Plasminogen activator inhibitor 1, transforming growth factor-beta(1), andBMI are closely associated in human adipose tissue during morbid obesity

In adipose tissue from both obese mice and humans, plasminogen activator in hibitor 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 pa rtly controlled by tumor necrosis factor (TNF)-alpha in mice. In humans, in creased PAI-1 expression is associated with insulin resistance characterize d by visceral fat accumulation. Therefore, the aim of this study was to inv estigate the expression pattern of PAI-1 and TNF-alpha (antigen and mRNA) i n visceral human adipose fat in comparison with subcutaneous (SC) fat. Beca use transforming growth factor (TGF)-beta(1) is a potent inducer of PAI-1 s ynthesis and has been shown to influence adipocyte metabolism, this work wa s extended to TGF-beta(1) quantification, A total of 32 obese individuals ( BMI 42 +/- 6.8 kg/m(2)) were investigated. Freshly collected visceral adipo se 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 lim it of the methods, TNF-alpha antigen was 3-fold higher and TNF-alpha mRNA w as 1.2-fold higher in visceral fat. The levels of tissue TGF-beta(1) antige n 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 an d PGI-1 or TNF-alpha and BMI, Tissue PAI-1 levels were also significantly c orrelated with those of circulating PAI-1. These results describe, in sever e obesity, a proportional increase in tissue PAI-1 and TGF-beta(1) in visce ral and SC tissues, This increased PAI-1 expression could be the result of tissue cytokine disturbances, such as elevated TGF-beta(1) expression.