的蛋白质合成。重组人白细胞介素1α仅降低LPL活性,但不降低mRNA水平。这项研究表明,在压力时期,活化巨噬细胞分泌的细胞因子可以通过影响脂肪细胞的转录和转录后过程来改变能量平衡。

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