Regional Variation in Plasminogen Activator Inhibitor-1 Expression in Adipose Tissue from Obese Individuals

2000 ◽  
Vol 83 (04) ◽  
pp. 545-548 ◽  
Author(s):  
Vanessa Van Harmelen ◽  
Johan Hoffstedt ◽  
Per Lundquist ◽  
Hubert Vidal ◽  
Veronika Stemme ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Visceral Adipose ◽  
Subcutaneous Adipose ◽  
Activator Inhibitor ◽  
Pai 1

SummaryHigh plasma plasminogen activator inhibitor-1 (PAI-1) activity is a frequent finding in obesity and adipose tissue has recently been suggested to be a source of circulating PAI-1 in humans. In the present study, differences in adipose tissue gene expression and protein secretion rate of PAI-1 between subcutaneous and visceral adipose tissue was analysed in specimens obtained from 22 obese individuals. The secretion rate of PAI-1 was two-fold higher in subcutaneous adipose tissue than in visceral adipose tissue (292 ± 50 vs 138 ± 24 ng PAI-1/107 cells, P <0.05). In accordance with the secretion data, subcutaneous adipose tissue contained about three-fold higher levels of PAI-1 mRNA than visceral adipose tissue (2.43 ± 0.37 vs 0.81 ± 0.12 attomole PAI-1 mRNA/µg total RNA, P <0.001). PAI-1 secretion from subcutaneous but not from visceral adipose tissue correlated significantly with cell size (r = 0.43, P <0.05). In summary, subcutaneous adipose tissue secreted greater amounts of PAI-1 and had a higher PAI-1 gene expression than visceral adipose tissue from the same obese individuals. Bearing in mind that subcutaneous adipose tissue is the largest fat depot these finding may be important for the coagulation abnormalities associated with obesity.

Role of Gender and Genetic Variance in Plasminogen Activator Inhibitor-1 Secretion from Human Adipose Tissue

2000 ◽  
Vol 83 (02) ◽  
pp. 304-308 ◽  
Author(s):  
Hans Wahrenberg ◽  
Per Eriksson ◽  
Peter Arner ◽  
Vanessa Van Harmelen
Keyword(s):  
Body Mass Index ◽  
Adipose Tissue ◽  
Gender Difference ◽  
Subcutaneous Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Plasma Triglycerides ◽  
Subcutaneous Adipose ◽  
Activator Inhibitor ◽  
Pai 1

SummaryGender and the 4G/5G polymorphism in the plasminogen activator inhibitor 1 (PAI-1) gene are believed to play a role in the regulation of plasma PAI-1 activity. Adipose tissue has been found to be an important source of PAI-1. The possible influence of gender and the 4G/5G polymorphism in the PAI-1 gene on PAI-1 secretion from abdominal subcutaneous adipose tissue was investigated in 59 women and 32 men. The subjects were apparantly healthy, although they differed markedly inter-individually in body mass index (21-53 kg/m2). The 4G/5G polymorphism did not influence the adipose secretion rate of PAI-1 or plasma PAI-1 activity. There was no gender difference in the adipose secretion of PAI-1. In multiple regression, including body mass index (BMI), waist-to-hip ratio (WHR), plasma insulin and plasma triglycerides as the independent and adipose PAI-1 secretion as the dependent variable, only BMI and plasma triglycerides correlated independently with adipose PAI-1 secretion (r = 0.54, p <0.05; r = 0.51, p <0.05, respectively). Men had a two times higher plasma PAI-1 activity than women (p <0.05). This gender difference was mainly due to gender differences in WHR. In multiple regression analysis, BMI and WHR were identified to be independently correlated with plasma PAI-1 activity (r = 0.60, p <0.05; r = 0.52, p = 0.01, respectively). In conclusion, neither gender nor the 4G/5G polymorphism in the PAI-1 gene are associated with secretion of PAI-1 from abdominal subcutaneous adipose tissue.

TNF-α, but not IL-6, stimulates plasminogen activator inhibitor-1 expression in human subcutaneous adipose tissue

2005 ◽  
Vol 98 (6) ◽  
pp. 2019-2023 ◽  
Author(s):  
Peter Plomgaard ◽  
Pernille Keller ◽  
Charlotte Keller ◽  
Bente Klarlund Pedersen
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Plasminogen Activator ◽  
Subcutaneous Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tnf Α ◽  
Subcutaneous Adipose ◽  
Activator Inhibitor ◽  
Pai 1

Plasminogen activator inhibitor-1 (PAI-1) is produced by adipose tissue, and elevated PAI-1 levels in plasma are a risk factor in the metabolic syndrome. We investigated the regulatory effects of TNF-α and IL-6 on PAI-1 gene induction in human adipose tissue. Twenty healthy men underwent a 3-h infusion of either recombinant human TNF-α ( n = 8), recombinant human IL-6 ( n = 6), or vehicle ( n = 6). Biopsies were obtained from the subcutaneous abdominal adipose tissue at preinfusion, at 1, 2, and 3 h during the infusion, and at 2 h after the infusion. The mRNA expression of PAI-1 in the adipose tissue was measured using real-time PCR. The plasma levels of TNF-α and IL-6 reached 18 and 99 pg/ml, respectively, during the infusions. During the TNF-α infusion, adipose PAI-1 mRNA expression increased 2.5-fold at 1 h, 6-fold at 2 h, 9-fold at 3 h, and declined to 2-fold 2 h after the infusion stopped but did not change during IL-6 infusion and vehicle. These data demonstrate that TNF-α rather than IL-6 stimulates an increase in PAI-1 mRNA in the subcutaneous adipose tissue, suggesting that TNF-α may be involved in the pathogenesis of related metabolic disorders.

Inverse relationship between plasminogen activator inhibitor-1 activity and adiponectin in overweight and obese women

2005 ◽  
Vol 94 (12) ◽  
pp. 1190-1195 ◽  
Author(s):  
Ilse Mertens ◽  
Dominique Ballaux ◽  
Tohru Funahashi ◽  
Yuji Matsuzawa ◽  
Marc Van der Planken ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Obese Women ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Difference ◽  
Hs Crp ◽  
Visceral Adipose ◽  
The Relationship ◽  
Activator Inhibitor ◽  
Pai 1

SummaryAdipose tissue is an active endocrine organ secreting different adipokines such as plasminogen activator inhibitor-1 (PAI-1) and adiponectin, among many others. In this study, we investigated the association between PAI-1 activity and serum adiponectin levels in a group of 444 overweight and obese women and assessed the interrelationship with visceral adipose tissue (VAT; CT-scan L4-L5), insulin resistance (HOMA-IR), HDL cholesterol (HDL-chol) and inflammation (hs-CRP). PAI-1 was inversely related to adiponectin (r=-0.25, p<0.001; adjusted for age and BMI).After adjustment for age, VAT, HOMA-IR and hs-CRP, the relationship remained significant (r=-0.15; p=0.001), but disappeared after additional adjustment for HDL-chol (r=-0.09; p=0.067). Subjects were divided in two groups according to the median levels of adiponectin or PAI-1 levels. PAI-1 activity (19.1±11.4 vs. 15.8±8.6 AU/ml; p=0.003) and adiponectin levels (9.8±4.6 vs. 8.4±4.0 μg/ml; p<0.001) were significantly higher in the low adiponectin/PAI-1 groups. The difference in PAI-1 remained significant after adjustment for age and BMI (p=0.001), became borderline significant after adjustment for age and VAT (p=0.052), and disappeared after adjustment for age and HOMA-IR (p=0.116) or age and HDL-chol (p=0.443).The difference in adiponectin levels remained significant after adjustment for age, VAT, HOMA-IR and hs-CRP (p=0.006), but disappeared after additional adjustment for HDL-chol (p=0.089). Further analyses suggest a contribution of HOMA-IR and/or HDL-chol in the relationship between PAI-1 and adiponectin. HDL-chol was found to be the only factor independently determining both factors. In conclusion, in overweight and obese women, PAI-1 activity was inversely related to serum adiponectin, independent of visceral adipose tissue.

scholarly journals Increased adipose tissue secretion of interleukin-6, but not of leptin, plasminogen activator inhibitor-1 or tumour necrosis factor alpha, in Graves' hyperthyroidism

2002 ◽  
pp. 607-611 ◽  
Author(s):  
H Wahrenberg ◽  
A Wennlund ◽  
J Hoffstedt
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Tumour Necrosis Factor Alpha ◽  
Tnf Alpha ◽  
Plasminogen Activator Inhibitor 1 ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Activator Inhibitor ◽  
Necrosis Factor ◽  
Pai 1

OBJECTIVE: This study was designed to investigate adipose tissue secretion of interleukin-6 (IL-6), leptin, tumour necrosis factor alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) in Graves' hyperthyroidism. DESIGN: We studied 10 patients before and during (after 8 weeks) anti-thyroid treatment for Graves' hyperthyroidism and 16 healthy, euthyroid control subjects. METHODS: Plasma levels of thyroid hormones and serum/plasma levels of IL-6, leptin, TNF-alpha and PAI-1 were analysed. Subcutaneous fat biopsies were taken for subsequent measurement of IL-6, leptin, TNF-alpha and PAI-1 protein secretion. RESULTS: In patients with Graves' disease, the anti-thyroid treatment resulted in significant reductions of plasma thyroxine and triiodothyronine levels. No differences in serum concentration or adipose tissue secretion of leptin or TNF-alpha were observed either before, as compared with during, anti-thyroid treatment, or in comparison with euthyroid controls. In contrast, plasma PAI-1 activity, but not adipose tissue secretion of PAI-1, was increased both in Graves' disease before as compared with during anti-thyroid treatment (P=0.01) and in thyrotoxic patients compared with euthyroid controls (P=0.0001). Finally, adipose secretion of IL-6 was increased both before (8-fold, P=0.001) and during (6-fold, P<0.0001) treatment as compared with control subjects. Accordingly, serum concentration of IL-6 was also increased by about 50% in thyrotoxic patients as compared with healthy controls (P=0.03). CONCLUSIONS: In Graves' hyperthyroidism regardless of thyroid status, adipose tissue secretion of IL-6, but not of leptin, TNF-alpha or PAI-1, is markedly increased in comparison with euthyroid controls. This suggests that autoimmune thyroidal disorder may regulate adipose tissue release of IL-6.

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