CYTOKINES INDUCE CATABOLIC EFFECTS IN CULTURED ADIPOCYTES BY MULTIPLE MECHANISMS
CYTOKINES INDUCE CATABOLIC EFFECTS IN CULTURED ADIPOCYTES BY MULTIPLE MECHANISMS
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DOI：
10.1016/1043-4666(94)90074-4
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发表时间：
1994-09-01
期刊：
影响因子：
3.8
通讯作者：
GRUNFELD, C
中科院分区：
文献类型：
--
作者：
DOERRLER, W;FEINGOLD, KR;GRUNFELD, C
以往的研究表明，某些细胞因子在脂肪细胞中诱导协调的分解代谢反应，从而导致脂肪储存减少。细胞因子导致这些效应的机制尚不清楚。本研究的主要目的是探讨肿瘤坏死因子、白介素1、干扰素-α和干扰素-α对3T3-F442A脂肪细胞脂肪代谢关键酶基因表达的影响。肿瘤坏死因子、白介素1、干扰素-α和干扰素-γ降低脂肪细胞脂蛋白脂酶活性，增加脂肪细胞的脂解作用。肿瘤坏死因子、干扰素-α和干扰素-γ使脂肪酸合成减少，而IL-1增加脂肪酸合成。然而，细胞因子对mRNA水平的影响并不总是与观察到的活性变化一致，并且对每种细胞因子都是独特的。具体地说，虽然所有的细胞因子都降低了LPL的活性，但只有肿瘤坏死因子和干扰素-γ降低了LPL的mRNA水平。此外，虽然肿瘤坏死因子、干扰素-α和干扰素-γ降低了脂肪酸的合成，但只有肿瘤坏死因子显著降低了脂肪酸合成的关键酶--乙酰辅酶A羧基酶和脂肪酸合成酶的mRNA水平。干扰素-α和干扰素-γ可降低脂肪酸合酶基因表达水平，但对乙酰辅酶A羧基酶基因表达无明显影响。IL-1使脂肪酸合成略有增加，乙酰辅酶A羧基酶基因表达水平升高。最后，在所有细胞因子促进脂解的同时，肿瘤坏死因子、干扰素-α和干扰素-γ处理降低了激素敏感脂肪酶的mRNA水平。这些结果表明，细胞因子对脂肪细胞脂代谢的调节是复杂的，并且mRNA水平的协调变化不能解释观察到的代谢变化。每种细胞因子通过不同的信号通路发挥作用，并在3T3-F442a脂肪细胞中诱导特定的代谢改变和mRNA调节模式。
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. Each cytokine works via a different signalling pathway and induces specific patterns of metabolic alterations and mRNA regulation in 3T3-F442A adipocytes.