Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes
Abstract
Recently, it has been demonstrated that the fat-derived protein adiponectin is an important insulin-sensitizing adipocytokine which is downregulated in insulin resistance and obesity and replenishment of which in adiponectin-deficient states improves insulin sensitivity. To clarify the regulation of adiponectin gene expression, 3T3-L1 adipocytes were treated with various hormones known to induce insulin resistance in vivo and adiponectin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, treatment of 3T3-L1 cells with 100 nM insulin, 10 ng/ml tumor necrosis factor (TNF) alpha, or 100 nM dexamethasone for 16 h suppressed adiponectin gene expression by about 50 to 85% while angiotensin 2, growth hormone, and triiodothyronine did not have any effect. Furthermore, insulin reduced the level of adiponectin mRNA in a dose- and time-dependent fashion with inhibition detectable at concentrations as low as 10 nM insulin and as early as 4 h after effector addition. The inhibitory effect of insulin was partially reversed by pretreatment of 3T3-L1 cells with pharmacological inhibitors of p44/42 mitogen-activated protein (MAP) kinase, phosphatidylinositol (PI) 3-kinase, and p70S6 kinase. Moreover, the negative effects of insulin, TNFalpha, and dexamethasone on adiponectin gene expression could be completely reversed by withdrawal of the hormones for 24 h. Taken together, our results suggest that adiponectin gene expression is reversibly downregulated by insulin, TNFalpha, and dexamethasone. The data support the concept of adiponectin being an important selectively controlled modulator of insulin sensitivity.
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In obesity, adiponectin levels are found to be reduced, given that its expression is inhibited by hypoxia, oxidative stress, insulin resistance, TNF-α, IL-6, 'catecholamine resistance', fetuin A, and SeP.
“In obesity, adiponectin levels are found to be reduced [216], given that its expression is inhibited by hypoxia, oxidative stress [228], insulin resistance [229], TNF-α, IL-6 [229], “catecholamine resistance” [239], fetuin A [148], and SeP [136].”
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- Authors
- Fasshauer, M., Klein, J., Neumann, S., Eszlinger, M., & Paschke, R.
- Affiliations
- Leipzig University (DE)
- University of Lübeck (DE)
- Corresponding author
- Paschke, Ralf
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 290
- Issue
- 3
- Pages
- 1084-1089
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1975898092
- Cited by
- 655
- References
- 30
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 11 · 2023: 11 · 2022: 10 · 2021: 16 · 2020: 14 · 2019: 20 · 2018: 23 · 2017: 12 · 2016: 22 · 2015: 34 · 2014: 26 · 2013: 26 · 2012: 34
- FWCI
- 37.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adiponectin, gene expression regulation, 3T3-L1 adipocytes, insulin, TNF-α, dexamethasone, insulin resistance, insulin sensitivity, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, p70 S6 kinase, adipokines, obesity
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Dexamethasone, Enzyme Inhibitors, Gene Expression Regulation, Glucocorticoids, Hormones, Insulin, Kinetics, Proteins, RNA, Messenger, Transcription, Genetic, Tumor Necrosis Factor-alpha, Down-Regulation, 3T3 Cells, Adipocytes, Ribosomal Protein S6 Kinases, Mitogen-Activated Protein Kinases, Intercellular Signaling Peptides and Proteins, Mice, Adiponectin
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