The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol

The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol
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肿瘤坏死因子-α 或异丙肾上腺素可增强脂肪细胞产生凝血因子 VII

DOI:
10.1038/ijo.2014.208
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发表时间:
2015
影响因子:
4.9
通讯作者:
M Ieko
M Ieko
中科院分区:
医学2区
文献类型:
--
作者:
N Takahashi;T Yoshizaki;N Hiranaka;O Kumano;T Suzuki;M Akanuma;T Yui;K Kanazawa;M Yoshida;S Naito;M Fujiya;Y Kohgo;M Ieko

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背景:有报道称凝血因子VII(FVII)的血药浓度与肥胖之间存在相关性。除了其在凝血中的作用之外,FVII还显示出抑制脂肪细胞中的胰岛素信号。然而,FVII的生产脂肪cytes.Objective:我们在此调查的生产和分泌的FVII脂肪细胞,特别是在肥胖相关的条件,包括脂肪炎症和交感神经activation.Methods:C57 B1/6 J小鼠喂养低或高脂饮食和FVII信使RNA(mRNA)的表达,然后在脂肪组织中进行了检查。将3 T3-L1细胞用作体外实验的脂肪细胞模型,其中这些细胞用肿瘤坏死因子-α(TNF-α)或异丙肾上腺素处理。结果:高脂组小鼠脂肪组织中FVII mRNA的表达量显著高于低脂组小鼠,高脂组小鼠脂肪组织中FVII mRNA的表达量显著高于低脂组小鼠。FVII基因和蛋白的表达在脂肪形成过程中被诱导,并在成熟脂肪细胞中维持。TNF-α处理的3 T3-L1脂肪细胞培养液中FVII mRNA的表达和分泌增加,而这些作用在这些细胞暴露于丝裂原活化激酶或NF-κB活化的抑制剂时被阻断。β-肾上腺素受体激动剂异丙肾上腺素通过环AMP/蛋白激酶A途径刺激成熟脂肪细胞分泌FVII。用抗FVII抗体阻断FVII的分泌并不影响异丙肾上腺素刺激的脂肪细胞中Akt的磷酸化。TNF-α和异丙肾上腺素通过不同的机制促进脂肪细胞产生和分泌FVII。这些结果表明,FVII是一种脂肪因子,在肥胖的发病机制中起着重要作用。
Background:A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear.Objective:We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation.Methods:C57Bl/6J mice were fed a low-or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays.Results:The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. The β-adrenoceptor agonist isoproterenol stimulated the secretion of FVII from mature adipocytes via the cyclic AMP/protein kinase A pathway. Blockade of secreted FVII with the anti-FVII antibody did not affect the phosphorylation of Akt in the isoproterenol-stimulated adipocytes.Conclusion:Obese adipose tissue produced FVII. The production and secretion of FVII by adipocytes was enhanced by TNF-α or isoproterenol via different mechanisms. These results indicate that FVII is an adipokine that plays an important role in the pathogenesis of obesity.
DOI: 10.1160/th03-01-0014
发表时间: 2004-04-01
影响因子: 6.7
作者:
Rosito, GA;D'Agostino, RB;Tofler, GH
通讯作者: Tofler, GH
饮食和凝血因子 VII——动脉血栓形成的关键蛋白
DOI: --
发表时间: 1998
影响因子: 4.7
作者:
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DOI: 10.1152/ajpregu.1995.268.3.r744
发表时间: 1995-03-01
影响因子: 2.8
作者:
YOUNGSTROM, TG;BARTNESS, TJ
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β-肾上腺素受体激动剂和其他 cAMP 升高剂抑制原代培养中人脂肪细胞 PAI-1 的产生
DOI: 10.1055/s-2007-978678
发表时间: 2000
影响因子: 2.2
作者:
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DOI: 10.1210/jc.2004-1292
发表时间: 2005-01-01
影响因子: 5.8
作者:
Godsland, IF;Crook, D;Stevenson, JC
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