Plasminogen activator inhibitor 1, transforming growth factor-β1, and BMI are closely associated in human adipose tissue during morbid obesity
Plasminogen activator inhibitor 1, transforming growth factor-β1, and BMI are closely associated in human adipose tissue during morbid obesity
复制标题
DOI：
10.2337/diabetes.49.8.1374
复制
发表时间：
2000-08-01
期刊：
影响因子：
7.7
通讯作者：
Juhan-Vague, I
中科院分区：
文献类型：
--
作者：
Alessi, MC;Bastelica, D;Juhan-Vague, I
在来自肥胖小鼠和人的脂肪组织中，纤溶酶原激活物抑制剂1（派-1）表达已被报道上调至增加的血浆派-1水平。在小鼠中，这种升高的表达已被证明部分受肿瘤坏死因子（TNF）-α的控制。在人类中，派-1表达增加与以内脏脂肪积累为特征的胰岛素抵抗相关。因此，本研究的目的是研究派-1和TNF-α（抗原和mRNA）的表达模式在内脏脂肪的人相比，皮下（SC）脂肪。因为转化生长因子（TGF）-β（1）是派-1合成的有效诱导剂，并且已被证明影响脂肪细胞代谢，所以这项工作扩展到TGF-β（1）定量。总共研究了32名肥胖个体（BMI 42 +/- 6.8 kg/m2）。新鲜采集的内脏脂肪组织中派-1或TGF-β 1的含量并不高于SC组织。尽管大多数TNF-α值处于方法的检测限，但在内脏脂肪中TNF-α抗原高3倍，TNF-α mRNA高1.2倍。组织TGF-β（1）抗原水平与派-1抗原水平相关性良好，与研究的脂肪储库无关（SC组织：n = 21，r = 0.72，P = 0.0006;内脏组织：n = 20，r = 0.49，P < 0.03），两者均与BMI显著相关。TNF-α与PGI-1、TNF-α与BMI之间无相关性，组织PAI-1与循环派-1之间亦有显著相关性。这些结果描述了在严重肥胖中，内脏和SC组织中派-1和TGF-β（1）的成比例增加。这种派-1表达增加可能是组织细胞因子紊乱的结果，例如TGF-β（1）表达升高。
In adipose tissue from both obese mice and humans, plasminogen activator inhibitor 1 (PAI-1) expression has been reported to be upregulated to levels of increased plasma PAI-1. This elevated expression has been shown to be partly controlled by tumor necrosis factor (TNF)-alpha in mice. In humans, increased PAI-1 expression is associated with insulin resistance characterized by visceral fat accumulation. Therefore, the aim of this study was to investigate the expression pattern of PAI-1 and TNF-alpha (antigen and mRNA) in visceral human adipose fat in comparison with subcutaneous (SC) fat. Because transforming growth factor (TGF)-beta(1) is a potent inducer of PAI-1 synthesis and has been shown to influence adipocyte metabolism, this work was extended to TGF-beta(1) quantification, A total of 32 obese individuals (BMI 42 +/- 6.8 kg/m(2)) were investigated. Freshly collected visceral adipose tissue did not exhibit a higher content of PAI-1 or TGF-beta(1) than did SC tissue. Although most of the TNF-alpha values were at the detection limit of the methods, TNF-alpha antigen was 3-fold higher and TNF-alpha mRNA was 1.2-fold higher in visceral fat. The levels of tissue TGF-beta(1) antigen correlated well with those of PAI-1 antigen, regardless of the fat depot studied (SC tissue: n = 21, r = 0.72, P = 0.0006; visceral tissue: n = 20, r = 0.49, P < 0.03), and they were both significantly associated with BMI. Conversely, no relationship was observed between the levels of TNF-alpha and PGI-1 or TNF-alpha and BMI, Tissue PAI-1 levels were also significantly correlated with those of circulating PAI-1. These results describe, in severe obesity, a proportional increase in tissue PAI-1 and TGF-beta(1) in visceral and SC tissues, This increased PAI-1 expression could be the result of tissue cytokine disturbances, such as elevated TGF-beta(1) expression.