Plasminogen activator inhibitor 1, transforming growth factor-beta1, and BMI are closely associated in human adipose tissue during morbid obesity.
Open accessAbstract
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)-beta1 is a potent inducer of PAI-1 synthesis and has been shown to influence adipocyte metabolism, this work was extended to TGF-beta1 quantification. A total of 32 obese individuals (BMI 42 +/- 6.8 kg/m2) were investigated. Freshly collected visceral adipose tissue did not exhibit a higher content of PAI-1 or TGF-beta1 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-beta1 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 PAI-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-beta1 in visceral and SC tissues. This increased PAI-1 expression could be the result of tissue cytokine disturbances, such as elevated TGF-beta1 expression.
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TGF-β expression in fat is paradoxically increased with obesity in rodents and humans.
“While TGF-β inhibits adipocyte differentiation in vitro 97 and TGF-β expression in fat is paradoxically increased with obesity in rodents and humans 98,99.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [98]
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- Authors
- Alessi, M. C., Bastelica, D., Morange, P., Berthet, B., Leduc, I., Verdier, M., Geel, O., & Juhan-Vague, I.
- Affiliations
- Hôpital de la Timone (FR)
- Corresponding author
- Leduc, I
- Verdier, M
- Juhan-Vague, I
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-08-01
- Volume
- 49
- Issue
- 8
- Pages
- 1374-1380
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2134059227
- Cited by
- 344
- References
- 49
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 13 · 2022: 9 · 2021: 13 · 2020: 9 · 2019: 5 · 2018: 8 · 2017: 10 · 2016: 19 · 2015: 10 · 2014: 17 · 2013: 21 · 2012: 26
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- plasminogen activator inhibitor-1, TGF-β1, TNF-α, morbid obesity, visceral adipose tissue, subcutaneous adipose tissue, body mass index, adipose tissue cytokines, insulin resistance
- MeSH terms
- Adipose Tissue, Adult, Animals, Female, Humans, Male, Obesity, Morbid, Regression Analysis, RNA, Messenger, Skin, Transcription, Genetic, Tumor Necrosis Factor-alpha, Viscera, Body Mass Index, Transforming Growth Factor beta, Plasminogen Activator Inhibitor 1, Mice
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