Lack of Evidence for Secretion of Plasminogen Activator Inhibitor-1 by Human Subcutaneous Adipose Tissue in Vivo

Yudkin, John; Coppack, Simon W.; Bulmer, Karen; Rawesh, A.; Mohamed‐Ali, Vidya

doi:10.1016/s0049-3848(99)00061-4

Cited by 35 publications

(21 citation statements)

References 50 publications

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“…in subcutaneous and visceral adipose tissue, respectively), and contrary to expectations we observed an inverse relationship between adipose tissue PAI-1 expression and BMI (r ¼ -0.85 (Po0.01) and À0.49 (P ¼ 0.08) for visceral and subcutaneous adipose tissue, respectively). Second, significant PAI-1 release from subcutaneous adipose tissue explants apparently contrasts with in vivo data of Yudkin et al 14 showing that human subcutaneous adipose tissue does not release PAI-1. Third, PAI-1 production by adipose tissue explants is preceded by several hour lag-phase with minimal PAI-1 protein release that is followed by an exponential increase in PAI-1 protein production and a concomitant several 100-fold increase in PAI-1 mRNA expression (data not shown).…”

Section: Resultsmentioning

confidence: 57%

Human visceral adipose tissue and the plasminogen activator inhibitor type 1

Lindeman

Pijl

Toet³

et al. 2007

Int J Obes

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Objective: The objective of this study was to systematically evaluate the molecular basis of the association between visceral fat mass and plasma plasminogen activator inhibitor-1 (PAI-1) levels in man. Design: A comprehensive approach comprising observational, in vitro, and human intervention studies. Measurements and results:We confirmed an exclusive relationship between visceral fat and plasma PAI-1 levels (r ¼ 0.79, Po0.001) and corroborated preferential PAI-1 release from adipose tissue explants. Yet, messenger RNA analysis and in vivo measurement of PAI-1 release from visceral fat (AV-differences over the omentum) not only excluded visceral adipose tissue as a relevant source of circulating PAI-1, but also excluded visceral fat as a significant source of proinflammatory mediators such as tumor necrosis factor-a, IL-1 or transforming growth factor-b that could induce PAI-1 expression in tissues other than visceral fat. Short-term interventions with acipimox and growth hormone (GH) as well as statistical evaluation excluded free fatty acids and GH as metabolic links. Further analysis of the metabolic data in a stepwise regression model indicated that plasma PAI-1 levels and visceral fat rather are co-correlates that both relate to impaired lipid handling. Conclusion: Our PAI-1 studies show that visceral fat mass and plasma PAI-1 levels are co-correlated rather than causatively related, with lipid load as common denominator.

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Section: Resultsmentioning

confidence: 57%

Human visceral adipose tissue and the plasminogen activator inhibitor type 1

Lindeman

Pijl

Toet³

et al. 2007

Int J Obes

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“…They found no evidence that subcutaneous adipose tissue contributes significantly to circulating PAI-1 levels in lean subjects. 25 However, it is also interesting to note that in another study a clear relationship between adipose tissue-derived PAI-1 expression and circulating plasma levels was established, further supporting a physiological role of PAI-1 produced by adipose tissue. 26 Thus, there is at least sufficient data to conclude that adipose tissue is an important source of circulating PAI-1.…”

Section: 24mentioning

confidence: 83%

Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1

2004

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Obesity is the central promoter of the metabolic syndrome which also includes disturbed fibrinolysis in addition to hypertension, dyslipidaemia and impaired glucose tolerance/type 2 diabetes mellitus. Plasminogen activator inhibitor-1 (PAI-1) is the most important endogenous inhibitor of tissue plasminogen activator and uro-plasminogen activator, and is a main determinant of fibrinolytic activity. There is now compelling evidence that obesity and, in particular, an abdominal type of body fat distribution are associated with elevated PAI-1 antigen and activity levels. Recent studies established that PAI-1 is expressed in adipose tissue. The greater the fat cell size and the adipose tissue mass, the greater is the contribution of adipose production to circulating PAI-1. Experimental data show that visceral adipose tissue has a higher capacity to produce PAI-1 than subcutaneous adipose tissue. Studies in human adipocytes indicate that PAI-1 synthesis is upregulated by insulin, glucocorticoids, angiotensin II, some fatty acids and, most potently, by cytokines such as tumour necrosis factor-a and transforming growth factor-b, whereas catecholamines reduce PAI-1 production. Interestingly, pharmacological agents such as thiazolidinediones, metformin and AT 1 -receptor antagonists were found to reduce adipose expression of PAI-1. In addition, weight loss by dietary restriction or comprehensive lifestyle modification is effective in lowering PAI-1 plasma levels. In conclusion, impaired fibrinolysis in obesity is probably also due to an increased expression of PAI-1 in adipose tissue. An altered function of the endocrine system and an impaired auto-/paracrine function at the fat cell levels may mediate this disturbance of the fibrinolytic system and thereby increase the risk for cardiovascular disease.

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“…Again, even here, opinions are divided, as some authors have suggested that subcutaneous fat tissue does not contribute to circulating plasma PAI-1 concentrations. 24 Significant associations between the amount of visceral rather than subcutaneous adipose tissue and plasma PAI-1 concentrations have been found. 25 Visceral fat may produce more PAI-1 than subcutaneous fat.…”

Section: Pai-1 Expression In Adipose Tissuementioning

confidence: 95%

Regulation of Plasma PAI-1 Concentrations in HAART-Associated Lipodystrophy During Rosiglitazone Therapy

Yki‐Järvinen

Sutinen

Silveira

et al. 2003

ATVB

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Objective-Patients with highly active antiretroviral therapy-associated lipodystrophy (HAARTϩLDϩ) have high plasminogen activator inhibitor-1 (PAI-1) concentrations for unknown reasons. We determined whether (1) plasma PAI-1 antigen concentrations are related to liver fat content (LFAT) independently of the size of other fat depots and (2) rosiglitazone decreases PAI-1 and LFAT in these patients. Methods and Results-In the cross-sectional study, 3 groups were investigated: 30 HIV-positive patients with HAARTϩLDϩ, 13 HIV-positive patients without lipodystrophy (HAARTϩLDϪ), and 15 HIV-negative subjects (HIVϪ). In the treatment study, the HAARTϩLDϩ group received either rosiglitazone (8 mg, nϭ15) or placebo (nϭ15) for 24 weeks. Plasma PAI-1 was increased in HAARTϩLDϩ (28Ϯ2 ng/mL) compared with the HAARTϩLDϪ (18Ϯ3, PϽ0.02) and HIVϪ (10Ϯ3, PϽ0.001) groups. LFAT was higher in HAARTϩLDϩ (7.6Ϯ1.7%) than in the HAARTϩLDϪ (2.1Ϯ1.1%, PϽ0.001) and HIVϪ (3.6Ϯ1.2%, PϽ0.05) groups. Within the HAARTϩLDϩ group, plasma PAI-1 was correlated with LFAT (rϭ0.49, PϽ0.01) but not with subcutaneous or intra-abdominal fat or serum insulin or triglycerides. In subcutaneous adipose tissue, PAI-1 mRNA was 2-to 3-fold higher in the HAARTϩLDϩ group than in either the HAARTϩLDϪ or HIVϪ group. Rosiglitazone decreased LFAT, serum insulin, and plasma PAI-1 and increased serum triglycerides but had no effect on intra-abdominal or subcutaneous fat mass or PAI-1 mRNA. Conclusions-Plasma PAI-1 concentrations are increased in direct proportion to LFAT in HAARTϩLDϩ patients.Rosiglitazone decreases LFAT, serum insulin, and plasma PAI-1 without changing the size of other fat depots or PAI-1 mRNA in subcutaneous fat. These data suggest that liver fat contributes to plasma PAI-1 concentrations in these patients.

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Lack of Evidence for Secretion of Plasminogen Activator Inhibitor-1 by Human Subcutaneous Adipose Tissue in Vivo

Cited by 35 publications

References 50 publications

Human visceral adipose tissue and the plasminogen activator inhibitor type 1

Human visceral adipose tissue and the plasminogen activator inhibitor type 1

Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1

Regulation of Plasma PAI-1 Concentrations in HAART-Associated Lipodystrophy During Rosiglitazone Therapy

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