Human visceral adipose tissue and the plasminogen activator inhibitor type 1

Abstract

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.

Contribution of Genetic and Metabolic Syndrome to Omental Adipose Tissue PAI-1 Gene mRNA and Plasma Levels in Obesity

“…This is in contrast with the negative correlation observed with plasma PAI-1 levels in the present study and to what we might have expected [29][30][31]. In accordance with our observations, Lindeman et al [30] found an inverse relationship between abdominal subcutaneous and visceral AT PAI-1 mRNA levels and BMI values.…”

“…This is in contrast with the negative correlation observed with plasma PAI-1 levels in the present study and to what we might have expected [29][30][31]. In accordance with our observations, Lindeman et al [30] found an inverse relationship between abdominal subcutaneous and visceral AT PAI-1 mRNA levels and BMI values. In addition, Bastard et al [32] reported that PAI-1 mRNA and protein abundance in subcutaneous abdominal AT of non-diabetic obese individuals were increased following very low caloric diet induced weight loss.…”

Heart failure and inflammation-related biomarkers as predictors of new-onset diabetes in the general population

“…Individuals who developed T2DM also demonstrated a significant increase in waist-hip ratio, indicating that PAI-1, DM and central obesity are closely related. This is also in line with previous studies that demonstrated a significant association between PAI-1 levels and the amount of visceral adipose tissue [40]; overexpression of PAI-1 has also been observed in cultured adipocytes and in adipose tissue of mice and humans [41] strengthening the concept that (visceral) adipose tissue is an important source of PAI-1. Interestingly, PAI-1 KO mouse models on high-fat diet displayed a significant reduction in obesity, hyperglycaemia and hyperinsulinaemia compared to wild type mice fed on a similar diet [42].…”

Effect of Short-Term Hyperglycemia on Adipose Tissue Fluxes of Selected Cytokines In Vivo During Multiple Phases of Diet-Induced Weight Loss in Obese Women

“…Another limitation of the study could be associated with a rather high variability of A-V differences present in this as well as in other studies (22,31). When taking into account this variability we cannot rule out, that a release of some cytokines with low production in scAT could be missed.…”