Elevated Expression of Transforming Growth Factor-β in Adipose Tissue from Obese Mice
Open accessAbstract
Background Tumor necrosis factor-alpha (TNF-alpha) is chronically elevated in the adipose tissue from obese humans and mice. This increase in TNF-alpha contributes to the insulin resistance, elevated plasminogen activator inhibitor-1 (PAI-1) levels, and cardiovascular complications associated with obesity and noninsulin-dependent diabetes (NIDDM). PAI-1 gene expression in adipose tissue is also stimulated by transforming growth factor-beta (TGF-beta). Experiments were performed to determine whether TGF-beta is regulated by TNF-alpha and elevated in obesity.Materials and methods The concentration of TGF-beta and PAI-1 mRNA in murine adipose tissue and cultured 3T3-L1 adipocytes was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR), and the cellular localization of these molecules was evaluated using in situ hybridization and cell fractionation. Total TGF-beta protein was determined by employing an ELISA assay.Results TGF-beta mRNA and protein were increased in the adipose tissue from two different strains of genetically obese mice (i.e., ob/ob and db/db), compared with their lean counterparts. This increase in TGF-beta may result from TNF-alpha since TNF-alpha increased TGF-beta mRNA expression in the adipose tissue of lean mice and stimulated TGF-beta production by cultured adipocytes. Administration of TGF-beta increased PAI-1 antigen in the plasma and PAI-1 mRNA in the adipocytes of lean mice, and enhanced the rate of PAI-1 synthesis by adipocytes in vitro.Conclusions TNF-alpha contributes to the elevated TGF-beta expression demonstrated in the adipose tissue of obese mice. A potential role for TGF-beta in the increased PAI-1 and vascular pathologies associated with obesity/NIDDM is suggested.
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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 [99]
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- Authors
- Samad, F., Yamamoto, K., Pandey, M., & Loskutoff, D. J.
- Affiliations
- Scripps Research Institute (US)
- Venue
- Molecular Medicine
- Published
- 1997-01
- Volume
- 3
- Issue
- 1
- Pages
- 37-48
- ISSN
- 1076-1551 (ISSN-L)
- 1528-3658
- PMC
- PMC2230108
- OpenAlex
- W1533523963
- Cited by
- 303
- References
- 59
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 14 · 2023: 11 · 2022: 15 · 2021: 8 · 2020: 12 · 2019: 14 · 2018: 16 · 2017: 9 · 2016: 8 · 2015: 13 · 2014: 7 · 2013: 15 · 2012: 14
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl047819-12)
- National Heart, Lung, and Blood Institute (HL47819)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- TGF-beta, adipose tissue, obesity, TNF-α, plasminogen activator inhibitor-1, 3T3-L1 adipocytes, ob/ob mice, db/db mice, insulin resistance, type 2 diabetes, vascular complications, gene expression regulation
- MeSH terms
- Adipose Tissue, Animals, Cell Fractionation, Gene Expression Regulation, Insulin, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, RNA, Messenger, Transforming Growth Factor alpha, Transforming Growth Factor beta, 3T3 Cells, Plasminogen Activator Inhibitor 1, Mice
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